HIV and Bone Loss

Abstract

The use of antiretroviral therapy has significantly reduced the number of deaths due to HIV/AIDS. However, no current therapy can suppress the virus completely, and as the HIV-infected population continues to live longer new complications are emerging from the persistence of the virus and use of antiretroviral therapy. This review summarizes the clinical evidence linking HIV-associated osteoporosis to direct infection and antiretroviral therapy (ART) use. The purported molecular mechanisms involved in bone loss are also reviewed. Additionally, recommendations regarding the pharmacologic management of HIV/ART-related osteoporosis are given.

Osteopenia and osteoporosis among patients with human immunodeficiency virus infection

“…In patients treated with tenofovir who had normal renal function the prevalence of hypophosphatemia and skeletal abnormalities was not higher than in patients treated with other antiretroviral drugs. Thus, the adverse skeletal effects of tenofovir are indirect, and their key mechanism is based on the renal damage caused by tenofovir [18].…”

“…Low-density lipoprotein receptor-related protein 5 (Lr5) and Lr6, which are co-receptors of Wnt, act on frizzled receptors which results in formation of dephosphorylated ␤-catenin. ␤-catenin interacts with Tcf/Lef transcription factors and this eventually leads to increased differentiation of osteoblasts [18].…”

“…The balance between RUNX2 and peroxisome proliferator-activated receptor-␥ (PPAR-␥) is decisive for the differentiation of mesenchymal cells into osteoblasts (when RUNX2 activity prevails) or adipocytes (when PPAR-␥ activity prevails) [18]. Cotter et al [37] demonstrated, that HIV p55gag protein inhibits differentiation of osteoblasts, which was confirmed by decreased activity of RUNX2.…”

Changes in Bone Mineral Density After 96 Weeks of Treatment With Atazanavir/Ritonavir or Lopinavir/Ritonavir Plus Tenofovir DF/Emtricitabine in Treatment-Naive Patients With HIV-1 Infection

“…2,5,12,14,16,17 ART-induced BMD reductions and accelerated bone loss may also be related to immune reconstitution 18,19 or increased levels of pro-inflammatory cytokines. 20 The aim of the CASTLE BMD substudy was to evaluate treatment-related differences in regional BMD over 96 weeks in HIV-infected treatment-naive patients randomized to receive tenofovir DF/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r).…”

Bone Metabolism and HIV Infection

“…HIV infection has been shown to play an important role in the development of OP (3) and high prevalence of both osteopenia (OPe) and OP have been reported in subjects with chronic HIV infection (4). Loss of body weight, low body mass index (BMI) and diminished functional capacity are among some of the risk factors which, to a large extent, contribute to the loss of bone tissues in subjects suffering from chronic HIV infection (2)(3)(4)(5)(6)(7)(8).Furthermore, the drugs used to treat HIV+ patients can also interfere with bone metabolism and contribute to loss of bone mass (16). A reduction in bone mineral density (BMD) was observed in both HIV+ patients with hypogonadism and in those without (9)(10)(11).…”