Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study
Hosking, D.; Adami, S.; Felsenberg, D.et al.
2003 • In Current Medical Research and Opinion, 19 (5), p. 383-394
alendronate; biochemical markers of bone resorption; bone mineral density; comparability; efficacy; osteoporosis; risedronate
Abstract :
[en] Objective: To compare the effects of alendronate (ALN) 70 mg once weekly (OW) and risedronate (RIS) 5 mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density (BMD) in postmenopausal women with osteoporosis. Research design and methods: This was a 3-month, randomised, double-blind, placebo-controlled study with a double-blind extension to 12 months. The study enrolled 549 postmenopausal women (ALN 219, RIS 222 and placebo (PBO) 108) who were : 60 years of age at outpatient centres. Main outcome measures: The primary endpoint was reduction in urine N-telopeptides of type 1 collagen (NTx) corrected for creatinine level at 3 months. Secondary parameters included change in BMD at the spine and hip at 6 and 12 months, NTx at 1, 6 and 12 months, and serum bone-specific alkaline phosphatase (BSAP) at 1, 3, 6 and 12 months. Adverse experiences (AEs) were recorded throughout the study for an assessment of treatment safety profiles and tolerability. Results: Over 3 months, ALN produced a significantly greater mean reduction in urine NTx than did RIS (-52% vs -32%, p < 0.001), which was maintained at 12 months. ALN produced a significantly greater mean BMD increase than did RIS at 6 months, and it was maintained at 12 months at the lumbar spine (4.8% vs 2.8%, p < 0.001) and total hip (2.7% vs 0.9%, p < 0.001), as well as at the trochanter and femoral neck. Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment. Study size did not allow for meaningful assessment of differences in fracture rates. Tolerability was generally similar between ALN, RIS and PBO, and the incidence of upper GI AEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups. Conclusion: In this study, ALN 70 mg OW produced a 50% greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily. The treatments had similar safety profiles and were generally well-tolerated. Additional studies are needed comparing OW ALN with OW RIS, which became available after the commencement of the present study.
Disciplines :
General & internal medicine Laboratory medicine & medical technology
Author, co-author :
Hosking, D.
Adami, S.
Felsenberg, D.
Andia, J. C.
Valimaki, M.
Benhamou, L.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Yacik, C.
Rybak-Feglin, A.
Petruschke, R. A.
Zaru, L.
Santora, A. C.
Language :
English
Title :
Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study
World Health Organization. Aging and osteoporosis: World Health Day, Geneva, Switzerland, April 7, 1999 [Online]. Available from http://www.who.imt/archives/whday/en/documents1999/osteo.html: [Accessed July 26, 2002]
National Institute of Health. Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement 2000;17:1-45
Riggs BL, Melton LJ, III. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 1995;7(5 Suppl):505S-511S
Walker-Bone K, Dennison E, Cooper C. Epidemiology of osteoporosis. Rheum Dis Clin North Am 2001;27:1-18
World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Tech Rep Ser 1994. Geneva: World Health Organization
Javaid MK, Cooper C. How to prevent fractures in the individual with osteoporosis. Best Pract Res Clin Rheumatol 2001;15:497-515
National Osteoporosis Foundation (NOF). Physician's Guide to Prevention and Treatment of Osteoporosis [Online]. Available from www.nof.org//physguide/risk_assessment.htm: [Accessed July 26, 2002]
Hodsman AB, Hanley DA, Josse R. Do bisphosphonates reduce the risk of osteoporotic fractures? An evaluation of the evidence to date. CMAJ 2002;166:1426-30
Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in post-menopausal osteoporosis. N Engl J Med 1995;333:1437-43
Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996;348:1535-41
Ensrud KE, Black DM, Palermo, et al. Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial. Arch Intern Med 1997;157:2617-24
Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998;280:2077-82
Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with post-menopausal osteoporosis. Fracture Intervention Trial Research Group. Arthritis Rheum 1999;42:1246-54
Pols HAP, Felsenberg D, Hanley DA, et al. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporosis Int 1999;9:461-8
