A-158 Exploring the relationship between bone formation and resorption creating Bone Balance Index formulas in adults using kidney-independent bone turnover markers

Abstract

Individual bone turnover markers inform on current whole-skeletal remodeling, but not the balance between bone formation and bone resorption. A calculated bone balance index (BBI) has been suggested to bridge this gap. This study aims to establish a BBI based on the relationship between non-kidney cleared biomarkers of bone formation (bone-specific alkaline phosphatase [BALP], intact pro-collagen type I N-terminal pro-peptide, [iPINP])) and bone resorption (tartrate resistant acid phosphatase isoform-5b [TRACP5b]) in a cohort of healthy individuals, and to utilize this BBI to explore net bone resorption relative to bone formation in an independent test cohort. BBI was constructed leveraging data from in a population of 235 healthy volunteers, (147 premenopausal women and 88 age-comparable men with BMD T-score >-1.0), presumed to be in a state of neutral bone remodeling. Equations were built using either iP1NP or BALP as the bone formation marker and TRACP5b and C-terminal telopeptide of type I collagen (ß-CTX-I) as the bone resorption markers. We used linear regression to quantify the relationship between pairs of bone formation and bone resorption markers and calculate BBI in a test population of postmenopausal women and age-comparable men. BBI=0 indicates a balanced or neutral bone remodeling. Positive BBI-values indicate higher net formation relative to resorption while negative indicate higher net resorption. The relationship between bone formation and bone resorption was sex-dependent for several biomarker-pairs. For the BALP/TRACP5b pair, slopes differed significantly between men (TRACP5b = 1 .967 + 0.042 * BALP) and women (TRACP5b = 1.081 + 0.104 * BALP), indicating non-parallel relationships and supporting sex-specific equations. For iPINP/TRACP5b, regression lines were statistically indistinguishable, suggesting that a single equation may be acceptable for both sexes (TRACP5b = 1.259 + 0.020 × iPINP). For iPINP/ß-CTX-I (men: ß-CTX-I = 116.749 + 4.921 * iPINP, women: ß-CTXI = 63.738 + 5.255 * iPINP), and BALP/ß-CTX-I (men: ß-CTX-I = 251.999 + 11.173 * BALP, women: ß-CTX-I = 97.988 + 21.300 * BALP) slopes were similar, but intercepts differed, again favoring sex-specific equations. Once calculated by sex-appropriate equations, BBI was more positive in men compared to women across age groups in all biomarker combinations. BBI was significantly higher in subjects with normal BMD compared to subjects with osteopenia or osteoporosis, when utilizing biomarker pairs consisting of TRACP5b as the resorption marker. We provide a calculated BBI based on bone formation and resorption markers that are not affected by kidney function that could be utilized in the setting of kidney dysfunction. Future studies should explore the value of the BBI in predicting clinically relevant outcomes such as ongoing bone loss.