Lanthanum accumulation in bone minmal and impact on bone needs to be studied
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium deficiency is likely to be an issue in osteporosis as it is crucial for osteoblast and osteoclast function and activity in bone remodellig.
strontium as
the ranelate compound is being used as an anti-osteoporotic
agent, it is contra-indicated in patients with a GFR<30 mL and it could be linked to oseteomalacia
Lanthanum accumulation in bone minmal and impact on bone needs to be studied
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium deficiency is likely to be an issue in osteporosis as it is crucial for osteoblast and osteoclast function and activity in bone remodellig.
strontium as
the ranelate compound is being used as an anti-osteoporotic
agent, it is contra-indicated in patients with a GFR<30 mL and it could be linked to oseteomalacia
According to KDIGO guidelines, what are the 3 components of CKD-MBD?Mineral and Endocrine Abnormalities of calcium and phosphate and PTH . (ii) abnormalities of turnover , mineralisation, volume and linear growth. (iii) Extra Skeletal Manifestation
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
in 2009 there was clear indication for bone biopsy namely (i) unexplained fractures, (ii) hypercalcaemia, (iii)(hypophosphataemia) , (iv) suspected alumminum toxicity(V) or before osteoporosis while in 2017 experts recommended doing a bone biopsy if it would change management. this is as centres lack access to bone biopsy facilities ( bone biopsy and interpretation of histopathology) and lack of funding . this could have impacted KDIGO to change its guidelines concerning bone biopsy.
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement
Invasive procedure
needs technical expertise in acquring ,processing and interpreting sample.
Time delay of weeks to get results
Sample size might be limited and not enough to correspond to actual pathology /also sampling errors and one shot vision
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turnover bone disease
Diagnosis: FGF 23 , RANK/RANKL/Osteoprotegerin system, also the sclerostin and Winglessrelated integration site (Wnt)/beta-catenin system will be
active and participate in a low bone turnover disease
Biopsy: no osteoclast , few osteoblast no osteoid formation and acellular bone.
High turonver
Diagnosis: low vitamin D , high PTH, High BALP , FGF23
Biopsy: Increased Osteoblast and Osteoclast numbers, increase in cancellous bone volume, decrease in cortical bone and porosity
Bone mineralisation is normal tho there might be a lag in mineralisation due to accelerated bone formation
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontiumon bone?
Aluminium has been associated with the deposition of aluminum at the osteoid-calcifed bone boundary
whereby the element acts as an inhibitor of hydroxyapatite
formation/growth in osteomalacia while in adynamic bone disease is due to direct effect on osteoblastic activity or inhibitory effect on PTH
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
a)mineral and endocrine abnormalities of calcium, phosphorus, parathyroid hormone, or vitamin D metabolism
b)abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength.
c)extra-skeletal calcifications. 2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
In KDIGO 2009 the bone biopsy is done in following situations:
-Multiple Fractures
-Unexplained hypercalcemia or hypophosphatemia
-suspected aluminium intoxication
-before osteoporosis treatment
In KDIGO 2017 , the bone biopsy is recommended only if it influence the treatment
i think bone biopsy is especially beneficial in patient with non conclusive labs or symptoms. However it need an expert pathologist and excellent skills.
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.Bone biopsy provide information about volume, turnover, mineralization, architecture and cortical bone related aspects such as porosity or thickness. It still the gold standard for ROD diagnosis since it allows us to analyse both cortical and trabecular bone, gives us information about static and dynamic parameters of bone turnover and is the only method able to assess mineralization.
Limitation are due to its a)invasivness b) it is a one shot vision at one time point c) can be impaired by sampling errors d) a time consuming process e) it need expertise in collecting and processing bone fragments.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?Bone turnover can be normal , high or low.
Non invasively we will find in high turnover bone disease high levels of FGF23, low levels of vitamin D and high levels of PTH. high level of TRAP5.
In low turnover bone disease we will find RANK/RANKL Osteoprotegerin system also the sclerostin and wingless related integration site Wnt/Beta-Catenin system will be active and participate in low turnover bone disease.
In Clinical practice these markers are not all availabe. Nephrologist use normally PTH level and BALP for follow up bone turnover status .
Bone biopsy remain the gold standard of diagnosing bone turnover and mineralisation. Characteristics of high bone turnover in bone biopsy: increased osteoblast and osteoclast number, increased cancellous bone volume and a decrease in cortical bone volume in terms of cortical thinning and increased cortical porosity. Intertrabecular fibrosis may be also severe and impact erythropoesis.
Bone mineralisation is normal
in Low turnover bone disease:
there is no osteoclasts and few osteoblasts , no osteoid formation. low dynamic parameters , and when associated with low volume, is termed adynamic bone disease.
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?-Aluminium is a bone seeking element that can accumulate in bones and lead to low turnover bone disease and osteomalacia. it inhibit hydroxyapatite formation, affect osteoblastic activity and PTH secretion /Sythesis.
-Lanthanum is a rare earth element and does not seem to have any side effect on bone mineralization or osteoblastic activity.
-Iron overload is associated with increased frequency of adynamic bone disease, it also compete with aluminium.
-The role of Magnesium is still a matter of debate. it was suggested that it causes osteomalacia and ROD due to its calcimimetic effect on CaSR and to its inhibiton of calcification and mineralisation. Study failed to demonstrate that.
-Strontium can accumulate in CKD Patient with GFR under 30 and cause mineralisation defect (Osteomalacia), it was used as anti osteoportic drug.
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD? (1) mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism; (2) abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength; and (3) extra-skeletal calcifcations
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
In 2009 stating that a bone biopsy should be performed in at least fve situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity or before osteoporosis treatment)
KDIGO guidelines in 2017 : bone biopsies should be performed if the diagnosis impacts treatment . It’s the gold standard for the diagnosis of ROD.
A bone biopsy is very useful and should be performed for bone disease differentiation, I believe it is equally necessary to consider the challenges of performing a bone marrow biopsy. Given the cost, invasiveness, and lack of competence in conducting and diagnosing, so I agree to be performed if the diagnosis has an impact on therapy.
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
The cost of histopathological analysis (with insufcient reimbursement)
And the lack of centers with sufcient expertise
Is an invasive procedure
Isa one-shot vision at a time-point
Can be affected by sampling errors
Time consuming
3. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turn over; High sclerostin, low PTH, low BALP, No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone
High turn over; High FGF-23,low vitamin D, high PTH, high BALP, increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization
4. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum : Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease . Chelation therapy with desferrioxamine results in improvements of clinical symptoms and bone histology Lanthanum: accumulation of lanthanum in bone is minimal. It is not found at critical sites of bone mineralization and no serious efects on either bone mineralization and/or osteoblastic activity have been reported in dialysis patient . Iron : Iron overload or deficiency has been linked to bone problems & osteoporotic lesions Magnesium: hypermagnesemia is associated with the development of osteomalacia and/or renal osteodystrophy.It is a well-known essential element for multiple biological processes in the body. It it is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling Strontium: It is an anti-osteoporotic agent, it is contra-indicated in patients with a GFR< 30 mL/ min. strontium accumulates in dialysis patient . It is a causal role of the element in the development of osteomalacia
A-According to KDIGO guidelines, what are the 3 components of CKD-MBD 1. mineral and endocrine abnormalities (balance of calcium, phosphorus, parathyroid hormone (PTH), FGF23 and vitamin D metabolism) 2. abnormalities related bone to turnover, mineralization, bone volume, linear growth, or strength. 3. extra-skeletal calcifications. B-KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it: in 2009 stating that bone biopsy indications were *Multiple fractures, *Unexplained hypercalcemia / hypophosphatemia, * Suspected aluminum toxicity or before osteoporosis treatment but the KDIGO guidelines were revised in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment. and I think although the bone biopsy is very informative and should be done for differentiations of bone disease, it’s also important to think about challenges of performing the bone marrow biopsy. including the cost, invasiveness and lack of experience in performing and diagnosis, so I agree to performed if the diagnosis impacts treatment. C-Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement. the limitations are an invasive procedure, one-shot vision at a time-point, can be impaired by sampling errors; is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis. D-What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy. Extra-osseous calcifications,abnormal , high turnover bone diseases E-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum:Aluminum accumulation in the bone results in certain forms of
renal osteodystrophy, most especially osteomalacia and ady-namic bone disease
Lanthanum: accumulation of lanthanum in bone is minimal and no serious effects on either.
bone mineralization
Iron: increases the frequency of a dynamic bone diseases
Mg:hypermagnezemia is associated with osteomalacia and renal osteodystrophy
Strontium:
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
Abnormalities in ca , po4 , PTH , vitamin D
Abnormalities in bone turnover, mineralization, volume, linear growth and strength
extraoseois calcification
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
guidelines published in 2009 state that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity or before osteoporosis treatment) .
In contrast to this , the revised KDIGO guidelines launched in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment .
I think this will complicate the situation.
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
there are limitations, as it (a) is an invasive procedure; (b) a one-shot vision at a time-point, (c) can be impaired by sampling errors; (4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and (5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turnover bone disease
and
high turnover bone disease
*Noninvasive diagnosis:
–Low turn over High sclerostin, low PTH, low BALP
–High turn over High FGF-23,low vitamin D, high PTH, high BALP
*Bone biopsy findings:
–High turn over; increase osteoclast and osteoblast number, increase bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization. There is increase expression of the tart rate-resistant acid phosphatase by osteoclast.
–Low turn over there is No osteoclast, few osteoblast, and no osteoid formation. In one ward acellular bone.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum/ ABD
Lanthanum/ no known effect
Iron/ABD
Mg/ osteoporosis
Strontium/osteomalacia.
According to KDIGO guidelines, what are the 3 components of CKD-MBD?(1) mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism;
(2) abnormalities of bone related to turnover, mineralization, volume,linear growth, or strength; and
(3) extra-skeletal calcications KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?This is in line with the revised KDIGO guidelines launched in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment , which to a certain extent is in contrast to the guidelines published in 2009 stating that a bone biopsy should be performed in at least ve situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxic- ity or before osteoporosis treatment). Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
A bone biopsy provides highly valuable and in-depth information that is required for the patient’s treatment. This technique remains the gold standard for ROD diagnosis since it (a) allows analysis of both cortical and trabecular bone, (b) gives information on static and dynamic parameters of bone turnover, and (c) is the only method able to assess mineralization.
Nevertheless, there are limitations, as it (a) is an invasive procedure; (b) a one-shot vision at a time-point, (c) can be impaired by sampling errors; (4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and (5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?On the one hand, there will be high levels of FGF23, low levels of vitamin D, and high levels of PTH, transforming the remodeling process in a high turnover bone disease. On the other hand, aside from the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and Wingless- related integration site (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease, along with the other known risk factors for low turnover, such as vigorous treatment of secondary hyperparathyroidism, dia- betes, age, and the use of high flux dialysis’ membranes.
