Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture

Abstract

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.

Figure 1. Study flow diagram

Osteoporosis drugs were oral bisphosphonates (alendronate, 10 mg or 70 mg; risedronate, 5 mg or 35 mg), nasal calcitonin, or raloxifene. *May meet >1 exclusion criterion.

Figure 2. Cumulative incidence of nonvertebral fractures within 12 months of treatment initiation, by drug

Figure 3. Nonvertebral fracture risk within 12 months of treatment initiation compared with alendronate

Hazard ratios and 95% CIs (error bars) were calculated by using Cox proportional hazard models stratified by state and adjusted for propensity score quintiles, age, race, diagnosis of osteoporosis, and fracture history (previous nonvertebral and vertebral fracture). The intent-to-treat analysis (Primary) was censored on the date of death or end of follow-up (12 months after treatment initiation, 31 December 2003 [New Jersey], or 31 December 2005 [Pennsylvania]). OT 15 = patients receiving treatment who were censored on the first day of switching agents, losing drug plan eligibility, entering a nursing home, or discontinuing use of the drug (last date covered by drug plan plus 15 days, allowing for 30-day gaps between prescriptions) on the date of death or end of follow-up; OT 90 = patients receiving treatment who were censored as for OT 15, except that follow-up was extended to 90 d after drug discontinuation; Fx Hx = patients with a history of any fracture within 12 mo before treatment initiation; No Fx Hx = patients with no known history of fracture within 12 mo before treatment initiation; ≥2 Script = patients who filled ≥2 consecutive prescriptions of their index drug, excluding those who lost drug plan eligibility, entered a nursing home, died, had a nonvertebral fracture, or switched agents within the first 30 d; No Cancer = patients with no diagnosis of malignant neoplasm within 12 months before drug initiation; OP = patients with a medical claim for osteoporosis diagnosis within 12 mo before drug initiation; No OP = patients with no medical claim for osteoporosis diagnosis within 12 mo before treatment initiation; No HT = women with no history of hormone therapy within 12 mo before treatment initiation.

Figure 4. Nonvertebral fracture rates within 12 months, by fracture risk group and drug

Age cut-off was determined by the median cohort age (79 y). Fracture history was identified by Medicare claims within 12 months before treatment initiation. 65–79 y, No Fx = patients age 65 to 79 years without fracture history (lowest risk); ≥80 y, No Fx = patients age ≥80 years without fracture history; 65–79 y, Fx = patients age 65 to 79 years with fracture history; ≥80 y, Fx = patients age ≥80 years with fracture history (highest risk).