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 markers 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.