In the case of high bone turnover, the most typical bone findings in static histomorphometry are a signi cant increase in osteoblast and osteoclast number, which can be accompanied by an increased cancellous bone volume and a decrease in cortical bone volume in terms of cortical thinning and increased cortical porosity. The inter-trabecular brosis can be massive if secondary hyperparathyroidism is severe that can even compromise the bone marrow erythropoiesis. Usually, bone mineralization is normal, even though osteoid surface and even volume may be slightly increased, due to the accelerated bone formation process along with a delay in bone mineralization. In severe high turnover bone dis- ease, osteoclast surface and osteoclast number are typically increased. Using a histochemical method to optimize the tartrate-resistant acid phosphatase expressed and secreted by osteoclasts, we can obtain an exuberant expression of these cells, when they are active, in the bone resorption process
At the opposite extreme of bone turnover, we nd low turnover bone disease, with no osteoclasts and few osteoblast numbers, no osteoid formation, and, in extreme cases, fea- tures of an acellular bone. This low bone remodeling aspect, with low dynamic parameters when associated with low vol- ume, is termed adynamic bone disease.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease. the impaired mineralization has been associated with the deposition of aluminum at the osteoid-calcied bone boundary whereby the element acts as an inhibitor of hydroxyapatite formation/growth.
Lanthanum: accumulation of lanthanum in bone is minimal
It is not found at critical sites of bone mineralization and so far no serious e ects on either bone mineralization and/or osteoblastic activity have been reported in lanthanum-treated dialysis patients
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium defciency is likely to be an issue in osteoporosis as it is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling
Strontium: Moreover, a bone biopsy- based study in 100 dialysis patients revealed increased bone strontium concentrations in patients with osteomalacia
1.According to KDIGO guidelines, what are the 3 components of CKD-MBD?
Abnormalities of: Ca, PO4, PTH, & vitamin D, bone histomorphometry, Extra-skeletal calcification.
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
2017 recommendation: if the diagnosis impacts treatment
2009 recommendation: Bone biopsy is indicated the following situations: Multiple fractures, Unexplained hypercalemia, hypophosphatemi, Suspected aluminum toxicity, Before osteoporosis
I go with The 2017 guidelines: as it’s the gold standard for the diagnosis of ROD.
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
Invasive, A one-shot vision at a time-point, sampling errors, Time consuming, expertise is required.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turn over and high turn over
Noninvasive diagnosis:
–Low turn over; High sclerostin, low PTH, low BALP
–High turn over; High FGF-23,low vitamin D, high PTH, high BALP
Bone biopsy findings:
–High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization. There is increase expression of the tart rate-resistant acid phosphatase by osteoclast.
–Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum; Accumulates in bone-osteomalacia due to inhibition of hydroxapatite formation, growth or ABD due to direct effects on osteoblast or indirectly interference with PTH synthesis.
Lanthanum; no reported serious effect on mineralization or osteoblast activities in dialysis patients who were treated with lanthaum.
Iron; Historically,usually found concomitantly with aluminum overload
Magnesium: Mg contributes in regulation of osteoblast and osteoclast function/activity in bone remodeling, Hypomagesemia may have negative effect on the bone especially in osteoporosis
Strontium: Animal studies revealed that, it may have a causal role in osteomalacia and other effects on the bone
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
The components are:
Mineral and endocrine abnormalities of calcium, phosphorus, parathyroid hormone, or vitD metabolism
Abnormalities of bone are related to turnover, mineralization, volume, linear growth, or strength
Extra-skeletal calcification
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
2017 suggests bone biopsies if it will change management of disease
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.ations. Explain the aforementioned statement.
Invasive nature of the bone biopsy
Sampling errors
Time consuming – takes along time to get the results
requires histopathologists trained in the field
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Abnormalities is classified into:
Low turn over and high turn over
Diagnosis:
In low turn over
High sclerostin, low PTH, low BSAP
In high turn over
High FGF-23,low vitamin D, high PTH, high BSAP
Histological findings:
For high turn over:
Increase osteoclast and osteoblast number
Increase trabecular bone volume, Cortical thinning
Increased porosity
For low turn over:
Absence of osteoclasts
Very few osteoblasts
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
· Abnormalities in Ca, PO4, PTH, and Vit D
· Abnormalities in bone, turnover, mineralization, volume, linear growth, or strength
· Extraosseous (soft tissue) Calcifications
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
The 2009 recommendations listed specific indications for bone biopsy (eg unexplained fractures, hypercalcemia, hypophosphatemia etc), while the 2017 update mentioned that bone biopsy should be done only if expected result would impact treatment.
I think the 2017 update would leave MORE patient with unsettled bone disease, as there is often a discrepancy between lab parameters and what is actually happening in the bones.
3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
The gold standard for the diagnosis of renal osteodystrophy in CKD is bone biopsy.
In addition, it provides information regarding bone volume, turnover, mineralization, architecture, and cortical bone-related factors.
Bone biopsies are invasive, time consuming, require expertise in collecting and processing bone fragments, and have a high cost for histopathological examination. 4. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy? 1. Low bone turnover (ABD and Osteomalacia); High sclerostin, low PTH, low bALP, low Ca, High PO4 Biopsy finding: No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone 2. High bone turnover (secondary or tertiary HPT, mixed osteodystrophy); High FGF-23,low vitamin D, high PTH, high bALP, high PO4, low or high Ca Biopsy finding: Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation with under mineralization 5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone? A- Aluminium : Accumulates in bone and binds to the calcification front leading to ABD and Osteomalacia B- Lanthanum: Similar properties to Al but does not bind to any bony microstructure C- Iron: Can bind to Calcification front and produce ABD D-Magnesium: deficiency may contribute to Osteoporosis E- Strontium: used for treatment of Osteoporosis, it enhances Osteoblasts and inhibits Osteoclasts
1-According to KDIGO guidelines, what are the 3 components of CKD-MBD?
laboratory abnormalities in calcium, phosphorous, PTH and vitamin D
abnormalities in bone turnover, mineralization, volume and
Cardiovascular calcification.
2-KDIGO changed its recommendations
regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
KDIGO,2017start ckd mbd in patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choice take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy .
KDIGO 2009 in patients with CKD G4–G5D having biochemical abnormalities of CKD-MBD, and low BMD and/or fragility fractures, we suggest additional investigation with a bone biopsy prior to therapy with antiresorptive agents .
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment.and differs from the 2009 guidelines, which stated that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment).
My think about bone biopsy is beneficial to patients especially in symptomatic with other Lab cannot explain these symptoms but still an invasive procedure and needs an expert nephrologist and histopathologist.
3-Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
bone biopsy is considered a gold standard for diagnosis of ROD.
give valuable information about histomorphometry analysis and evaluation dynamic and static parameter in addition quantitative and qualitative study but still invasive procedure.
needs expertise to collect and process the bone fragments and measuring the indices that lead to accurate diagnosis.
4-What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
The abnormality in bone turn over low turn over and high turn over.
Non invasive parameters in
Low bone turn over; High sclerostin, low PTH, low BALP
High bone turn over; High FGF-23,low vitamin D, high PTH, high BALP
Bone biopsy findings:
High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness.
Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization.
Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone.
5-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone.
Iron accumulation İn non ckd patients, both iron deficiency and overload were associated with osteoporotic lesions. In ckd patients associated with adynamic bone disease.
Regarding Lantanum, it was not proven or stained yet and is not reported to accumulate in the bone.
Magnesium considered for the regulation of both osteoblasts and osteoclast so in magnesium deficiency cause osteoporosis or oesteomalicia
Strontium accumulate in bone and may be associated with osteomalacia as it competes for calcium.
According to KDIGO guidelines, what are the 3 components of CKD-MBD?The first component
The mineral and endocrine abnormalities of calcium, phosphorus, parathyroid hormone, or vitD metabolism.
The second component
The abnormalities of bone are related to turnover, mineralization, volume, linear growth, or strength.
The third component
The extra-skeletal calcification.
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?KDIGO2009 guideline stated that; Bone biopsy should be performed in at least five situations;
Multiple fractures.
Unexplained hypercalcemia.
Unexplained hypophosphatemia.
Suspected aluminum toxicity.
Before osteoporosis treatment.
KDIGO2017 stated that; a bone biopsy should be performed if the diagnosis impact treatment. Ithink that a bone biopsy is not a routine workup for diagnosing CKD-MBD, as it is not available In most centers and needs expert interpretation of the result. Still, the certain conflicting condition may necessitate bone biopsy to help establish a diagnosis. A bone biopsy can give valuable information about CKD; however, it has some limitations. Explain the aforementioned statement.
Invasive procedure.
A one-shot vision at a time-point.
Sampling errors.
It is restricted by the time needed to complete the technique and analyze the sample, (time-consuming).
Expertise is needed.
What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
Bone volume can be
low.
Normal.
High.
The change in bone volume can be part of ROD (uremic osteoporosis), or a shored risk factor of osteoporosis
Non-invasive diagnosis of osteoporosis;
a) DXA. b) HR-pQCT. c) MRI. 2. Bone turnover, can be
Low.
Normal.
High.
Non-invasive diagnosis;
a) Sclerostin. b) Kloth. c) FGF23. d) VitD. e) PTH. f) RANK/RANKL/Osteoprotegrin system. g) Wnt/beta-catenin system. h) BALP.
Biopsy characteristic;
a) High turnover; increase in osteoblast/osteoclast numbers, with the increase in bone cancellous volume, decrease bone critical bone volume, +/- inter-trabecular fibrosis in severe 2ndary HPT, normal bone mineralization. b) Low turnover; no osteoclast, few osteoblast numbers, no osteoid formation, and acellular bone in severe cases. 3. Bone mineralization; biopsy shows mineralization defect. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum;
Osteomalcai and dynamic bone disease.
Aluminum deposition at the steoid-calciied bone boundary.
2. Lanthanum;
Not affect bone mineralization or osteoblast activity.
According to KDIGO guidelines, what are the 3 components of CKD-MBD? 1.lab abnormalities in calcium, phosphorous, PTH and vitamin D 2 abnormalities in bone turnover, mineralization, volume . 3 vascular calcification.
2- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it? 2017 guidelines
In patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choices take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy.
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment.
2009 guidelines,
stated that a bone biopsy should be performed in:
multiple fractures,
unexplained hypercalcemia or hypophosphatemia,
suspected aluminum toxicity,
before osteoporosis treatment
my opinion :
It is an invasive procedure and needs an expert nephrologist . 3- Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
bone biopsy is a gold standard for diagnosis of ROD.
give valuable information about histomorphometry analysis and evaluation dynamic and static parameter in Addison quantitative and qualitative study
it is invasive procedure.
it needs expertise to collect and process the bone fragments and measuring the indices that lead to accurate diagnosis.
4- What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy? Bone turnover in CKD
Adynamic bone disease Low bone turnover Hight bone turnover.
in high bone turnover increase FGF 23 , decrease vit D , high PTH and increase BALP .
in low bone turn over the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease.
