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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

Schematic representation of changes in bone turnover markers (BTM) at 3–6 months and corresponding increase in bone mineral density (BMD) during treatment of osteoporosis. (a) Bone antiresorptive treatment (i.e. bisphosphonate): a more pronounced decrease in bone resorption marker at 3–6 months is associated with larger increases in BMD. (b) Bone formation-stimulating treatment (i.e. recombinant parathyroid hormone): a greater increase in bone formation marker is associated with a larger increase in BMD. * Mild response in changes in BTM and BMD. † Moderate response in changes in BTM and BMD. ‡ Pronounced response in changes in BTM and BMD. The diagrams show the relationship between early changes (3–6 months) in BTM and changes in BMD after 2 years of either bone resorption inhibition (a) or bone formation stimulation (b). Fig. 3(a) is based on quantitative data obtained by antiresorptive treatment with alendronate, documenting tertile changes at 6 months of the bone resorption marker urinary N-terminal telopeptide (u-NTX) and the changes in BMD as assessed by dual-energy X-ray absorptiometry (DXA) in total hip, trochanter and spine at 3 years in postmenopausal women(98). Fig. 3(b) is based on quantitative data obtained by anabolic treatment with parathyroid hormone documenting tertile changes at 3 months of the bone formation marker N-terminal procollagen I propeptide (PINP) and the change in areal and volumetric BMD at 12 months, as assessed in the spine by DXA and quantitative computed tomography in postmenopausal women(98,113).
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fig3: Schematic representation of changes in bone turnover markers (BTM) at 3–6 months and corresponding increase in bone mineral density (BMD) during treatment of osteoporosis. (a) Bone antiresorptive treatment (i.e. bisphosphonate): a more pronounced decrease in bone resorption marker at 3–6 months is associated with larger increases in BMD. (b) Bone formation-stimulating treatment (i.e. recombinant parathyroid hormone): a greater increase in bone formation marker is associated with a larger increase in BMD. * Mild response in changes in BTM and BMD. † Moderate response in changes in BTM and BMD. ‡ Pronounced response in changes in BTM and BMD. The diagrams show the relationship between early changes (3–6 months) in BTM and changes in BMD after 2 years of either bone resorption inhibition (a) or bone formation stimulation (b). Fig. 3(a) is based on quantitative data obtained by antiresorptive treatment with alendronate, documenting tertile changes at 6 months of the bone resorption marker urinary N-terminal telopeptide (u-NTX) and the changes in BMD as assessed by dual-energy X-ray absorptiometry (DXA) in total hip, trochanter and spine at 3 years in postmenopausal women(98). Fig. 3(b) is based on quantitative data obtained by anabolic treatment with parathyroid hormone documenting tertile changes at 3 months of the bone formation marker N-terminal procollagen I propeptide (PINP) and the change in areal and volumetric BMD at 12 months, as assessed in the spine by DXA and quantitative computed tomography in postmenopausal women(98,113).

Mentions: The main domain for the clinical use of BTM is the monitoring of osteoporosis therapy. The ultimate goal in treating patients with osteoporosis is to reduce their fracture risk. However, the short-term incidence of osteoporotic fractures is low, and the absence of fracture during treatment does not necessarily mean that the treatment is effective. Consequently, serial measurements of changes in aBMD as a surrogate marker of therapeutic efficacy are currently the standard approach to monitor osteoporosis therapy. Yet, changes in aBMD occur slowly and therapeutic effects are usually not detectable before 1–2 or more years of treatment(80,91–94). In contrast, BTM levels change much faster than aBMD in response to therapeutic interventions(80). Antiresorptive treatment generates a rapid decrease in bone resorption markers after only 2–4 weeks, reaching a plateau after 3 to 6 months of treatment(80,95) (Fig. 3(a)). The decrease in bone formation markers, reflecting the physiological coupling of bone formation to bone resorption, is delayed and reaches a plateau after 6–12 months. The magnitude of the decreases varies according to the type and dose of the drug and the marker used to assess the effect (Table 2).Fig. 3


