Opioid analgesics and the risk of fractures in older adults with arthritis

Abstract

Objectives: To compare the risk of fracture associated with initiating opioids with that of nonsteroidal anti-inflammatory drugs (NSAIDs) and the variation in risk according to opioid dose, duration of action, and duration of use.

Design: Retrospective cohort study.

Setting: Two statewide pharmaceutical benefit programs for persons aged 65 and older.

Participants: Twelve thousand four hundred thirty-six initiators of opioids and 4,874 initiators of NSAIDs began treatment between January 1, 1999, and December 31, 2006. Mean age at initiation of analgesia was 81; 85% of participants were female, and all had arthritis.

Measurements: Cox proportional hazards models, adjusted for several potential confounders, quantified fracture risk. Study outcomes were fractures of the hip, humerus or ulna, or wrist, identified using a combination of diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification) and procedure (Common Procedural Terminology) codes.

Results: There were 587 fracture events among the participants initiating opioids (120 fractures per 1,000 person-years) and 38 fracture events among participants initiating NSAIDs (25 fractures per 1,000 person-years) (hazard ratio (HR)=4.9, 95% confidence interval (CI)=3.5-6.9). Fracture risk was greater with higher opioid dose. Risk was greater for short-acting opioids (HR=5.1, 95% CI=3.7-7.1) than for long-acting opioids (HR=2.6, 95% CI=1.5-4.4), even in participants taking equianalgesic doses, with differential fracture risk apparent for the first 2 weeks after starting opioids but not thereafter.

Conclusion: Older people with arthritis who initiate therapy with opioids are more likely to experience a fracture than those who initiate NSAIDs. For the first 2 weeks after initiating opioid therapy, but not thereafter, short-acting opioids are associated with a greater risk of fracture than are long-acting opioids.

Figure 1

Kaplan-Meier Survival Curves Showing Fracture-free Survival for the First 52 Weeks After Initiating NSAIDs vs. Short-acting Opioids vs. Long-acting Opioids, Among Medicare Beneficiaries with Arthritis

Figure 2

Hazard Ratios* (95% Confidence intervals) for Fracture Risk Comparing Users of Opioids vs. NSAIDs among Medicare Beneficiaries with Arthritis Initiating Analgesic Medications, by Subgroup *All hazards ratios are multivariate adjusted, with non-propensity score models including as independent variables all the characteristics in Table 1