Bone biopsy findings:
High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume .
Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone.
5-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone? 1- Aluminum
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone, inhibiting hydroxyapatite formation and growth and inhibits mineralization.
2- Lanthanum
No affect on mineralization or osteoblastic activity
No lanthanum histochemical bone biopsy staining method exists.
3- Iron,both iron overload and iron defciency have been associated with osteoporotic .
4)magnesium
causes osteomalacia , renal osteodystrophy and decrease mineralization .
5) Strontium
strontium accumulates in the body causes Osteomalacia
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD? 3b
1- Blood abnormalities: calcium, phosphorus, PTH, vit D, FGF-23
2- Bone abnormalities: volume, turnover and mineralization
3- Blood vessel calcification
4- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it? 2009 guidelines had clear 5 indications for renal biopsy, including hypercalcemia, hyperphosphatemia, suspected aluminium toxicity, and multiple fractures, Before starting osteoporotic treatment. 2017 guidelines, make unclear statement, that renal biopsy should be considered when diagnosis will impact therapy What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy? Turnover in CKD may be low, normal, or high Bone turnover markers include Bone formation markers: Bsalp and p1NP While bone resorption includes CTX biopsy allows to quantify bone volume and relate volume to turnover and mineralization in the same sample Bone biopsy is the gold standard for diagnosis of renal osteodystrophy Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement. 1- Volume: biopsy allows to quantify bone volume and relate volume to turnover and mineralization in the same sample 2- 2- turnover: in ABD, biopsy shows no osteoclast, few osteoblasts with no ostoid formation. In osteotis fibrosa, there will be increased No of osteobalsts and osteoclasts, increased cabcellous bone, decreased cortical bone and increased ostoid. Aluminium Aluminium toxicity can occur in HD patients and in CKD patients with egfr less than 30 ml/min/1.73m2. Sources of aluminium will include dialysis fluids due changes in aluminium content of municipal water, aluminium containing phosphate binder and aluminium utensils. Aluminium toxicity can be acute or chronic. Chronic toxicity can be manifested as osteomalcia, iron resistant microcytic anemia or hypercalcemia Lanthanum: It has some physicochemical characters of alumihnium, raising the concern of its potential deleterious effects on the bone. But there are obstacles to confirm these effects, like no bone biopsy stain for l lanthanum By Synchroton base scanning x-ray microflurorescence lanthanum is not found at the critical sites of bone mineralization Iron Both iron deficiency and overload are associated with bone disease Overload may be associated with ABD, and may precipitate aluminium toxicity In normal individuals both iron deficiency and overload are associated with osteoporosis. Mg: there is no clear evidence than mg disorders are associated with any type of renal osteodystrophy. Strontrium: It has some physicochemical characters of calcium, it is precipitated in CKD esp. HD patients and can precipitate osteomalcia
According to KDIGO guidelines, what are the 3 components of CKD-MBD?1-biochemical abnormalities of calcium ,phosphorous and vitamin D and PTH
2-bone disorders (mineralisation ,turnover and strenght h)
3-vascular and soft tissue calcifications KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?in new 2017 guidelines recommend
In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions
===========================
in 2009 indications for bone biopsy
unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and prior to therapy with bisphosphonates in patients with CKD-MBD
=========================== What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?bone turnover could be high ,normal or low
how to diagnose :
Thiere now markers of CKD -MBD like sclerostin, klotho, and fbroblast growth factor 23 (FGF23) could help
. . Nephrologists use non-invasive biochemical markers of bone formation/resorption to support clinical and therapeutic decisions. PTH and, , bonespecifc alkaline phosphatase (BALP)
====================== Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?aluminum >>can cause Adynamic bone disease and osteomalacia
lanthanum >>no effect on mineralization
1. According to KDIGO guidelines, what are the three components of CKD-MBD?
As in 2006 guidelines, it was the first time the definition broadened to include 1- mineral and endocrine abnormalities of C/P/PTH or vit. D metabolism. 2- abnormalities in bone turnover (mineralization, volüme, strength, and linear growth) and 3rd extraskeletal calcifications 2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009, and what do you think about it?
Opposite to the previous recommendation of five indications to perform a bone biopsy (multiple fractures, unexplained hypercalcemia, low P, suspected AL toxicity or before osteoporosis treatment), the last suggestion was to do it whenever the result will impact and guide the treatment. 3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
Bone biopsy is the only way to assess mineralization, in addition to other valuable information regarding static and dynamic parameters of bone, but limited by time-consuming, being invasive, and handicap of mistakes during preparation. Last but not least it is a one-point screenshot about bone health at that time. 4. What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
Turnover can be low, normal or high. Bone biopsy can give us information regarding this turnover, the volüme and the mineralization. No other imaging technique could replace it alone. DEXA gives us information about the volüme but can not differentiate mineralization defect from turnover defect. . It can not give information about microarchitecture. Qct gives us information about microarchitecture. High-resolution pQCT and MRI can give us separate information about cortical and trabecular bone. Despite that, HR-pQCT do not provide us with information about mineralization and turnover. 5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone, inhibiting hydroxyapatite formation and growth. By this way inhibits mineralization.
Before EPO treatment, iron was a challenge and was thought to be a cause of adynamic bone disease; it could not be associated with a specific type of bone disease. İn non-kidney patients, both iron deficiency and overload were associated with osteoporotic lesions.
Regarding Lantanum, it was not proven or stained yet and is not reported to accumulate in the bone.
Magnesium excess or hypermagnesemia was hypothesized to be harmful but could not be linked to any renal osteodystrophy. Furthermore, the magnesium-based phosphate binders were not found to have documented adverse effects on bone. RATHER MAGNEİUM DEFECEİNCY İS LİKELY İMPORTANT İN OSTEOPROSİS as it is crucial for the regulation of both osteoblasts and osteoclasts.
Strontium, contraindicated in advanced CKD (eGFR<30) found to accumulate in bone and may be associated with osteomalacia as it competes for calcium.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation in the bone lead to osteomalacia and adynamic bone disease, the deposition of the aluminum at the osteoid calcified bone boundaries causes impaired bone mineralization whereby the element act as inhibitor of hydroxyapatite formation /growth.
There will be staining of aluminum at mineralization front
The role of aluminum in the development of adynamic bone disease either direct inhibitory effect on osteoblast or indirect inhibitor effects on PTH synthesis and secretion
Lanthanum
Accumelation in the bone is minimal, the use of synchrotron based scanning x ray microflourescent there is no Lanthanum in the critical sites of bone mineralization and no serious effects on bone mineralization and osteoblastic activity in dialysis patients.
No procedure for histochemical bone biopsy staining for Lanthanum.
Iron
Has 2faced Janus as the deficiency or overload causes bone disease.
Bone histology after an iron specific staining show that iron overload associated with Adynamic bone disease in dialysis patients, there is an iron deposition at the mineralization front indicated by positive perl staining.
Magnesium
An association between hypermagnesemia and development of osteomalacia and or renal osteodystrophy was hypothesized from a. Element of calcimimetic effect on calcium sensing Receptor and PTH synthesis and secretion b. It’s ability to prevent mineralization and or calcification.
Mg deficiency is important in osteoporosis as it is crucial for osteoblast and osteoclast activity and function in bone remodeling
Strontium
Is ranelate compound used as antiosteoporotic agents
Bone biopsy in dialysis patients show increase Strontium in bone in patients with osteomalacia on dialysis.
Rhodizonate histochemical staining show increase Strontium in calcified bone, mainly in new formed bone proximal to the mineralization front surrounding osteoid.
**According to KDIGO guidelines, what are the 3 components of CKD-MBD?
1.mineral and endocrinal abnormalities in calcium, phosphorous, PTH and vitamin D
2 abnormalities in bone turnover, mineralization, volume and linear growth and strength
3.extraskeletal calcification
**KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
Bone biopsy should be done if the diagnosis affects the treatment
It is done when there is :
1.severe and disabiling bone pain
2.fragility fracture (>2)
3.before parathyroidectomy
4.before treatment of osteoporosis
5.rapid progressive vascular calcification in a young patients
6.suspected aluminum toxicity
Unexplained hypercalcimia or hypophosphametia
**Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
1.it is invasive
2.it is one shot vision at time point
3.can be impaired by sample error
4.it is restricted by time needed to complete technique and analyze the sample, it is time consuming process
5.it needs expertise to collect and process the bone fragments and measuring the indices that lead to accurate diagnosis
**What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Bone turnover may be normal, high or low and in extreme cases associated with extraskeletal calcification.
Diagnosis noninvasively by markers like sclerostin, klotho, FGF23, PTH, vitamin D, RANK/RANKL /osteoprotegren system wingless related integration site /beta catenin system, bone specific alkaline phosphotase
18F-NaF PET but need analysis in uremic patients
Bone biopsy show static histomorphometry as increase osteoblast and osteoclast number with increase cancellous bone volume and decrease cortical bone volume cortical thinning and increase porosity. In severe hyperparathyroidism there will be inter trabecular fibrosis that might compromise erythropoietin production.
Normal mineralization, slightly increase osteoid surface and volume.
As there will be increase in osteoclast activity and number and use of tartarate acid phosphotase which is secreted by osteoclast using histochemical methods there is a plenty expression of osteoclast which reflect bone resorption, the use of a dynamic parameters lead to accurate diagnosis
Low turnover bone
Low osteoblast and no osteoclast, no bone formation, when low volume and low dynamic parameters called a dynamic bone disease
1- According to KDIGO guidelines, what are the 3 components of CKD-MBD?Vitamin D, Parathyroid Hormone, and Calcium Deficiencies
Bone histomorphometric abnormalities in terms of total mineral content, linear growth, and strength
Calcium deposition outside of bones, in places like blood vessels and other soft tissues. 2- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
New 4.3.3: In patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choices take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy (2D). Old 4.3.4: In patients with CKD G4–G5D having biochemical abnormalities of CKD-MBD, and low BMD and/or fragility fractures, we suggest additional investigation with a bone biopsy prior to therapy with antiresorptive agents (2C).
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment. This differs from the 2009 guidelines, which stated that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment).
It is an invasive procedure and needs an expert nephrologist and histopathologist. Additionally, sometimes the results of the biopsy are not too beneficial.
3- Bone biopsy can give valuable information about CKD; however, it has some limitations. Explain the aforementioned statement.bone biopsy’s pervasive and all-encompassing nature. Additionally, a snapshot was taken at a certain moment in time. The possibility of a mistake in the sampling
Time-consuming. It is necessary to have a great deal of expertise.
4- What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
A high turnover rate results in an increase in the number of osteoclasts and osteoblasts, an increase in the volume of trabecular bone, a reduction in the thickness of the cortical bone (cortical thinning), and an increase in the porosity of the cortical bone. The combination of rapid bone production and a delay in mineralization results in normal bone mineralization and osteoid, as well as a minor increase in bone volume. There has been an increase in the osteoclast’s expression of tartrate-resistant acid phosphatase.
