Association of Mental Disorders and Related Medication Use With Risk for Major Osteoporotic Fractures

Abstract

Importance: Osteoporotic fractures are a leading cause of disability, costs, and mortality. FRAX is a tool used to assess fracture risk in the general population. Mental disorders and medications to treat them have been reported to adversely affect bone health, but, to date, they have not been systematically studied in relation to osteoporotic fractures.

Objective: To examine the association of mental disorders and psychotropic medication use with osteoporotic fracture risk in routine clinical practice.

Design, setting, and participants: In this population-based cohort study, bone mineral density and risk factors were used to calculate FRAX scores using data from the Manitoba Bone Density Program database of all women and men 40 years of age or older in Manitoba, Canada, referred for a baseline dual-energy x-ray absorptiometry scan from January 1, 1996, to March 28, 2013. Population-based health services data were used to identify primary mental disorders during the 3 prior years, psychotropic medication use during the prior year, and incident fractures. Cox proportional hazards regression models estimated the risk for incident fractures based on mental disorders and use of psychotropic medications. Data analysis was conducted from November 25, 2013, to October 15, 2016.

Main outcomes and measures: Incident nontraumatic major osteoporotic fractures (MOFs) and hip fractures.

Results: Of the 68 730 individuals (62 275 women and 6455 men; mean age, 64.2 [11.2] years) in the study, during 485 322 person-years (median, 6.7 years) of observation, 5750 (8.4%) sustained an incident MOF, 1579 (2.3%) sustained an incident hip fracture, and 8998 (13.1%) died. In analyses adjusted for FRAX score, depression was associated with MOF (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.27-1.51; P < .05) and hip fracture (aHR, 1.43; 95% CI, 1.22-1.69; P < .05) before adjustment for medication use, but these associations were not significant after adjustment for medication use. In contrast, the use of selective serotonin reuptake inhibitors (aHR for MOF, 1.43; 95% CI, 1.27-1.60; P < .05; aHR for hip fracture, 1.48; 95% CI, 1.18-1.85; P < .05), antipsychotics (aHR for MOF, 1.43; 95% CI, 1.15-1.77; P < .05; aHR for hip fracture, 2.14; 95% CI, 1.52-3.02; P < .05), and benzodiazepines (aHR for MOF, 1.15; 95% CI, 1.04-1.26; P < .05; aHR for hip fracture, 1.24; 95% CI, 1.05-1.47; P < .05) were each independently associated with significantly increased risk for both MOF and hip fracture. FRAX significantly underestimated the 10-year risk of MOF by 29% and of hip fracture by 51% for those with depression. It also underestimated the 10-year risk of MOF by 36% for use of selective serotonin reuptake inhibitors, by 63% for use of mood stabilizers, by 60% for use of antipsychotics, and by 13% for use of benzodiazepines. FRAX underestimated the 10-year risk of hip fracture by 57% for use of selective serotonin reuptake inhibitors, by 98% for use of mood stabilizers, by 171% for use of antipsychotics, and by 31% for use of benzodiazepines. FRAX correctly estimated fracture risk in people without mental disorders and those not taking psychotropic medications.

Conclusions and relevance: Mental disorders and medication use were associated with an increased risk for fracture, but in simultaneous analyses, only medication use was independently associated with fracture. Depression and psychotropic medication use are potential risk indicators that are independent of FRAX estimates.

Figure 1.. Relative Calibration of Major Osteoporotic Fracture FRAX Scores With Mental Disorders or Psychotropic Medications Present

The solid blue vertical line at 100% indicates perfect calibration. Results show the percentage change from perfect calibration based on the difference between the observed cumulative fracture probability at 10 years vs the expected 10-year fracture probability estimated by FRAX (a tool developed for the general population to estimate fracture risk). The referent indicates those without mental disorders or psychotropic medication exposure. Error bars indicate 95% CIs. ^aSignificant differences in calibration.

Figure 2.. Relative Calibration of Hip Fracture FRAX Scores With Mental Disorders or Psychotropic Medications Present

The solid blue vertical line at 100% indicates perfect calibration. Results show the percentage change from perfect calibration based on the difference between the observed cumulative fracture probability at 10 years vs the expected 10-year fracture probability estimated by FRAX (a tool developed for the general population to estimate fracture risk). The referent indicates those without mental disorders or psychotropic medication exposure. Error bars indicate 95% CIs. Lithium results are not available owing to small cell size. ^aSignificant differences in calibration.