Incidence of fractures rises earlier in HIV-positive men

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The incidence of fractures begins to rise a full decade earlier in HIV-positive men compared to their HIV-negative peers, research led by investigators at the Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health, report. Analysis by age group showed that fracture incidence among men in their 50s was double that observed in HIV-negative men in the same age range (the control group).

“A significant increase in fracture incidence was found among 50 – 59-year-old HIV + men, highlighting the importance of osteoporosis screening for HIV-infected men above the age of 50,” note the authors.

Bone problems such as osteopenia and osteoporosis are more common among HIV-positive men and women compared to their HIV-negative peers. Bone loss also occurs at a younger age in patients with HIV. This means that patients with HIV have a higher risk of fractures, with several studies showing that rates of all fractures and fragility fractures are elevated among HIV-positive individuals.

Possible risk factors for fracture risk in patients with HIV include treatment with specific antiretroviral drugs (tenofovir and protease inhibitors) and co-infection with hepatitis C virus (HCV). Traditional risk factors such as ageing, smoking, body weight, alcohol use and co-morbidities also increase the risk of fractures.

There is still uncertainty concerning the age at which fracture risk screening should start for patients with HIV.

Investigators from the ongoing MACS cohort study, therefore, designed a prospective, multi-centre study comparing fracture incidence among middle-aged and elderly HIV-positive and HIV-negative men. The authors hypothesised that HIV infection would increase the risk of fracture associated with ageing.

Self-reported fracture data were obtained from 1221 HIV-positive men and 1408 HIV-negative men.

The two groups were well matched for traditional risk factors associated with fracture, including age, BMI, kidney function and alcohol use. However, patients with HIV were more likely to be non-white, co-infected with HIV and current smokers.

Median CD4 cell count among the HIV-positive patients was 490 cells/mm3. Two-thirds were taking tenofovir with a median cumulative exposure of just over three years. Protease inhibitor use was reported by 44% of patients; median cumulative exposure was 4.5 years.

During approximately 34,000 person-years of follow-up, 379 patients experienced fractures, an overall incidence of 11.2 fractures per 1,000 person-years.

A total of 182 fractures occurred in patients with HIV (incidence rate, 12.8 per 1000 person-years) and 197 in HIV-negative individuals (incidence rate, 10.0 per 1000 person-years). When stratified according to age, fracture incidence among HIV-negative men was similar for those in their 40s and 50s, only increasing once individuals reached the age of 60. However, for those with HIV, there was an increased incidence of fractures for men in their 50s as well as those aged 60 and over.

After adjusting for potential confounders, hypertension was the only risk factor significantly associated with an increased risk of all fractures (aIRR = 1.32; 95% CI, 1.04-1.69).

HIV significantly modified the effect of age on fracture risk (p= 0.002). There was a significant increase in the incidence of all fractures in HIV-negative men aged 60 plus (aIIR= 1.51; 95% CI, 1.06-2.16) and for HIV-positive men in their 50s (aIRR = 1.92; 95% CI, 1.41-2.61), as compared to HIV-negative men in their 40s.

In the analysis restricted to HIV-positive men, there was an increased incidence of fractures among men in their 50s compared those in their 40s (aIRR = 1.66; 95% CI, 1.18-2.34). Antiretroviral therapy was associated with an increased risk of fractures (aIRR = 2.11; 95% CI, 1.22-3.63). Higher BMI was protective. Neither tenofovir nor protease inhibitor use was associated with a higher rate of all fractures.

A total of 140 fragility fractures occurred among 36,060 person-years. Incidence was higher in HIV-positive patients compared to HIV-negative patients (4.6 vs. 3.4 per 1000 person years).

Analysis by age showed that HIV-negative men in their 40s and 50s had a similar incidence of fragility fractures (2.9 per 1,000 person-years), with incidence jumping among men aged 60 and over (5.1 per 1,000 person years).

Within the HIV-positive group, the incidence of fragility fractures increased from 2.6 per 1000 person years among men in their 40s to 6.3 per 1,000 person years for those in their 50s and 7.6 per 1,000 person years for individuals aged 60 and older.

HIV-positive men in their 50s had double the fragility fracture risk of HIV-negative men in their 40s (aIRR = 2.11; 95% CI, 1.24-3.55). Restricted analysis to the HIV-positive group showed that fragility fracture risk increased with age. Current HIV therapy increased the risk of fragility fracture, but this finding was only of marginal significance (aIRR = 2.54; 95% 0.97-6.61). Viral load was not associated with an increased risk of fragility fracture, nor were the cumulative use of tenofovir or protease inhibitors.

“We found that HIV + MACS participants had higher incidence of all fractures and fragility fractures compared with HIV– controls and that the rate of fracture was higher among HIV + men aged 50-59 years compared with HIV- participants of a similar age,” conclude the authors. They recommend that all HIV-positive men aged 50 years and older should have DXA scans to assess their bone health.

Objectives: To determine the incidence of fracture among aging HIV-infected (HIV+) and uninfected men (HIV−). To evaluate factors independently associated with fracture risk.
Design: Prospective, multicenter cohort study of men with or at risk for HIV.
Methods: Outcome measures: all fractures (excluding skull, face and digits) and fragility fractures (vertebral column, femur, wrist and humerus) were collected semiannually in 1221 HIV+ and 1408 HIV− men aged at least 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40–49, 50–59 and ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors.
Results: Fracture incidence increased with age among both HIV+ and HIV− men. Although there was no significant difference in fracture incidence by HIV serostatus among men aged 40–49 years, the HIV+ men aged 50–59 years had a significantly higher incidence of all fractures [aIRR: 2.06 (1.49, 2.84)] and fragility fractures [aIRR: 2.06 (1.21, 3.50)] compared with HIV− participants of similar age. HIV modified the effect of age on all fractures (P = 0.002) but did not significantly modify the effect for fragility fractures (P = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates [aIRR: 1.32 (1.04, 1.69)].
Conclusion: Fracture incidence increased with age among HIV+ and HIV− men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50–59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV-infected men above the age of 50.

Gonciulea, Anda; Wang, Ruibin; Althoff, Keri N; Palella, Frank J; Lake, Jorda; Kingsley, Lawrence A; Brown, Todd T

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