The turnover rate is low, and there are no osteoclasts, just a few osteoblasts, and no osteoid development. In extreme circumstances, the bone might become totally acellular.
Both low and high rates of employee turnover
Noninvasive diagnosis: Reduced metabolic rate; high levels of sclerostin; low levels of both PTH and BALP
High rate of turnover; high levels of FGF-23 and BALP; low levels of vitamin D; high levels of PTH and BALP.
high-turnover bone disease remodeling. Nevertheless, the FGF23, RANK/RANKL/Osteoprotegerin, sclerostin, and Winglessrelated integration site (Wnt)/beta-catenin systems will also be active in low bone turnover illness, along with additional risk factors including robust secondary hyperparathyroidism therapy.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium) on bone.
Aluminum binds phosphate well. Daily therapeutic dosages of this bone-seeking element may cause skeletal deposition. Aluminum-contaminated dialysis fluids may enter the body parenterally. Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia, and adynamic bone disease.
As shown by synchrotron-based scanning X-ray microfluorescence, lanthanum, unlike aluminum, is not present at important bone mineralization sites and has not been shown to affect bone mineralization or osteoblastic activity in dialysis patients. No lanthanum histochemical bone biopsy staining method exists.
Iron overload and adynamic bone disease were linked in dialysis patients by histological bone biopsies and aluminum and iron-specific staining.
It is unclear how magnesium affects bone mineralization and renal bone disease.
Hypermagnesemia was first linked to osteomalacia and renal osteodystrophy decades ago due to (a) its calcimimetic effect on the calcium-sensing receptor and PTH secretion and synthesis and (b) its capacity to block mineralization and calcification.
Osteomalacia patients had higher bone strontium values in a 100-dialysis patient bone biopsy research.
Rhodizonate staining histochemically identifies strontium in calcified bone, mainly in young bone towards the mineralization front and around the osteoid in animal models.
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD? The 3 component of CKD -MBD are
lab . abnormalities( biochemical abnormalities ) Bone abnormalities (ROD) in addition to vascular calcification
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it? 2009 KDIGO CKD-MBD recommendations 3.2.1. In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy in various settings including, but not limited to: unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and prior to therapy with bisphosphonates in patients with CKD-MBD (Not Graded). 3.2.2. In patients with CKD G3a–G5D with evidence of CKD-MBD, we suggest that BMD testing not be performed routinely, because BMD does not predict fracture risk as it does in the general population, and BMD does not predict the type of renal osteodystrophy (2B). 2017 revised KDIGO CKD-MBD recommendations 3.2.1. In patients with CKD G3a–G5D with evidence of CKD-MBD and/or risk factors for osteoporosis, we suggest BMD testing to assess fracture risk if results will impact treatment decisions (2B). 3.2.2. In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions (Not Graded). Brief rationale for updating Multiple new prospective studies have documented that lower DXA BMD predicts incident fractures in patients with CKD G3a– G5D. The order of these first 2 recommendations was changed because a DXA BMD result might impact the decision to perform a bone biopsy. The primary motivation for this revision was the growing experience with osteoporosis medications in patients with CKD, low BMD, and a high risk of fracture. The inability to perform a bone biopsy may not justify withholding antiresorptive therapy from patients at high risk of fracture 3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
A bone biopsy is still considered the gold standard for diagnosis of renal osteodystrophy. It allows to measure both static and dynamic parameters of bone remodeling and is the only method able to evaluate mineralization and allows analysis of both cortical and trabecular bone. Bone biopsy give valuable information about histomorphometry analysis and evaluation dynamic and static parameter in Addison quantitative and qualitative study
provide information on all the abovementioned parameters: volume, turnover, mineralization, architecture, and cortical bone-related aspects, such as porosity or thickness. A bone biopsy provides highly valuable and in-depth information that is required for the patient’s treatment. In addition to the above valuable bone biopsy provides (a) allows analysis of both cortical and trabecular bone, (b) gives information on static and dynamic parameters of bone turnover, and (c) is the only method able to assess mineralization. Nevertheless, there are limitations, as it (a) is an invasive procedure; (b) a one-shot vision at a time-point, (c) can be impaired by sampling errors; (4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and (5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis When to Perform a Bone Biopsy The abovementioned makes it clear that turnover and mineralization are accessible through biopsy, and that serum markers, although important, do not reflect histological changes and findings in some clinical cases. Besides other eventual indications for a bone biopsy, it is the authors’ opinion that the following particular five situations are in need of a bone biopsy, in both uremic and kidney transplant patients, as the knowledge of the type of ROD in these five situations will impact treatment decisions: 1. Severe and disabling bone pain; 2. Fragility fractures (more than 2) 3. Before treatment of osteoporosis; 4. Before parathyroidectomy; 5. Fast progression of vascular calcifcation in a young patient
4. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Bone turnover in CKD Classified into Adynamic bone disease Low bone turnover Hight bone turnover Can differentiated by biochemical marker increase FGF 23 , decrease vit D , hight PTH and increase BALP assosciated with high bone turnover in low bone turn over the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and Winglessrelated integration site (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease BUT ON bone biopsy Can described static and dynamic parameter of bone turn over and quantify character of histomorphometry of bone turn over So still bone biopsy golden standard of diagnosis of bon turn ROD in CKD 5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1) Aluminum
Aluminum source from Medication aluminum containing phosphorus binding Or water treatment unit for dialysis Effect >>>> Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease And Chelation therapy with deferoxamine results in improvements of clinical symptoms and bone histology 2)lanthanum Accumulation of lanthanum on bone is minimal Is not found at critical site of bone mineralization and so farno serious effect on either bone mineralization or osteoblastic activity have been reported in lanthanum -treated dialysis patients 3)Iron Iron must be considered a two-faced Janus as both overload or defciency have been reported to cause bone disorders Although in subjects with normal renal function both iron overload and iron defciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients (Toxqui L, Vaquero MP (2015) Chronic iron defciency as an emerging risk factor for osteoporosis: a hypothesis. Nutrients 7:2324–2344
4)magnesium The role of magnesium in bone mineralization and in the pathogenesis of renal bone disease is still a matter of debate. An association between hypermagnesemia and the development of osteomalacia and/or renal osteodystrophy was frst hypothesized some decades ago, based on (a) the element’s calcimimetic efect on the calcium-sensing receptor and thus secretion/synthesis of PTH and (b) its ability to prevent mineralization and/or calcification
(Cunningham J, Rodriguez M, Messa P (2012) Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients. Clin Kidney J 5:i39–i51 80.)
( Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J (2009) Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 22:37–44) 5) Strontium Epidemiological studies indeed revealed that in CKD patients, in particular those treated by dialysis, strontium accumulates in the body
( Schrooten I, Elseviers MM, Lamberts LV, De Broe ME, D’Haese PC (1999) Increased serum strontium levels in dialysis patients: an epidemiological survey. Kidney Int 56:1886–1892 Moreover, a bone biopsybased study in 100 dialysis patients revealed increased bone strontium concentrations in patients with osteomalacia
(D’Haese PC, Schrooten I, Goodman WG et al (2000) Increased bone strontium levels in hemodialysis patients with osteomalacia. Kidney Int 57:1107–1114)
More study and research needed
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD? The three components of CKD-MBD are:
1. mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism;
2. Abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength
3. Extraskeletal calcifications.
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
The 2017 guidelines recommend performing bone biopsies only if the diagnosis impacts the treatment
2009 guideline recommends bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment)
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement. Bone biopsy is considered the gold standard for the diagnosis of renal osteodystrophy in CKD.it also provides information on volume, turnover, mineralization,architecture, and cortical bone related aspects.
Limitations of bone biopsy include being invasive, time-consuming, and requiring expertise in collecting and processing bone fragments and high the cost of histopathological analysis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy? In CKD, bone turnover can either be low turnover(a dynamic bone disease and Osteomalacia), or high turnover(SHPT and mixed uremic osteodystrophy) Low or high bone turnover can be diagnosed non-invasively by evaluating biochemical markers of bone metabolism, such as serum alkaline phosphatase, calcium, phosphorus, and parathyroid hormone. A bone biopsy is the gold standard for diagnosing renal osteodystrophy and can provide information on volume, turnover, mineralization, architecture, and cortical bone-related aspects, such as porosity or thickness. a Histomorphometric evaluation of both static and dynamic parameters. Even without a semiautomatic method and without measurements, it is useful to have the qualitative evaluation of a bone biopsy.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone? Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease.
Lanthanum, is not found at critical sites of bone mineralization and no serious effects on either bone mineralization and/or osteoblastic activity have been reported in lanthanum-treated dialysis patients.
Iron overload has been associated with an increased frequency of adynamic bone disease in dialysis patients.
Magnesium is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling.
Strontium accumulates in the body and is mainly found in new-formed bone in close proximity to the mineralization front.
1- A- mineral and bone abnormalities of serum calcium , phosphorus , PTH and vit D metabolism
B- bone abnormalities related to turnover , mineralization , volume , linear growth or strength
C- extra skeletal calcifications
2- In KDIGO 2017 guidelines , experts put their opinion that bone biopsy should be performed only if diagnosis impacts treatment in contrast to 2009 guidelines that advised to perform bone biopsy in at least five situations including multiple fractures , unexplained hypercalcemia , hypophosphatemia , suspected Aluminum toxicity and before osteoporosis treatment
in my opinion , this more practical and put bone biopsy performance in selected cases where it impacts diagnosis and treatment options as it is an invasive method and have many limitations
3- value of bone biopsy in CKD patients :
a- allows analysis of both cortical and trabecular bones
b- gives information on both static and dynamic parameters of turnover
c- the only method to assess mineralization
limitations include :
a- invasive procedure
b- one shot vision at a time point
c- can be impaired by sampling errors
d- time consuming process
e- needs expertise in collection and analysis of data
4- turnover abnormalities are either :
a- high turnover lesions….SHPTH and mixed uremic osteodystrophy
b- low turnover lesions…..ABD and osteomalacia
non invasive procedures include :
a- labs…..sclerostin , klotho , FGF 23 , wnt / beta catenin system , RANKL / osteoprotegnin system
b- imaging….pQCT , MRI , trabecular bone score , DXA BMD
findings in bone biopsy :
a- high turnover ….increased ostoblasts and osteoclasts number , cortical thinning and porosity with fibrosis in severe SHPTH
b- low turnover…..no osteoclasts , few osteoblasts , no osteoid tissue up to acellular bone
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it? A. 2017 recommendation:
Bone biopsy should be performed if the diagnosis impacts treatment (Expert opinion)
B. 2009 recommendation: Bone biopsy is indicated the following 5 situations:
Multiple fractures
Unexplained hypercalemia
Unexplained hypophosphatemia
Suspected aluminum toxicity
Before osteoporosis
C. My thoughts about it: The 2017 guidelines are more practical,simply because bone biopsy is the gold standard for the diagnosis of ROD and beyond
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
Invasive nature of the bone biopsy
A one-shot vision at a time-point
Potential for sampling errors
Time consuming e.g., you get complete results after 4 weeks from the procedure
A lot of expertise is required
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
A. Low turn over and high turn over
B.Noninvasive diagnosis:
Low turn over; High sclerostin, low PTH, low BALP
High turn over; High FGF-23,low vitamin D, high PTH, high BALP
C.Bone biopsy findings:
High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization. There is increase expression of the tart rate-resistant acid phosphatase by osteoclast
Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone? 1.Aluminum;
Accumulates in bone and cause ROD in form of osteomalacia due to inhibition of hydroxapatite formation/growth or ABD due to direct effects on osteoblast or indirectly interference with PTH synthesis.
