Higher Fracture Risk Predicted by Bone Turnover Markers

Two reference bone turnover markers were shown to be associated with an increased risk for future fractures, according to a meta-analysis by researchers from the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine.

“This is the first meta-analysis of [bone turnover markers] that was made possible by standardizing the expression of risk,” working group co-chair Howard A. Morris, Ph.D., F.A.A.C.B., F.F.Sc(RCPA), of the School of Pharmacy and Medical Sciences at the University of South Australia, said in a news release. “One strength of the study is that we were able to standardize the metric of predictive power.”

The researchers analyzed data from six publications identified through PubMed between 2000 and 2010, which included tabulated evidence from the Agency for Healthcare Research and Quality on bone turnover markers. Because the risk for fracture reported in the studies was represented in different ways, including a number of methods for calculating heart rate (HR), the researchers transformed the measurements into a standardized gradient of risk, which was defined as the HR per standard deviation increase.

The gradient of risk has “the advantage of maximizing the use that can be made of publications that used differing indices of risk,” Morris said in the press release.

Studies eligible for inclusion in the meta-analysis were prospective cohort studies of serum procollagen type 1 N-terminal propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type 1 collagen (s-CTX) measured at baseline in untreated individuals with first incident fracture in middle age, or older men and women. Nested case-control and case-cohort studies were included, but cross-sectional studies were excluded.

Researchers reported a significant association between s-PINP and the risk for fracture. In men and women, unadjusted for bone mineral density, the gradient of risk was 1.23 (95 percent CI, 1.09-1.39). There also was a significant association between s-CTX and the risk for fracture, in which the gradient of risk was 1.18 (95 percent CI, 1.05-1.34). A slightly higher association was observed for hip fractures and s-CTX (gradient of risk=1.23; 95 percent CI, 1.04-1.47).