Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study

SUMMARY Objective: To compare the effects of alendronate (ALN) 70mg once weekly (OW) and risedronate (RIS) 5mg 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 GIAEs 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.

[1]  J. Kanis,et al.  Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report , 1994, Osteoporosis International.

[2]  Thomas R. Riley,et al.  A Randomized Double-blind Placebo-controlled Trial , 2004 .

[3]  R. Rizzoli.  Two‐Year Results of Once‐Weekly Administration of Alendronate 70 mg for the Treatment of Postmenopausal Osteoporosis , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  S. Greenspan,et al.  Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study. , 2002, Mayo Clinic proceedings.

[5]  Jacques P. Brown,et al.  The Efficacy and Tolerability of Risedronate Once a week for the Treatment of Postmenopausal Osteoporosis , 2002, Calcified Tissue International.

[6]  R. Josse,et al.  Do bisphosphonates reduce the risk of osteoporotic fractures? An evaluation of the evidence to date. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[7]  T. Schnitzer,et al.  Alendronate Improves Bone Mineral Density in Elderly Women with Osteoporosis Residing in Long-Term Care Facilities , 2002, Annals of Internal Medicine.

[8]  M. Hochberg,et al.  Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. , 2002, The Journal of clinical endocrinology and metabolism.

[9]  Fran Harris,et al.  Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. , 2002, The American journal of medicine.

[10]  M. Hochberg,et al.  Alendronate Reduces the Risk of Multiple Symptomatic Fractures: Results from the Fracture Intervention Trial , 2002, Journal of the American Geriatrics Society.

[11]  P. Geusens,et al.  Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women , 2002, Osteoporosis International.

[12]  C. Cooper,et al.  How to prevent fractures in the individual with osteoporosis. , 2001, Best practice & research. Clinical rheumatology.

[13]  Susan R. Johnson,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2001, JAMA.

[14]  P Geusens,et al.  Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. , 2001, The New England journal of medicine.

[15]  R. Goodman,et al.  The effect of risedronate on the risk of hip fracture in elderly women. , 2001, The New England journal of medicine.

[16]  M. Fukunaga,et al.  Guidelines on the use of biochemical markers of bone turnover in osteoporosis (2001) , 2001, Journal of Bone and Mineral Metabolism.

[17]  D. Graham,et al.  An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae , 2000, American Journal of Gastroenterology.

[18]  S. Cummings,et al.  Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. , 2000, The Journal of clinical endocrinology and metabolism.

[19]  J. Reginster,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. , 2000, The Journal of clinical endocrinology and metabolism.

[20]  D. Kiel,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. , 2000 .

[21]  D. Kiel,et al.  Therapeutic equivalence of alendronate 70 mg onceweekly and alendronate 10 mg daily in the treatment of osteoporosis , 2000, Aging.

[22]  P. Miller,et al.  Antifracture efficacy of antiresorptive agents are related to changes in bone density. , 2000, The Journal of clinical endocrinology and metabolism.

[23]  P. Delmas.  Markers of Bone Turnover for Monitoring Treatment of Osteoporosis with Antiresorptive Drugs , 2000, Osteoporosis International.

[24]  M. Hooper,et al.  Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis , 2000, Osteoporosis International.

[25]  M. Nevitt,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 Trial Research Group. , 1999, Bone.

[26]  H K Genant,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. , 1999, JAMA.

[27]  M. Clay,et al.  The effect of dosing regimen on the pharmacokinetics of risedronate. , 1999, British journal of clinical pharmacology.

[28]  D. Felsenberg,et al.  Alendronate Increases Bone Density and Bone Strength at the Distal Radius in Postmenopausal Women , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  S. Cummings,et al.  Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. , 1999, Arthritis and rheumatism.

[30]  D. Felsenberg,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 , 1999, Osteoporosis International.

[31]  A. LaCroix,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. , 1998, JAMA.

[32]  R. Parker,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 , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  J. Eisman,et al.  Alendronate Prevents Postmenopausal Bone Loss in Women without Osteoporosis: A Double-Blind, Randomized, Controlled Trial , 1998, Annals of Internal Medicine.

[34]  D. Eyre.  Bone biomarkers as tools in osteoporosis management. , 1997, Spine.

[35]  E. Barrett-Connor,et al.  Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial. , 1997, Archives of internal medicine.

[36]  G. Blake,et al.  Interpretation of bone densitometry studies. , 1997, Seminars in nuclear medicine.

[37]  D. Kimmel,et al.  Dose-Response Relationships for Alendronate Treatment in Osteoporotic Elderly Women , 1997 .

[38]  D. Kimmel,et al.  Dose-response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers. , 1997, The Journal of clinical endocrinology and metabolism.

[39]  C. Christiansen,et al.  A 2-Year Phase II Study with 1-Year of Follow-up of Risedronate (NE-58095) in Postmenopausal Osteoporosis , 1997, Osteoporosis International.

[40]  S. Cummings,et al.  Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures , 1996, The Lancet.

[41]  J. Tucci,et al.  Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. , 1996, The American journal of medicine.

[42]  R. Recker,et al.  Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis , 1996 .

[43]  L. Melton,et al.  Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. , 1996, Bone.

[44]  P. Delmas,et al.  Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[45]  C. Cooper,et al.  Epidemiology of osteoporosis. , 2002, Best practice & research. Clinical rheumatology.

[46]  L. Melton,et al.  The worldwide problem of osteoporosis: insights afforded by epidemiology. , 1995, Bone.

[47]  S. Adami,et al.  Long‐term effects of a treatment course with oral alendronate of postmenopausal osteoporosis , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[48]  R. Mazess.  Bone densitometry. , 1986, British medical journal.