2.Lanthanum;
Physio-chemically similar to aluminum
Synochroton-dased scanning X ray microfluoresence showed no lanthanum deposition at the mineralization zone and to dates, no reported serious effect on mineralization or osteoblast activities in dialysis patients who were treated with lanthaum.
3.Iron;
Historically before the era of EPO, iron overload was a problem and usually found concomitantly with aluminum overload
At the moment,it is important to consider evaluation of biopsy sample for iron status due to frequent use of iron in dialysis patients for correction of anemia and hyperphosphatemia
4.Magnesium
Mg play important in many biologic activities in the body
Mg contributes in regulation of osteoblast and osteoclast function/activity in bone remodeling
Hypomagesemia may have negative effect on the bone especially in osteoporosis
5.Strontium
Physio-chemically similar to calcium and hence it may potentially affect the bone
Animal studies revealed that, it may have a causal role in osteomalacia and other effects on the bone
Lanthanum accumulation in bone minmal and impact on bone needs to be studied
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium deficiency is likely to be an issue in osteporosis as it is crucial for osteoblast and osteoclast function and activity in bone remodellig.
strontium as
the ranelate compound is being used as an anti-osteoporotic
agent, it is contra-indicated in patients with a GFR<30 mL and it could be linked to oseteomalacia
Lanthanum accumulation in bone minmal and impact on bone needs to be studied
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium deficiency is likely to be an issue in osteporosis as it is crucial for osteoblast and osteoclast function and activity in bone remodellig.
strontium as
the ranelate compound is being used as an anti-osteoporotic
agent, it is contra-indicated in patients with a GFR<30 mL and it could be linked to oseteomalacia
According to KDIGO guidelines, what are the 3 components of CKD-MBD?Mineral and Endocrine Abnormalities of calcium and phosphate and PTH . (ii) abnormalities of turnover , mineralisation, volume and linear growth. (iii) Extra Skeletal Manifestation
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
in 2009 there was clear indication for bone biopsy namely (i) unexplained fractures, (ii) hypercalcaemia, (iii)(hypophosphataemia) , (iv) suspected alumminum toxicity(V) or before osteoporosis while in 2017 experts recommended doing a bone biopsy if it would change management. this is as centres lack access to bone biopsy facilities ( bone biopsy and interpretation of histopathology) and lack of funding . this could have impacted KDIGO to change its guidelines concerning bone biopsy.
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement
Invasive procedure
needs technical expertise in acquring ,processing and interpreting sample.
Time delay of weeks to get results
Sample size might be limited and not enough to correspond to actual pathology /also sampling errors and one shot vision
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turnover bone disease
Diagnosis: FGF 23 , RANK/RANKL/Osteoprotegerin system, also the sclerostin and Winglessrelated integration site (Wnt)/beta-catenin system will be
active and participate in a low bone turnover disease
Biopsy: no osteoclast , few osteoblast no osteoid formation and acellular bone.
High turonver
Diagnosis: low vitamin D , high PTH, High BALP , FGF23
Biopsy: Increased Osteoblast and Osteoclast numbers, increase in cancellous bone volume, decrease in cortical bone and porosity
Bone mineralisation is normal tho there might be a lag in mineralisation due to accelerated bone formation
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontiumon bone?
Aluminium has been associated with the deposition of aluminum at the osteoid-calcifed bone boundary
whereby the element acts as an inhibitor of hydroxyapatite
formation/growth in osteomalacia while in adynamic bone disease is due to direct effect on osteoblastic activity or inhibitory effect on PTH
Lanthanum
a)mineral and endocrine abnormalities of calcium, phosphorus, parathyroid hormone, or vitamin D metabolism
b)abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength.
c)extra-skeletal calcifications.
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
In KDIGO 2009 the bone biopsy is done in following situations:
-Multiple Fractures
-Unexplained hypercalcemia or hypophosphatemia
-suspected aluminium intoxication
-before osteoporosis treatment
In KDIGO 2017 , the bone biopsy is recommended only if it influence the treatment
i think bone biopsy is especially beneficial in patient with non conclusive labs or symptoms. However it need an expert pathologist and excellent skills.
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.Bone biopsy provide information about volume, turnover, mineralization, architecture and cortical bone related aspects such as porosity or thickness. It still the gold standard for ROD diagnosis since it allows us to analyse both cortical and trabecular bone, gives us information about static and dynamic parameters of bone turnover and is the only method able to assess mineralization.
Limitation are due to its a)invasivness b) it is a one shot vision at one time point c) can be impaired by sampling errors d) a time consuming process e) it need expertise in collecting and processing bone fragments.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?Bone turnover can be normal , high or low.
Non invasively we will find in high turnover bone disease high levels of FGF23, low levels of vitamin D and high levels of PTH. high level of TRAP5.
In low turnover bone disease we will find RANK/RANKL Osteoprotegerin system also the sclerostin and wingless related integration site Wnt/Beta-Catenin system will be active and participate in low turnover bone disease.
In Clinical practice these markers are not all availabe. Nephrologist use normally PTH level and BALP for follow up bone turnover status .
Bone biopsy remain the gold standard of diagnosing bone turnover and mineralisation.
Characteristics of high bone turnover in bone biopsy: increased osteoblast and osteoclast number, increased cancellous bone volume and a decrease in cortical bone volume in terms of cortical thinning and increased cortical porosity. Intertrabecular fibrosis may be also severe and impact erythropoesis.
Bone mineralisation is normal
in Low turnover bone disease:
there is no osteoclasts and few osteoblasts , no osteoid formation. low dynamic parameters , and when associated with low volume, is termed adynamic bone disease.
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?-Aluminium is a bone seeking element that can accumulate in bones and lead to low turnover bone disease and osteomalacia. it inhibit hydroxyapatite formation, affect osteoblastic activity and PTH secretion /Sythesis.
-Lanthanum is a rare earth element and does not seem to have any side effect on bone mineralization or osteoblastic activity.
-Iron overload is associated with increased frequency of adynamic bone disease, it also compete with aluminium.
-The role of Magnesium is still a matter of debate. it was suggested that it causes osteomalacia and ROD due to its calcimimetic effect on CaSR and to its inhibiton of calcification and mineralisation. Study failed to demonstrate that.
-Strontium can accumulate in CKD Patient with GFR under 30 and cause mineralisation defect (Osteomalacia), it was used as anti osteoportic drug.
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
(1) mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism;
(2) abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength; and
(3) extra-skeletal calcifcations
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
3. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
4. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum : Aluminum accumulation in the bone results in particular forms of
renal osteodystrophy, most notably osteomalacia and adynamic bone disease . Chelation therapy with desferrioxamine results in improvements of clinical symptoms and bone histology
Lanthanum: accumulation of lanthanum in bone is minimal. It is not found at critical sites of bone mineralization and no serious efects on either bone mineralization and/or osteoblastic activity have been reported in dialysis patient .
Iron : Iron overload or deficiency has been linked to bone problems & osteoporotic lesions
Magnesium: hypermagnesemia is associated with the development of osteomalacia and/or renal osteodystrophy.It is a well-known essential element for multiple biological processes in the body. It it is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling
Strontium: It is an anti-osteoporotic agent, it is contra-indicated in patients with a GFR< 30 mL/ min. strontium accumulates in dialysis patient . It is a causal role of the element in the development of osteomalacia
A-According to KDIGO guidelines, what are the 3 components of CKD-MBD
1. mineral and endocrine abnormalities (balance of calcium, phosphorus, parathyroid hormone (PTH), FGF23 and vitamin D metabolism)
2. abnormalities related bone to turnover, mineralization, bone volume, linear growth, or strength.
3. extra-skeletal calcifications.
B-KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it:
in 2009 stating that bone biopsy indications were
*Multiple fractures,
*Unexplained hypercalcemia / hypophosphatemia,
* Suspected aluminum toxicity or before osteoporosis treatment
but the KDIGO guidelines were revised in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment.
and I think although the bone biopsy is very informative and should be done for differentiations of bone disease, it’s also important to think about challenges of performing the bone marrow biopsy. including the cost, invasiveness and lack of experience in performing and diagnosis, so I agree to performed if the diagnosis impacts treatment.
C-Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
the limitations are an invasive procedure, one-shot vision at a time-point,
can be impaired by sampling errors; is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis.
D-What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy.
Extra-osseous calcifications,abnormal , high turnover bone diseases
E-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum:Aluminum accumulation in the bone results in certain forms of
renal osteodystrophy, most especially osteomalacia and ady-namic bone disease
Lanthanum: accumulation of lanthanum in bone is minimal and no serious effects on either.
bone mineralization
Iron: increases the frequency of a dynamic bone diseases
Mg:hypermagnezemia is associated with osteomalacia and renal osteodystrophy
Strontium:
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
Abnormalities in ca , po4 , PTH , vitamin D
Abnormalities in bone turnover, mineralization, volume, linear growth and strength
extraoseois calcification
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
guidelines published in 2009 state that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity or before osteoporosis treatment) .
In contrast to this , the revised KDIGO guidelines launched in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment .
I think this will complicate the situation.
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
there are limitations, as it (a) is an invasive procedure; (b) a one-shot vision at a time-point, (c) can be impaired by sampling errors; (4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and (5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Low turnover bone disease
and
high turnover bone disease
*Noninvasive diagnosis:
–Low turn over High sclerostin, low PTH, low BALP
–High turn over High FGF-23,low vitamin D, high PTH, high BALP
*Bone biopsy findings:
–High turn over; increase osteoclast and osteoblast number, increase bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization. There is increase expression of the tart rate-resistant acid phosphatase by osteoclast.
–Low turn over there is No osteoclast, few osteoblast, and no osteoid formation. In one ward acellular bone.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum/ ABD
Lanthanum/ no known effect
Iron/ABD
Mg/ osteoporosis
Strontium/osteomalacia.
According to KDIGO guidelines, what are the 3 components of CKD-MBD?(1) mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism;
(2) abnormalities of bone related to turnover, mineralization, volume,linear growth, or strength; and
(3) extra-skeletal calcications
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?This is in line with the revised KDIGO guidelines launched in 2017 where experts put forward their opinion that bone biopsies should be performed if the diagnosis impacts treatment , which to a certain extent is in contrast to the guidelines published in 2009 stating that a bone biopsy should be performed in at least ve situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxic- ity or before osteoporosis treatment).
