Scenario 3:
A 62-year-old man, who has been on for 10 years, presents with gradually increasing bone pain. Current medications include alfacalcidol 1 mcg/day and calcium carbonate 1500 mg. The patient’s labs are shown in table 1
Test |
Value |
S. Creatinine |
3.9 mg/dL |
S. corrected Calcium |
10.5 mg/dL |
S. Phosphorus |
7.1 mg/dL |
iPTH |
18 pg/mL |
A- Interpret the above laboratory investigations.
B- Would you recommend a bone biopsy for this patient?
The patient underwent a bone biopsy which is revealed in figure 1
Salusky and goodman et.al.,2001, 12 (9) 1978-1985
C- Interpret the above bone specimen.
D- Discuss the mechanisms contributing to this pathology.
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A – high calcium and high phosphate and suppressed PTH due too to much alfacalcidol and calcium tablet
B- reduce alfacalcidol, stop calcium tablets and check CKD MBD parameters before bone biopsy.
C adynamic bone disease due low cells and low osteoid volume
D due to overtreatment with alfacalcidol , calcium supplements pth is over suppressed. this leads to bone formation being reduced and decreased mobilisation of Ca from ECF,
A- Interpret the above laboratory investigations.
keeping with ABD
B- Would you recommend a bone biopsy for this patient?
C- Interpret the above bone specimen.
low bone formation in conjunction with thin osteoid seams, decreased cellularity, and minimal bone marrow fibrosis.
D- Discuss the mechanisms contributing to this pathology.
Oversuppression of PTH release:
A-hypercalcemia, hyperphosphatemia and a very low PTH level.
B- No it is a case of ABD
he needs to stop one alpha and ca supplement ,use renvela to treat po4 and low ca dialysate to stimulate pth
C- hypo cellularity with low osteoid bone case of ABD
D- prolonged use of one alpha and Ca supplement with hyper phosphoremia
A- Interpret the above laboratory investigations.
ESRD with hypercalcemia and hyperphosphatemia, with low PTH level could be attributed to drug indcued- prolonged use of alfacalcidol.
B- Would you recommend a bone biopsy for this patient.Not at this stage, I would stop alfacalcidol, calcium supplements and add phosphate binder. Then will monitor bone profile and BTMs and clinical condition. Based on biochemical markers results and clinical condition will decide about further evaluation.
C- Interpret the above bone specimen.
Hypocellularity, low osteoclasts and osteoblasts activity, low osteoid bone, low mineralization causing low bone volume and low turnover- Adynamic bone disease.
D- Discuss the mechanisms contributing to this pathology
Prolonged use of alfacalcidol- active Vit D – is the main cause of low bone turnover- Adynamic bone disease.
A- Interpret the above laboratory investigations.HYPERCALCEMIA, HYPERPHOSPHATEMIA AND VERY LOW PTH.
THE PATIENT WAS ON ALFACALCIDOL AND CALCIUM CARBONATE BOTH CAN COTRIBUTE TO LOW PTHB- Would you recommend a bone biopsy for this patient?LOW PTH WILL HAVE LOW TRUNOVER BONE DISEASE
I WOULD NOT RECCOMEND BONE BIOPSY
C- Interpret the above bone specimen.LOW STEOID VOLUME PICTURE OF DYNAMIC BONE DISEASE
D- Discuss the mechanisms contributing to this pathology.long duration or over correction with Alfacalcidol and calcium carbonate causes suppress PTH which will lead to dynamic bone diseases
Model answer by the board:
A. Interpret the above laboratory investigations.
According to the previous lab abnormalities, the patient has hypercalcemia, hyperphosphatemia and a very low PTH level. The patient was maintained on alfacalcidol with high dose and calcium carbonate. Both cause more decrease in PTH level and both hyperphosphatemia and hypercalcemia. The very low bone turnover in this case is the cause of failure of mobilisation of calcium into the bone so hypercalcemia occurs and subsequent vascular calcifications.
B. Would you recommend a bone biopsy for this patient?
Patients with very low PTH levels are most likely to have low turnover bone disease and therefore bone biopsy is not needed. The patient should stop calcium and vitamin D supplementation first and non calcium phosphate binders are important to be added to control high phosphorus levels, then repeat his lab again. Persistent bone pain despite improvement of his laboratory investigations is an indication for bone biopsy.
C. Interpret the above bone specimen.
Paucity of bone cells with low osteoid volume is highly suggestive of adynamic bone disease.
D. Discuss the mechanisms contributing to this pathology.
` Prolonged use of active vitamin D and calcium supplementation lead to suppression of PTH. Low PTH level makes the bone hypoactive and hypocellular because of the inability to mobilise calcium from extracellular and suppressed bone formation.The pathophysiology of ADB is certainly multifactorial , comprising patient related and iatrogenic factors on a predisposed genetic background. A state of imbalance between the low circulating levels of bone anabolic factors (e.g., insulin-like growth factor(IGF)-I) and the increased expression of bone-turnover–inhibitory factors, such as sclerostin and Dickkopf-related protein-1 (Dkk-1), largely predominates. This imbalance ultimately suppresses bone formation through repression of WNT/β-catenin signalling. Moreover, uremic toxins may play a role in this setting. Circulating cytokines like IL-1,IL-6 and TNF alpha are associated with impaired bone forming and resorbing cells.
A- Interpret the above laboratory investigations.Is the patient was on regullar dialysis for 10 yrs or on what he was for 10 yrs ???
A- Interpret the above laboratory investigations.
Patient has hypercalcemia , hyperphosphatemia with suppresed parathyroied, mostlikly
B- Would you recommend a bone biopsy for this patient?
Yes i will recommend bone biopsy but also hold alfacalcidol and calcium with phosphorous binder noncalcium containing.
C- Interpret the above bone specimen.There is acellular bone, no osteoid formation low bone volume picture of adynamic bone disease
D- Discuss the mechanisms contributing to this pathology.
Mostly b/o suppressed parathyroieds due to overtreatment with caclium and alfacalcidol no lession in the biopsy to think of aluminium intoxication
A. Hypercalcemia, hyperphophatemia, and over suppressed PTH level.
B. No , i eill try to measure BALP and to reduce vitamin D and change to non calcium phosphate binders.
C.Adynamic bone disease
D. Treatment induced Oversuppression of parathyroid gland. Aluminum intoxication should be also excluded.
A- Interpret the above laboratory investigations.Hyperphosphatemia- Hypercalcemia &low PTH
B- Would you recommend a bone biopsy for this patient?
C- Interpret the above bone specimen.There is interrupted trabeculae
low osteoid volume
no osteoblasts
no osteoclasts
defective mineralization
D- Discuss the mechanisms contributing to this pathology.High doses of one Alfa and calcium leading to PTH suppression causing adynamic bone disease.
A- Interpret the above laboratory investigations.
Hyperphosphatemia- low PTH
B- Would you recommend a bone biopsy for this patient?
No, first asses other parameters and try medications
C- Interpret the above bone specimen
very little osteoid and interrupted trabeculae
D- Discuss the mechanisms contributing to this pathology.
Overuse of Alfacalcidol and calcium carbonate which further suppress PTH as shown above case
A- Interpret the above laboratory investigations.
high ca and phosphate
very low PTH
low bone turnover, adynamic bone disease
B- Would you recommend a bone biopsy for this patient?
no
i can try medical correction first
C- Interpret the above bone specimen.
There is interrupted trabeculae
low osteoid volume
no osteoblasts
no osteoclasts
defective mineralization
D- Discuss the mechanisms contributing to this pathology.
high doses of one Alfa and calcium leading to PTH suppression causing adynamic bone disease.
We have high phosphorus and very low PTH; biopsy shows decreased bone volume with low osteoid level. A biopsy is needed to differentiate dynamic bone disease from osteomalacia. Biopsy shows osteoporosis and low turnover parallel to very low PHT
A- Interpret the above laboratory investigations.
B- Would you recommend a bone biopsy for this patient?
C- Interpret the above bone specimen.
D- Discuss the mechanisms contributing to this pathology.
nterpret the above laboratory investigations.high serum , hyperphosphatemia and
Hypoparathyroidism suggestive for low turn oner over bone disease (dynamic bone disease)
B- Would you recommend a bone biopsy for this patient?
No as will not change management first stop active vit D and stop oral calcium Bone pain and lab derangement could be explained by over suppression of PTH by calcium and active vitamin d , hyperphosphatemia which should be treated with holding active vitamin d start non calcium phosphate binder
if no clinical or lab improvement
bone biopsy may be indicated
C- Interpret the above bone specimen.
Acellular bone section no osteoid formation low bone volume picture of adynamic bone disease
D- Discuss the mechanisms contributing to this pathology.Over suppression of PTH by calcium and active vitamin d
old age , DM, aluminium intoxication (should be excluded especially with staining the bone with solochrome azurine stain
A- Interpret the above laboratory investigations.
Hypercalcimia, hyperphosphatemia and Hypoparathyroidism
B- Would you recommend a bone biopsy for this patient?
No, first I will do biomarkers like BSAP, 25OH vitamin D and DXA scan then according to the result
C- Interpret the above bone specimen.
Show discontinus trabeculae goes with osteoporosis
D- Discuss the mechanisms contributing to this pathology.
Due to excessive use of calcium and vitamin D causing suppression of PTH and Adynamic bone disease
A: Adynamic bone disease
B: Yes – exclude osteoporosis
C: Decreased osteoblasts and osteoclasts
D: Hypoparathyroidism and osteoporosis
Interpret the above laboratory investigations. the patient has hypercalcemia, hyperphosphatemia, low PTH point to adynamic bone disease
Would you recommend a bone biopsy for this patient? yes, to rule out aluminium toxicity and osteoporosis
Interpret the above bone specimen decreased osteoblast and osteoclast, increased ostoid, fragements of trabeculae
Discuss the mechanisms contributing to this pathology hypoparthyroidism and assosciated osteoporosis
Interpret the above laboratory investigations.
Would you recommend a bone biopsy for this patient?Yes; unexplained hypercalcemia, after a trial of treatment modulation
Interpret the above bone specimen.
