This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (883)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Rheumatology  • Osteoporosis  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Steven T. Harris, MD; Nelson B. Watts, MD; Harry K. Genant, MD; Clark D. McKeever, MD; Thomas Hangartner, PhD; Michael Keller, MD; Charles H. Chesnut III, MD; Jacques Brown, MD; Erik F. Eriksen, MD; Mohammad S. Hoseyni, PhD; Douglas W. Axelrod, MD, PhD; Paul D. Miller, MD; for the Vertebral Efficacy With Risedronate Therapy (VERT) Study Group

JAMA. 1999;282:1344-1352.

Context  Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis.

Objective  To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998.

Interventions  Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low.

Main Outcome Measures  Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry.

Results  The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41% (95% confidence interval [CI], 18%-58%) over 3 years (11.3% vs 16.3%;P=.003). A fracture reduction of 65% (95% CI, 38%-81%) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61%) (5.2% vs 8.4%; P=.02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1%), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo.

Conclusions  These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.

Author Affiliations: University of California, San Francisco (Drs Harris and Genant); Department of Medicine, Emory University, Atlanta, Ga (Dr Watts); reSearch for Health/Health Advance, Houston, Tex (Dr McKeever); Biomedical Imaging Laboratory, Wright State University, Dayton, Ohio (Dr Hangartner); San Diego Arthritis & Osteoporosis Medical Clinic, San Diego, Calif (Dr Keller); Department of Nuclear Medicine, University of Washington, Seattle (Dr Chesnut); Department of Rheumatology, Hospital Center, Laval University, Ste-Foy, Quebec (Dr Brown); Department of Endocrinology, Aarhus Amtssygehus, Aarhus, Denmark (Dr Eriksen); Procter & Gamble Pharmaceuticals, Cincinnati, Ohio (Drs Hoseyni and Axelrod); and Colorado Center for Bone Research, Lakewood (Dr Miller).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Trends and determinants of prescription medication use for treatment of osteoporosis
Farley and Blalock
Am J Health Syst Pharm 2009;66:1191-1201.
ABSTRACT | FULL TEXT  

Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management
Kennel and Drake
Mayo Clin Proc. 2009;84:632-638.
ABSTRACT | FULL TEXT  

Prediction of Changes in Bone Mineral Density in Postmenopausal Women Treated with Once-Weekly Bisphosphonates
Burnett-Bowie et al.
J. Clin. Endocrinol. Metab. 2009;94:1097-1103.
ABSTRACT | FULL TEXT  

Risk of Severe Gastrointestinal Events in Women Treated with Monthly Ibandronate or Weekly Alendronate and Risedronate
Blumentals et al.
The Annals of Pharmacotherapy 2009;43:577-585.
ABSTRACT | FULL TEXT  

Is Monitoring Osteoporosis Therapy Worthwhile?
Compston
IBMS BoneKEy 2009;6:99-106.
ABSTRACT | FULL TEXT  

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women
Grey et al.
J. Clin. Endocrinol. Metab. 2009;94:538-544.
ABSTRACT | FULL TEXT  

Bisphosphonates and osteonecrosis of the jaw: Innocent association or significant risk?
CAREY and PALOMO
Cleveland Clinic Journal of Medicine 2008;75:871-879.
ABSTRACT | FULL TEXT  

Osteoporosis
Davies
InnovAiT 2008;1:808-812.
ABSTRACT | FULL TEXT  

Mammalian hibernation as a model of disuse osteoporosis: the effects of physical inactivity on bone metabolism, structure, and strength
McGee-Lawrence et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008;295:R1999-R2014.
ABSTRACT | FULL TEXT  

The Role of Bone Biopsy in Patients with Chronic Renal Failure
Miller
CJASN 2008;3:S140-S150.
ABSTRACT | FULL TEXT  

Using biochemical markers of bone turnover in clinical practice
SINGER and EYRE
Cleveland Clinic Journal of Medicine 2008;75:739-750.
ABSTRACT | FULL TEXT  

Prevention, Diagnosis, and Management of Osteoporosis-Related Fracture: A Multifactoral Osteopathic Approach
Gronholz
JAOA: Journal of the American Osteopathic Association 2008;108:575-585.
ABSTRACT | FULL TEXT  

