SAT-730 Evaluating the Association Between Bone Metabolism Markers and Bone Mineral Density in Men with and without HIV

Abstract Disclosure: S.M. Cohen: None. J. Sun: None. F.J. Palella: None. J.E. Lake: None. S.L. Koletar: None. N.L. Haw: None. R.D. Ross: None. T.T. Brown: None. Background: People living with HIV (PLWH) experience higher rates of osteoporosis and fractures as they age compared to the general population, though mechanisms connecting HIV to bone loss remain incompletely understood. It is thought that HIV-related chronic inflammation alters bone metabolism—potentially via sclerostin/Wnt/β-catenin signaling, which regulates bone formation, or the RANK-RANK ligand (RANKL)/osteoprotegerin (OPG) axis, which regulates bone resorption. We hypothesized that sclerostin, OPG, and RANKL levels would be altered in PLWH and associated with BMD, inflammation, and HIV-specific factors. Methods: In a sub-study of the Multicenter AIDS Cohort Study, we enrolled 204 men with HIV on antiretroviral therapy (ART) and 204 men without HIV, all aged 50-69 years. Participants underwent dual-energy X-ray absorptiometry (DXA) scans at the lumbar spine (LS), total hip (TH), and femoral neck (FN), morning phlebotomy, and a detailed assessment of osteoporosis risk factors. We used the Wilcoxon Rank-Sum test to compare the two groups and multivariable linear regression to determine associations of sclerostin, OPG, and RANKL concentrations with 1) BMD, 2) inflammatory markers, and 3) HIV-1 viral load and nadir CD4+ count among PLWH. We adjusted for HIV and hepatitis C virus serostatus, demographic and behavioral covariates, osteoporosis risk factors, and ART types. Results: The median age was 60 years and median BMI was 25.3 kg/m2; these were similar by HIV serostatus. Men who were PLWH had significantly lower TH BMD (p=0.03), but LS and FN BMD did not differ between the two groups (LS p=0.86, FN p=0.30). PLWH had higher plasma OPG concentrations (p=0.03), lower RANKL concentrations (p=0.001), and higher soluble TNF-α receptor (sTNF-R) 1 and 2 concentrations (sTNF-R1 p=0.01, sTNF-R2 p<0.001). OPG and RANKL concentrations were both were positively associated with sTNF-R concentrations (OPG vs. sTNF-R1 p<0.001, OPG vs. sTNF-R2 p=0.003, RANKL vs. sTNF-R1 p=0.001, RANKL vs. sTNF-R2 p=0.002). However, OPG and RANKL concentrations were not associated with BMD. Sclerostin concentrations were not associated with sTNF-R concentrations, but lower sclerostin concentrations were associated with lower BMD at all sites regardless of HIV serostatus (LS p<0.001, TH p<0.001, FN p<0.001). Conclusion: Sclerostin concentrations were associated with BMD in men with and without HIV, which suggests that sclerostin is a marker of bone mass and osteocyte number. Circulating concentrations of OPG and RANKL were associated with HIV serostatus and systemic inflammation, but not with bone mineral density, among men with or at risk for HIV. These findings suggest that immune dysfunction in PLWH contributes to dysregulation of the RANK-RANKL/OPG axis, but these changes are not associated with changes in bone mass. Presentation: Saturday, July 12, 2025