BIOCHEMICAL MARKERS FOR ASSESSING SKELETAL GROWTH

Many of the biochemical markers for assessing skeletal turnover are ba sed on the unique metabolism of fibrillar collagens. Intracellular mod ifications lead to the formation of hydroxyproline and hydroxylysine g lycosides, both of which have been used as markers of collagen degrada tion. However, hydroxyproline is metabolised extensively in the liver and both components may be derived from several different tissue sourc es. The pyridinium crosslinks of collagen have been shown to provide m ore specific and sensitive markers of collagen degradation, since thes e compounds are only present in the mature, insoluble fibrils. In addi tion, pyridinium crosslinks are unaffected by diet and are not metabol ised in the body. Following development of HPLC methods for the quanti fication of urinary crosslinks, these techniques have been validated a s indices of bone resorption in studies of a wide range of metabolic b one diseases. Subsequently, the proportion of free crosslinks in urine was shown to be relatively consistent in different individuals, allow ing development of a simple, direct immunoassay. The excretion of cros slinks in children was related to growth velocity and, in studies of m alnourished children, the values before treatment were related to the child's growth response. For measuring bone formation, the serum conce ntrations of the C-terminal propeptide of procollagen type I (PICP) ap pear to reflect the activity of the osteoblasts, but additional inform ation on physiological variations is necessary. The major non-collagen ous components of bone in serum, osteocalcin or bone Gla protein, has long been used as a marker of bone formation, but there are a number o f factors that complicate interpretation of the results. These include variations in the immunochemical reactivity, the possible presence of degradation fragments in serum and the dependence on vitamin K status for adequate enzymatic carboxylation. Nevertheless, assays for intact osteocalcin have been shown to be related to growth velocity in child ren. There are few suitable serum or urinary indices for cartilage met abolism and development of more specific markers, particularly for gro wth plate cartilage, are required to distinguish between linear growth and bone remodelling. Assessments of skeletal metabolism should, wher ever possible, include a combination of different markers so that the balance between formative and resorptive events can be adequately eval uated.