Drug-based and non-drug-based interventions to improve the bone mineral density in patients living with HIV

Osteoporosis is caused by bone loss, and people who have the condition are at higher risk of having a fracture. Measuring a person's bone mass density (BMD) is a way to measure his or her risk of having a fracture due to fragile bones. Decreased BMD is much more common in HIV patients than in the general population. The cause of this decrease is not certain, but it may be because of the HIV infection itself or because of the antiretroviral medications that patients with HIV take. Although patients with HIV often get fractures because of their sometimes more fragile bones, it has been shown that this bone loss is often not effectively treated in this population. This review examines the randomised controlled trials investigating treatments for bone loss in patients with HIV infection.

Three trials examined the use of the drug alendronate to improve BMD in patients with HIV. These three studies were quite different from each other in terms of the populations studied and the interventions used, but even similar studies did not always have heterogeneity. A fourth study examined the use of testosterone in male patients with HIV and AIDS wasting syndrome. The four studies in this review were limited by the fact they were all very small and lasted a short amount of time, and thus they were unable to detect prevention of fractures or changes in number of patients with osteoporosis. There were also further compromises in study design. However, the limited available data show that there may be safe and perhaps effective treatments in the form of alendronate for patients with HIV who have decreased bone mineral density and, in those with AIDS wasting syndrome, testosterone.

Larger studies further examining the issue of decreased BMD are currently underway.

Authors' conclusions: 

The very limited data reviewed showed that bisphosphonate therapy andin those with AIDS wasting syndrome, testosteronemay be safe and possibly effective methods to improve bone mineral density in HIV patients. The available studies are small, of short duration, and not powered to detect changes in WHO categories and fracture rates.

Larger studies using bisphosphonates are currently underway. The role of colecalciferol, androgen replacement in women, and growth hormone are also under investigation.

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Background: 

Decreased bone mineral density (BMD) occurs more commonly in patients with HIV than in the general population, making this group more susceptible to fragility fractures. However, bone loss is under-treated in patients with HIV.

Objectives: 

To assess the effects of interventions aimed at increasing bone mineral density in HIV-infected adults.

Search strategy: 

We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, and CenterWatch (search date July 2006).

Selection criteria: 

Randomised trials comparing any pharmacological or non-pharmacological therapy with placebo, no treatment, or an alternative therapy, with the goal of increasing bone mineral density in adult (age 18 years or over) patients with HIV.

Data collection and analysis: 

Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, conflicts were resolved with discussion and/or trial authors were contacted for further details.

Main results: 

Three completed randomised-controlled studies examined the role of alendronate in patients with HIV and osteopenia or osteoporosis. When all three studies were combined, much heterogeneity was seen (p<0.0001), most likely due to different populations and interventions. A sensitivity analysis showed that in two studies without heterogeneity (p=0.11), alendronate, calcium and vitamin D improved lumbar BMD after one year when compared with calcium and vitamin D (weighted mean difference +2.65 95% confidence interval (CI) 0.80, 4.51 percent). However the alendronate group did not have less fragility fractures, relative risk (RR) 1.28 (95% CI 0.20, 8.21), or osteoporosis, RR 0.50 (95% CI 0.24, 1.01). Adverse events were not significantly different between groups, RR 1.28 (95% 0.20, 8.21). One randomised-controlled study done in patients with AIDS wasting found that after three months, testosterone enanthane improved lumbar BMD compared to placebo by +3.70 (95% CI 0.48, 6.92) percent, but progressive resistance training did not improve lumbar BMD (+0.40 95% CI -2.81, 3.61 percent). No group in this study had any adverse effects.

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