Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: -23.6% (spine) and -13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11-1.92) and incident (OR 1.55; 95% CI, 1.03-2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38-0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).