Low Incidence of Anti-Osteoporosis Treatment After Hip Fracture
Rabenda et al.
JBJS 2008;90:2142-2148.
ABSTRACT | FULL TEXT  

Prevention of Anastrozole-Induced Bone Loss with Monthly Oral Ibandronate during Adjuvant Aromatase Inhibitor Therapy for Breast Cancer
Lester et al.
Clin. Cancer Res. 2008;14:6336-6342.
ABSTRACT | FULL TEXT  

Bisphosphonates: Mechanism of Action and Role in Clinical Practice
Drake et al.
Mayo Clin Proc. 2008;83:1032-1045.
ABSTRACT | FULL TEXT  

A Coordinator Program in Post-Fracture Osteoporosis Management Improves Outcomes and Saves Costs
Sander et al.
JBJS 2008;90:1197-1205.
ABSTRACT | FULL TEXT  

Osteoporosis: Management and Treatment Strategies for Orthopaedic Surgeons
Gehrig et al.
JBJS 2008;90:1362-1374.
FULL TEXT  

Randomized Trial of Once-Weekly Parathyroid Hormone (1-84) on Bone Mineral Density and Remodeling
Black et al.
J. Clin. Endocrinol. Metab. 2008;93:2166-2172.
ABSTRACT | FULL TEXT  

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Greenspan et al.
JCO 2008;26:2644-2652.
ABSTRACT | FULL TEXT  

Update on the treatment of post-menopausal osteoporosis
Cole et al.
Br Med Bull 2008;86:129-143.
ABSTRACT | FULL TEXT  

Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate
Papapoulos and Schimmer
Postgrad. Med. J. 2008;84:307-312.
ABSTRACT | FULL TEXT  

Osteoporosis and Its Implications for Dental Patients
Edwards and Migliorati
Journal of the American Dental Association 2008;139:545-552.
ABSTRACT | FULL TEXT  

Clinical Pharmacists' Role in Improving Osteoporosis Treatment Rates Among Elderly Patients with Untreated Atraumatic Fractures
Nadrash et al.
The Annals of Pharmacotherapy 2008;42:334-340.
ABSTRACT | FULL TEXT  

ASHP Therapeutic Position Statement on the Prevention and Treatment of Osteoporosis in Adults
MacLaughlin and Raehl
Am J Health Syst Pharm 2008;65:343-357.
FULL TEXT  

Incidence of Osteonecrosis of the Jaw in Women With Postmenopausal Osteoporosis in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial
Grbic et al.
Journal of the American Dental Association 2008;139:32-40.
ABSTRACT | FULL TEXT  

Long-term Risk of Incident Vertebral Fractures
Cauley et al.
JAMA 2007;298:2761-2767.
ABSTRACT | FULL TEXT  

Telephone Counseling to Improve Osteoporosis Treatment Adherence: An Effectiveness Study in Community Practice Settings
Cook et al.
American Journal of Medical Quality 2007;22:445-456.
ABSTRACT  

Is Radiographic Vertebral Fracture a Risk Factor for Mortality?
Trone et al.
Am J Epidemiol 2007;166:1191-1197.
ABSTRACT | FULL TEXT  

Development and Internal Validation of the Male Osteoporosis Risk Estimation Score
Shepherd et al.
Ann Fam Med 2007;5:540-546.
ABSTRACT | FULL TEXT  

Bisphosphonate Treatment and Fracture Repair
McDonald et al.
IBMS BoneKEy 2007;4:236-251.
ABSTRACT | FULL TEXT  

Yearly zoledronic acid in postmenopausal osteoporosis.
de Nijs et al.
NEJM 2007;357:711-712.
FULL TEXT  

Relationship between Bone Mineral Density Changes and Fracture Risk Reduction in Patients Treated with Strontium Ranelate
Bruyere et al.
J. Clin. Endocrinol. Metab. 2007;92:3076-3081.
ABSTRACT | FULL TEXT  

The role of DXA bone density scans in the diagnosis and treatment of osteoporosis
Blake and Fogelman
Postgrad. Med. J. 2007;83:509-517.
ABSTRACT | FULL TEXT  

Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate
Papapoulos and Schimmer
Ann Rheum Dis 2007;66:853-858.
ABSTRACT | FULL TEXT  

