An index of net bone formation relative to resorption is associated with incident fracture during the menopause transition and postmenopause

Abstract We previously created a bone balance index (BBI) that combines bone resorption and formation markers (collagen type I C-telopeptide CTX and procollagen N-terminal propeptide PINP, respectively) to estimate bone balance. BBI quantifies net bone formation relative to resorption; greater values indicate more favorable balance. This study examined the association of BBI with incident fracture across the menopause transition and tested each individual bone turnover marker (CTX or PINP) as separate predictors of fracture. We included 451 participants from the Study of Women’s Health Across the Nation (SWAN) cohort study with 2667 longitudinal observations from pre-, early peri-, late peri-, or postmenoapuse. Participants did not report fractures or use bone-active medications before their bone turnover marker assessments. Using repeated measures Cox proportional hazards regression, we examined the associations of BBI, CTX, or PINP with two different fracture outcomes: incident fracture at any site or incident fracture at a major osteoporotic fracture (MOF) site (spine, hip, radius, humerus). Women were censored at first use of bone-beneficial medications during follow-up. Covariates were age, BMI, race/ethnicity, family history of hip fracture, cigarette use, diabetes mellitus, bone-detrimental medication use, menopause transition stage, femoral neck (FN) bone mineral density, and SWAN study site. Mean age across BBI, CTX and PINP assessments was 52 yr. Seventy-eight women sustained an incident fracture over 15.1 yr of follow-up. Adjusted for covariates, each SD increment in BBI was associated with a 20% smaller hazard for fracture at any site (HR 95% CI: 0.80 0.67, 0.97, p = .02) or a 25% lesser hazard for fracture at a MOF site (HR 95% CI: 0.75 0.61, 0.85), p = .01). In contrast, considered singly in adjusted analyses, neither CTX (p .2) nor PINP (p .1) related to either fracture outcome. We conclude that BBI predicts fracture, independent of clinical and densitometric fracture risk factors.