The role of biochemical markers in detection of bone metabolism and diseases

Metabolic bone disease appears in many different ways and is considered to be the major health issue particularly in the elderly. Osteoporosis is the most common and widespread of metabolic bone diseases in which bone resorption proceeds at a pace acceding that of bone Formation. In osteoporosis the reduced bone mass leads to skeletal fragility. The volume of bone is basically determined by the actions of osteoblasts and osteoclasts. There are basically three approaches to the study of bone that complement clinical examination - imaging, histologic, and biochemical techniques. Biochemical techniques for monitoring bone turnover have proved one of the growth areas in clinical biochemistry in recent years. The measurements of calcium, phosphate and calciotropic hormones have been well established. However, markers of collagen metabolism and bone cell activity will advance the biochemical diagnosis of bone diseases. The classification of biochemical markers should help to understand the pathologic mechanism involved, and assessment of the activity of cells involved in bone formation and resorption. Considering this approach the biochemical markers can be broadly categorized into calciotropic hormones, and formation and resorption markers. Alternatively the markers can be viewed as factors that influence the activity of the bone cells, markers of the activity of the cell and precursors or products of bone cell activity. Markers of osteoblastic (bone formation) activity are the bone alkaline phosphatase, osteocalcin and procollagen-1-extension peptides. These newer markers of bone formation through the specificity of monoclonal antibodies have been shown to be relatively specific for bone and to have a clear advantage over older markers of bone formation. Bone formation markers are released during osteoblast synthesis of the new bone protein matrix and include serum bone-specific alkaline phosphatase, osteocalcin and carboxyl-terminal propeptide of procollagen type I. Many diseases affect the bone because of their effects on the processes of bone resorption and formation. These disorders include both primary bone diseases and non-bone disease with secondary effects on bone metabolism. Biochemical markers that may be of value in the screening, diagnosis and monitoring of osteoporosis reflect the activity of cells responsible for bone turnover. The activities of the osteoblasts and osteoclasts are tightly coupled, thus, the increase in bone resorption that occurs leads to a secondary increase in bone formation. Significant increases in markers of bone formation (bone alkaline phosphatase, osteocalcin and serum procollagen-1-peptide concentration) are observed in patients with osteoporosis. There is a greater incidence of changes in markers of bone resorption compared with those of formation in patients with osteoporosis. The clinical performance of the resorption products galactosyl hydroxylysine, pyridinoline crosslinks and hydroxyproline in urine is observe. Whilst there is now a wide range of studies indicating changes in bone markers in osteoporosis, it is not possible to determine which is likely to offer the greatest sensitivity or specificity for the diagnosis or monitoring of osteoporosis. The relative merits of the indices of collagen and mineral turnover require further study after improvements in methodology and more detailed experimental design.