Sex Differences and Positive Dose-Response Relationships between Serum Osteocalcin Levels and Low Muscle Strength

Introduction: Impaired handgrip strength is an indication for sarcopenia and frailty screening, and is associated with increased osteoporotic risks and all-cause mortality. Osteocalcin, secreted by osteoblasts, is a versatile factor that participates in bone turnover and muscle adaptation. The role of osteocalcin in muscle strength has mainly been discussed in animal models and requires more human data. The study aimed to investigate the association between the serum osteocalcin level and handgrip strength in middle-aged individuals and older adults with diabetes. Methods: Adult participants (aged 40 and above, N = 237) with diabetes were enrolled in a medical center in northern Taiwan. Subjects were divided into normal, low muscle mass without dynapenia, dynapenia without low muscle mass, and groups of low muscle mass with dynapenia according to their handgrip strength and muscle mass measurements. Physical performance, including handgrip strength, repeated sit-to-stand tests, walking speed, and short physical performance batteries, was documented. Body composition was measured by bioelectrical impedance analysis. Results: The median serum osteocalcin level was highest in the dynapenic group without low muscle mass (median [Q1, Q3], 14.1 [11.2, 16.3] ng/mL). Multivariate logistic regression showed that a higher serum osteocalcin level was associated with worse handgrip strength (OR: 3.89, 95% CI: 1.66–9.10) after adjusting for body mass index (adiposity), skeletal muscle mass index (muscle), and medication with dipeptidyl peptidase-4 inhibitor. Further sex stratification revealed a more significant association between serum osteocalcin level and impaired handgrip strength in women but not in men. The female groups showed increases in the risk of impaired handgrip strength: 4.84-fold in the osteocalcin T2 group (11.4 ≤ osteocalcin <15.0 ng/mL) and 4.54-fold in the osteocalcin T3 group (osteocalcin ≥15.0 ng/mL). Moreover, after adjusting for various confounders, 8.41-fold and 8.03-fold increases in the risk of impaired handgrip strength were observed in the osteocalcin T2 group (11.4≤ osteocalcin <15.0 ng/mL) and osteocalcin T3 group (osteocalcin ≥14.5 ng/mL), respectively. Conclusion: Higher serum osteocalcin is associated with increased risks of impaired handgrip strength and impaired physical performance. Dose-dependent associations were found especially in postmenopausal women but not in men.