Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis
Bone markers may be useful to monitor response to treatment withdrawal in osteoporosis. We used two criteria for investigating the change in BTMs after withdrawal of bisphosphonate treatment. A larger increase in BTMs was associated with greater bone loss. Bone markers may be useful in monitoring of patients taking a pause from treatment.
Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD).
We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2 years of treatment, participants with BMD T-score > − 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value.
Fifty women completed the study. At 48 weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was − 2.98%, 95%CI − 4.75 to − 1.22, P < 0.001, PINP − 2.25%, 95% CI − 4.46 to − 0.032, P = 0.046).
The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment.
KeywordsBisphosphonate Bone density Bone markers Osteoporosis
We are grateful to the data safety monitoring board, the Clinical Trials Research Unit, School of Health and Related Research, for data management and statistical support and the staff of the Academic Unit of Bone Metabolism for conducting the study. We would also like to acknowledge the Lay Advisory Panel for Bone Research and the participants of the study. We acknowledge the support of the NIHR Clinical Research Facility, Northern General Hospital, Sheffield. This work was supported by the South Yorkshire and North Derbyshire Musculoskeletal Biobank, which received ethics approval from NRES REC South Central Oxford C, (REC ref. 15/SC/0132) and is housed in the University of Sheffield Biorepository (HTA Licence no. 12182). The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR.
The TRIO study was funded by Warner-Chilcott, the bone turnover marker measurements were funded by Immunodiagnostics Systems. Professor Richard Eastell (Academic Unit of Bone Metabolism, The University of Sheffield) is a National Institute for Health Research (NIHR) Senior Investigator (Emeritus). The authors approved the manuscript for publication and vouched for the completeness and accuracy of the data. The funder was involved in the design, but not in the conduct, analysis or reporting of the study.
Compliance with ethical standards
Conflict of interest
NP has received speaker’s honoraria and funding to attend educational events from Warner-Chilcott, Eli Lilly, Amgen, GSK and Prostrakan and consultancy fees from Internis Pharma and Eli Lilly. JW has received speaker’s honoraria from Eli Lilly, grant funding from Alexion and Immunodiagnostic Systems, research drug and kits from Eli Lilly, Prostrakan (Kyowa Kirin), Consilient and Biomedica, consulting fees from Shire and Mereo Biopharma. EM has received speaker’s honoraria and/or research funding and/or advisory board funding from Warner-Chilcott, Merck, AgNovos, Amgen, GSK, Bayer, Consilient Healthcare, Hologic, Eli Lilly, Novartis, Pfizer, Radius Pharmaceuticals, Servier, Wyeth, UCB and Roche. RE has received grant funding from Warner-Chilcott and the National Institute for Health Research (NIHR) and consultancy funding from Warner-Chilcott, Roche, Immunodiagnostic Systems and Merck. KN, RJ, MP and FG have nothing to disclose.
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