Abstract and Introduction
Abstract
Objective: Antiretroviral therapy (ART) has been implicated in bone loss in HIV. The role of inflammation and vitamin D is unclear and better investigated in ART-naive individuals.
Design and methods: This is a 48-week, prospective cohort study to compare baseline and change in hip and spine bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in HIV-infected, ART-naive adults and healthy controls matched by age, sex, and race. We also studied associations between bone loss and inflammation markers and plasma 25-hydroxyvitamin D [25(OH)D] using logistic regression.
Results: Forty-seven HIV-infected adults and 41 controls were included. Baseline 25(OH)D, BMD at total hip, trochanter, and spine, and prevalence of osteopenia and osteoporosis were similar between groups. In the HIV-infected group, total hip and trochanter, but not spine, BMD decreased over 48 weeks [hip -0.005 (−0.026–0.008) g/cm2, P = 0.02 within group; trochanter -0.013 (-0.03–0.003), P < 0.01]. BMD did not change at any site within controls. The HIV-infected group was more likely to have bone loss at the trochanter (P = 0.03). This risk persisted after adjustment for age, sex, race, BMI, smoking, and hepatitis C (odds ratio 4, 95% confidence interval 1.2–15.8). In the HIV-infected group, higher interleukin-6 concentrations (P = 0.04) and Caucasian race (P < 0.01) were independently associated with progression to osteopenia or osteoporosis, but not 25(OH)D levels.
Conclusion: BMD at the total hip and trochanter sites decreased in the HIV-infected, ART-naive adults, but not controls, over this 48-week study. Higher serum interleukin-6 concentrations were associated with progression to osteopenia or osteoporosis status in the HIV-infected group.
Introduction
People are living with HIV infection longer than ever before due to advances in antiretroviral therapy (ART) over the past two decades.[1] Bone health has become an increasingly important aspect of the long-term care of HIV-infected individuals because of the higher prevalence of osteoporosis[2] and demonstrated higher risk of fractures including fragility fractures compared with the general population.[3] Understanding the pathogenesis of bone loss in HIV is imperative for developing targeted approaches to fracture prevention in this high-risk group.
Multiple factors likely contribute to the pathogenesis of low bone mineral density (BMD) and bone loss in HIV. Some traditional osteoporosis risk factors may disproportionately affect HIV-infected individuals including low body weight, hypogonadism, and smoking, and these have been shown to be important causes of low BMD in HIV.[4,5] Direct effects of ART, specifically tenofovir and protease inhibitors, have been implicated as well.[6–9] However, regardless of the regimen selected, ART initiation has been shown to result in a 2–6% loss of BMD after 48–96 weeks[10,11] with subsequent stabilization.[12] Further, the degree of bone loss after ART initiation has been linked with CD4+ T-cell count, suggesting a role for degree of pre-ART immunodeficiency.[13] Most recently, the effect of HIV itself and consequent chronic inflammation has been suggested as a contributor.[14] Low BMD is prevalent in ART-naive, HIV-infected individuals.[8,11,15] At the time of enrollment into A5224s, a substudy of AIDS Clinical Trials Group Study A5202, 39% of HIV-infected, ART-naive participants were osteopenic at the hip or spine.[11] It is notable that 85% of these participants were men and the median age was 38 years, which, if HIV-uninfected, should have been considered at low risk for bone disease. This suggests that HIV infection and/or heightened inflammation may be impacting BMD in HIV, independently of the effect of ART. Higher markers of inflammation have been linked with risk of fracture in HIV-uninfected adults as well.[16]
To date, studies evaluating changes in BMD over time in HIV have included participants initiating ART[10,13] or ART-experienced.[4,5,17–22] The aim of this study was to evaluate the change in BMD without the confounding effect of ART with a well matched HIV-uninfected comparator group and report the association with markers of systemic inflammation. In addition, given the very high prevalence of vitamin D deficiency in HIV,[23] we aimed to assess the effect of vitamin D status on skeletal health. The hypothesis of this study was that over 48 weeks, HIV-infected, ART-naive adults would have greater loss of BMD at the hip and spine measured by dual-energy X-ray absorptiometry (DXA) compared to HIV-uninfected controls matched by age, sex, and race. Secondary hypotheses were that bone loss in the HIV-infected group would be associated with higher markers of systemic inflammation and lower vitamin D levels.
AIDS. 2014;28(12):1759-1767. © 2014 Lippincott Williams & Wilkins
Lippincott Williams & Wilkins
