HIV: inflammation and bone

Abstract

HIV infection and antiretroviral therapy (ART) are now established independent risk factors for osteoporosis. With a spate of recent studies reporting significant elevations in fracture prevalence in HIV patients, and a rapidly aging demographic, defining the mechanisms underlying HIV/ART-induced skeletal decline has become imperative. The recent emergence of the field of "osteoimmunology" has provided a conceptual framework to explain how the immune and skeletal systems interact. Furthermore, it is becoming clear that inflammatory states leading to perturbations in the immuno-skeletal interface, a convergence of common cells and cytokine mediators that regulate both immune and skeletal systems, conspire to imbalance bone turnover and induce osteoporosis. In this review we examine the role of inflammation in the bone loss associated with diverse inflammatory conditions and new concepts into how the underlying mechanisms by which inflammation and immune dysregulation impact bone turnover may be pertinent to the mechanisms involved in HIV/ART-induced bone loss.

Figure 1

Model of HIV-induced disruption of the immune-skeletal interface: 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 infection 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. (Adapted with permission from Ofotokun et al. [18].)