of Endocrinology UZ Gent Bisphosphonates vs denosumab Advantages and risks Osteoporosis in Belgium Figure from osteopolicynetworkorg Importance of timely diagnosis and ID: 1040640
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1. Charlotte VerrokenDepartment of EndocrinologyUZ GentBisphosphonates vs. denosumab:Advantages and risks
2. Osteoporosis in BelgiumFigure from osteopolicynetwork.orgImportance of timely diagnosis and treatment of women with high fracture risk ↔ life expectancy ± 80y Need for antiosteoporotic agents that can be administered for prolonged periods with both efficacy and safety
3. AntiresorptivesAnastasilakis et al., 2018
4. BisphosphonatesAlendronate 70mg / week (ALN - Fosamax®)Risedronate 35mg / week (RIS - Bonviva®)Ibandronate 150mg / month (IBN - Actonel®)Zoledronate 5mg / year (ZOL - Aclasta®)Potency ~ degree of bone remodeling inhibitionNew bone turnover equilibrium after 3-6 months (IV faster)
5. BisphosphonatesRelative fracture risk reductionBMD increaseGreater BMD gain in those with high baseline bone remodelingPlateau after 2-3 years (esp. at hip)ALNRISIBNZOL24-48 months Vertebral fracture49%41-43%36-51%63-72% Non-vertebral fracture17-20%21%26-31% Hip fracture38-40%26-37%39-41%Hopkins et al., 2011. Zhou et al., 2016
6. AntiresorptivesAnastasilakis et al., 2018
7. DenosumabDenosumab 60mg / 6 months (Dmab - Prolia®)Rapid decline in bone resorption (nadir after 1 month)Relative fracture risk reductionVertebral fracture: - 68%Non-vertebral fracture: - 20%Hip fracture: - 40%BMD increaseNo plateauGreater than with bisphosphonates
8. Dmab vs. BP: fracture risk reductionLyu et al., 2019
9. Bisphosphonates: residual effectAfter initial binding in bone → inactive state Reactivation when burial site is subjected to remodeling againElimination half-time of the skeleton up to 8-10 yearsPossibility of drug holidayBlack et al., 2006
10. Risks: atypical femoral fracture (AFF)3.2–50 / 100.000 patient years for bisphosphonates, similar for denosumabRisk factors:Prolonged antiresorptive useGlucocorticoid treatmentChemotherapyOlder ageFor denosumab: previous BP use
11. Risks: osteonecrosis of the jaw (ONJ)In doses used for osteoporosis: 1-10 / 100.000 patient years for bisphosphonates, similar for denosumabOnly marginally higher than general population!Risk factors: Potency of antiresorptiveProlonged antiresorptive useGlucocorticoid useChemotherapyOlder agePre-existing oral infectionInvasive dental proceduresSmoking
12. Risks: hypocalcemiaMore frequent with denosumabRisk factor: CKDMost frequent in first 1 – 2 months after injectionEnsure adequate calcium and vitamin D suppletion
13. Denosumab: rebound phenomenonTsourdi et al., 2017Bone turnoverBMD
14. Denosumab: rebound phenomenonAnastasilakis et al., 2020
15. Denosumab: rebound phenomenonIncrease in bone turnover and loss of bone mineral density early after denosumab discontinuation Risk of multiple clinical vertebral fractures1.2 - 7.1 / 100.000 patient years for single VF, much higher risk for multiple VFLow thoracic and high lumbar spineEven in those at ‘low risk’ in terms of BMD and absence of previous fracturesRisk factors:Long duration of treatment Prevalent VFsNo other treatment before denosumabBMD loss upon discontinuation
16. Denosumab: rebound phenomenonIncrease in bone turnover and loss of bone mineral density early after denosumab discontinuation Risk of multiple clinical vertebral fractures1.2 - 7.1 / 100.000 patient years for single VF, much higher risk for multiple VFLow thoracic and high lumbar spineEven in those at ‘low risk’ in terms of BMD and absence of previous fracturesRisk factors:Long duration of treatment Prevalent VFsNo other treatment before denosumabBMD loss upon discontinuationDenosumab should not be stopped without considering alternative treatment
17. Reimbursement criteria – postmenopausal osteoporosisZoledronate1 of the following:VF (≥25% and ≥4mm) Hip fractureT-score < -2.5 at LS / hip / femoral neck DenosumabPrevious treatment with bisphosphonate or contra-indication for bisphosphonateAND 1 of the following:VF (≥25% and ≥4mm)T-score < -2.5 at LS / hip / femoral neck on DXA < 6 months old
18. SummaryAnastasilakis et al., 2018VFx after discontinuation(AF)Other advantagesCan be used in CKDNo reimbursement restrictions
19. Questions?