Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture

Ann Intern Med. 2008 May 6;148(9):637-46. doi: 10.7326/0003-4819-148-9-200805060-00003.


Background: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies.

Objective: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults.

Design: Cohort study.

Setting: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older.

Patients: 43,135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women.

Measurements: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses.

Results: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups.

Limitation: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents.

Conclusion: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Aged
  • Alendronate / therapeutic use
  • Bone Density Conservation Agents / therapeutic use*
  • Calcitonin / therapeutic use
  • Cohort Studies
  • Etidronic Acid / analogs & derivatives
  • Etidronic Acid / therapeutic use
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / prevention & control*
  • Humans
  • Incidence
  • Male
  • New Jersey / epidemiology
  • Osteoporosis / drug therapy
  • Osteoporosis, Postmenopausal / drug therapy*
  • Pennsylvania / epidemiology
  • Raloxifene Hydrochloride / therapeutic use
  • Risedronic Acid
  • Risk Factors


  • Bone Density Conservation Agents
  • Raloxifene Hydrochloride
  • Calcitonin
  • Risedronic Acid
  • Etidronic Acid
  • Alendronate