Bone and fat hormonal crosstalk with antiretroviral initiation

Background: Bone mineral density (BMD) loss and fat gain is common in people living with HIV (PLWH), particularly after initiating combination antiretroviral therapy (cART). Given the close metabolic interaction between bone and fat, we tested the hypotheses that changes in bone-derived hormones are associated with fat accumulation and changes in fat-derived hormones are associated with BMD loss following cART initiation. Methods: HIV-seropositive subjects (n = 15) initiating fixed dose cART of tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) underwent dual X-ray absorptiometry (DXA) assessment pre-cART and again 12-months post-cART initiation. DXA-derived measurements included BMD at the lumbar spine, femoral neck, total hip, and trochanter and the trunk and total fat. Serum undercarboxylated osteocalcin (ucOCN), sclerostin, lipocalin-2, leptin, and adiponectin were measured pre and post-cART. Spearman's rank-order correlations assessed the cross-sectional associations between hormones and bone and fat mass pre- and post-cART. Linear regression models adjusting for baseline bone or fat mass assessed the association between hormone change and BMD/fat changes following cART initiation. Results: ucOCN (p = 0.04) and lipocalin-2 (p = 0.03) increased post-cART while sclerostin, leptin, and adiponectin remained unchanged. BMD significantly decreased post-cART at all skeletal sites. Trunk and total fat increased post-cART but not significantly, while weight and BMI remained unchanged. In models adjusting for baseline BMD and fat mass, change in ucOCN was negatively associated with change in trunk (p = 0.008) and total fat (p = 0.01) and the change in leptin was positively associated with change in total hip (p = 0.03) and trochanteric BMD (p = 0.02). Conclusion: The current study demonstrates bone-fat crosstalk in cART initiating PLWH.