The assessment of bone metabolism in vivo using biochemical approaches

The processes of bone formation and resorption can be monitored in vivo by measuring enzymes and other protein products released by osteoblasts and osteoclasts respectively. The major validated biochemical markers of bone formation currently in use include the bone isoenzyme of alkaline phosphatase, osteocalcin (also known as BGP, bone Gla protein) and propeptides derived from the N or C terminal ends of the Type I procollagen molecule. The most useful markers of bone resorption are breakdown products of Type I collagen. The longest established of these is the measurement in urine of hydroxyproline in collagen peptides, but the assays are cumbersome. Furthermore, hydroxyproline is not specific to bone collagen and is also derived from the diet. There is therefore much current interest in collagen products that are more specific to bone, including galactosyl hydroxylysine, and the collagen crosslinks, pyridinoline and deoxypyridinoline. The pyridinolines and peptides derived from crosslinked regions in collagens appear to be the most promising markers of resorption and enable quantitative evaluation of rates of bone resorption in man. These biochemical methods are of use in the diagnosis and evaluation of bone diseases, in population studies, and for monitoring responses to hormones and drugs in clinical studies. It is important to remember that individual markers reflect different biochemical and physiological processes and may not, therefore, always show identical changes. There is an increasing amount of work being devoted to the study of bone biomarkers in osteoporosis. In population studies biochemical measurements may predict rates of bone loss and occurrence of fractures. However their value in the diagnosis and management of individual patients is less clear, partly because of the considerable biological and analytical variation in their measurement. There are exciting challenges ahead for improvements in technical methods and for the use of new markers derived from bone cells and bone matrix.