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Bone Loss and Fracture Risk are 'Modest' among HIV+ People, Linked to Tenofovir, Smoking, and HCV

Continued bone loss among HIV positive men with osteopenia was modest overall, but about 25% of those taking tenofovir (Viread, also in 4 antiretroviral coformulations) experienced significant loss, according to a recent study. A related meta-analysis found that HIV infection is associated with a modest likelihood of new fractures, with smoking and hepatitis C virus (HCV) coinfection further increasing the risk.

Conditions associated with aging are a growing concern among people with HIV. Over the course of the epidemic many studies have looked at the risk of bone loss -- osteopenia, or the more severe osteoporosis-- and fractures in this population, but results have been inconsistent.

As described in the June 3, 2013, advance online edition of AIDS, Lambert Assoumou and the French ANRS Osteovir study group looked at changes in bone mineral density over 2 years among HIV positive people with osteopenia at baseline.

The analysis included 94 HIV positive men on antiretroviral therapy (median age 46 years; median time on ART 7.5 years). The median nadir (lowest-ever) CD4 T-cell count was 164 cells/mm³, indicating advanced immune suppression. At study entry they had low bone mineral density but were not taking anti-osteoporosis medications. They had dual energy X-ray-absorptiometry (DEXA) results available at baseline and a second DEXA performed between months 24 and 36.

Results

• Over a median interval of 2.6 years between the 2 DEXA scans, bone mineral density decreased by an average of 0.5% per year at the lumbar spine and by 0.4% per year at the hip, both statistically significant decreases.
• 25.5% and 27.7% of participants saw their bone density at the spine and hip, respectively, fall by more than the smallest detectable difference (SDD).
• Use of tenofovir was independently associated with a larger decline in bone density at both the spine and hip (odds ratio  2.4 and 2.8, respectively, or more than double the risk).

"Although osteopenia overall modestly changes over two years in long term combination ART treated patients, a quarter of patients experienced a significant loss (>1 SDD) associated with tenofovir exposure," the study authors concluded.

Fracture Risk

The clinical significance of small changes in bone density among people with HIV is not yet clear. Bone loss can potentially result in non-traumatic fragility fractures, which can lead to a variety of complications.

In the April 6, 2013, advance edition of the same journal, StephanieShiaufromColumbia University Medical Center and colleagues described findings from a systematic review and meta-analysis investigating whether incidence of fractures -- both overall and fragility fractures -- differs between HIV positive and HIV negative people.

The authors searchers Medline, Scopus, and the Cochrane Library database for studies published through September 2012, as well as online conference abstracts from relevant scientific meetings (ASBMR, CROI, IAS, and International AIDS Conference). They included all studies that reported incidence of overall fractures or fragility fractures among HIV positive adults. They identified 13 eligible studies, of which 7 included HIV negative control subjects; 9 reported all incident fractures and 10 reported fragility fractures.

Results.

• The pooled incidence rate ratio (IRR) for all fractures was 1.58.
• The pooled IRR for fragility fractures was 1.35.
• Among the 4 studies that reported IRRs for all fractures, those with mainly Caucasian participants reported increased risk, while 2 studies with a majority of black participants did not reach statistical significance.
• Several traditional risk factors were associated with fractures among HIV positive individuals, including smoking, use of glucocorticoids or proton pump inhibitors, heavy alcohol or drug use, low weight or body mass index (BMI), and co-morbidities such as diabetes and liver disease.
• Smoking, white race, and older age were consistent independent predictors of fragility fractures.
• Current and nadir CD4 cell count was associated with increased fracture risk in some, but not all, studies.
• Some studies found that use of antiretrovirals -- including tenofovir and protease inhibitors -- was associated with increased fracture risk, but again data were inconsistent.
• HCV was consistently identified as an independent risk factor for both fragility and non-fragility fractures, raising risk by 1.5- to 2-fold.

"We found that HIV-infected individuals have a modestly increased risk for all fractures and fragility fractures compared to uninfected individuals or the general population," the researchers summarized.

"Our results indicate that HIV-infection is associated with a modest increase in incident fracture," they concluded. "Future research should focus on clarifying risk factors, designing appropriate interventions, and the long-term implications of this increased risk for an aging HIV-infected population."

"Although the mechanisms are not well understood, HIV/HCV coinfection appears to have a negative effect on bone strength and fracture risk," they added. "The relationship between HIV/HCV coinfection and fracture risk warrants further study."

6/6/13

References

L Assoumou, C Katlama, JP Viard, et al (ANRS Osteovir study group). Changes in bone mineral density over a two-year period in HIV-1-infected men under cART with osteopenia. AIDS. June 3, 2013 (Epub ahead of print).

EC Broun, SM Arpadi, and MT Yin. Incident fractures in HIV-infected individuals: a systematic review and meta-analysis. AIDS.April 6, 2013 (Epub ahead of print).