Plasma polyunsaturated fatty acid metabolism associations with bone mineral density and bone turnover in pre- and postmenopausal women living with HIV

BACKGROUND: Women living with HIV (WLWH) are at high-risk of osteoporosis and fracture. Studies suggest that polyunsaturated fatty acid (PUFA) metabolism may modulate bone mineral density (BMD) in populations without HIV. We aimed to use untargeted high-resolution metabolomics (HRM) to profile the plasma metabolome and identify biochemical pathways and metabolites associated with indices of bone health in WLWH. A secondary objective was to assess the association between plasma PUFA concentrations and bone health indices. METHODS: In a cross-sectional study of WLWH (n = 68) and women without HIV (n = 42), BMD at the lumbar spine, femoral neck, and total hip was determined by dual energy X-ray absorptiometry. Serum concentrations of bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin (OCN), were determined. Plasma HRM and pathway enrichment analysis were conducted by HIV status to determine associations of each BMD Z-score and bone turnover markers with the plasma metabolome. Relationships between plasma PUFA concentrations and each BMD index and bone turnover marker were assessed by multivariable linear regression. RESULTS: The median age was 49 (Q1, Q3: 41, 56) years and median Z-scores for lumbar spine, total hip, and femoral neck BMD were -0.2 (-1.2, 0.7), -0.5 (-1.3, 0.2), and -0.8 (-1.4, 0.1), respectively, with no significant differences between HIV status groups (all p > 0.05). Among WLWH, BMD Z-scores were associated with metabolites significantly enriched in metabolic pathways including those related to arachidonic acid, fatty acid oxidation, energy metabolism, and steroid hormones (all p < 0.05). Bone turnover markers were associated with metabolites significantly enriched in multiple metabolic pathways, including PUFA and other lipid metabolic pathways (all p < 0.05). Plasma n-3 and n-6 PUFA concentrations were not significantly associated with BMD Z-scores or serum bone turnover markers (all p > 0.05). CONCLUSIONS: This study demonstrates linkages between PUFA metabolism and bone health in WLWH providing potential targets for focused interventions to improve bone health in this population.