713-T. Indinavir Administration Leads to Bone Loss in Mice

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Session 94 Poster Session
Osteopenia/Osteoporosis
Session Time: 4:30-6:30 pm
Room 4E-F

713-T.

Indinavir Administration Leads to Bone Loss in Mice
M. W. H. Wang*, S. L. Teitelbaum, P. Tebas, W. G. Powderly, and F. P. Ross
Washington Univ., St. Louis, MO

Background: Highly active antiretroviral therapy for HIV is associated with multiple metabolic abnormalities, including bone demineralization. Previously, we found that indinavir, one of the protease inhibitors, blocks in vitro and ex vivo differentiation and function of osteoblasts, the bone-forming cells. This study was conducted to determine if indinavir can decrease bone mass in vivo.
Methods: 4-week-old C56/BL6 male mice (n=10 for each group) were injected with 100 mg/kg of indinavir or vehicle intraperitoneally, once a day, for 5 weeks. This dose is comparable to that used in previous murine studies to assess human exposure (as described by the manufacturer). Bone mineral density was assessed utilizing a dual-energy x-ray absorptiometry (DEXA) machine. Mice were also examined radiographically by Faxitron. Isolated tibiae and femora were then analyzed histologically.
Results: Regional BMD of the lumbar vetebrae, tibiae, and femora showed a 17-20% decrease with indinavir treatment (p<0.001). Radiographically, both cortical and trabecular bone mass were reduced with treatment. Histologic analysis showed a 25% decrease in bone volume with treatment (p<0.005). The numbers of osteoclasts and osteoblasts were not significantly changed.
Conclusions: Our results show that indinavir given to young mice promotes bone loss in vivo, in the absence of HIV disease or other confounding drug therapy. These findings support our previous data demonstrating that this protease inhibitor blocks bone formation in vitro and ex vivo. Further clinical studies are needed to explore the effect of indinavir and other protease inhibitors on bone biology in humans.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections