Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club.
[en] OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. METHODOLOGY: Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women. RESULTS: Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance. DISCUSSION: Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable. Conclusion: Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication.
Disciplines :
General & internal medicine
Author, co-author :
Bergmann, Pierre
Body, Jean-Jacques
Boonen, Steven
Boutsen, Yves
Devogelaer, Jean-Pierre
Goemaere, Stefan
Kaufman, Jean-Marc
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Gangji, Valérie
Language :
English
Title :
Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club.
Consensus development conference: Diagnosis, prophylaxis and treatment of osteoporosis (1993) Am J Med, 94, pp. 646-50
Van Hoof, V.O., Hoylaerts, M.F., Geryl, H., Age and sex distribution of alkaline phosphatase isoenzymes by agarose electrophoresis (1990) Clin Chem, 36, pp. 875-8
Broyles, D.L., Nielsen, R.G., Bussett, E.M., Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase (1998) Clin Chem, 44, pp. 2139-47
Gundberg, C.M., Markowitz, M.E., Mizruchi, M., Osteocalcin in human serum: A circadian rhythm (1985) J Clin Endocrinol Metab, 60, pp. 736-9
Delmas, P.D., Wilson, D.M., Mann, K.G., Effect of renal function on plasma levels of bone Gla-protein (1983) J Clin Endocrinol Metab, 57, pp. 1028-30
Diaz Diego, E.M., Guerrero, R., De La Piedra, C., Six osteocalcin assays compared (1994) Clin Chem, 40, pp. 2071-7
Blumsohn, A., Hannon, R.A., Eastell, R., Apparent instability of osteocalcin in serum as measured with different commercially available immunoassays (1995) Clin Chem, 41, pp. 318-9
Melkko, J., Niemi, S., Ristelli, L., Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen (1990) Clin Chem, 36, pp. 1328-32
Melkko, J., Kauppila, S., Niemi, S., Immunoassay for intact amino-terminal propeptide of human type 1 procollagen (1996) Clin Chem, 42, pp. 947-54
Brandt, J., Krogh, T.N., Jensen, C.H., Thermal instability of the trimeric structure of the N-terminal propeptide of human procollagen type I in relation to assay technology (1999) Clin Chem, 45, pp. 47-53
Scariano, J.K., Garry, P.J., Montoya, G.D., Critical differences in the serial measurement of three biochemical markers of bone turnover in the sera of pre- and postmenopausal women (2001) Clin Biochem, 34, pp. 639-44
Uebelhart, D., Schlemmer, A., Johansen, J.S., Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links (1991) J Clin Endocrinol Metab, 72, pp. 367-73
Garnero, P., Gineyts, E., Arbault, P., Different effects of bisphosphonate and estrogen therapy on free and peptide-bound bone cross-links excretion (1995) J Bone Miner Res, 10, pp. 641-9
Ristelli, J., Niemi, S., Elomaa, I., Bone resorption assay based on a peptide liberated during type I collagen degradation (1991) J Bone Miner Res, 6, pp. S251
Bonde, M., Garnero, P., Fledelius, C., Measurement of bone degradation products in serum using antibodies reactive with an isomerized form of an 8 amino acid sequence of the C-telopeptide of type I collagen (1997) J Bone Miner Res, 12, pp. 1028-34
Hanson, D.A., Weis, M.A., Bollen, A.M., A specific immunoassay for monitoring human bone resorption: Quantitation of type I collagen cross-linked N-telopeptide in urine (1992) J Bone Miner Res, 7, pp. 1251-8
Nagant De Deuxchaisnes, C., Devogelaer, J.P., Endocrinological status of postmenopausal osteoporosis (1986) Clin Rheum Dis, 12, pp. 559-635
Devogelaer, J.P., How do you know who needs prevention or treatment? (1997) Baillières Clin Rheumatol, 11, pp. 539-63
Garnero, P., Sornay-Rendu, E., Chapuy, M.C., Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis (1996) J Bone Miner Res, 11, pp. 337-49
Dresner-Pollak, R., Parker, R.A., Poku, M., Biochemical markers of bone turnover reflect femoral bone loss in elderly women (1996) Calcif Tissue Int, 59, pp. 328-33
Recker, R., Lappe, J., Davies, K.M., Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients (2004) J Bone Miner Res, 19, pp. 1628-33
Ross, P.D., Knowlton, W., Rapid bone loss is associated with increased levels of biochemical markers (1998) J Bone Miner Res, 13, pp. 297-302
Hansen, M.A., Overgaard, K., Riis, B.J., Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study (1991) BMJ, 303, pp. 961-4
Garnero, P., Sornay-Rendu, E., Duboeuf, F., Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: The OFELY study (1999) J Bone Miner Res, 14, pp. 1614-21
Boonen, S., Body, J.J., Boutsen, Y., Evidence-based guidelines for the treatment of postmenopausal osteoporosis: A consensus document of the Belgian Bone Club (2005) Osteoporos Int, 16, pp. 239-54
Lenora, J., Ivaska, K.K., Obrant, K.J., Prediction of bone loss using biochemical markers of bone turnover (2007) Osteoporos Int, 18, pp. 1297-305