Discuss the mechanisms contributing to this pathology.
A- Interpret the above laboratory investigations.hypercalcemia and hypophosphatemia, low iPTH => ABD
B- Would you recommend a bone biopsy for this patient?No, unlikely to impact management at this time
C- Interpret the above bone specimen.
Acellular sample with no osteoid –> ABD
D- Discuss the mechanisms contributing to this pathology.Inhibition of parathyroid gland by the active VitaminD and high the hypercalcemia
A- Interpret the above laboratory investigations.
Hypercalcimia and hyperphosphatemia with low pth.
B- Would you recommend a bone biopsy for this patient?
First i will ask for vit d level serum mg stop vit d replacement and if still symptomatic will ask bone biopsy.
C- Interpret the above bone specimen.
no osteoblast or osteoclast no osteoid formation low bone volume picture of adynamic bone disease
D- Discuss the mechanisms contributing to this pathology
ExessCa supplements and Vit D
high Ca dialysate
Aluminum intoxication
Old age if patient diabetic
high ncalcium, hyperphosphatemia and low PTH level
low turn oner bone disease mostly dynamic bone disease
b-no
c-osteoblast or osteoclastno osteoid formation low bone volume picture of adynamic bone disease
d-over control hyperparathyrodsim
A- Interpret the above laboratory investigations.high normal serum calcium, hyperphosphatemia and low PTH level
low turn oner bone disease mostly dynamic bone disease
B- Would you recommend a bone biopsy for this patient?Bone pain and lab derangement could be explained by over suppression of PTH by calcium and active vitamin d , hyperphosphatemia explained by active vitamin d
stop these medications, if no clinical or lab improvement
proceed to bone biopsy as it is the gold standard
C- Interpret the above bone specimen.no osteoblast or osteoclastno osteoid formation low bone volume picture of adynamic bone disease
D- Discuss the mechanisms contributing to this pathology.Over suppression of PTH by calcium and active vitamin d
old age , if DM is present
May be related to aluminium intoxication (should be excluded especially if there is history of using aluminium containing drugs or inadequate water treatment system)
aluminium intoxication could be diagnosed with staining the bone with solochrome azurine stain
Interpret the above bone specimen.
This patient with CKD styage 5 is having severe hypoPTH weith hypercalcemias and hyperphophatemias
he ios having biochemical featuers of ABD
Would you recommend a bone biopsy for this patient? not really ,we can diagnose him according to the biochemical result and follow him in the coming 3 to 6 month with the following approach:
reduce Ca supplements and reduce Ca in the dialysate.
vit D is also need to be reduced
check aluminum level which is not the case now adays
The bone biopsy of this patient showed
low bone cellularity with low bone formation and miniralization .
Discuss the mechanisms contributing to this pathology.overuse of Ca supplements and Vit D
high Ca dialysate
Aluminum intoxication
age
]diabetes
metabolic acidosis
CKD 5D
high phosphate and calcium with low PTH
=================
2-we need to stop alfacalcidol and calcium carbonate
and reduce dialysate calcium 1.25 mmol/l
================
– Discuss the mechanisms contributing to this pathology.overuse of alfacalcidol and calcium without fu
A- Interpret the above laboratory investigations.
B- Would you recommend a bone biopsy for this patient?
C- Interpret the above bone specimen.
D- Discuss the mechanisms contributing to this pathology.
C- Interpret the above bone specimen.
D- Discuss the mechanisms contributing to this pathology.
A- Interpret the above laboratory investigations.
B- Would you recommend a bone biopsy for this patient?
A- Interpret the above laboratory investigations.
B- Would you recommend a bone biopsy for this patient?NO.
correct the hypoparahtyrodism by stop Ca and alfacacidol .
C- Interpret the above bone specimen.
D- Discuss the mechanisms contributing to this pathology.ABD due to high ca and use alfacacidol causing low PTH
A- Interpret the above laboratory investigations.high calcium and PO4 with very low PTH
Picture of low bone turnover
B- Would you recommend a bone biopsy for this patient?No, I will stop the calcium and one-alfa and follow up on the symptoms and the lab.
C- Interpret the above bone specimen.Low osteoid volume, osteoblast, and osteoclast with a defect in the mineralization. interrupted trabeculae.
D- Discuss the mechanisms contributing to this pathology.High doses one alfa and calcium lead to suppression of the PTH, adynamic bone disease, and low bone turnover histopathologically.
the lab revealed
pt. is CKD
hypercalcemia
hyperphosphatemia
hypoparathyroidism .>> supressed PTH>>>> may suppressed by alfacalcidole over dose
the pathology of this bone specimen >>> low bone turnover ???
A- case with renal impairment , hypercalcemia , hyperphosphatemia with over suppressed iPTH levels
B- i don’t recommend bone biopsy for this patient as hypercalcemia is explained by over correction with calcium and vit D analogues that cause the symptoms
C – decreased osteoblasts and osteoclasts with no osteoid tissue consistant with ABD
D – overcorrection of calcium by calcium supplements and vit D which leads to suppression of PTH
other risk factors include DM , aging , Al toxicity and high flux filters