Skip to main content
Top
Published in: Osteoporosis International 5/2016

01-05-2016 | Original Article

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday

Authors: L. H. R. Xu, B. Adams-Huet, J. R. Poindexter, N. M. Maalouf

Published in: Osteoporosis International | Issue 5/2016

Login to get access

Abstract

Summary

In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture.

Introduction

A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants.

Methods

Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday.

Results

A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m2. Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday.

Conclusions

BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.
Literature
1.
go back to reference Russell RG, Rogers MJ (1999) Bisphosphonates: from the laboratory to the clinic and back again. Bone 25:97–106CrossRefPubMed Russell RG, Rogers MJ (1999) Bisphosphonates: from the laboratory to the clinic and back again. Bone 25:97–106CrossRefPubMed
2.
go back to reference Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822CrossRefPubMed Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822CrossRefPubMed
3.
go back to reference Reginster J, Minne HW, Sorensen OH et al (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91CrossRefPubMed Reginster J, Minne HW, Sorensen OH et al (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91CrossRefPubMed
4.
go back to reference Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541CrossRefPubMed Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541CrossRefPubMed
5.
go back to reference Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB, Weiler PJ, Laupacis A (2011) Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 305:783–789CrossRefPubMed Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB, Weiler PJ, Laupacis A (2011) Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 305:783–789CrossRefPubMed
6.
go back to reference Armamento-Villareal R, Napoli N, Diemer K, Watkins M, Civitelli R, Teitelbaum S, Novack D (2009) Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series. Calcif Tissue Int 85:37–44CrossRefPubMed Armamento-Villareal R, Napoli N, Diemer K, Watkins M, Civitelli R, Teitelbaum S, Novack D (2009) Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series. Calcif Tissue Int 85:37–44CrossRefPubMed
7.
go back to reference Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg (Br) 89:349–353CrossRef Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg (Br) 89:349–353CrossRef
8.
go back to reference Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301CrossRefPubMed Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301CrossRefPubMed
10.
go back to reference Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555–1565CrossRefPubMed Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555–1565CrossRefPubMed
11.
go back to reference Black DM, Reid IR, Cauley JA et al (2015) The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 30:934–944CrossRefPubMed Black DM, Reid IR, Cauley JA et al (2015) The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 30:934–944CrossRefPubMed
12.
go back to reference Black DM, Reid IR, Boonen S et al (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–254CrossRefPubMedPubMedCentral Black DM, Reid IR, Boonen S et al (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–254CrossRefPubMedPubMedCentral
13.
go back to reference 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
14.
go back to reference Bauer DC, Schwartz A, Palermo L, Cauley J, Hochberg M, Santora A, Cummings SR, Black DM (2014) Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study. JAMA Intern Med 174:1126–1134CrossRefPubMedPubMedCentral Bauer DC, Schwartz A, Palermo L, Cauley J, Hochberg M, Santora A, Cummings SR, Black DM (2014) Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study. JAMA Intern Med 174:1126–1134CrossRefPubMedPubMedCentral
15.
go back to reference Black DM, Schwartz AV, Ensrud KE et al (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 et al (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
16.
go back to reference Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, Grauer A (2008) Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 19:365–372CrossRefPubMed Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, Grauer A (2008) Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 19:365–372CrossRefPubMed
17.
go back to reference Kong SY, Kim DY, Han EJ, Park SY, Yim CH, Kim SH, Yoon HK (2013) Effects of a ‘drug holiday’ on bone mineral density and bone turnover marker during bisphosphonate therapy. J Bone Metab 20:31–35CrossRefPubMedPubMedCentral Kong SY, Kim DY, Han EJ, Park SY, Yim CH, Kim SH, Yoon HK (2013) Effects of a ‘drug holiday’ on bone mineral density and bone turnover marker during bisphosphonate therapy. J Bone Metab 20:31–35CrossRefPubMedPubMedCentral
18.
go back to reference Chiha M, Myers LE, Ball CA, Sinacore JM, Camacho PM (2013) Long-term follow-up of patients on drug holiday from bisphosphonates: real-world setting. Endocr Pract 19:989–994CrossRefPubMed Chiha M, Myers LE, Ball CA, Sinacore JM, Camacho PM (2013) Long-term follow-up of patients on drug holiday from bisphosphonates: real-world setting. Endocr Pract 19:989–994CrossRefPubMed
19.
go back to reference Tower RJ, Campbell GM, Muller M, Gluer CC, Tiwari S (2015) Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo. Bone 74:171–181CrossRefPubMed Tower RJ, Campbell GM, Muller M, Gluer CC, Tiwari S (2015) Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo. Bone 74:171–181CrossRefPubMed
20.
go back to reference Wilsgaard T, Emaus N, Ahmed LA, Grimnes G, Joakimsen RM, Omsland TK, Berntsen GR (2009) Lifestyle impact on lifetime bone loss in women and men: the Tromso Study. Am J Epidemiol 169:877–886CrossRefPubMed Wilsgaard T, Emaus N, Ahmed LA, Grimnes G, Joakimsen RM, Omsland TK, Berntsen GR (2009) Lifestyle impact on lifetime bone loss in women and men: the Tromso Study. Am J Epidemiol 169:877–886CrossRefPubMed
21.
go back to reference Bainbridge KE, Sowers M, Lin X, Harlow SD (2004) Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women. Osteoporos Int 15:439–446CrossRefPubMed Bainbridge KE, Sowers M, Lin X, Harlow SD (2004) Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women. Osteoporos Int 15:439–446CrossRefPubMed
22.
go back to reference Villareal DT, Fontana L, Weiss EP, Racette SB, Steger-May K, Schechtman KB, Klein S, Holloszy JO (2006) Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 166:2502–2510CrossRefPubMed Villareal DT, Fontana L, Weiss EP, Racette SB, Steger-May K, Schechtman KB, Klein S, Holloszy JO (2006) Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 166:2502–2510CrossRefPubMed
23.
go back to reference Jensen LB, Kollerup G, Quaade F, Sorensen OH (2001) Bone minerals changes in obese women during a moderate weight loss with and without calcium supplementation. J Bone Miner Res 16:141–147CrossRefPubMed Jensen LB, Kollerup G, Quaade F, Sorensen OH (2001) Bone minerals changes in obese women during a moderate weight loss with and without calcium supplementation. J Bone Miner Res 16:141–147CrossRefPubMed
24.
go back to reference Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH (2006) Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38:617–627CrossRefPubMed Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH (2006) Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38:617–627CrossRefPubMed
Metadata
Title
Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday
Authors
L. H. R. Xu
B. Adams-Huet
J. R. Poindexter
N. M. Maalouf
Publication date
01-05-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 5/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3447-9

Other articles of this Issue 5/2016

Osteoporosis International 5/2016 Go to the issue