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Osteopenia/Osteoporosis Linked to Age and BMI, But Not TDF, in French Cohort
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Older age and lower body mass index (BMI)--but not tenofovir (TDF) use--were associated with high rates of osteopenia and osteoporosis in a French group studied in 2005-2011 [1]. Almost 20% of study participants broke a bone during the study period, and CD4 counts were significantly lower in people with fractures.
Plentiful research has documented high rates of osteopenia, osteoporosis, and fracture in HIV populations studied over the last decade. Classic risk factors certainly play a role in risk of low bone mineral density (BMD) in people with HIV, but the impact of HIV- and treatment-related risk factors has been harder to pin down (see final paragraph). To gauge osteopenia and osteoporosis prevalence and to identify risk factors, clinicians in Tourcoing and Lille in northern France conducted this study.
This single-center retrospective study involved 199 adults (148 men and 51 women) with an average age of 46.8 (+/- 11.3) who had DEXA assessment of BMD at the femoral neck, total hip, and lumbar spine as part of routine follow-up between March 2005 and July 2011. The investigators recorded numerous variables at the date of the DEXA scan: osteoporosis risk factors, HCV coinfection, CD4 count, viral load, vitamin D status, antiretroviral therapy, and cumulative treatment duration. Osteoporosis risk factors were BMI, family or personal history of fracture, smoking or alcohol use, corticosteroids at a dose above 7.5 mg daily for at least 3 months, and hyperthyroidism or hypogonadism.
Thirty-two men (22%) and 8 women (16%) had osteoporosis, while 70 men (47%) and 20 women (39%) had osteopenia. Osteoporosis usually involved the femoral neck in both men and women.
People with osteoporosis or osteopenia were significantly older than people with normal BMD (50.6 versus 48.1 versus 43.2, P < 0.01). And people with osteoporosis had significantly lower BMI than those with normal BMD (21.5 versus 24.9 kg/m2, P < 0.001). Study participants with osteoporosis and osteopenia did not differ significantly from those with normal BMD in smoking or alcohol habits, HCV coinfection, duration of HIV infection, CD4 count, viral load, lipodystrophy, fracture history, duration of exposure to each antiretroviral class, duration of tenofovir exposure, or vitamin D status.
Thirty-seven study participants (19%) had a history fracture, including 6 rib fractures, 5 forearm fractures, and 4 fractures each of the femur, wrist, or foot. After statistical adjustment for age and BMI, lower CD4 count was significantly associated with a fracture history (P = 0.031).
One quarter of the study group (24%) had a vitamin D deficiency (25OHD level below 10 ng/mL), while two thirds (65%) had vitamin D insufficiency (25OHD between 10 and 30 ng/mL).
Simple regression analysis found significant associations between lower femoral neck BMD and older age, lower BMI, and longer nucleoside treatment without tenofovir. Multiple regression analysis determined that age and BMI explained 20.8% of BMD variability at the femoral neck (P < 0.001), while BMI alone explained 10.1% of BMD variability at the total tip (P < 0.001), and BMI and duration of tenofovir therapy explained 7.1% of BMD variability at the spine (P < 0.001).
The researchers concluded that only age and BMI were consistently associated with low BMD in their population. Tenofovir use was not associated with low BMD in this study group. Low CD4 count appeared to boost fracture risk, but probably because of confounding factors, the researchers suggested.
Randomized trials have documented greater BMD loss with ongoing antiretroviral therapy, but results of these trials differ in risks associated with specific regimens. A trial that randomized antiretroviral-naive adults to tenofovir/emtricitabine (TDF/FTC) versus abacavir/lamivudine (ABC/3TC) plus efavirenz versus atazanavir/ritonavir (ACTG A5202) found a significantly greater decrease in spine and hip BMD with TDF/FTC than with ABC/3TC after 96 weeks and significantly greater losses in spine BMD with atazanavir/ritonavir than with efavirenz [2]. A trial that randomized naive adults to efavirenz or lopinavir/ritonavir (both with zidovudine/3TC) found similar BMD drops in both study arms through 96 weeks [3]. Lower pretreatment CD4 count was associated with a higher risk of more than a 5% drop in BMD. The SMART trial of continuous versus intermittent antiretroviral therapy found a greater BMD decline and a higher fracture rate in the continuous-therapy group [4]. But there was no consistent drug-specific association with lower BMD.
Reference
1. Lemeunier L, Viget N, Biver E, Cortet B. An observational study of bone status in HIV-infected patients. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-231.
2. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791-1801. http://jid.oxfordjournals.org/content/203/12/1791.long.
3. Brown TT, McComsey GA, King MS, et al. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr. 2009;51:554-561.
4. Grund B, Peng G, Gibert CL, et al. Continuous antiretroviral therapy decreases bone mineral density. AIDS. 2009;23:1519-1529. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748675/
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