THE ASSESSMENT OF BONE METABOLISM IN-VIVO USING BIOCHEMICAL APPROACHES

The processes of bone formation and resorption can be monitored in viv o by measuring enzymes and other protein products released by osteobla sts and osteoclasts respectively. The major validated biochemical mark ers of bone formation currently in use include the bone isoenzyme of a lkaline phosphatase, osteocalcin (also known as BGP, bone Gla protein) and propeptides derived from the N or C terminal ends of the Type I p rocollagen molecule. The most useful markers of bone resorption are br eakdown products of Type I collagen. The longest established of these is the measurement in urine of hydroxyproline in collagen peptides, bu t the assays are cumbersome. Furthermore, hydroxyproline is not specif ic to bone collagen a nd is a Iso derived from the diet. There is ther efore much current interest in collagen products that are more specifi c to bone, including galactosyl hydroxylysine, and the collagen crossl inks, pyridinoline and deoxypyridinoline. The pyridinolines and peptid es 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 studi es, and for monitoring responses to hormones and drugs in clinical stu dies. It is important to remember that individual markers reflect diff erent biochemical and physiological processes and may not, therefore, always show identical changes. There is an increasing amount of work b eing devoted to the study of bone biomarkers in osteoporosis. In popul ation 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 me thods and for the use of new markers derived from bone cells and bone matrix.