Skip to main content
Erschienen in: Osteoporosis International 3/2008

01.03.2008 | Original Article

Fracture risk remains reduced one year after discontinuation of risedronate

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

Erschienen in: Osteoporosis International | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795 NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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, 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMed Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMed
26.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Colon-Emeric CS (2006) Ten vs. five years of bisphosphonate treatment for postmenopausal osteoporosis: enough of a good thing. JAMA 296:2968–2969PubMedCrossRef Colon-Emeric CS (2006) Ten vs. five years of bisphosphonate treatment for postmenopausal osteoporosis: enough of a good thing. JAMA 296:2968–2969PubMedCrossRef
Metadaten
Titel
Fracture risk remains reduced one year after discontinuation of risedronate
verfasst von
N. B. Watts
A. Chines
W. P. Olszynski
C. D. McKeever
M. R. McClung
X. Zhou
A. Grauer
Publikationsdatum
01.03.2008
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 3/2008
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0460-7

Weitere Artikel der Ausgabe 3/2008

Osteoporosis International 3/2008 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.