Correlations Between Changes in Undercarboxylated Osteocalcin and Muscle Function in Hypoparathyroidism

Area of Science:

• Endocrinology
• Bone Metabolism
• Muscle Physiology

Background:

• The interplay between bone and muscle is increasingly recognized.
• Undercarboxylated osteocalcin (ucOC), a bone-derived protein, is hypothesized to influence muscle mass and strength.
• Prospective human data on this relationship are lacking.

Purpose of the Study:

• To investigate the prospective relationship between changes in undercarboxylated osteocalcin (ucOC) and muscle function in patients with hypoparathyroidism.
• To determine if parathyroid hormone (PTH) treatment, which increases ucOC, affects muscle mass, strength, or function.

Main Methods:

• A secondary analysis of a randomized, placebo-controlled trial involving hypoparathyroid patients treated with PTH or placebo.
• Muscle mass assessed by Dual-energy X-ray Absorptiometry (DXA).
• Muscle strength measured by maximal voluntary isometric strength testing and functional tests including repeated chair stands and Timed Up and Go, with postural stability assessed.

Main Results:

• A positive and significant association was found between the ratio of ucOC to total osteocalcin (ucOC%/OC%) and the percentage change in maximal elbow extension force (β = 0.28, P = 0.034).
• No other significant associations were observed between ucOC changes and various measures of muscle mass, strength, or function.
• The single significant finding may be a false positive due to multiple statistical tests.

Conclusions:

• The study's results do not support a role for ucOC in modulating muscle function in humans with hypoparathyroidism.
• Findings contradict previous cross-sectional human studies, highlighting the limitations of inferring causality from such designs.
• Larger, prospective randomized trials, including healthy individuals, are recommended to validate these findings and elucidate the ucOC-muscle relationship.