Alendronate (Fosamax) is a safe and effective treatment for decreased bone mineral density in people with HIV, according to a study presented on Monday at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles.
Grace McComsey of Case Western Reserve University in Cleveland, Ohio, presented final results from ACTG 5163, a study evaluating the effect of alendronate plus calcium and vitamin D supplements on bone mineral density (BMD) in HIV-positive people.
Bone loss - osteopenia and its more severe form, osteoporosis - appears to be a frequent metabolic complication in people with HIV, and some studies suggest it may be associated with antiretroviral therapy. Alendronate, a member of the bisphosphonate class of drugs, works by slowing the re-absorption of bone by cells called osteoclasts. It is approved in Europe and the United States for the treatment of osteoporosis in HIV-negative people, and previous small studies in people with HIV have yielded promising results.
This multicentre study enrolled 82 HIV-positive people with documented bone loss, indicated by decreased lumbar spine BMD. At baseline, the median lumbar spine t-score (a measure of bone density) was –2.1. All had t-scores below –1.5, and about 20% had osteoporosis, defined as t-scores below –2.5.
Most participants were white (77%) and male (71%), with a median age of 48 years. McComsey noted that the study was delayed by a year in order to enroll more women – an important consideration since women in the general population are more prone to bone loss than men, especially after menopause.
About one-third of the participants smoked tobacco, and the median body mass index was about 24.0; both smoking and low body weight are risk factors for bone loss. Individuals who had hepatitis C virus (HCV) co-infection, used steroids, received treatment for osteoporosis or had recent bone fractures were excluded. (McComsey said co-infected people were excluded because animal studies suggest alendronate might cause liver toxicity.)
Most participants had well-controlled HIV disease, with a median CD4 cell count approaching 500 cells/mm3; 91% had an HIV viral load below 400 copies/mL. About 65% were taking protease inhibitors and 38% were taking tenofovir (Viread), which has been linked to bone loss in some studies.
Participants were randomly assigned to receive either once-weekly alendronate (70mg orally) plus calcium and vitamin D supplements (42 people), or else the two supplements alone without alendronate (40 people). Calcium and vitamin D are known to be important for bone maintenance. Baseline characteristics were similar in the two arms. Treatment continued for 48 weeks. Bone mineral density was evaluated using dual energy x-ray absorptiometry (DEXA).
At week 48, the group receiving alendronate plus calcium and vitamin D had significantly greater increases in BMD compared with the supplements-only group. These increases were seen in the lumbar spine (3.38% vs 1.10%), the hip (3.95% vs 1.31%) and the trochanter, the upper prominence of the femur (thigh bone) near the ball-and-socket hip joint (4.52% vs 0.72%). There was a slightly greater increase in BMD of the femoral neck (the slender part of the thigh bone below the hip joint), but this did not reach statistical significance (2.21% vs 1.24%).
Supplementation with calcium and vitamin D alone led to modest increases BMD at all locations measured, but the improvement was greater among participants receiving supplements plus alendronate.
The sex of the participants did not appear to affect response to therapy, but black participants receiving alendronate experienced a smaller increase in lumbar spine BMD compared with white individuals. Five people added or stopped tenofovir during the study, but the main study results did not change when they were excluded from the analysis.
As for safety, alendronate was well tolerated and did not cause significant adverse events. There were no differences between the two arms in the frequency of grade 2 or higher laboratory abnormalities, and no participants in either group discontinued therapy due to toxicity.
“The results demonstrate that searchers once-weekly alendronate is safe and efficacious in the treatment of decreased bone mineral density in HIV-infected patients,” the researchers concluded. “Vitamin D and calcium alone is associated with modest improvements in bone mineral density.”
McComsey G et al. Alendronate with calcium and vitamin D supplementation is superior to calcium and vitamin D alone in the management of decreased bone mineral density in HIV-infected patients: results from ACTG 5163. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 42, 2007.