Scenario 2 - Part 2:

Further laboratory investigations revealed normal thyroid and liver function tests, 25 (OH) vit D was 14 ng/mL. The patient underwent surgical decompression of the spinal cord and correction of the kyphosis according to the neurosurgeon’s recommendations. Denosumab 60 mg SC biyearly was started together with calcium and Vitamin D supplementation, however the patient experienced severe lower back pain and eczema. Follow up of the patient’s investigation revealed:

Test

Value

S. Creatinine

4.3 mg/dL

S. Corrected Calcium

7.2 mg/dL

S. Phosphorus

5.3 mg/dL

25 (OH) Vit D

27 pg/mL

 

D- Would you agree with the patient’s management plan?

E- Appraise the rationale of bisphosphonates in this patient.

31 Comments

  • Muhammad Soobadar


    D patient has adynamic bone disease and demosumab is antiresorptive agent

    E it cannot be used in ESRF as it not cleared and accumulates

  • Khaldon Rashed Ahmed Moqbil


    D- stop active vit d
    E- not recommend in ESRd

  • Amna Kununa


    D- Would you agree with the patient’s management plan?

    • Part of it. I agreed with giving Ca supp and Vitamin D, but not antiresorptive therapies.
    • Osteoporosis and ABD are highly prevalent in CKD-MBD. They have been consistently associated with low bone mass.
    • Antiresorptive drugs approved by FDA for the treatment of osteoporosis. These therapies may benefit people with high bone turnover disease because they all decrease bone turnover.
    • Denosumab use carries risks of severe hypocalcemia, which can be prolonged over weeks and observed even after a single dose. This side effect is more common in patients with advanced CKD, particularly on dialysis.

    Anabolic agents will play a critical role in the management of osteoporosis in this patient because anabolics will increase bone turnover.

    PTH analogues, including teriparatide and abaloparatide, stimulate bone turnover.

    E- Appraise the rationale of bisphosphonates in this patient.

    • The main risks of bisphosphonate use in patients with advanced CKD or on dialysis include more rapid GFR decline and long-term effects within bone that may induce or exacerbate low turnover states.
  • Rania Mahmoud


    D- Would you agree with the patient’s management plan?

    • Stop vitamin D supplements since it worsen the situation and to avoid more suppression of the PTH level and hyperphosphatemia.
    • Monitor serum calcium levels. Denosumab will be benefited by this patient

    E- Appraise the rationale of bisphosphonates in this patient.Bisphosphonate is not recommended in this case due to hypocalcemia and ADB. Denosumab helps to reduce bone turnover.

  • MOHAMMED HAJI HASSAN


    D- Would you agree with the patient’s management plan?
    Stop vitamin D supplements since it worsen the situation and monitor serum calcium levels. Denosumab will be benefited by this patient

    E- Appraise the rationale of bisphosphonates in this patient.
    Bisphosphonates is not advised in ESRD patients but sometimes a lower dose is used as an antiresorptive drug

  • Hagar Ali


    D- I am agree with ca suuplementation but we have to avoid acive VD
    denosmap as antiresorptive therapy isn’t best choice in a case of ABD but we can use romosozumab

    E- bisphosphonate is not recommended in this case due to hypocalcemia and ADB

  • Ahmed Altalawy


    D- Would you agree with the patient’s management plan? Yes.
    E- Appraise the rationale of bisphosphonates in this patient.The most problematic drug class for osteoporosis patients with renal impairment is likely bisphosphonates. All bisphosphonates, once absorbed from the intestine or injected into the blood, are excreted via the kidney. Therefore, the accumulation of these drugs in the bones is suspected to be faster in advanced-stage CKD patients than in those with normal renal function, possibly due to the early development of adynamic bone disease in these patients. There are no large-scale clinical safety data on bisphosphonate use in patients with CKD G4 or eGFR <35 mL/min/1.73 m2. Therefore, the use of any bisphosphonate drug is generally avoided in these patients.

  • Asma Aljaberi


    D- Would you agree with the patient’s management plan?
    I agree with Ca carb and Vit D3 supplementation (not active Vit D) but do not agree with giving denosumab.
    The patient has low bone turnover, giving him denosumab, anti resorptive agent, will cause further suppression of the bone turnover and put him at a risk of severe hypocalcemia.

    E- Appraise the rationale of bisphosphonates in this patient.
    Bisphosphanate is an anti-resorptive agent, usually not given to ESRD as it is cleared by kidney, but in some cases can be given at a lower dose 2.5 mg IV Q 18 months. For this patient, who has low bone turnover, I would not recommend giving him bisphosphonates as it might cause hypocalcemia.

