Biochemical markers for assessing skeletal growth

Abstract

Many of the biochemical markers for assessing skeletal turnover are based on the unique metabolism of fibrillar collagens. Intracellular modifications lead to the formation of hydroxyproline and hydroxylysine glycosides, both of which have been used as markers of collagen degradation. However, hydroxyproline is metabolised extensively in the liver and both components may be derived from several different tissue sources. The pyridinium crosslinks of collagen have been shown to provide more specific and sensitive markers of collagen degradation, since these compounds are only present in the mature, insoluble fibrils. In addition, pyridinium crosslinks are unaffected by diet and are not metabolised in the body. Following development of HPLC methods for the quantification of urinary crosslinks, these techniques have been validated as indices of bone resorption in studies of a wide range of metabolic bone diseases. Subsequently, the proportion of free crosslinks in urine was shown to be relatively consistent in different individuals, allowing development of a simple, direct immunoassay. The excretion of crosslinks in children was related to growth velocity and, in studies of malnourished children, the values before treatment were related to the child's growth response. For measuring bone formation, the serum concentrations of the C-terminal propeptide of procollagen type I (PICP) appear to reflect the activity of the osteoblasts, but additional information on physiological variations is necessary. The major non-collagenous 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 of 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 of vitamin K status for adequate enzymatic carboxylation. Nevertheless, assays for intact osteocalcin have been shown to be related to growth velocity in children. There are few suitable serum or urinary indices for cartilage metabolism and development of more specific markers, particularly for growth plate cartilage, are required to distinguish between linear growth and bone remodelling. Assessments of skeletal metabolism should, wherever possible, include a combination of different markers so that the balance between formative and resorptive events can be adequately evaluated.