Understanding bone metabolism biomarker variability across the menstrual cycle: A systematic review

Abstract

Bone metabolism is a dynamic process regulated by systemic and local factors, including sex hormones. While in vitro studies suggest that hormonal fluctuations impact bone biomarkers, in vivo findings remain inconsistent. Therefore, this systematic review aimed to evaluate whether biochemical markers of bone resorption and bone formation fluctuate across different phases of the menstrual cycle in healthy regular menstruating females. Following PRISMA guidelines, a comprehensive search was conducted in PubMed and Web of Science (January 2025). A total of 18 studies were included and assessed for quality using the NHLBI Quality Assessment Tool. Considerable heterogeneity was found across studies in design, phase classification, and outcome reporting. While 5 out of 7 studies on β-CTX-I reported lower concentrations during the luteal phase, 6 out of 8 studies showed that osteocalcin concentrations did not vary across the MC. Findings concerning other biomarkers included in this review were limited and inconsistent, hindering the identification of a clear trend. Current evidence does not establish a consistent pattern in bone metabolism biomarker fluctuations across the MC. Variability in methodology, hormone verification, and participant characteristics may contribute to these inconsistencies.PROSPERO registration CRD42022375821.