Nevitt MC, Ross PD, Palermo L, et al. Association of prevalent vertebral fractures, bone density, and alendronate treatment with incident vertebral fractures: effect of number and spinal location of fractures. The Fracture Intervention Research Trial Group. Bone 1999;25:613-19
Black DM, Thompson DE, Bauer DC, et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 2000;85:4118-24
Levis S, Quandt SA, Thompson D, et al. Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention trial. J Am Geriatr Soc 2002;50:409-15
Clemmesen B, Ravn P, Zegels B, et al. A 2-year phase II study with I-year follow-up of risedronate (NE-58095) in postmenopausal osteoporosis. Osteoporosis Int 1997;7:488-95
Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporosis Int 2000;11:83-91
Harris ST, Watts NB, Genant HK, et al. 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 1999;282:1344-52
Heaney RP, Zizic TM, Fogelman I, et al. Risedronate reduces the risk of first vertebral fracture in osteoporotic women. Osteoporosis Int 2002;13:501-5
McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001;344:333-40
Riggs BL, Melton LJ III, O'Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone 1996;18(Suppl 3):197S-201S
Greenspan SL, Parker RA, Ferguson L, et al. Early changes in biochemical markers of bone turnover predict the long term response to alendronate therapy in representative elderly women: a randomized clinical trial. J Bone Miner Res 1998;13:1431-8
Delmas PD. Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs. Osteoporosis Int 2000;11(Suppl 6):S66-S76
Maricic M, Chen Z. Bone densitometry. Clin Lab Med 2000;20:469-88
Schneider PF, Fischer M, Allolio B, et al. Alendronate increases bone density and bone strength at the distal radius in post-menopausal women. J Bone Miner Res 1999;14:1387-93
McClung M, Clemmesen B, Daifotis A, et al. Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group. Ann Intern Med 1998;128:253-61
Downs RW Jr, Bone HG, McIlwain H, et al. An open-label extension study of alendronate treatment in elderly women with osteoporosis. Calcif Tissue Int 1999;64:463-9
Bone HG, Downs RW Jr, Tucci JR, et al. Dose-response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers. J Clin Endocrinol Metab 1997;82:265-74
Rossini M, Gatti D, Zamberlan D, et al. Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Min Res 1994;9:1833-7
Fogelman I, Ribot C, Smith R, et al. Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group. J Clin Endocrinol Metab 2000;85:1895-900
Schnitzer T, Bone HG, Crepaldi G, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. Aging (Milano) 2000;12:1-12
The Alendronate Once-weekly Study Group. Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. J Bone Miner Res 2002;17:1988-96
Risedronate Prescribing Information. Physician's Desk. Reference 55th Edition. Montvale, NJ; Medical Economics Company Inc. 2001:2664-9
Mitchell DV, Heise MA, Pallone DA, et al. The effect of dosing regimen on the pharmacokinetics of risedronate. Br J Clin Pharmacol 1999;48:536-42
Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996;11:337-49
Eyre DR. Bone biomarkers as tools in osteoporosis management. Spine 1997;22(Suppl 24):17S-24S
Nishizawa Y, Nakamura T, Ohata H, et al. Guidelines on the use of biochemical markers of bone turnover in osteoporosis (2001). J Bone Miner Metab 2001;19:338-44
Tucci JR, Tonino RP, Emkey RD, et al. Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. Am J Med 1996;101:488-501
Lanza F, Schwartz H, Sahba B, et al. An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae. Am J Gastroenterol 2000;95:3112-17
Brown JD, Kendler DL, McClung MR, et al. The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 2002;71:103-11
Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000;85:231-6
Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with anti-resorptive agents. J Clin Endocrinol Metab 2002;87:1586-92
Cummings SR, Karpf DB, Harris F, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002;112:281-9
Blake GM, Fogelman I. Interpretation of bone densitometry studies. Semin Nucl Med 1997;27:248-60
Brown, JP, Kendler DL, McClung MR, et al. The efficacy and tolerability of risedronate once a week for the treatment of post-menopausal osteoporosis. Calcif Tissue Int 2002;71:103-11
Greenspan SL, Schneider DL, McClung MR, et al. Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002;136:742-6
Greenspan S, Field-Munves E, Tonino R, Smith M, Petruschke R, Wang L, Yates J, de Papp AE, Palmisano J. Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study. Mayo Clin Proc 2002;77:1044-52
