Estimating net bone formation relative to resorption using reference bone turnover markers

Context

Individually, bone resorption or formation markers do not reflect bone balance.

Objective

(1) Combine reference bone resorption [collagen type I C-telopeptide (CTX)] and formation [procollagen type I propeptide (PINP)] markers to estimate balance by creating a bone balance index (BBI); (2) examine associations of BBI, CTX, or PINP with bone mineral density (BMD) change.

Design

Mixed effects linear regression quantified associations of BBI, CTX, or PINP with BMD change rate.

Setting

Community-based cohort (Study of Women's Health Across the Nation).

Participants

535 women transitioning through menopause.

Main Outcome Measures

Annualized percent change in lumbar spine (LS) and femoral neck (FN) BMD.

Results

In mixed effects linear regression, adjusted for age, body mass index, race/ethnicity, menopause transition stage, and study site, more negative BBI (less favorable balance) related to more BMD loss. Each SD decrement in BBI was associated with a 0.26% greater decline in LS BMD annually and 0.42% greater decline in FN BMD annually (each P < .0001). In separate models, accounting for the previous covariates, greater CTX or PINP predicted more bone loss. Per SD increment in log2CTX, annual BMD decline was 0.37% greater (P < .0001) and 0.47% greater (P < .0001) at the LS and FN, respectively. Per SD increment in log2PINP, annual BMD loss was 0.22% (P < .0001, LS) and 0.19% (P = .01, FN) greater.

Conclusion

When combined as a BBI, CTX and PINP estimate bone balance; more negative BBI predicts faster BMD loss. Separately, CTX or PINP reflect overall amount of bone turnover; greater CTX or PINP are related to more bone loss.