New developments in biochemical markers for osteoporosis.

The noninvasive assessment of bone turnover has markedly improved in the past few years with the development of sensitive and specific markers of bone formation and bone resorption. Markers of bone formation in serum include total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen carboxyterminal extension peptide. Assessment of bone resorption can be achieved by measuring plasma tartrate-resistant acid phosphate and the urinary excretion (and possibly serum levels) of bone type I collagen degradation products: hydroxyproline, hydroxylysine glycosides, and, more recently, the pyridinium crosslinks (pyridinoline and deoxypyridinoline) and associated peptides. The immunoassay of human osteocalcin and bone alkaline phosphatase for formation and the pyridinoline crosslinks measured by high-pressure liquid chromatography or by immunoassay for bone resorption are currently the most sensitive and specific markers of bone turnover for the clinical assessment of osteoporosis. Using these new markers, several studies have shown that bone turnover increases after the menopause and remains elevated in late postmenopausal and elderly women. An increased bone turnover rate is related to a high rate of bone loss in postmenopausal women and to a decreased bone mass in elderly women. Recent data suggest that some of the new immunoassays for pyridinoline crosslinks could predict the subsequent risk of hip fracture in elderly women. Thus, bone markers might be used in combination with bone mass measurement to improve the prognostic assessment of postmenopausal women, i.e., their risk of developing osteoporosis and ultimately fractures. Treatment of postmenopausal women with antiresorptive drugs such as estrogens, bisphosphonates, and calcitonin induces a rapid decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass. Thus, bone markers should be very useful in monitoring treatment efficacy in patients with osteoporosis.