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
A bone biopsy provides highly valuable and in-depth information that is required for the patient’s treatment. This technique remains the gold standard for ROD diagnosis since it (a) allows analysis of both cortical and trabecular bone, (b) gives information on static and dynamic parameters of bone turnover, and (c) is the only method able to assess mineralization.
Nevertheless, there are limitations, as it (a) is an invasive procedure; (b) a one-shot vision at a time-point, (c) can be impaired by sampling errors; (4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and (5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?On the one hand, there will be high levels of FGF23, low levels of vitamin D, and high levels of PTH, transforming the remodeling process in a high turnover bone disease. On the other hand, aside from the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and Wingless- related integration site (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease, along with the other known risk factors for low turnover, such as vigorous treatment of secondary hyperparathyroidism, dia- betes, age, and the use of high flux dialysis’ membranes.
In the case of high bone turnover, the most typical bone findings in static histomorphometry are a signi cant increase in osteoblast and osteoclast number, which can be accompanied by an increased cancellous bone volume and a decrease in cortical bone volume in terms of cortical thinning and increased cortical porosity. The inter-trabecular brosis can be massive if secondary hyperparathyroidism is severe that can even compromise the bone marrow erythropoiesis. Usually, bone mineralization is normal, even though osteoid surface and even volume may be slightly increased, due to the accelerated bone formation process along with a delay in bone mineralization. In severe high turnover bone dis- ease, osteoclast surface and osteoclast number are typically increased. Using a histochemical method to optimize the tartrate-resistant acid phosphatase expressed and secreted by osteoclasts, we can obtain an exuberant expression of these cells, when they are active, in the bone resorption process
At the opposite extreme of bone turnover, we nd low turnover bone disease, with no osteoclasts and few osteoblast numbers, no osteoid formation, and, in extreme cases, fea- tures of an acellular bone. This low bone remodeling aspect, with low dynamic parameters when associated with low vol- ume, is termed adynamic bone disease.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease. the impaired mineralization has been associated with the deposition of aluminum at the osteoid-calcied bone boundary whereby the element acts as an inhibitor of hydroxyapatite formation/growth.
Lanthanum: accumulation of lanthanum in bone is minimal
It is not found at critical sites of bone mineralization and so far no serious e ects on either bone mineralization and/or osteoblastic activity have been reported in lanthanum-treated dialysis patients
Iron must be considered a two-faced Janus as both overload or de ciency have been reported to cause bone disorders.
A study found an association between iron overload and an increased frequency of adynamic bone disease was reported in dialysis patients
Although in subjects with normal renal function both iron overload and iron de ciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients
Magnesium defciency is likely to be an issue in osteoporosis as it is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling
Strontium: Moreover, a bone biopsy- based study in 100 dialysis patients revealed increased bone strontium concentrations in patients with osteomalacia
1.According to KDIGO guidelines, what are the 3 components of CKD-MBD?
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
–Low turn over; High sclerostin, low PTH, low BALP
–High turn over; High FGF-23,low vitamin D, high PTH, high BALP
–High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness (cortical thinning), and increase cortical bone porosity. Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization. There is increase expression of the tart rate-resistant acid phosphatase by osteoclast.
–Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.ations. Explain the aforementioned statement.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
· Abnormalities in Ca, PO4, PTH, and Vit D
· Abnormalities in bone, turnover, mineralization, volume, linear growth, or strength
· Extraosseous (soft tissue) Calcifications
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
The 2009 recommendations listed specific indications for bone biopsy (eg unexplained fractures, hypercalcemia, hypophosphatemia etc), while the 2017 update mentioned that bone biopsy should be done only if expected result would impact treatment.
I think the 2017 update would leave MORE patient with unsettled bone disease, as there is often a discrepancy between lab parameters and what is actually happening in the bones.
3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
The gold standard for the diagnosis of renal osteodystrophy in CKD is bone biopsy.
In addition, it provides information regarding bone volume, turnover, mineralization, architecture, and cortical bone-related factors.
Bone biopsies are invasive, time consuming, require expertise in collecting and processing bone fragments, and have a high cost for histopathological examination.
4. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
1. Low bone turnover (ABD and Osteomalacia); High sclerostin, low PTH, low bALP, low Ca, High PO4
Biopsy finding: No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone
2. High bone turnover (secondary or tertiary HPT, mixed osteodystrophy); High FGF-23,low vitamin D, high PTH, high bALP, high PO4, low or high Ca
Biopsy finding: Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation with under mineralization
5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
A- Aluminium : Accumulates in bone and binds to the calcification front leading to ABD and Osteomalacia
B- Lanthanum: Similar properties to Al but does not bind to any bony microstructure
C- Iron: Can bind to Calcification front and produce ABD
D-Magnesium: deficiency may contribute to Osteoporosis
E- Strontium: used for treatment of Osteoporosis, it enhances Osteoblasts and inhibits Osteoclasts
1-According to KDIGO guidelines, what are the 3 components of CKD-MBD?
laboratory abnormalities in calcium, phosphorous, PTH and vitamin D
abnormalities in bone turnover, mineralization, volume and
Cardiovascular calcification.
2-KDIGO changed its recommendations
regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
KDIGO,2017start ckd mbd in patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choice take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy .
KDIGO 2009 in patients with CKD G4–G5D having biochemical abnormalities of CKD-MBD, and low BMD and/or fragility fractures, we suggest additional investigation with a bone biopsy prior to therapy with antiresorptive agents .
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment.and differs from the 2009 guidelines, which stated that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment).
My think about bone biopsy is beneficial to patients especially in symptomatic with other Lab cannot explain these symptoms but still an invasive procedure and needs an expert nephrologist and histopathologist.
3-Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
bone biopsy is considered a gold standard for diagnosis of ROD.
give valuable information about histomorphometry analysis and evaluation dynamic and static parameter in addition quantitative and qualitative study but still invasive procedure.
needs expertise to collect and process the bone fragments and measuring the indices that lead to accurate diagnosis.
4-What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
The abnormality in bone turn over low turn over and high turn over.
Non invasive parameters in
Low bone turn over; High sclerostin, low PTH, low BALP
High bone turn over; High FGF-23,low vitamin D, high PTH, high BALP
Bone biopsy findings:
High turn over; increase osteoclast and osteoblast number, increase trabecular bone volume, decrease cortical bone thickness.
Normal mineralization, osteoid, and slight increased in bone volume due to accelerated bone formation coupled with a delay in mineralization.
Low turn over; No osteoclast, few osteoblast, and no osteoid formation. In severe cases you can get completely acellular bone.
5-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone.
Iron accumulation İn non ckd patients, both iron deficiency and overload were associated with osteoporotic lesions. In ckd patients associated with adynamic bone disease.
Regarding Lantanum, it was not proven or stained yet and is not reported to accumulate in the bone.
Magnesium considered for the regulation of both osteoblasts and osteoclast so in magnesium deficiency cause osteoporosis or oesteomalicia
Strontium accumulate in bone and may be associated with osteomalacia as it competes for calcium.
According to KDIGO guidelines, what are the 3 components of CKD-MBD?The first component
The second component
The third component
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?KDIGO 2009 guideline stated that; Bone biopsy should be performed in at least five situations;
KDIGO 2017 stated that; a bone biopsy should be performed if the diagnosis impact treatment.
I think that a bone biopsy is not a routine workup for diagnosing CKD-MBD, as it is not available In most centers and needs expert interpretation of the result. Still, the certain conflicting condition may necessitate bone biopsy to help establish a diagnosis.
A bone biopsy can give valuable information about CKD; however, it has some limitations. Explain the aforementioned statement.
What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
The change in bone volume can be part of ROD (uremic osteoporosis), or a shored risk factor of osteoporosis
a) DXA.
b) HR-pQCT.
c) MRI.
2. Bone turnover, can be
a) Sclerostin.
b) Kloth.
c) FGF23.
d) VitD.
e) PTH.
f) RANK/RANKL/Osteoprotegrin system.
g) Wnt/beta-catenin system.
h) BALP.
a) High turnover; increase in osteoblast/osteoclast numbers, with the increase in bone cancellous volume, decrease bone critical bone volume, +/- inter-trabecular fibrosis in severe 2ndary HPT, normal bone mineralization.
b) Low turnover; no osteoclast, few osteoblast numbers, no osteoid formation, and acellular bone in severe cases.
3. Bone mineralization; biopsy shows mineralization defect.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
2. Lanthanum;
3. Iron;
4. Mg.
5. Strontium.
According to KDIGO guidelines, what are the 3 components of CKD-MBD?
1.lab abnormalities in calcium, phosphorous, PTH and vitamin D
2 abnormalities in bone turnover, mineralization, volume .
3 vascular calcification.
2- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
2017 guidelines
In patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choices take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy.
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment.
2009 guidelines,
stated that a bone biopsy should be performed in:
my opinion :
It is an invasive procedure and needs an expert nephrologist .
3- Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
4- What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Bone turnover in CKD
Adynamic bone disease
Low bone turnover
Hight bone turnover.
in high bone turnover
increase FGF 23 , decrease vit D , high PTH and increase BALP .
in low bone turn over
the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease.
Bone biopsy findings:
5-Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1- Aluminum
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone, inhibiting hydroxyapatite formation and growth and inhibits mineralization.
2- Lanthanum
3- Iron,both iron overload and iron defciency have been associated with osteoporotic .
4)magnesium
causes osteomalacia , renal osteodystrophy and decrease mineralization .
5) Strontium
strontium accumulates in the body causes Osteomalacia
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
3b
1- Blood abnormalities: calcium, phosphorus, PTH, vit D, FGF-23
2- Bone abnormalities: volume, turnover and mineralization
3- Blood vessel calcification
4- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
2009 guidelines had clear 5 indications for renal biopsy, including hypercalcemia, hyperphosphatemia, suspected aluminium toxicity, and multiple fractures, Before starting osteoporotic treatment.
2017 guidelines, make unclear statement, that renal biopsy should be considered when diagnosis will impact therapy
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Turnover in CKD may be low, normal, or high
Bone turnover markers include
Bone formation markers: Bsalp and p1NP
While bone resorption includes CTX
biopsy allows to quantify bone volume and relate volume to turnover and mineralization in the same sample
Bone biopsy is the gold standard for diagnosis of renal osteodystrophy
Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
1- Volume: biopsy allows to quantify bone volume and relate volume to turnover and mineralization in the same sample
2- 2- turnover: in ABD, biopsy shows no osteoclast, few osteoblasts with no ostoid formation. In osteotis fibrosa, there will be increased No of osteobalsts and osteoclasts, increased cabcellous bone, decreased cortical bone and increased ostoid.
Aluminium
Aluminium toxicity can occur in HD patients and in CKD patients with egfr less than 30 ml/min/1.73m2.