  • Rihab Elidrisi


     Would you agree with the patient’s management plan?This patient is showing features of low bone turn over and in such cases, we see weak bone formation with a fragility fracture.
    This patient received Denosumab 60 mg SC biyearly which is an antiresorptive measure,and this is not the correct approach for this patient.
    I believe this patient will need to bone builder agent like teriparatide.

    Appraise the rationale of bisphosphonates in this patient.Bisphosphonates may be the right option, especially as we know it is mainly excreted by the kidney and accumulate in the bone for a long time which leads to complication.

  • Mahmud ISLAM


    Because of low turnover, we need Teriparatide or romosuzumab, not denosumab. Bisphosphonate are antiresorptive drugs as well.

  • Rabab Elrefaey


    D. Would you agree with the patient’s management plan?

    Patients with CKD should be assessed for osteoporosis and receive adequate treatment together with correction of other abnormalities like hypocalcemia, hyperphosphatemia and low vitamin D level. Active vitamin D supplementation should be avoided in this case to avoid more suppression of the PTH level and hyperphosphatemia. Serum calcium should be monitored at least 10 days after starting denosumab administration and if hypocalcemia is present, measure more frequently. Denosumab is antiresorptive therapy so it would be helpful in patients with high turnover bone disease with increased bone resorption. This is not the case for his patient as this patient’s major problem is suppressed bone formation. This patient would probably benefit from osteo anabolics (teriparatide, abaloparatide and romosozumab) as these agents can particularly improve the bone formation rate and help to build up the skeleton.  

    E.       Appraise the rationale of bisphosphonates in this patient.

    Denosumab, unlike bisphosphonates, is not cleared by the kidney, and as a consequence, there is no restriction of its use in patients with creatinine clearances below 35 mL/min, for whom bisphosphonates might not be appropriate. Denosumab helps to reduce bone turnover and maintain or increase BMD in patients with CKD. long term Denosumab therapy may result in adverse effects on bone like osteonecrosis of the jaw and atypical fractures.

    • Ben Lomatayo


      Thank you, Dr. Rahab,

      • In question D, native vitamin D is needed as this pt is still vtiamin D insufficient and hypocalcemic. It is just a complicated case.
      • Denosumab may be considered for osteoprosis ; because this case is complex and the pt has double pathology of osteoprosis and ABD
      • In question E, Osteonecronecrosis of the jaw, is it a complication of denosumab or just a typo and you meant bisphosphonate.
  • Mahmoud Elsheikh


    Would you agree with the patient’s management plan?

    • Yes

    Appraise the rationale of bisphosphonates in this patient.
    challenging …

    • It may stay in the bone for long period and precipitate mineralization defects and osteomalacia
    • GFR is low, and its really excreted.
    • bone biopsy is mandatory

    exclude mineralization disorders before the use

  • Asmaa Salih KHUDHUR


    D- Would you agree with the patient’s management plan?

    Yes good management plan .
    E- Appraise the rationale of bisphosphonates in this patient.

    This drug is eliminated by kidneys, so its use in patients with renal impairment may lead to accumulation of this drug for long time with aggravation of bone mineralization defects .

  • KAMAL ELGORASHI


    Would you agree with the patient’s management plan?

    • increase the dose of calcium and vitD.

    Appraise the rationale of bisphosphonates in this patient.

    • also use in osteoporosis, but uses in ESKD, and hypocalcemia, are conflicting, however uses to be individualized
  • Riaan Flooks


    D- Would you agree with the patient’s management plan?

    • Yes, correct treatment administered

    E- Appraise the rationale of bisphosphonates in this patient.

    • A bone biopsy should be done, before initiating treatment
    • It is contra-indicated in patients with CKD
  • Ahmed Wagih


    Would you agree with the patient’s management plan? as patient has hypocalcemia which should be corrected to avoid its complications, plus calcium supplementation will act as phosphate binder, denosumab is antiresorping agent, and pt has adynamic bone disease so we should avoid ti
    Appraise the rationale of bisphosphonates in this patientbisphosphate is atteched to bone for longer time will aggrevate ABD

  • Rabab ALaa Eldin keshk Rabab


    D-Would you agree with the patient’s management plan?

    Yes I agree about the management plane dueto patient need to correct vit d deficiency and oesteoprosis

    E- Appraise the rationale of bisphosphonates in this patient.

    We can use bisphoshonate in ESKD patient and useful when pt have n adynamic bone disease due to prevent more bone resorption and increase bone volume via inhibition of oesteoclast

  • Ben Lomatayo


    D- Would you agree with the patient’s management plan?

