Exploring the Interrelationship Among Bone Status Indices: A Structural Equation Modeling Approach Reveals the Role of Osteocalcin as a Marker of Overall Bone Turnover

Objective: Bone status indices (BSIs) are key tools to monitor cell metabolic activity but lack specificity for clinical use. By applying a new statistical approach, this study aimed at highlighting the association between osteocalcin (OC), a regulatory molecule of bone turnover, often considered a putative biomarker of bone formation, and bone resorption markers like the β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) and urinary lysil-pyridinoline (uLysPYD), also investigating on the impact of vitamin D, age, and sex on their levels. Methods: Path analysis within the Structural Equation Modeling framework was applied to investigate relationships among BSIs. This model hypothesized OC as the outcome variable, affected by the direct effect of β-CTX-I, uLysPYD and 25-hydroxy-vitamin D [25-(OH)D] and by two 25-(OH)D indirect effects, through β-CTX-I and uLysPYD. Results: OC showed positive association with bone resorption markers, also when the model was run separately for sex and age groups. 25-(OH)D negatively associated with each bone biomarker. Age represented an effect modifier for 25-(OH)D relationship with both OC and β-CTX-I: the main differences were observed between the youngest (18–45) and the oldest cohorts (56–65 and >75) in both OC and β-CTX-I relationships with 25-(OH)D, and 46–55 and 66–75 groups in β-CTX-I and 25-(OH)D relationship. Both indirect effects were negative; the main effect of 25-(OH)D on OC was exerted through β-CTX-I. Conclusion: Rather than index of osteoblast activity, OC behaves as an overall turnover marker and possibly associated with resorption in elderly. The osteoclast-mediated bone resorption could impact OC serum levels, as it impacts β-CTX-I.