Sources of aluminium will include dialysis fluids due changes in aluminium content of municipal water, aluminium containing phosphate binder and aluminium utensils. Aluminium toxicity can be acute or chronic. Chronic toxicity can be manifested as osteomalcia, iron resistant microcytic anemia or hypercalcemia
Lanthanum: It has some physicochemical characters of alumihnium, raising the concern of its potential deleterious effects on the bone. But there are obstacles to confirm these effects, like no bone biopsy stain for l lanthanum
By Synchroton base scanning x-ray microflurorescence lanthanum is not found at the critical sites of bone mineralization
Iron
Both iron deficiency and overload are associated with bone disease
Overload may be associated with ABD, and may precipitate aluminium toxicity
In normal individuals both iron deficiency and overload are associated with osteoporosis.
Mg: there is no clear evidence than mg disorders are associated with any type of renal osteodystrophy.
Strontrium: It has some physicochemical characters of calcium, it is precipitated in CKD esp. HD patients and can precipitate osteomalcia
According to KDIGO guidelines, what are the 3 components of CKD-MBD?1-biochemical abnormalities of calcium ,phosphorous and vitamin D and PTH
2-bone disorders (mineralisation ,turnover and strenght h)
3-vascular and soft tissue calcifications
KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?in new 2017 guidelines recommend
In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions
===========================
in 2009 indications for bone biopsy
unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and prior to therapy with bisphosphonates in patients with CKD-MBD
===========================
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?bone turnover could be high ,normal or low
how to diagnose :
Thiere now markers of CKD -MBD like sclerostin, klotho, and fbroblast growth factor 23 (FGF23) could help
. . Nephrologists use non-invasive biochemical markers of bone formation/resorption to support clinical and therapeutic decisions. PTH and, , bonespecifc alkaline phosphatase (BALP)
======================
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?aluminum >>can cause Adynamic bone disease and osteomalacia
lanthanum >>no effect on mineralization
1. According to KDIGO guidelines, what are the three components of CKD-MBD?
As in 2006 guidelines, it was the first time the definition broadened to include 1- mineral and endocrine abnormalities of C/P/PTH or vit. D metabolism. 2- abnormalities in bone turnover (mineralization, volüme, strength, and linear growth) and 3rd extraskeletal calcifications
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009, and what do you think about it?
Opposite to the previous recommendation of five indications to perform a bone biopsy (multiple fractures, unexplained hypercalcemia, low P, suspected AL toxicity or before osteoporosis treatment), the last suggestion was to do it whenever the result will impact and guide the treatment.
3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
Bone biopsy is the only way to assess mineralization, in addition to other valuable information regarding static and dynamic parameters of bone, but limited by time-consuming, being invasive, and handicap of mistakes during preparation. Last but not least it is a one-point screenshot about bone health at that time.
4. What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
Turnover can be low, normal or high. Bone biopsy can give us information regarding this turnover, the volüme and the mineralization. No other imaging technique could replace it alone. DEXA gives us information about the volüme but can not differentiate mineralization defect from turnover defect. . It can not give information about microarchitecture. Qct gives us information about microarchitecture. High-resolution pQCT and MRI can give us separate information about cortical and trabecular bone. Despite that, HR-pQCT do not provide us with information about mineralization and turnover.
5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation can lead to osteomalacia and adynamic bone disease. It accumulates at the boundary of osteoid and calcified bone, inhibiting hydroxyapatite formation and growth. By this way inhibits mineralization.
Before EPO treatment, iron was a challenge and was thought to be a cause of adynamic bone disease; it could not be associated with a specific type of bone disease. İn non-kidney patients, both iron deficiency and overload were associated with osteoporotic lesions.
Regarding Lantanum, it was not proven or stained yet and is not reported to accumulate in the bone.
Magnesium excess or hypermagnesemia was hypothesized to be harmful but could not be linked to any renal osteodystrophy. Furthermore, the magnesium-based phosphate binders were not found to have documented adverse effects on bone. RATHER MAGNEİUM DEFECEİNCY İS LİKELY İMPORTANT İN OSTEOPROSİS as it is crucial for the regulation of both osteoblasts and osteoclasts.
Strontium, contraindicated in advanced CKD (eGFR<30) found to accumulate in bone and may be associated with osteomalacia as it competes for calcium.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation in the bone lead to osteomalacia and adynamic bone disease, the deposition of the aluminum at the osteoid calcified bone boundaries causes impaired bone mineralization whereby the element act as inhibitor of hydroxyapatite formation /growth.
There will be staining of aluminum at mineralization front
The role of aluminum in the development of adynamic bone disease either direct inhibitory effect on osteoblast or indirect inhibitor effects on PTH synthesis and secretion
Lanthanum
Accumelation in the bone is minimal, the use of synchrotron based scanning x ray microflourescent there is no Lanthanum in the critical sites of bone mineralization and no serious effects on bone mineralization and osteoblastic activity in dialysis patients.
No procedure for histochemical bone biopsy staining for Lanthanum.
Iron
Has 2faced Janus as the deficiency or overload causes bone disease.
Bone histology after an iron specific staining show that iron overload associated with Adynamic bone disease in dialysis patients, there is an iron deposition at the mineralization front indicated by positive perl staining.
Magnesium
An association between hypermagnesemia and development of osteomalacia and or renal osteodystrophy was hypothesized from a. Element of calcimimetic effect on calcium sensing Receptor and PTH synthesis and secretion b. It’s ability to prevent mineralization and or calcification.
Mg deficiency is important in osteoporosis as it is crucial for osteoblast and osteoclast activity and function in bone remodeling
Strontium
Is ranelate compound used as antiosteoporotic agents
Bone biopsy in dialysis patients show increase Strontium in bone in patients with osteomalacia on dialysis.
Rhodizonate histochemical staining show increase Strontium in calcified bone, mainly in new formed bone proximal to the mineralization front surrounding osteoid.
**According to KDIGO guidelines, what are the 3 components of CKD-MBD?
1.mineral and endocrinal abnormalities in calcium, phosphorous, PTH and vitamin D
2 abnormalities in bone turnover, mineralization, volume and linear growth and strength
3.extraskeletal calcification
**KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
Bone biopsy should be done if the diagnosis affects the treatment
It is done when there is :
1.severe and disabiling bone pain
2.fragility fracture (>2)
3.before parathyroidectomy
4.before treatment of osteoporosis
5.rapid progressive vascular calcification in a young patients
6.suspected aluminum toxicity
Unexplained hypercalcimia or hypophosphametia
**Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
1.it is invasive
2.it is one shot vision at time point
3.can be impaired by sample error
4.it is restricted by time needed to complete technique and analyze the sample, it is time consuming process
5.it needs expertise to collect and process the bone fragments and measuring the indices that lead to accurate diagnosis
**What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Bone turnover may be normal, high or low and in extreme cases associated with extraskeletal calcification.
Diagnosis noninvasively by markers like sclerostin, klotho, FGF23, PTH, vitamin D, RANK/RANKL /osteoprotegren system wingless related integration site /beta catenin system, bone specific alkaline phosphotase
18F-NaF PET but need analysis in uremic patients
Bone biopsy show static histomorphometry as increase osteoblast and osteoclast number with increase cancellous bone volume and decrease cortical bone volume cortical thinning and increase porosity. In severe hyperparathyroidism there will be inter trabecular fibrosis that might compromise erythropoietin production.
Normal mineralization, slightly increase osteoid surface and volume.
As there will be increase in osteoclast activity and number and use of tartarate acid phosphotase which is secreted by osteoclast using histochemical methods there is a plenty expression of osteoclast which reflect bone resorption, the use of a dynamic parameters lead to accurate diagnosis
Low turnover bone
Low osteoblast and no osteoclast, no bone formation, when low volume and low dynamic parameters called a dynamic bone disease
1- According to KDIGO guidelines, what are the 3 components of CKD-MBD?Vitamin D, Parathyroid Hormone, and Calcium Deficiencies
Bone histomorphometric abnormalities in terms of total mineral content, linear growth, and strength
Calcium deposition outside of bones, in places like blood vessels and other soft tissues.
2- KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
New 4.3.3: In patients with CKD G3a–G5D and biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choices take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy (2D).
Old 4.3.4: In patients with CKD G4–G5D having biochemical abnormalities of CKD-MBD, and low BMD and/or fragility fractures, we suggest additional investigation with a bone biopsy prior to therapy with antiresorptive agents (2C).
This is consistent with the 2017 KDIGO guidelines, which state that bone biopsies should be performed if the diagnosis affects treatment. This differs from the 2009 guidelines, which stated that a bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment).
It is an invasive procedure and needs an expert nephrologist and histopathologist. Additionally, sometimes the results of the biopsy are not too beneficial.
3- Bone biopsy can give valuable information about CKD; however, it has some limitations. Explain the aforementioned statement.bone biopsy’s pervasive and all-encompassing nature. Additionally, a snapshot was taken at a certain moment in time. The possibility of a mistake in the sampling
Time-consuming. It is necessary to have a great deal of expertise.
4- What are the abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in the bone biopsy?
A high turnover rate results in an increase in the number of osteoclasts and osteoblasts, an increase in the volume of trabecular bone, a reduction in the thickness of the cortical bone (cortical thinning), and an increase in the porosity of the cortical bone. The combination of rapid bone production and a delay in mineralization results in normal bone mineralization and osteoid, as well as a minor increase in bone volume. There has been an increase in the osteoclast’s expression of tartrate-resistant acid phosphatase.
The turnover rate is low, and there are no osteoclasts, just a few osteoblasts, and no osteoid development. In extreme circumstances, the bone might become totally acellular.
Both low and high rates of employee turnover
Noninvasive diagnosis: Reduced metabolic rate; high levels of sclerostin; low levels of both PTH and BALP
High rate of turnover; high levels of FGF-23 and BALP; low levels of vitamin D; high levels of PTH and BALP.
high-turnover bone disease remodeling. Nevertheless, the FGF23, RANK/RANKL/Osteoprotegerin, sclerostin, and Winglessrelated integration site (Wnt)/beta-catenin systems will also be active in low bone turnover illness, along with additional risk factors including robust secondary hyperparathyroidism therapy.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium) on bone.
Aluminum binds phosphate well. Daily therapeutic dosages of this bone-seeking element may cause skeletal deposition. Aluminum-contaminated dialysis fluids may enter the body parenterally. Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia, and adynamic bone disease.
As shown by synchrotron-based scanning X-ray microfluorescence, lanthanum, unlike aluminum, is not present at important bone mineralization sites and has not been shown to affect bone mineralization or osteoblastic activity in dialysis patients. No lanthanum histochemical bone biopsy staining method exists.
Iron overload and adynamic bone disease were linked in dialysis patients by histological bone biopsies and aluminum and iron-specific staining.
It is unclear how magnesium affects bone mineralization and renal bone disease.
Hypermagnesemia was first linked to osteomalacia and renal osteodystrophy decades ago due to (a) its calcimimetic effect on the calcium-sensing receptor and PTH secretion and synthesis and (b) its capacity to block mineralization and calcification.
