• Slide 207: Accelerated Bone Mineral Loss in HIV-Infected Patients Receiving Potent Antiretroviral Therapy (Authored by P. Tebas, W.G. Powderly, S. Claxton, D. Marin, W. Tantisiriwat, S. L.Teitelbaum, and K.E. Yarasheski. Washington Univ. Sch. of Med., St. Louis, MO)
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• Slide 208: Osteopenia in a Randomized, Multicenter Study of Protease Inhibitor (PI) Substitution in Patients with the Lipodystrophy Syndrome and Well-Controlled HIV Viremia (Authored by J. Hoy, J. Hudson, M. Law, D.A. Cooper, and for the PIILR investigators. The Alfred Hosp., Melbourne, Natl. Ctr. in HIV Epidemiology and Clin. Res.; and St. Vincent's Hosp., Sydney, Australia)
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Loss of Bone Density: Yet Another Metabolic Complication of Antiretroviral Therapy?

Osteopenia and osteoporosis -- loss of mineralization of bone that can lead to stooped posture and fractures -- is common in association with diabetes, low testosterone, and cytokine abnormalities, all issues for patient with HIV infection due to effects of the disease or the therapy. For this reason, the Australian group that performed the antiretroviral switch study described above decided to check for the presence of osteopenia and osteoporosis (see: poster 208). This was an easy task, since DEXA scanning, one of the modalities used to assess body fat, can be used to measure the density of bone. The scan measures the regional bone density of the lumbar spine or femur (thigh bone) and then two scores are calculated. The t-score signifies a person's bone density relative to that of the average person of the same sex and race who is 30 years old. The z-score signifies a person's bone density relative to that of the average person of the same sex, race, and age. A normal t-score is >1; osteoporosis is present if the patient's t-score is -1 to -2.5; and osteoporosis is present if the patient has a t-score is less than -2.5 or his/her z-score is less than 2.

At the time of enrollment into the study, 28.4% of the 74 male patients enrolled in the switch study had evidence of osteopenia, and an additional 8.6% had osteoporosis. There was no change in t- or z-scores over the next 24 weeks in patients who continued on their same protease inhibitor inclusive combination, or switched therapy to abacavir, adefovir, nevirapine, and hydroxyurea.

Risk factors for osteopenia and osteoporosis were calculated in a multivariate regression model. Factors associated with osteopenia and osteoporosis included increased age and weight; while a history of AIDS, low CD4+ count, higher viral load, duration of prior treatment, or experience with specific drugs was not associated with osteopenia and osteoporosis. Osteoporosis and osteopenia was also not associated with the presence of other metabolic abnormalities, since there was no association with testosterone, cholesterol, triglyceride, or insulin levels.

Osteopenia and osteoporosis was also reported by another group (see: poster 207), though their results had one important difference. Tebas and colleagues studied 112 men, 60 HIV+ men on protease inhibitors, 35 HIV+ men on no therapy or combinations that did not include protease inhibitors, and 17 HIV negative men. He admitted that it was the technician who was performing the DEXA scans on patients participating in a study of fat redistribution who discovered that a number of patients had low bone density. Their results are shown in the table below:

No correlation was made between the presence or severity of fat redistribution and osteopenia. Osteopenia was also not related to testosterone levels.

Thus, we have two studies documenting loss of bone density in HIV patients. Both studies suggest that this may another metabolic effect of HIV infection, though the second study suggests that this effect can be worsened by therapy. Neither study demonstrated an association between bone density loss and fat redistribution or lipid abnormalities, implying that these were independent complications of therapy.

Methods

80 HIV-infected patients with lipodystrophy (defined by total body fat <20% on DEXA scanning) and suppressed viremia (viral load <400 copies/ml) enrolled in the PIILR study. Body composition measurements including determination of regional bone mineral densities (BMD) and t- and z-scores by DEXA scans were performed at screening, weeks 12 and 24 after randomization to either continue the PI based regimen or switch to a non-PI regimen. Osteopenia was defined as a t-score between -1 and -2.5, and osteoporosis as a t-score less than -2.5.

Results

21 of 74 patients (28.4%) had evidence of osteopenia at baseline, and a further 7 (9.5%) had osteoporosis. There was no change in the proportion of individuals with osteopenia, over 24 weeks. There was no significant change from baseline in BMD and t-scores for arms, legs, trunk and total scores and no statistically significant differences by treatment group. There was no association between baseline insulin level, CD4 cell count, duration of antiretroviral therapy, duration of PI use and baseline t-scores.

Conclusions

There is a high prevalence of osteopenia and osteoporosis in HIV-infected men with lipodystrophy. Further study into the etiology of loss of bone mineral density in the HIV population is indicated, in addition to identification of risk factors and appropriate prevention strategies.