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Osteoporosis International

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01-03-2008 | Original Article

Fracture risk remains reduced one year after discontinuation of risedronate

Authors: N. B. Watts, A. Chines, W. P. Olszynski, C. D. McKeever, M. R. McClung, X. Zhou, A. Grauer

Published in: Osteoporosis International | Issue 3/2008

Abstract

Summary

One year after discontinuation of three year’s treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients.

Introduction

Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers—bone mineral density (BMD) and bone turnover markers (BTM)—and fracture risk after discontinuation of treatment with risedronate.

Methods

Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later.

Results

In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p ≤ 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]).

Conclusions

Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

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NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

Felsenberg D, Boonen S (2005) The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1–11PubMedCrossRef

Lindsay R, Boonen S, Burgio D et al (2004) Significant reduction of bone resorption with risedronate treatment in as soon as one week. J Bone Miner Res 19(Suppl. 1):SU434

Borah B, Ritman EL, Dufresne TE et al (2005) The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover. Bone 37:1–9PubMedCrossRef

Dufresne TE, Chmielewski PA, Manhart MD et al (2003) Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography. Calcif Tissue Int 73:423–432PubMedCrossRef

Watts NB, Cooper C, Lindsay R et al (2004) Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 7:255–261PubMedCrossRef

Watts NB, Geusens P, Barton I et al (2005) The relationship between changes in bone mineral density and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in bone mineral density. J Bone Miner Res 20:2097–2104PubMedCrossRef

Eastell R, Barton I, Hannon RA et al (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056PubMedCrossRef

Chapurlat RD, Palermo L, Ramsay P et al (2005) Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial. Osteoporos Int 16:842–848PubMedCrossRef

10.

Watts NB, Magowan S, Brown JP et al (2005) Risedronate demonstrates efficacy to reduce fragility fractures independent of treatment-related BMD changes. J Bone Miner Res 20(Suppl. 1):SA407

11.

Bauer DC, Black DM, Garnero P et al (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258PubMedCrossRef

12.

Roux C, Seeman E, Eastell R et al (2004) Efficacy of risedronate on clinical vertebral fractures within six months. Curr Med Res Opin 20:433–439PubMedCrossRef

13.

Harrington JT, Ste-Marie LG, Brandi ML et al (2004) Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis. Calcif Tiss Int 74:129–135CrossRef

14.

Sorensen OH, Crawford GM, Mulder H et al (2003) Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 32:120–126PubMedCrossRef

15.

Reid IR, Brown JP, Burckhardt P et al (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661PubMedCrossRef

16.

Harris ST, Watts NB, Genant HK et al (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352PubMedCrossRef

17.

Borah B, Dufresne TE, Chmielewski PA et al (2004) Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34:736–746PubMedCrossRef

18.

Sarkar S, Reginster JY, Crans GG et al (2004) Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res 19:394–401PubMedCrossRef

19.

Cummings SR, Karpf DB, Harris F et al (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289PubMedCrossRef

20.

Mellstrom DD, Sorensen OH, Goemaere S et al (2004) Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 75:462–468PubMedCrossRef

21.

Bone HG, Hosking D, Devogelaer J-P et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199PubMedCrossRef

22.

Ensrud KE, Barrett-Connor EL, Schwartz A et al (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 19:1259–1269PubMedCrossRef

23.

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 296:2927–2938PubMedCrossRef

24.

Ruggiero SL, Mehrotra B, Rosenberg TJ et al (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534PubMedCrossRef

25.

Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMed

26.

Odvina CV, Zerwekh JE, Rao DS et al (2005) Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301PubMedCrossRef

27.

Greenspan SL, Emkey RD, Bone HG et al (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:875–883PubMed

28.

Stock JL, Bell NH, Chesnut CH et al (1997) Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women. Am J Med 103:291–297PubMedCrossRef

29.

Colon-Emeric CS (2006) Ten vs. five years of bisphosphonate treatment for postmenopausal osteoporosis: enough of a good thing. JAMA 296:2968–2969PubMedCrossRef

Title: Fracture risk remains reduced one year after discontinuation of risedronate
Authors: N. B. Watts
A. Chines
W. P. Olszynski
C. D. McKeever
M. R. McClung
X. Zhou
A. Grauer
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 3/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-007-0460-7

ACC 2024 Congress

Springer Medicine

Fracture risk remains reduced one year after discontinuation of risedronate

Abstract

Summary

Introduction

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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