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Osteoporosis Experts Discuss Bisphosphonate Holidays

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Prevention & Treatment

Strategies to reduce AFF risk in patients on bisphosphonates include drug holidays, but rheumatologists may also watch for prodromal pain symptoms, and ask patients about unexplained hip or thigh pain at office visits.18,13 Imaging, including extended femur DXA scans or single-energy femoral scans, may help identify incipient AFFs.19,20

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Surgical treatments include fixation with intramedullary, full-length nails and fracture augmentation with bone marrow aspirate.21,22 After surgery, physicians should image the contralateral femur to assess for incomplete fracture on the other side, because bilaterality is so common, Dr. Shane noted.

Dr. Shane said she stops antiresorptive therapy after surgery, and that some physicians prescribe teriparatide after surgery to speed healing. Data from a 2020 study showed 40% of patients with incomplete AFFs progressed while on teriparatide, although patients with complete AFFs seemed to heal faster. However, no evidence has shown teriparatide enhances AFF healing, and in patients with AFFs who are still at high risk for fractures, three to six months of teriparatide may suffice. If patients are on teriparatide for two years, Dr. Shane recommends that physicians monitor bone turnover markers and bone mineral density, and then consider another antiresorptive therapy, such as estrogen, synthetic estrogen receptor modulators, calcitonin, denosumab or bisphosphonates.23

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“While AFFs are definitely related to long-term bisphosphonate use, we are not yet sure that it is causal,” said Dr. Shane. “In my patients’ view, AFFs are not rare. They feel that AFFs are underreported, and to quote one of my patients, ‘the risk is low unless it happens to you.’ As clinicians and scientists, we have to find more effective ways to communicate that osteoporotic fractures have devastating effects on people’s lives. Bisphosphonates and denosumab can reduce these fractures. But we need to listen to patients’ concerns.”

Susan Bernstein is a freelance journalist based in Atlanta.

References

  1. Solomon CG. Bisphosphonates and osteoporosis. New Engl J Med. 2002 Feb 28;346(9):642.
  2. Khan SA, Kanis JA, Vasikaran S, et al. Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Miner Res. 1997 Oct;12(10):1700–1707.
  3. Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012 Feb;27(2):243–254.
  4. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: The Fracture Intervention Trial Long-Term Extension (FLEX): A randomized trial. JAMA. 2006 Dec 27;296(24):2927–2938.
  5. Black DM, Bauer DC, Schwartz AV, et al. Continuing bisphosphonate treatment for osteoporosis—For whom and for how long? New Engl J Med. 2012 May 31;366(22):2051–2053.
  6. Bauer DC, Schwartz AV, Palermo L, et al. Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: The FLEX study. JAMA Intern Med; 2014 Jul;174(7):1126–1134.
  7. Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan;31(1):16–35.
  8. McNabb B, Vittinghoff E, Eastell R, et al. A model of BMD changes after alendronate discontinuation to guide post-alendronate BMD monitoring. J Clin Endocrinol Metab. 2014 Nov;99(11):4094–4100.
  9. Jha S, Wang Z, Laucis N, et al. Trends in media reports, oral bisphosphonate prescriptions and hip fractures: 1996–2012: An ecological analysis. J Bone Miner Res. 2015 Dec;30(12):2179–2187.
  10. Kim SC, Kim DH, Mogun H, et al. Impact of U.S. Food and Drug Administration’s safety-related announcements on the use of bisphosphonates after hip fracture. J Bone Miner Res. 2016 Aug;31(8):1536–1540.
  11. Black DM, Abrahamsen B, Bouxsein ML, et al. Atypical femur fractures: Review of epidemiology, relationship to bisphosphonates, prevention and clinical management. Endocr Rev. 2019 Apr 1;40(2):333–368.
  12. Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: Second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014 Jan;29(1):1–23.
  13. Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267–2294.
  14. Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft and atypical femur fracture: A systematic review and meta-analysis. J Bone Miner Res. 2013 Aug;28(8):1729–1737.
  15. Black DM, Geiger EJ, Eastell R, et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. New Engl J Med. 2020 Aug 20;383(8):743–753.
  16. Unnanuntana A, Ton QV, Kleimeyer JP, et al. A fracture does not adversely affect bone mineral density responses after teriparatide treatment. Clin Orthop Relat Res. 2012 Mar;470(3):927–936.
  17. Unnanuntana A, Rebolledo BJ, Khair MM, et al. Diseases affecting bone quality: Beyond osteoporosis. Clin Orthop Relat Res. 2011 Aug;469(8):2194–2206.
  18. Schilcher J, Michaelsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. New Engl J Med. 2011 May 5;364(18):1728–1737.
  19. Van de Laarschot DM, Smits AA, Buitendijk SK, et al. Screening for atypical femur fractures using extended femur scans by DXA. J Bone Miner Res. 2017 Aug;32(8):1632–1639.
  20. McKenna MJ, McKiernan FE, McGowan B, et al. Identifying incomplete atypical femoral fractures with single-energy absorptiometry: Declining prevalence. J Endocr Soc. 2017 Feb 13;1(3):211–220.
  21. Weil YA, Rivkin G, Safran O, et al. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma. 2011 Jul;71(1):186–190.
  22. Lovy AJ, Kim JS, Di Capua J, et al. Intramedullary nail fixation of atypical femur fractures with bone marrow aspirate concentrate leads to faster union: A case-control study. J Orthop Trauma. 2017 Jul;31(7):358–362.
  23. Van de Laarschot DM, McKenna MJ, Abrahamsen B, et al. Medical management of patients after atypical femur fractures: A systematic review and recommendations from the European Calcified Tissue Society. J Clin Endocrinol Metab. 2020 May 1;105(5):1682–1699.

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