Serum methylmalonic acid levels predict multisite bone mineral density decline in patients with suspected
Tengbo Pei1, Yutian Lei2, Yingfang Gao3
1Department of Medical Laboratory, Xianyang Central Hospital, Xianyang, 712000, Shaanxi, China.
Journal of Orthopaedic Surgery and Research
|September 27, 2025
Summary
Elevated methylmalonic acid (MMA), a marker of mitochondrial dysfunction, is linked to lower bone mineral density (BMD). This highlights the importance of metabolic health for preventing osteoporosis.
Area of Science:
- Biochemistry
- Bone Metabolism
- Gerontology
Background:
- Methylmalonic acid (MMA) is a biomarker for mitochondrial dysfunction.
- Bone mineral density (BMD) is crucial for skeletal health and osteoporosis assessment.
- Mitochondrial dysfunction may impact various physiological processes, including bone health.
Purpose of the Study:
- To investigate the association between MMA levels and BMD using NHANES data.
- To explore potential dose-response relationships between MMA and BMD.
- To understand the role of metabolic regulation in bone health.
Main Methods:
- Utilized data from the National Health and Nutrition Examination Survey (NHANES).
- Employed multivariable linear regression to analyze the relationship between log10-transformed MMA and BMD.
- Applied weighted restricted cubic spline analyses to visualize nonlinear dose-response relationships.
Main Results:
- A significant negative association was found between log10 MMA levels and BMD across multiple skeletal sites (P < 0.0001).
- Nonlinear dose-response relationships between MMA and BMD were identified (P < 0.05).
- Stratified analyses confirmed consistent associations, indicating robustness of the findings.
Conclusions:
- Elevated MMA levels, reflecting mitochondrial dysfunction, are significantly associated with reduced BMD.
- Mitochondrial metabolic disturbances may negatively affect bone health.
- Metabolic regulation is crucial for osteoporosis prevention and management, warranting further research.
