Serum methylmalonic acid levels predict multisite bone mineral density decline in patients with suspected mitochondrial dysfunction.

This study leverages NHANES data to examine the relationship between methylmalonic acid (MMA), a marker of mitochondrial dysfunction, and bone mineral density (BMD). Multivariable linear regression reveals a negative correlation between log10-transformed MMA(Log10 MMA) levels and BMD, along with nonlinear dose-response relationships. Elevated MMA levels are associated with lower BMD, suggesting a negative impact on bone health and highlighting the importance of metabolic regulation in osteoporosis prevention and areas for further research.

Methods: Using NHANES data, multivariable linear regression analyzed the association between log10-transformed MMA levels and BMD, considering covariates like age, race and education. MEC weights were applied to adjust for the complex survey design, and weighted restricted cubic spline (RCS) analyses were used to visualiz the dose - response relationships.

Results: The study included 19,393 participants. Log10 MMA levels showed negative associations with BMD across skeletal sites (P < 0.0001 in final models), and nonlinear relationships were identified through restricted cubic spline analysis (P < 0.05). Stratified analyses confirmed consistent associations without significant interactions.

Conclusion: Elevated MMA levels, indicative of mitochondrial dysfunction, are significantly associated with lower BMD at multiple skeletal sites. This suggests that mitochondrial metabolic disturbances may compromise bone health, highlighting the importance of metabolic regulation in osteoporosis prevention and management, and emphasizing the need for further research into the mechanisms and treatments.