Melton Iii., L.J., Khosla, S., Atkinson, E.J., Relationship of bone turnover to bone density and fractures (1997) J Bone Miner Res, 12, pp. 1083-91
Reginster, J.Y., Henrotin, Y., Christiansen, C., Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I (2001) Calcif Tissue Int, 69, pp. 130-7
Marshall, D., Johnell, O., Wedel, H., Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures (1996) BMJ, 312, pp. 1254-9
Van Daele, P.L., Seibel, M.J., Burger, H., Case-control analysis of bone resorption markers, disability, and hip fracture risk: The Rotterdam study (1996) BMJ, 312, pp. 482-3
Garnero, P., Hausherr, E., Chapuy, M.C., Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study (1996) J Bone Miner Res, 11, pp. 1531-8
Garnero, P., Sornay-Rendu, E., Claustrat, B., Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: The OFELY study (2000) J Bone Miner Res, 15, pp. 1526-36
Ross, P.D., Kress, B.C., Parson, R.E., Serum bone alkaline phosphatase and calcaneus bone density predict fractures: A prospective study (2000) Osteoporos Int, 11, pp. 76-82
Sornay-Rendu, E., Munoz, F., Garnero, P., Identification of osteopenic women at high risk of fracture: The OFELY study (2005) J Bone Miner Res, 20, pp. 1813-9
Chapurlat, R.D., Garnero, P., Bréart, G., Serum type 1 collagen breakdown products (serum CTX) predicts hip fracture in elderly women: The EPIDOS study (2000) Bone, 27, pp. 283-6
Szulc, P., Chapuy, M.C., Meunier, P.J., Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: A three year follow-up study (1996) Bone, 5, pp. 487-8
Vergnaud, P., Garnero, P., Meunier, P.J., Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: The EPIDOS Study (1997) J Clin Endocrinol Metab, 82, pp. 719-24
Schousboe, J.T., Bauer, D.C., Nyman, J.A., Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of facture for bisphosphonate therapy (2007) Osteoporos Int, 18, pp. 201-10
Bauer, D.C., Garnero, P., Hochberg, M.C., Pretreatment levels of bone turnover and antifracture efficacy of alendronate: The fracture intervention trial (2006) J Bone Miner Res, 21, pp. 292-9
Seibel, M.J., Naganathan, V., Barton, I., Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate (2004) J Bone Miner Res, 19, pp. 323-9
Seibel, M.J., Biochemical markers of bone turnover part II: Clinical applications in the management of osteoporosis (2006) Clin Biochem Rev, 27, pp. 123-38
Ravn, P., Hosking, D., Thompson, D., Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the Early Postmenopausal Intervention Cohort study (1999) J Clin Endocrinol Metab, 84, pp. 2363-8
Fink, E., Cormier, C., Steinmetz, P., Differences in the capacity of several biochemical bone markers to assess high bone turnover in early menopause and response to alendronate therapy (2000) Osteoporos Int, 11, pp. 295-303
Bauer, D.C., Black, D.M., Garnero, P., Fracture Intervention Trial Study Group. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: The fracture intervention trial (2004) J Bone Miner Res, 19, pp. 1250-8
Eastell, R., Barton, I., Hannon, R.A., Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate (2003) J Bone Miner Res, 18, pp. 1051-6
Delmas, P.D., Recker, R.R., Chesnut, C.H., Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: Results from the BONE study (2004) Osteoporos Int, 15, pp. 792-8
Reginster, J.Y., Gieschke, R., Clinical utility of a pharmacostatistical model for ibandronate in postmenopausal osteoporosis (2006) Curr Drug Metab, 7, pp. 827-36
Reginster, J.Y., Adami, S., Lakatos, P., Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2-year results from the MOBILE study (2006) Ann Rheum Dis, 65, pp. 654-61
Reginster, J.Y., Felsenberg, D., Cooper, C., A new concept for bisphosphonate therapy: A rationale for the development of monthly oral dosing of ibandronate (2006) Osteoporos Int, 17, pp. 159-66
Papapoulos, S.E., Schimmer, R.C., Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy:implications from clinical studies with ibandronate (2007) Ann Rheum Dis, 66, pp. 853-8
Seibel, M.J., Biochemical markers of bone metabolism in the assessment of osteoporosis: Useful or not? (2003) J Endocrinol Invest, 26, pp. 464-71
Clowes, J.A., Peel, N.F.A., Eastell, R., The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: A randomized controlled trial (2004) J Clin Endocrinol Metab, 89, pp. 1117-23
Delmas, P.D., Vrijens, B., Eastell, R., Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis (2007) J Clin Endocrinol Metab, 92, pp. 1296-304
Seibel, M.J., Lang, M., Geilenkeuser, W.J., Interlaboratory variation of biochemical markers of bone turnover (2001) Clin Chem, 47, pp. 1443-50
Seibel, M.J., Biochemical markers of bone turnover. Part I: Biochemistry and variability (2005) Clin Biochem Rev, 26, pp. 97-122
Hannon, R., Eastell, R., Preanalytical variability of biochemical markers of bone turnover (2000) Osteoporos Int, 11 (6), pp. S30-44