Assessment of non-vertebral fracture risk in postmenopausal women
Roux et al.
Ann Rheum Dis 2007;66:931-935.
ABSTRACT | FULL TEXT  

Review of Postmenopausal Osteoporosis Pharmacotherapy
Mayes
Nutr Clin Pract 2007;22:276-285.
ABSTRACT | FULL TEXT  

Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
Black et al.
NEJM 2007;356:1809-1822.
ABSTRACT | FULL TEXT  

Americans are not meeting current calcium recommendations
Ma et al.
Am. J. Clin. Nutr. 2007;85:1361-1366.
ABSTRACT | FULL TEXT  

Risedronate or Alendronate for the Prevention of Osteoporotic Fractures: Is There a REAL Difference?
Ferrari and Rizzoli
IBMS BoneKEy 2007;4:141-143.
FULL TEXT  

Effect of Monitoring Bone Turnover Markers on Persistence with Risedronate Treatment of Postmenopausal Osteoporosis
Delmas et al.
J. Clin. Endocrinol. Metab. 2007;92:1296-1304.
ABSTRACT | FULL TEXT  

Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease
Sato et al.
Neurology 2007;68:911-915.
ABSTRACT | FULL TEXT  

Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Randomized Trial
Greenspan et al.
ANN INTERN MED 2007;146:326-339.
ABSTRACT | FULL TEXT  

Monitoring Cancer Treatment with PET/CT: Does It Make a Difference?
Weber and Figlin
JNM 2007;48:36S-44S.
ABSTRACT | FULL TEXT  

Effects of Continuing or Stopping Alendronate After 5 Years of Treatment: The Fracture Intervention Trial Long-term Extension (FLEX): A Randomized Trial
Black et al.
JAMA 2006;296:2927-2938.
ABSTRACT | FULL TEXT  

Osteoporosis and its management
Poole and Compston
BMJ 2006;333:1251-1256.
FULL TEXT  

Characterization of patients with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO)
Jakob et al.
QJM 2006;99:531-543.
ABSTRACT | FULL TEXT  

A New Look at Osteoporosis Outcomes: The Influence of Treatment, Compliance, Persistence, and Adherence
Badamgarav and Fitzpatrick
Mayo Clin Proc. 2006;81:1009-1012.
FULL TEXT  

Adherence to Bisphosphonate Therapy and Fracture Rates in Osteoporotic Women: Relationship to Vertebral and Nonvertebral Fractures From 2 US Claims Databases
Siris et al.
Mayo Clin Proc. 2006;81:1013-1022.
ABSTRACT | FULL TEXT  

Clinical practice guidelines for the use of parathyroid hormone in the treatment of osteoporosis.
Hodsman et al.
CMAJ 2006;175:48-48.
FULL TEXT  

Comparison of Weekly Treatment of Postmenopausal Osteoporosis with Alendronate Versus Risedronate Over Two Years
Bonnick et al.
J. Clin. Endocrinol. Metab. 2006;91:2631-2637.
ABSTRACT | FULL TEXT  

The Cost-effectiveness of Therapy With Teriparatide and Alendronate in Women With Severe Osteoporosis.
Liu et al.
Arch Intern Med 2006;166:1209-1217.
ABSTRACT | FULL TEXT  

Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.
Nayak et al.
ANN INTERN MED 2006;144:832-841.
ABSTRACT | FULL TEXT  

Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study
Reginster et al.
Ann Rheum Dis 2006;65:654-661.
ABSTRACT | FULL TEXT  

Cancer-treatment-induced bone loss, part 2
Michaud and Goodin
Am J Health Syst Pharm 2006;63:534-546.
ABSTRACT | FULL TEXT  

Knowledge and Opinions of Orthopaedic Surgeons Concerning Medical Evaluation and Treatment of Patients with Osteoporotic Fracture
Skedros et al.
JBJS 2006;88:18-24.
ABSTRACT | FULL TEXT  

Effective Initiation of Osteoporosis Diagnosis and Treatment for Patients with a Fragility Fracture in an Orthopaedic Environment
Bogoch et al.
JBJS 2006;88:25-34.
ABSTRACT | FULL TEXT  

The prevention of osteoporotic fractures
Karlsson et al.
J Bone Joint Surg Br 2005;87-B:1320-1327.
FULL TEXT  

Alendronate and Vertebral Fracture Risk-Reply-I
Quandt et al.
Mayo Clin Proc. 2005;80:1238-1240.
 

