Background:  Low bone mineral density is common among HIV-infected persons and has raised concerns for increased risk of fracture in this population. We sought to compare rates of fracture over time among HIV-infected persons to those in the general U.S. adult population and explore risk factors for fractures in contemporary HIV-infected patients.

Methods:  We analyzed data from 8,456 HIV Outpatient Study (HOPS) participants followed at 10 HIV clinics in the US, who had at least 2 clinical encounters from 1994 to 2008. Only first fractures during the observation period were analyzed. We calculated age-standardized rates of fracture using the National Hospital Discharge Survey (NHDS) data from urgent care, emergency department and inpatient settings. We compared the magnitude and temporal trends in rates of fracture in the HOPS and NHDS using linear regression. Among HOPS patients observed during 2002 to 2008, we studied associations between fracture risk and demographic, clinical, and behavioral factors measured on 1 January 2002 or first HOPS visit, thereafter using multivariable Cox proportional hazards models.

Results:  Of 8,456 HOPS patients included in the study (median age: 37 years; 80.5% male; 55.7% white), 276 patients had a fracture during a median follow-up of 4.8 years. Among HOPS patients, age-standardized fracture rates per 10,000 increased from 36.0 during 1994 to 165.3 during 2002 (P =0.03). Among persons 25 to 54 years of age, rates of fracture were higher among HOPS than NHDS patients; since 2002, rates have remained steady at a rate 4.3 times higher (see figure). Non-extremity fractures were more common in the HOPS than NHDS patients (40.4% vs 34.2%, respectively, figure). Among contemporary HOPS patients, nadir CD4 cell count < 200 cells/mm³ (adjusted hazard ratio (aHR) = 1.60, 95% confidence interval 1.11 to 2.31), hepatitis C infection (aHR = 1.61, 95%CI 1.13 to 2.29), diabetes (aHR = 1.62, 95%CI 1.00 to 2.64), and substance abuse (aHR = 1.52, 95%CI 1.00 to 2.32) were independently associated with increased fracture risk.

Conclusions:  Rates of fracture among HIV-infected persons were higher than in the general U.S. population (as captured by NHDS), particularly among younger adults. Although rates of fracture in NHDS have decreased, rates among HIV-infected persons increased and then remained steady since 2002. The pathophysiology of bone disease in this population may reflect lifestyle, viral, or pharmacologic effects, and deserves attention in HIV care practice.