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)

Schematic representation of changes in bone turnover markers (BTM) at 3–6 months and corresponding increase in bone mineral density (BMD) during treatment of osteoporosis. (a) Bone antiresorptive treatment (i.e. bisphosphonate): a more pronounced decrease in bone resorption marker at 3–6 months is associated with larger increases in BMD. (b) Bone formation-stimulating treatment (i.e. recombinant parathyroid hormone): a greater increase in bone formation marker is associated with a larger increase in BMD. * Mild response in changes in BTM and BMD. † Moderate response in changes in BTM and BMD. ‡ Pronounced response in changes in BTM and BMD. The diagrams show the relationship between early changes (3–6 months) in BTM and changes in BMD after 2 years of either bone resorption inhibition (a) or bone formation stimulation (b). Fig. 3(a) is based on quantitative data obtained by antiresorptive treatment with alendronate, documenting tertile changes at 6 months of the bone resorption marker urinary N-terminal telopeptide (u-NTX) and the changes in BMD as assessed by dual-energy X-ray absorptiometry (DXA) in total hip, trochanter and spine at 3 years in postmenopausal women(98). Fig. 3(b) is based on quantitative data obtained by anabolic treatment with parathyroid hormone documenting tertile changes at 3 months of the bone formation marker N-terminal procollagen I propeptide (PINP) and the change in areal and volumetric BMD at 12 months, as assessed in the spine by DXA and quantitative computed tomography in postmenopausal women(98,113).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Schematic representation of changes in bone turnover markers (BTM) at 3–6 months and corresponding increase in bone mineral density (BMD) during treatment of osteoporosis. (a) Bone antiresorptive treatment (i.e. bisphosphonate): a more pronounced decrease in bone resorption marker at 3–6 months is associated with larger increases in BMD. (b) Bone formation-stimulating treatment (i.e. recombinant parathyroid hormone): a greater increase in bone formation marker is associated with a larger increase in BMD. * Mild response in changes in BTM and BMD. † Moderate response in changes in BTM and BMD. ‡ Pronounced response in changes in BTM and BMD. The diagrams show the relationship between early changes (3–6 months) in BTM and changes in BMD after 2 years of either bone resorption inhibition (a) or bone formation stimulation (b). Fig. 3(a) is based on quantitative data obtained by antiresorptive treatment with alendronate, documenting tertile changes at 6 months of the bone resorption marker urinary N-terminal telopeptide (u-NTX) and the changes in BMD as assessed by dual-energy X-ray absorptiometry (DXA) in total hip, trochanter and spine at 3 years in postmenopausal women(98). Fig. 3(b) is based on quantitative data obtained by anabolic treatment with parathyroid hormone documenting tertile changes at 3 months of the bone formation marker N-terminal procollagen I propeptide (PINP) and the change in areal and volumetric BMD at 12 months, as assessed in the spine by DXA and quantitative computed tomography in postmenopausal women(98,113).
Mentions: The main domain for the clinical use of BTM is the monitoring of osteoporosis therapy. The ultimate goal in treating patients with osteoporosis is to reduce their fracture risk. However, the short-term incidence of osteoporotic fractures is low, and the absence of fracture during treatment does not necessarily mean that the treatment is effective. Consequently, serial measurements of changes in aBMD as a surrogate marker of therapeutic efficacy are currently the standard approach to monitor osteoporosis therapy. Yet, changes in aBMD occur slowly and therapeutic effects are usually not detectable before 1–2 or more years of treatment(80,91–94). In contrast, BTM levels change much faster than aBMD in response to therapeutic interventions(80). Antiresorptive treatment generates a rapid decrease in bone resorption markers after only 2–4 weeks, reaching a plateau after 3 to 6 months of treatment(80,95) (Fig. 3(a)). The decrease in bone formation markers, reflecting the physiological coupling of bone formation to bone resorption, is delayed and reaches a plateau after 6–12 months. The magnitude of the decreases varies according to the type and dose of the drug and the marker used to assess the effect (Table 2).Fig. 3

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