PMC Canada Author Manuscript
PubMed Central CANADA Author Manuscript / Manuscrit d'auteur N Engl J Med. Author manuscript; available in PMC 2016 November 26. Published in final edited form as: N Engl J Med. 2016 May 26; 374(21): 2095–2097. doi:10.1056/NEJMc1602599.
Postmenopausal Osteoporosis Karl Michaëlsson, M.D., Ph.D. and Uppsala University, Uppsala, Sweden Per Aspenberg, M.D., Ph.D. Linköping University, Linköping, Sweden Karl Michaëlsson: [email protected]
TO THE EDITOR PMC Canada Author Manuscript PMC Canada Author Manuscript
According to the results of two trials presented in Table 3 of the article by Black and Rosen (Jan. 21 issue),1 the first 3 years of bisphosphonate use are beneficial for the prevention of fracture. However, the data presented in the table are misleading. The steep increase in the incidence of atypical fracture with prolonged bis-phosphonate use is concomitant with little or no added efficacy in the prevention of fracture. On the basis of population-based data,2 rather than theoretical calculations,1 the risk of atypical femoral fractures for patients who receive 4 years of treatment is 126 times as high as the risk for those who did not receive treatment, which corresponds to a number needed to harm of 909 per year (odds ratio for the fifth year, 116).2 When all available data on the efficacy of treatment for the prevention of hip fracture are considered — not just two out of all randomized, controlled trials — the number needed to treat (NNT) is 501 per year for the initial 3 years of use.3 Because the extension of treatment beyond 5 years does not appear to prevent nonvertebral or hip fractures,4 the NNT for a sixth year would be high — close to infinity. For the fourth and fifth years, the NNT would lie somewhere between 501 and infinity. It is uncertain whether there is a positive benefit:risk ratio when the duration of treatment is longer than 3 to 4 years. Recently suggested widening of the treatment indications5 will increase the NNT. A consequence may be that the risks will outweigh the benefits even after treatment of shorter duration.
References 1. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016; 374:254–62. [PubMed: 26789873] 2. Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. N Engl J Med. 2014; 371:974–6. [PubMed: 25184886] 3. Järvinen TL, Michaëlsson K, Jokihaara J, et al. Overdiagnosis of bone fragility in the quest to prevent hip fracture. BMJ. 2015; 350:h2088. [PubMed: 26013536]
Dr. Aspenberg reports receiving consulting fees from Eli Lilly and Amgen and grant support to his institution, Linköping University, from Eli Lilly and Amgen; holding stock in AddBIO, a company trying to commercialize a method for applying a bis-phosphonate coating to implants to be inserted in bone; and holding a patent for this method. No other potential conflict of interest relevant to this letter was reported.
Michaëlsson and Aspenberg
Page 2
PMC Canada Author Manuscript
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; 296:2927–38. [PubMed: 17190893] 5. McCloskey E. A BMD threshold for treatment efficacy in osteoporosis? A need to consider the whole evidence base. Osteoporos Int. 2016; 27:417–9. [PubMed: 26564227]
PMC Canada Author Manuscript PMC Canada Author Manuscript N Engl J Med. Author manuscript; available in PMC 2016 November 26.
PubMed Central CANADA Author Manuscript / Manuscrit d'auteur N Engl J Med. Author manuscript; available in PMC 2016 November 26. Published in final edited form as: N Engl J Med. 2016 May 26; 374(21): 2095–2097. doi:10.1056/NEJMc1602599.
Postmenopausal Osteoporosis Karl Michaëlsson, M.D., Ph.D. and Uppsala University, Uppsala, Sweden Per Aspenberg, M.D., Ph.D. Linköping University, Linköping, Sweden Karl Michaëlsson: [email protected]
TO THE EDITOR PMC Canada Author Manuscript PMC Canada Author Manuscript
According to the results of two trials presented in Table 3 of the article by Black and Rosen (Jan. 21 issue),1 the first 3 years of bisphosphonate use are beneficial for the prevention of fracture. However, the data presented in the table are misleading. The steep increase in the incidence of atypical fracture with prolonged bis-phosphonate use is concomitant with little or no added efficacy in the prevention of fracture. On the basis of population-based data,2 rather than theoretical calculations,1 the risk of atypical femoral fractures for patients who receive 4 years of treatment is 126 times as high as the risk for those who did not receive treatment, which corresponds to a number needed to harm of 909 per year (odds ratio for the fifth year, 116).2 When all available data on the efficacy of treatment for the prevention of hip fracture are considered — not just two out of all randomized, controlled trials — the number needed to treat (NNT) is 501 per year for the initial 3 years of use.3 Because the extension of treatment beyond 5 years does not appear to prevent nonvertebral or hip fractures,4 the NNT for a sixth year would be high — close to infinity. For the fourth and fifth years, the NNT would lie somewhere between 501 and infinity. It is uncertain whether there is a positive benefit:risk ratio when the duration of treatment is longer than 3 to 4 years. Recently suggested widening of the treatment indications5 will increase the NNT. A consequence may be that the risks will outweigh the benefits even after treatment of shorter duration.
References 1. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016; 374:254–62. [PubMed: 26789873] 2. Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. N Engl J Med. 2014; 371:974–6. [PubMed: 25184886] 3. Järvinen TL, Michaëlsson K, Jokihaara J, et al. Overdiagnosis of bone fragility in the quest to prevent hip fracture. BMJ. 2015; 350:h2088. [PubMed: 26013536]
Dr. Aspenberg reports receiving consulting fees from Eli Lilly and Amgen and grant support to his institution, Linköping University, from Eli Lilly and Amgen; holding stock in AddBIO, a company trying to commercialize a method for applying a bis-phosphonate coating to implants to be inserted in bone; and holding a patent for this method. No other potential conflict of interest relevant to this letter was reported.
Michaëlsson and Aspenberg
Page 2
PMC Canada Author Manuscript
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; 296:2927–38. [PubMed: 17190893] 5. McCloskey E. A BMD threshold for treatment efficacy in osteoporosis? A need to consider the whole evidence base. Osteoporos Int. 2016; 27:417–9. [PubMed: 26564227]
PMC Canada Author Manuscript PMC Canada Author Manuscript N Engl J Med. Author manuscript; available in PMC 2016 November 26.
