HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture

Abstract

Purpose of review: Patients with HIV-1 infection/AIDS are living longer due to the success of highly active antiretroviral therapy (HAART). However, serious metabolic complications including bone loss and fractures are becoming common. Understanding the root causes of bone loss and its potential implications for aging AIDS patients will be critical to the design of effective interventions to stem a tidal wave of fractures in a population chronically exposed to HAART.

Recent findings: Paradoxically, bone loss may occur not only due to HIV/AIDS but also as a consequence of HAART. The cause and mechanisms driving these distinct forms of bone loss, however, are complex and controversial. This review examines our current understanding of the underlying causes of HIV-1 and HAART-associated bone loss, and recent findings pertaining to the relevance of the immuno-skeletal interface in this process.

Summary: It is projected that by 2015 more than half of the HIV/AIDS population in the USA will be over the age of 50 and the synergy between HIV and/or HAART-related bone loss with age-associated bone loss could lead to a significant health threat. Aggressive antiresorptive therapy may be warranted in high-risk patients.

Figures

Figure 1. Model of B-cell regulation of basal osteoclastogenesis through osteoprotegerin production and HIV-1-induced bone loss

B-cell production of OPG, regulated in part through CD40 to CD40 ligand co-stimulation by T cells, counteracts the key osteoclastogenic cytokine RANKL, moderating osteoclast formation and activity. HIV-1 interfering with/AIDS leads to a disruption of the immuno-skeletal interface disrupting T cell to B-cell communication and leading to elevated RANKL and diminished OPG production by B cells. The elevated RANKL/OPG ratio is biased in favor of increased osteoclast formation. OPG, osteoprotegerin.