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

Bonjour JP, Kohrt W, Levasseur R, Warren M, Whiting S, Kraenzlin M - Nutr Res Rev (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Bone Disease, University Hospitals and Faculty of Medicine,Geneva,Switzerland.

ABSTRACT
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.

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Related in: MedlinePlus

Diagram of the relationship between bone resorption or formation and bone turnover markers. On the resorption side, tartrate-resistant acid phosphatase (TRAP) reflects osteoclast number and activity, whereas pyridium cross-links, carboxy terminal telopeptide (CTX) and N-terminal telopeptide (NTX) are markers of bone matrix resorption. On the formation side, collagen type I propeptides, such as procollagen type I N-terminal propeptide (PINP), bone alkaline phosphatase (BAP) and osteocalcin reflect mainly osteoblastic bone formation. Osteoid corresponds to the non-mineralised bone matrix.
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fig2: Diagram of the relationship between bone resorption or formation and bone turnover markers. On the resorption side, tartrate-resistant acid phosphatase (TRAP) reflects osteoclast number and activity, whereas pyridium cross-links, carboxy terminal telopeptide (CTX) and N-terminal telopeptide (NTX) are markers of bone matrix resorption. On the formation side, collagen type I propeptides, such as procollagen type I N-terminal propeptide (PINP), bone alkaline phosphatase (BAP) and osteocalcin reflect mainly osteoblastic bone formation. Osteoid corresponds to the non-mineralised bone matrix.

Mentions: The BTM can be divided into two groups: markers of resorption and markers of formation (Fig. 2). The principal, specific markers of bone formation, measured in serum by immunoassays, are bone alkaline phosphatase (BAP), osteocalcin (OC) and PINP. Most assays are now adapted to automated platforms(7) (Fig. 2). Markers of bone resorption are the pyridinium cross-links (pyridinoline and deoxypyridinoline) and their associated peptides (telopeptides), released during collagen breakdown(6). Markers of osteoclast number include tartrate-resistant acid phosphatase isoenzyme 5b (TRAP 5b), the osteoclast-specific isoform of total TRAP, and, potentially, cathepsin K (Fig. 2). These enzymes are expressed and released by osteoclasts(67). TRAP 5b is the most commonly used marker of osteoclast number.Fig. 2


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

Bonjour JP, Kohrt W, Levasseur R, Warren M, Whiting S, Kraenzlin M - Nutr Res Rev (2014)

Diagram of the relationship between bone resorption or formation and bone turnover markers. On the resorption side, tartrate-resistant acid phosphatase (TRAP) reflects osteoclast number and activity, whereas pyridium cross-links, carboxy terminal telopeptide (CTX) and N-terminal telopeptide (NTX) are markers of bone matrix resorption. On the formation side, collagen type I propeptides, such as procollagen type I N-terminal propeptide (PINP), bone alkaline phosphatase (BAP) and osteocalcin reflect mainly osteoblastic bone formation. Osteoid corresponds to the non-mineralised bone matrix.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4307651&req=5

fig2: Diagram of the relationship between bone resorption or formation and bone turnover markers. On the resorption side, tartrate-resistant acid phosphatase (TRAP) reflects osteoclast number and activity, whereas pyridium cross-links, carboxy terminal telopeptide (CTX) and N-terminal telopeptide (NTX) are markers of bone matrix resorption. On the formation side, collagen type I propeptides, such as procollagen type I N-terminal propeptide (PINP), bone alkaline phosphatase (BAP) and osteocalcin reflect mainly osteoblastic bone formation. Osteoid corresponds to the non-mineralised bone matrix.
Mentions: The BTM can be divided into two groups: markers of resorption and markers of formation (Fig. 2). The principal, specific markers of bone formation, measured in serum by immunoassays, are bone alkaline phosphatase (BAP), osteocalcin (OC) and PINP. Most assays are now adapted to automated platforms(7) (Fig. 2). Markers of bone resorption are the pyridinium cross-links (pyridinoline and deoxypyridinoline) and their associated peptides (telopeptides), released during collagen breakdown(6). Markers of osteoclast number include tartrate-resistant acid phosphatase isoenzyme 5b (TRAP 5b), the osteoclast-specific isoform of total TRAP, and, potentially, cathepsin K (Fig. 2). These enzymes are expressed and released by osteoclasts(67). TRAP 5b is the most commonly used marker of osteoclast number.Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Bone Disease, University Hospitals and Faculty of Medicine,Geneva,Switzerland.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus