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Erschienen in: Osteoporosis International 4/2019

06.01.2019 | Short Scientific Communication

Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis

verfasst von: K.E. Naylor, E.V. McCloskey, R.M. Jacques, N.F.A. Peel, M.A. Paggiosi, F. Gossiel, J.S. Walsh, R. Eastell

Erschienen in: Osteoporosis International | Ausgabe 4/2019

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Abstract

Summary

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.

Introduction

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).

Methods

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.

Results

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).

Conclusion

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.
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Literatur
1.
2.
3.
Zurück zum Zitat Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM, for the Fracture Intervention Trial Long-Term Extension Research Group (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the fracture intervention trial long-term extension. JBone MinerRes 19:1259–1269CrossRef Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM, for the Fracture Intervention Trial Long-Term Extension Research Group (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the fracture intervention trial long-term extension. JBone MinerRes 19:1259–1269CrossRef
4.
Zurück zum Zitat Papapoulos SE, Cremers SC (2007) Prolonged bisphosphonate release after treatment in children. N Engl J Med 356:1075–1076CrossRefPubMed Papapoulos SE, Cremers SC (2007) Prolonged bisphosphonate release after treatment in children. N Engl J Med 356:1075–1076CrossRefPubMed
5.
Zurück zum Zitat Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMed Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMed
6.
Zurück zum Zitat Chubb SAP, Vasikaran SD (2017) Measurement and clinical utility of betaCTX in serum and plasma. Adv Clin Chem 81:97–134CrossRefPubMed Chubb SAP, Vasikaran SD (2017) Measurement and clinical utility of betaCTX in serum and plasma. Adv Clin Chem 81:97–134CrossRefPubMed
7.
Zurück zum Zitat Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420CrossRefPubMed Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420CrossRefPubMed
8.
Zurück zum Zitat Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. ClinChemLab Med 49:1271–1274 Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. ClinChemLab Med 49:1271–1274
9.
Zurück zum Zitat Diez-Perez A, Naylor KE, Abrahamsen B et al (2017) International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int 28:767–774CrossRefPubMedPubMedCentral Diez-Perez A, Naylor KE, Abrahamsen B et al (2017) International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int 28:767–774CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR, FLEX Research Group (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRefPubMed Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR, FLEX Research Group (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRefPubMed
11.
Zurück zum Zitat Eastell R, Hannon RA, Wenderoth D, Rodriguez-Moreno J, Sawicki A (2011) Effect of stopping risedronate after long-term treatment on bone turnover. J Clin Endocrinol Metab 96:3367–3373CrossRefPubMedPubMedCentral Eastell R, Hannon RA, Wenderoth D, Rodriguez-Moreno J, Sawicki A (2011) Effect of stopping risedronate after long-term treatment on bone turnover. J Clin Endocrinol Metab 96:3367–3373CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Paggiosi MA, Peel N, McCloskey E, Walsh JS, Eastell R (2014) Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 25:2729–2741CrossRefPubMed Paggiosi MA, Peel N, McCloskey E, Walsh JS, Eastell R (2014) Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 25:2729–2741CrossRefPubMed
13.
Zurück zum Zitat Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV, Walsh JS, Eastell R (2016) Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 27:21–31CrossRefPubMed Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV, Walsh JS, Eastell R (2016) Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 27:21–31CrossRefPubMed
14.
Zurück zum Zitat Naylor KE, Bradburn M, Paggiosi MA, Gossiel F, Peel NFA, McCloskey EV, Walsh JS, Eastell R (2018) Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density. Osteoporos Int 29:1407–1417CrossRefPubMed Naylor KE, Bradburn M, Paggiosi MA, Gossiel F, Peel NFA, McCloskey EV, Walsh JS, Eastell R (2018) Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density. Osteoporos Int 29:1407–1417CrossRefPubMed
15.
Zurück zum Zitat Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET, National Bone Health Alliance Bone Turnover Marker P (2017) Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 28:2541–2556CrossRefPubMed Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET, National Bone Health Alliance Bone Turnover Marker P (2017) Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 28:2541–2556CrossRefPubMed
16.
Zurück zum Zitat Morris HA, Eastell R, Jorgensen NR, Cavalier E, Vasikaran S, Chubb SAP, Kanis JA, Cooper C, Makris K, Assays I-IWGfSoBM (2017) Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin Chim Acta 467:34–41CrossRefPubMed Morris HA, Eastell R, Jorgensen NR, Cavalier E, Vasikaran S, Chubb SAP, Kanis JA, Cooper C, Makris K, Assays I-IWGfSoBM (2017) Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin Chim Acta 467:34–41CrossRefPubMed
17.
Zurück zum Zitat Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, Reid IR, Resch H, Siris E, Uebelhart D, Wang A, Weryha G, Cummings SR (2011) Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. JBone MinerRes 26:530–537CrossRef Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, Reid IR, Resch H, Siris E, Uebelhart D, Wang A, Weryha G, Cummings SR (2011) Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. JBone MinerRes 26:530–537CrossRef
18.
Zurück zum Zitat Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San MJ (2008) Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43:222–229CrossRefPubMed Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San MJ (2008) Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43:222–229CrossRefPubMed
19.
Zurück zum Zitat Jorgensen NR, Mollehave LT, Hansen YBL, Quardon N, Lylloff L, Linneberg A (2017) Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population. Osteoporos Int 28:2103–2113CrossRefPubMed Jorgensen NR, Mollehave LT, Hansen YBL, Quardon N, Lylloff L, Linneberg A (2017) Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population. Osteoporos Int 28:2103–2113CrossRefPubMed
20.
Zurück zum Zitat Silverman SL, Schousboe JT, Gold DT (2011) Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int 22:21–26CrossRefPubMed Silverman SL, Schousboe JT, Gold DT (2011) Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int 22:21–26CrossRefPubMed
Metadaten
Titel
Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis
verfasst von
K.E. Naylor
E.V. McCloskey
R.M. Jacques
N.F.A. Peel
M.A. Paggiosi
F. Gossiel
J.S. Walsh
R. Eastell
Publikationsdatum
06.01.2019
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 4/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-04823-5

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