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

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Abstract

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.

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Most cited references 56

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Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis.

(1993)

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Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

D. Marshall, O. Johnell, H. Wedel (1996)

To determine the ability of measurements of bone density in women to predict later fractures. Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Eleven separate study populations with about 90,000 person years of observation time and over 2000 fractures. Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density.

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Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis.

P Garnero, E Sornay-Rendu, M C Chapuy … (1996)

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Clin Pract

Journal ID (publisher-id): ijcp

Title: International Journal of Clinical Practice

Publisher: Blackwell Publishing Ltd

ISSN (Print): 1368-5031

ISSN (Electronic): 1742-1241

Publication date (Print): January 2009

Volume: 63

Issue: 1

Pages: 19-26

Affiliations

[1 ]simpleLaboratory of Clinical Chemistry, CHU Brugmann, Université Libre de Bruxelles Bruxelles, Belgium

[2 ]simpleDepartment of Medicine, CHU Brugmann, Université Libre de Bruxelles Bruxelles, Belgium

[3 ]simpleCenter for Metabolic Bone Diseases, KU-Leuven Leuven, Belgium

[4 ]simpleDepartment of Rheumatology, Mont-Godinne University Hospital, UCL-Brussels Brussels, Belgium

[5 ]simpleArthritis Unit, Saint-Luc University Hospital, UCL-Brussels Brussels, Belgium

[6 ]simpleDepartment of Endocrinology, University Hospital, UGent Gent, Belgium

[7 ]simpleBone and Cartilage Metabolism Research Unit, Department of Public Health, Epidemiology and Health Economics, ULg-Liège Liège, Belgium

[8 ]simpleDepartment of Rheumatology and Physical medicine and Rehabilitation, Erasme Hospital, Université Libre de Bruxelles Bruxelles, Belgium

Author notes

Correspondence to: Prof. Pierre Bergmann, Laboratory of Clinical Chemistry, CHU Brugmann, Université Libre de Bruxelles (ULB), CHU Brugmann – site Victor Horta, Place Van Gehuchten 4, 1020 Bruxelles (Laeken), Belgium Tel.: + 32 2 477 26 49 Fax: + 32 2 477 24 32 Email: pierre.bergmann@ 123456chu-brugmann.be

Disclosures Prof. P. Bergmann, Prof. J.-J. Body, Prof. S. Boonen, Prof. Y. Boutsen, Prof. J.-P. Devogelaer, Dr S. Goemaere, Prof. J.-M. Kaufman and Dr V. Gangji: none. Prof. J.-Y. Reginster: Consulting fees or paid advisory boards – Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB. Lecture fees when speaking at the invitation of a commercial sponsor: Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk. Grant Support from Industry: Bristol-Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier.

Article

DOI: 10.1111/j.1742-1241.2008.01911.x

PMC ID: 2705815

PubMed ID: 19125989

SO-VID: 43c8c9b7-002d-4619-bcfb-c8349a2207e9

License:

Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

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

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Abstract

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Methodology:

Results:

Discussion:

Conclusion:

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Karger: Coronavirus / COVID-19

Most cited references 56

Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis.

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis.

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