    • Yes, correction of vit D deficiency, surgical decompression of the spinal cord, and denosumab for osteoporosis are all required for his management.

    E- Appraise the rationale of bisphosphonates in this patient.

    • Bisphosphonate is tricky specialially if your dealing with eGFR < 30 ml/min/1.73m2
    • It is eliminated by the kidney, hence the prescription is challenging in CKD
    • May accumulate and stay in the bone
    • It may stay in the bone for long period and precipitate mineralization defects and osteomalacia
    • May be considered on case-by-case bases and bone biopsy is mandatory to guide its use
    • It is important to exclude mineralization disorders before the use of bisphosphonate as this is likely to aggravated by the drug
  • Abdulrahman Almutawakel


    D- Would you agree with the patient’s management plan?

    Yes for surgical correction as there is cord compression, but not agree for the Denusumab for this patient as he has mostlikly case of low turn over bone disease,
    further inhibition of of bone resorption either by denosumab or bisphosphonate will probably not improve bone volume
    Osteoanabolic agents like teriparatide and romososumab are the most suitable for increasing bone volume and stimulating bone formation
    denosumab aggravate hypocalcemia and calcium supplements can caused further PTH suppression.

    E- Appraise the rationale of bisphosphonates in this patient.

    In case of low turn over bone disease further inhibition of of bone resorption by bisphosphonate will probably not improve bone volume, as bisphosphonates are cleared by the kidney, these agents accumulate and are stored in bone tissues and therefore bisphosphonates might promote or precipitate mineralization defects and osteomalacia.

  • Israa Hammoodi


    D- Would you agree with the patient’s management plan?

    Yes as surgical correction needed for this patient and use of Donusumab which is bone building monoclonal antibodies is ANTIFGF23 but side effect is hypocalcimia that sometimes severe
    E- Appraise the rationale of bisphosphonates in this patient.

    The use of biphosphonate is useful as antiresorptive drugs but will not be able to build the bone and in case of patient with ESKD cannot be removed by dialysis

  • Alaa Abdel Nasser


    D- Would you agree with the patient’s management plan?no, it is case of low turn over bone disease
    further inhibition of of bone resorption either by denosumab or bisphosphonate will probably not improve bone volume
    osteoanabolic agents like teriparatide and romososumab are the most suitable for increasing bone volume and stimulating bone formation
    denosumab aggravate hypocalcemia
    and calcium supplement caused further PTH suppression

    E- Appraise the rationale of bisphosphonates in this patient.in case of low turn over bone disease
    further inhibition of of bone resorption by bisphosphonate will probably not improve bone volume
    Because bisphosphonates are cleared by the kidney, these agents accumulate and are stored in bone tissues and therefore bisphosphonates might promote or precipitatemineralization defects and osteomalacia. Hence, it is crucial to ensure the absence of mineralization disorders that could be aggravated.

  • Nour Al Natout


    D. Not completely, the patient need a osteoanabolic in case of ABD. Denosumab will worsen the adynamic bone disease.
    It will suggest to use teriparatide or romosozumab, a sklerostin inhibitor so we can increase the osteoblasts differentiation .
    E. Biphosphonate will worsen the mineralization process and aggravate the ABD

  • HASSAN ALYAMMAHI


    D- Would you agree with the patient’s management plan?
     Since we think this patient has ABD, denosumab will exacerbate this problem, also caution should be exercised for hypocalcemia can be sever in these patients

    E- Appraise the rationale of bisphosphonates in this patient.
    Bisphosphonates are potent inhibitors of bone resorption that reduce osteoclast recruitment and activity. They are cleared by the kidney as well as by dialysis, and the efficacy of dialysis clearance varies among bisphosphonates, likely due to variable protein binding. In subjects with mild or moderately reduced eGFR (up to CKD G4), bisphosphonates were found to have comparable efficacy, improved BMD, and reduced fractures to those with normal eGFR. Bisphosphonates naturally inhibit bone turnover, and the majority of osteoporosis patients treated with bisphosphonates develop a low bone formation rate. However, there is no evidence that remodeling suppression is greater in CKD than in the general population.