Osteomalacia patients had higher bone strontium values in a 100-dialysis patient bone biopsy research.
Rhodizonate staining histochemically identifies strontium in calcified bone, mainly in young bone towards the mineralization front and around the osteoid in animal models.
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
The 3 component of CKD -MBD are
lab . abnormalities( biochemical abnormalities )
Bone abnormalities (ROD)
in addition to vascular calcification
2. KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
2009 KDIGO CKD-MBD recommendations
3.2.1. In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy in various settings including, but not limited to: unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and prior to therapy with bisphosphonates in patients with CKD-MBD (Not Graded).
3.2.2. In patients with CKD G3a–G5D with evidence of CKD-MBD, we suggest that BMD testing not be performed routinely, because BMD does not predict fracture risk as it does in the general population, and BMD does not predict the type of renal osteodystrophy (2B).
2017 revised KDIGO CKD-MBD recommendations
3.2.1. In patients with CKD G3a–G5D with evidence of CKD-MBD and/or risk factors for osteoporosis, we suggest BMD testing to assess fracture risk if results will impact treatment decisions (2B).
3.2.2. In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions (Not Graded).
Brief rationale for updating
Multiple new prospective studies have documented that lower DXA BMD predicts incident fractures in patients with CKD G3a– G5D. The order of these first 2 recommendations was changed because a DXA BMD result might impact the decision to perform a bone biopsy.
The primary motivation for this revision was the growing experience with osteoporosis medications in patients with CKD, low BMD, and a high risk of fracture. The inability to perform a bone biopsy may not justify withholding antiresorptive therapy from patients at high risk of fracture
3. Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
A bone biopsy is still considered the gold standard for diagnosis of renal osteodystrophy. It allows to measure both static and dynamic parameters of bone remodeling and is the only method able to evaluate mineralization and allows analysis of both cortical and trabecular bone.
Bone biopsy give valuable information about histomorphometry analysis and evaluation dynamic and static parameter in Addison quantitative and qualitative study
provide information on all the abovementioned parameters: volume, turnover, mineralization, architecture, and cortical bone-related aspects, such as porosity or thickness. A bone biopsy provides highly valuable and in-depth information that is required for the patient’s treatment.
In addition to the above valuable
bone biopsy provides
(a) allows analysis of both cortical and trabecular bone,
(b) gives information on static and dynamic parameters of bone turnover, and
(c) is the only method able to assess mineralization.
Nevertheless, there are limitations, as it
(a) is an invasive procedure;
(b) a one-shot vision at a time-point,
(c) can be impaired by sampling errors;
(4) is restricted by the time needed to complete the technique and analyze the sample, being a time-consuming process; and
(5) expertise is needed not only in collecting and processing the bone fragments, but also in measuring the indices that will lead to an accurate diagnosis
When to Perform a Bone Biopsy
The abovementioned makes it clear that turnover and mineralization are accessible through biopsy, and that serum markers, although important, do not reflect histological changes and findings in some clinical cases. Besides other eventual indications for a bone biopsy,
it is the authors’ opinion that the following particular five situations are in need of a bone biopsy, in both uremic and kidney transplant patients, as the knowledge of the type of ROD in these five situations will impact treatment decisions:
1. Severe and disabling bone pain;
2. Fragility fractures (more than 2)
3. Before treatment of osteoporosis;
4. Before parathyroidectomy;
5. Fast progression of vascular calcifcation in a young patient
4. What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
Bone turnover in CKD
Classified into
Adynamic bone disease
Low bone turnover
Hight bone turnover
Can differentiated by biochemical marker
increase FGF 23 , decrease vit D , hight PTH and increase BALP assosciated with high bone turnover
in low bone turn over
the FGF23, RANK/RANKL/ Osteoprotegerin system, also the sclerostin and Winglessrelated integration site (Wnt)/beta-catenin system will be active and participate in a low bone turnover disease
BUT ON bone biopsy
Can described static and dynamic parameter of bone turn over and quantify character of histomorphometry of bone turn over
So still bone biopsy golden standard of diagnosis of bon turn ROD in CKD
5. Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1) Aluminum
Aluminum source from
Medication aluminum containing phosphorus binding
Or water treatment unit for dialysis
Effect >>>> Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease
And Chelation therapy with deferoxamine results in improvements of clinical symptoms and bone histology
2)lanthanum
Accumulation of lanthanum on bone is minimal
Is not found at critical site of bone mineralization and so farno serious effect on either bone mineralization or osteoblastic activity have been reported in lanthanum -treated dialysis patients
3)Iron
Iron must be considered a two-faced Janus as both overload or defciency have been reported to cause bone disorders
Although in subjects with normal renal function both iron overload and iron defciency have been associated with osteoporotic lesions, no evidence for such a relationship has been presented in CKD/ESKD patients (Toxqui L, Vaquero MP (2015) Chronic iron defciency as an emerging risk factor for osteoporosis: a hypothesis. Nutrients 7:2324–2344
4)magnesium
The role of magnesium in bone mineralization and in the pathogenesis of renal bone disease is still a matter of debate. An association between hypermagnesemia and the development of osteomalacia and/or renal osteodystrophy was frst hypothesized some decades ago, based on (a) the element’s calcimimetic efect on the calcium-sensing receptor and thus secretion/synthesis of PTH and (b) its ability to prevent mineralization and/or calcification
(Cunningham J, Rodriguez M, Messa P (2012) Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients. Clin Kidney J 5:i39–i51 80.)
( Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J (2009) Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 22:37–44)
5) Strontium
Epidemiological studies indeed revealed that in CKD patients, in particular those treated by dialysis, strontium accumulates in the body
( Schrooten I, Elseviers MM, Lamberts LV, De Broe ME, D’Haese PC (1999) Increased serum strontium levels in dialysis patients: an epidemiological survey. Kidney Int 56:1886–1892
Moreover, a bone biopsybased study in 100 dialysis patients revealed increased bone strontium concentrations in patients with osteomalacia
(D’Haese PC, Schrooten I, Goodman WG et al (2000) Increased bone strontium levels in hemodialysis patients with osteomalacia. Kidney Int 57:1107–1114)
More study and research needed
1. According to KDIGO guidelines, what are the 3 components of CKD-MBD?
The three components of CKD-MBD are:
1. mineral and endocrine abnormalities of calcium, phosphorous, parathyroid hormone (PTH), or vitamin D metabolism;
2. Abnormalities of bone related to turnover, mineralization, volume, linear growth, or strength
3. Extraskeletal calcifications.
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
The 2017 guidelines recommend performing bone biopsies only if the diagnosis impacts the treatment
2009 guideline recommends bone biopsy should be performed in at least five situations (multiple fractures, unexplained hypercalcemia or hypophosphatemia, suspected aluminum toxicity, or before osteoporosis treatment)
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
Bone biopsy is considered the gold standard for the diagnosis of renal osteodystrophy in CKD.it also provides information on volume, turnover, mineralization,architecture, and cortical bone related aspects.
Limitations of bone biopsy include being invasive, time-consuming, and requiring expertise in collecting and processing bone fragments and high the cost of histopathological analysis.
What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
In CKD, bone turnover can either be low turnover(a dynamic bone disease and Osteomalacia), or high turnover(SHPT and mixed uremic osteodystrophy)
Low or high bone turnover can be diagnosed non-invasively by evaluating biochemical markers of bone metabolism, such as serum alkaline phosphatase, calcium, phosphorus, and parathyroid hormone.
A bone biopsy is the gold standard for diagnosing renal osteodystrophy and can provide information on volume, turnover, mineralization, architecture, and cortical bone-related aspects, such as porosity or thickness. a Histomorphometric evaluation of both static and dynamic parameters. Even without a semiautomatic method and without measurements, it is useful to have the qualitative evaluation of a bone biopsy.
Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
Aluminum accumulation in the bone results in particular forms of renal osteodystrophy, most notably osteomalacia and adynamic bone disease.
Lanthanum, is not found at critical sites of bone mineralization and no serious effects on either bone mineralization and/or osteoblastic activity have been reported in lanthanum-treated dialysis patients.
Iron overload has been associated with an increased frequency of adynamic bone disease in dialysis patients.
Magnesium is crucial for regulation of osteoblast and osteoclast function and activity in bone remodeling.
Strontium accumulates in the body and is mainly found in new-formed bone in close proximity to the mineralization front.
1- A- mineral and bone abnormalities of serum calcium , phosphorus , PTH and vit D metabolism
B- bone abnormalities related to turnover , mineralization , volume , linear growth or strength
C- extra skeletal calcifications
2- In KDIGO 2017 guidelines , experts put their opinion that bone biopsy should be performed only if diagnosis impacts treatment in contrast to 2009 guidelines that advised to perform bone biopsy in at least five situations including multiple fractures , unexplained hypercalcemia , hypophosphatemia , suspected Aluminum toxicity and before osteoporosis treatment
in my opinion , this more practical and put bone biopsy performance in selected cases where it impacts diagnosis and treatment options as it is an invasive method and have many limitations
3- value of bone biopsy in CKD patients :
a- allows analysis of both cortical and trabecular bones
b- gives information on both static and dynamic parameters of turnover
c- the only method to assess mineralization
limitations include :
a- invasive procedure
b- one shot vision at a time point
c- can be impaired by sampling errors
d- time consuming process
e- needs expertise in collection and analysis of data
4- turnover abnormalities are either :
a- high turnover lesions….SHPTH and mixed uremic osteodystrophy
b- low turnover lesions…..ABD and osteomalacia
non invasive procedures include :
a- labs…..sclerostin , klotho , FGF 23 , wnt / beta catenin system , RANKL / osteoprotegnin system
b- imaging….pQCT , MRI , trabecular bone score , DXA BMD
findings in bone biopsy :
a- high turnover ….increased ostoblasts and osteoclasts number , cortical thinning and porosity with fibrosis in severe SHPTH
b- low turnover…..no osteoclasts , few osteoblasts , no osteoid tissue up to acellular bone
1.According to KDIGO guidelines, what are the 3 components of CKD-MBD?
2.KDIGO changed its recommendations regarding bone biopsy in 2017? What is this change compared to 2009 and what do you think about it?
A. 2017 recommendation:
B. 2009 recommendation: Bone biopsy is indicated the following 5 situations:
C. My thoughts about it: The 2017 guidelines are more practical,simply because bone biopsy is the gold standard for the diagnosis of ROD and beyond
3.Bone biopsy can give valuable information in CKD; however, it has some limitations. Explain the aforementioned statement.
4.What are abnormalities of bone turnover in CKD? How to diagnose them non-invasively and what are their characteristics in bone biopsy?
A. Low turn over and high turn over
B.Noninvasive diagnosis:
C.Bone biopsy findings:
5.Summarize the known effects of metal deposits: Aluminum, Lanthanum, Iron, Mg, and Strontium on bone?
1.Aluminum;
2.Lanthanum;
3.Iron;
4.Magnesium
5.Strontium