Biomarkers and Spinal Osteoarthritis in Postmenopausal Women

A possible relationship between homocysteine and C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) was investigated in a combined cross-sectional and longitudinal cohort study.

Elevated levels of homocysteine have been associated with age-related cardiovascular disorders, but the prevalence and progression of spinal osteoarthritis (OA) may also be associated with circulating homocysteine and a variant in the gene methylenetetrahydrofolate reductase (MTHFR), respectively. These study findings were published in the Journal of Clinical Endocrinology and Metabolism.

Data were sourced from the ongoing Nagano Cohort Study, launched in Japan in 1993. Ambulatory postmenopausal women (N=1306) with spinal OA and primary osteoporosis were recruited and assessed for an average period of 9.7±6.4 years for disease progression; all study enrollees were either postmenopausal or had reached menopause during the observation period.

At baseline, the participants were aged mean 63.9±11.1 years and had Kellgren-Lawrence (KL) grades 1 (n=577), 2 (n=496), 3 (n=190), and 4 (n=43). All clinical and demographic features differed on the basis of KL grade (all P £.05) except for low-density lipoprotein cholesterol concentration.

Prevalence of spinal OA at registration associated with age (odds ratio [OR], 2.73; 95% CI, 2.19-3.41; P <.001), working at a farm (OR, 1.67; 95% CI, 1.14-2.44; P <.01), BMI (OR, 1.52; 95% CI, 1.26-1.83; P <.001), and homocysteine concentration (OR, 1.38; 95% CI, 1.14-1.68; P <.001).

At follow-up, patient disease had progressed to KL grades 1 (n=429), 2 (n=513), 3 (n=303), and 4 (n=61).

A polymorphism in the MTHFR gene was found at site 677. Patients with a C to T substitution tended to have lower folic acid (P <.001), higher homocysteine (P <.001), and to have more advanced LH grade at baseline (P <.01) and follow-up (P <.001).

Progression of spinal OA associated with the MTHFR variant (adjusted hazard ratio [aHR], 1.67; 95% CI, 1.23-2.28; P <.001) but not with homocysteine concentration (aHR, 1.14; 95% CI, 0.98-1.34; P =.081).

The study researchers noted that their findings may not be generalizable to other populations, as the percentage of the homozygous C677T variant in the Japanese population is higher (23%) compared with White populations (10%-15%).

These data indicated to the researchers that the prevalence of spinal OA was associated with circulating homocysteine and the likelihood of progression with the C677T variant in the MTHFR gene. They suggest that these biomarkers may improve diagnostic and therapeutic strategies for physicians.


Nakano M, Nakamura Y, Urano T, et al. Associations of homocysteine metabolism with the risk of spinal osteoarthritis progression in postmenopausal women. J Clin Endocrinol Metab. 2021;dgab591. doi:10.1210/clinem/dgab591