Background: Plasma total cysteine (tCys) and homocysteine (tHcy) are associated with body composition, which in turn affects bone mineral density (BMD).
Objectives: To investigate whether associations of tCys and tHcy with BMD are mediated through body composition (fat mass and/or lean mass).
Design: Using data from 5238 Hordaland Homocysteine Study participants, we fit multiple linear regression models and concentration-response curves to explore the relationships between tCys, tHcy, and BMD, with and without adjustment for body mass index (BMI), lean mass and/or fat mass.
Results: All associations were stronger in women. tCys was positively associated with BMD (women, partial r=0.11; men, partial r=0.07, p<or=0.001 for both), but this association was markedly attenuated after adjustment for fat mass. tHcy showed an inverse association with BMD in women (partial r=-0.09, p<0.001), which remained significant after adjustment for lean mass and fat mass. In men and women, changes in tCys or tHcy during 6 years were not associated with BMD at follow-up. Weight gain during 6 years predicted higher BMD at follow-up (p<or=0.009) independent of nutrient intakes, physical activity and baseline BMI. Baseline tHcy inversely predicted BMD measured 6 years later (partial r=-0.11, p<0.001 in women; partial r=-0.07, p=0.002 in men) independent of baseline BMI, while a positive association of baseline tCys with BMD at follow-up (partial r=0.10 in women, 0.09 in men, p<or=0.001) disappeared after adjustment for baseline BMI.
Conclusion: tHcy is inversely associated with BMD independent of body composition, while the positive association of tCys with BMD appears to be mainly mediated through fat mass.