  • ahmed bhnassi


    Would you agree with the patient’s management plan?
    Yes, could be reasonable to use it as risk/ benefit ration in favor of using denosumab due to his fracture risk
    use of denosumab in hemodialysis patients had risk of symptomatic hypocalcemia, Hypocalcemia induced by denosumab in CKD could be avoided by administering oral calcium and active vitamin D to eligible CKD patients before starting denosumab. Our patient in the case scenario had low normal serum calcium and vitamin D insufficiency.
    to start denosumab in a hemodialysis patient, several precautions should be taken to ensure the safety and efficacy of its use in HD patients.
    1.   Evaluation of calcium and vitamin D status:
    it’s important to ensure that the patient has adequate calcium intake and vitamin D levels before starting treatment.
    2.   Monitoring of serum calcium:
    serum calcium should be monitored closely, during treatment with denosumab especially during the first several weeks. If hypocalcemia occurs, calcium supplementation may be necessary.
    3.   Monitoring of bone mineral density:
    BMD should be monitored regularly during denosumab treatment to assess its efficacy
    4.   Monitoring for adverse effects:
    Prolia has several adverse effects, including
    Hypocalcemia,
    Infections, and
    Skin reactions.
    Patients should be monitored closely for these and other adverse effects during treatment.
    Overall, the use of denosumab in hemodialysis patients requires careful consideration of the potential risks and benefits.
     
    Appraise the rationale of bisphosphonates in this patient.
    Bisphosphonates use in patients with end-stage renal disease (ESRD) is more limited due to concerns about their safety and efficacy in ESRD patients.
    In ESRD, bisphosphonates generally not recommended for routine use due to an increased risk of adverse effects, (hypocalcemia, osteonecrosis of the jaw. accumulate in the bones and soft tissues)
    However, could be used in severe osteoporosis or bone metastases who had high risk for fractures. the potential benefits of bisphosphonate therapy may outweigh the risks.

  • Ashraf Ahmed Mahmoud


    D- Would you agree with the patient’s management plan? Denosumab increase bone mass and increase bone mineral denisty.when use in ESKD must be start use 1000 mg Ca .and 400 iu vit D.because risk of hypocalcemia is very high .use of Denosumab it gets worse and increase spinal fractureso precautions must be taken .I prefer use of alendronate .
    E- Appraise the rationale of bisphosphonates in this patient.
    diagnose osteoporosis in this patient is by quantitative bone histomorphometry demonstrating low trabecular bone volume and disrupted microarchitecture. Once the diagnosis of osteoporosis is established, BPs should be considered

  • Elsayed Ghorab


    Would you agree with the patient’s management plan?YES agree this management plan
    preferred in CKD than bisphosphonate

    but should be controlled and correct hypocalcemia

    Appraise the rationale of bisphosphonates in this patient
    Bisphosphonates are powerful bone resorption inhibitors that work by lowering osteoclast recruitment and activity. They are cleared by the kidney and also by dialysis and the efficacy of dialytic clearance varies between bisphosphonates, probably owing to variable protein binding. Post hoc analysis of pivotal clinical trials evaluating bisphosphonates found that these drugs had similar efficacy, improved BMD and reduced fractures, in subjects with mild or moderately reduced eGFR (up to CKD G4) compared to those with normal eGFR. Suppression of bone turnover is inherent to bisphosphonates and most osteoporosis patients who are treated with bisphosphonates develop a low bone formation rate. However, there is no evidence that the level of remodeling suppression in CKD is more than that in the general population. REFERENCE Evenepoel, P., Cunningham, J., Ferrari, 

  • Weam El Nazer


    D- Would you agree with the patient’s management plan?
    Preliminary results showed that treatment with Prolia in dialysis patients had a substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death. Healthcare professionals are advised to consider the risks of hypocalcemia when using Prolia in dialysis patients.

    Hypocalcemia induced by denosumab in CKD patients can be a critical issue and should be avoided by practicing appropriate precautions and preemptively administering active vitamin D to eligible CKD patients before starting denosumab. The serum Ca levels usually reach their nadir around seven days after administration, with a less-extensive Ca decrease with the second denosumab administration.In our patient, he developed severe hypocalcemia (a Prolia side effect) and severe low back pain.
    The patient started denosumab while his serum calcium and vitamin D levels were low, which is against the recommendation.

    E- Appraise the rationale of bisphosphonates in this patient.

    The most problematic drug class for osteoporosis patients with renal impairment is likely bisphosphonates. All bisphosphonates, once absorbed from the intestine or injected into the blood, are excreted via the kidney. Therefore, the accumulation of these drugs in the bones is suspected to be faster in advanced-stage CKD patients than in those with normal renal function, possibly due to the early development of adynamic bone disease in these patients. There are no large-scale clinical safety data on bisphosphonate use in patients with CKD G4 or eGFR <35 mL/min/1.73 m2. Therefore, the use of any bisphosphonate drug is generally avoided in these patients.

    I will not recommend initiating bisphosphonates in patients with ESRD and osteoporosis without a bone biopsy.

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