Bone Mineral Density in HIV+ Patients Recently Started on Antiretroviral Therapy (ART)

The life expectancy of persons infected with HIV has improved greatly since the institution of combination antiretroviral therapy (cART). However, many metabolic derangements have been discovered with long-term cART therapy, including lipodystrophy, insulin resistance, and, more recently, abnormal bone metabolism. It is well documented that bone mineral density (BMD) in HIV+ patients is lower when compared with the expected BMD in non-HIV patients [1-10]. The underlying cause of lower BMD is unknown but it is felt to be a multifactorial process [10-14]. Current guidelines recommend first line treatments consist of a combination of protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). Despite the known change in BMD in HIV+ persons, less is known about the effect of antiretroviral (ART) exposure and duration of treatment, ART type, and cumulative HIV viremia on bone health. This is demonstrated by studies showing loss of BMD with use of protease inhibitors compared to other regimen [15], other studies showing more detrimental effect from NRTIs [6, 9, 16], and yet others that have shown that BMD improves with all ART therapy [17]. Tenofovir (an NRTI), in particular, has been implicated as playing a role in bone changes, possibly due to its effect at the proximal tubule leading to a Fanconi-like syndrome with phosphate wasting [18]. Tenofovir led to significant reductions in BMD of children and this loss reversed after tenofovir was stopped [9]; other studies have shown similar deleterious effects [16]. A recent study evaluating the effect of continuous ART therapy vs. intermittent use for viral suppression showed that patients receiving continuous ART had greater loss of BMD, despite an increased risk of AIDS progression, myocardial infarction, or renal- or liver-failure [19]. However, prior longitudinal studies with longer follow-up have shown that the initial loss of BMD following ART is recovered and longer-term BMD changes are similar to changes seen in HIV-negative persons [20-22]. There is evidence that there is a positive correlation between HIV viremia and proinflammatory cytokines and that up-regulated proinflammatory cytokines may play a role in both osteoclast and osteoblast function. Prior studies have shown that during HIV infection osteoblast and osteoclast function is uncoupled and following ART treatment, regulation of bone turnover and formation ensues [23]. However, changes in cytokines have not been correlated with BMD and changes in bone turnover during routine ART treatment, to our knowledge. Most studies to date have been cross-sectional studies comparing HIV+ (with varying ART exposure histories) and HIV- persons or small longitudinal studies with limited sample sizes and short duration. It is not known if the decline of proinflammatory cytokines which occurs concurrent with the fall in HIV viral loads leads to improved regulation of bone formation and hence a lower rate of bone loss and lower risk of fracture.