Bone metabolism dysfunction mediated by the increase of proinflammatory cytokines in chronic HIV infection

Abstract

Despite the efficacy of antiretroviral therapy (ART) on the control of viral replication, the current challenge is to decrease the chronic inflammatory status and toxicity of the antiretroviral drugs that contribute to increase the risk of metabolic complications. To verify the influence of proinflammatory cytokines on bone metabolism mediated by chronic HIV infection, a cross-sectional study was conducted with 50 HIV-infected adult men treated or not treated with ART. Dual energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analysis were performed of IL-6, TNF-α, osteocalcin, PTH, 25-OH-D, total calcium, albumin, 24 h urinary calcium, and urinary deoxypyridinoline. The participants not treated with ART exhibited higher values of IL-6 and TNF-α than the participants treated with ART for more than 2 years. The TNF-α values were higher in the participants treated with ART for <2 years than in participants treated with ART for more than 2 years (p < 0.05). The increased values of urinary deoxypyridinoline indicated a high reabsorptive activity of bone tissue in all groups, with a significant difference between the participants not treated with ART and the participants treated with ART for <2 years. Through the DXA we found a bone mass reduction in all bone sites in each group. The increase in production of proinflammatory cytokines, most notably in the viremic group, demonstrated the ability to stimulate osteoclast activity and subsequently affect bone mass. The reduction of bone mineral density was observed in all bone sites, principally for the groups receiving antiretroviral treatment.

The immune dysfunction in ankylosing spondylitis patients

“…Meanwhile, IL-6 level in CD8 + T cells was obviously higher in the AS group than the other two control groups. Proinflammatory cytokine IL-6 is known to induce the activation of osteoclasts (35), which might closely relate to the bone metabolism associated with AS.…”

Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study

“…Several factors including sex, body mass index (BMI), vitamin D level, hormonal effects, smoking, alcohol drinking and HIV-related factors such as advanced HIV disease and low baseline CD4+ cell count may contribute to BMD loss among PLHIV [8][9][10][11][12]. Additionally, HIV-infection induced immune activation and chronic inflammation may alter bone formation activities by negatively affecting osteoclasts and osteoblasts functions [13][14][15][16]. Those activities can be measured by using bone resorption and bone formation markers such as c-telopeptide crosslink of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP).…”

Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss

“…To explain the increase in osteolytic activity associated to HIV-1-induced bone loss, only a few mechanisms have been proposed: disruption of the immune system (6,18), increased production of proinflammatory cytokines (19), and direct infection of OC (20). Regarding the immune system, studies from the HIV-1-transgenic rat model revealed that bone damage results, in part, from an altered production of regulatory factors of osteoclastogenesis secreted by B cells (18).…”