Potential use of biochemical markers of bone turnover for assessing the effect of calcium supplementation and predicting fracture risk

Biochemical markers of bone remodeling have been extensively used (independent of bone mass measurements) to document the efficacy of various anticatabolic and anabolic bone-modifying medications in reducing fracture risk. Nonetheless, their usefulness in determining the effectiveness of osteoporosis prevention and treatment, particularly calcium supplementation, has not been well established. This article reviews the use of biochemical markers of bone remodeling as a measure of the effect of calcium supplementation and the implications for prediction of fracture risk. A generalized search of MEDLINE from 1966 through April 2004 using the terms osteoporosis, fracture risk, and the specific bone biomarkers of interest was conducted to identify articles relating to these biomarkers and their relationship to prediction of fracture risk. A second MEDLINE search for the same period used the terms calcium, biological markers, and fracture risk to identify studies of calcium supplementation and bone biomarkers. In both cases, the reference lists of identified review articles were searched for additional publications. Several biochemical markers of bone remodeling have been shown to be positively correlated with bone mineral density and fracture risk. Furthermore, calcium supplementation has been shown to have a significant correlation with levels of a number of these biomarkers ( P < 0.05): the markers of bone formation procollagen type I carboxy and amino terminal peptides and serum bone-specific alkaline phosphatase, and the markers of bone resorption urinary hydroxyproline, urinary pyridinoline, urinary deoxypyridinoline, urinary amino terminal crosslinked telopeptide, and urinary and serum carboxy terminal crosslinked telopeptide. Calcium supplementation has a significant effect on a number of biomarkers of bone remodeling, an effect that is, in turn, correlated with decreased fracture risk. Most studies of the efficacy of calcium supplementation in reducing bone remodeling and influencing bone mineral density and fracture risk have involved calcium carbonate, although a few studies have found that other calcium salts may produce similar results.