Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Fracture Prevention in Women with Osteoporosis

N Engl J Med; 2017 Oct 12; Saag, Petersen, et al

Romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture in postmenopausal women with osteoporosis at high risk for fracture, than alendronate alone. This according to a study of 4,093 postmenopausal women with osteoporosis and a fragility fracture who were randomly assigned 1:1 to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture at the time of primary analysis. Researchers found:

  • A 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group, over a period of 24 months.
  • Clinical fractures occurred in 198/2,046 patients (9.7%) in the romosozumab-to-alendronate group vs 266/2,047 patients in the alendronate-to-alendronate group (a 27% lower risk with romosozumab).
  • The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group, and the risk of hip fracture was lower by 38%.
  • There was no significant difference between the groups for adverse events, although serious cardiovascular adverse events occurred more often with romosozumab than with alendronate (50 of 2,040 patients [2.5%] vs 38 of 2,014 patients [1.9%]).


Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377:1417-1427. doi:10.1056/NEJMoa1708322.


Romosozumab is a bone-forming monoclonal antibody that binds to and inhibits sclerostin, and by so doing increases bone formation and decreases bone resorption. It has been shown to decrease the risk for new vertebral fractures and clinical fractures (a composite of non-vertebral fracture and symptomatic vertebral fracture) compared to placebo among postmenopausal women with osteoporosis. Alendronate is a bisphosphonate that works as an antiresorptive agent. In meta-analyses, alendronate has been shown to reduce vertebral, nonvertebral, and hip fractures in women with osteoporosis by approximately 50%.1,2 The above trial shows that romosozumab, a bone forming agent, followed by alendronate is more effective at decreasing fractures, particularly hip fractures, than alendronate alone in women with osteoporosis and a prior fragility fracture. In July 2017, the FDA rejected the submission of romosozumab due to concerns over potential cardiovascular side effects. It is anticipated that the increased data of 3 pooled studies will be re-submitted to the FDA in the next year.3 Another monoclonal antibody, abaloparatide injection, was FDA approved in May 2017 for the treatment of postmenopausal women with osteoporosis at high risk for fracture.4—Neil Skolnik, MD

  1. Cranney A, Wells G, Willan A, et al. Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev. 2002;23: 508-516.
  2. Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporos Int. 2005;16:468-474. doi:10.1007/s00198-004-1725-z.
  3. Safety scare prompts FDA to reject Amgen’s romosozumab. FierceBiotech. July 17, 2017.
  4. FDA approves Radius Health's Tymlos (abaloparatide), a bone building agent for the treatment of postmenopausal women with osteoporosis at high risk for fracture. [news release]. Waltham, MA. Radius Health; April 28, 2017: Accessed October 22, 2017.