Biochemical markers for assessment of calcium economy and bone metabolism: application in clinical trials from pharmaceutical agents to nutritional products

Nutrition plays an important role in osteoporosis prevention and treatment. Substantial progress in both laboratory analyses and clinical use of biochemical markers has modified the strategy of anti-osteoporotic drug development. The present review examines the use of biochemical markers in clinical research aimed at characterising the influence of foods or nutrients on bone metabolism. The two types of markers are: (i) specific hormonal factors related to bone; and (ii) bone turnover markers (BTM) that reflect bone cell metabolism. Of the former, vitamin D metabolites, parathyroid hormone, and insulin-like growth factor-I indicate responses to variations in the supply of bone-related nutrients, such as vitamin D, Ca, inorganic phosphate and protein. Thus modification in bone remodelling, the key process upon which both pharmaceutical agents and nutrients exert their anti-catabolic or anabolic actions, is revealed. Circulating BTM reflect either osteoclastic resorption or osteoblastic formation. Intervention with pharmacological agents showed that early changes in BTM predicted bone loss and subsequent osteoporotic fracture risk. New trials have documented the influence of nutrition on bone-tropic hormonal factors and BTM in adults, including situations of body-weight change, such as anorexia nervosa, and weight loss by obese subjects. In osteoporosis-prevention studies involving dietary manipulation, randomised cross-over trials are best suited to evaluate influences on bone metabolism, and insight into effects on bone metabolism may be gained within a relatively short time when biochemical markers are monitored.