Efficacy and Tolerability of Alendronate Once Weekly in Asian Postmenopausal Osteoporotic Women
Ho and Kung
The Annals of Pharmacotherapy 2005;39:1428-1433.
ABSTRACT | FULL TEXT  

Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate
Cosman et al.
NEJM 2005;353:566-575.
ABSTRACT | FULL TEXT  

Postmenopausal Osteoporosis
Rosen
NEJM 2005;353:595-603.
FULL TEXT  

Risedronate Sodium Therapy for Prevention of Hip Fracture in Men 65 Years or Older After Stroke
Sato et al.
Arch Intern Med 2005;165:1743-1748.
ABSTRACT | FULL TEXT  

Opposite Bone Remodeling Effects of Teriparatide and Alendronate in Increasing Bone Mass
McClung et al.
Arch Intern Med 2005;165:1762-1768.
ABSTRACT | FULL TEXT  

Parathyroid Hormone and Teriparatide for the Treatment of Osteoporosis: A Review of the Evidence and Suggested Guidelines for Its Use
Hodsman et al.
Endocr. Rev. 2005;26:688-703.
ABSTRACT | FULL TEXT  

Strontium ranelate for the treatment of osteoporosis
Fogelman and Blake
BMJ 2005;330:1400-1401.
FULL TEXT  

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study
Reginster et al.
J. Clin. Endocrinol. Metab. 2005;90:2816-2822.
ABSTRACT | FULL TEXT  

Discovery, Clinical Development, and Therapeutic Uses of Bisphosphonates
Licata
The Annals of Pharmacotherapy 2005;39:668-677.
ABSTRACT | FULL TEXT  

The Roles of Bone Mineral Density, Bone Turnover, and Other Properties in Reducing Fracture Risk During Antiresorptive Therapy
Epstein
Mayo Clin Proc. 2005;80:379-388.
ABSTRACT  

Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus
Mok et al.
Lupus 2005;14:106-112.
ABSTRACT  

Association between Screening for Osteoporosis and the Incidence of Hip Fracture
Kern et al.
ANN INTERN MED 2005;142:173-181.
ABSTRACT | FULL TEXT  

Bone Density Screening: A New Level of Evidence?
Cummings
ANN INTERN MED 2005;142:217-219.
FULL TEXT  

Medication Use Patterns for Osteoporosis: An Assessment of Guidelines, Treatment Rates, and Quality Improvement Interventions
Solomon et al.
Mayo Clin Proc. 2005;80:194-202.
ABSTRACT  

Long-Term Therapy of Osteoporosis with Bisphosphonates: Evidence and Implications for Daily Practice
Papapoulos
IBMS BoneKEy 2005;2:13-19.
FULL TEXT  

Extemporaneous Procedures for Dissolving Risedronate Tablets for Oral Administration and for Feeding Tubes
Dansereau and Crail
The Annals of Pharmacotherapy 2005;39:63-67.
ABSTRACT | FULL TEXT  

Recommendations for Optimal Care of the Fragility Fracture Patient to Reduce the Risk of Future Fracture
Bouxsein et al.
J Am Acad Orthop Surg 2004;12:385-395.
ABSTRACT | FULL TEXT  

Medication Undertreatment in Assisted Living Settings
Sloane et al.
Arch Intern Med 2004;164:2031-2037.
ABSTRACT | FULL TEXT  

A Controlled Trial To Increase Detection and Treatment of Osteoporosis in Older Patients with a Wrist Fracture
Majumdar et al.
ANN INTERN MED 2004;141:366-373.
ABSTRACT | FULL TEXT  

Classification Algorithms for Hip Fracture Prediction Based on Recursive Partitioning Methods
Jin et al.
Med Decis Making 2004;24:386-398.
ABSTRACT  

National Trends in Osteoporosis Visits and Osteoporosis Treatment, 1988-2003
Stafford et al.
Arch Intern Med 2004;164:1525-1530.
ABSTRACT | FULL TEXT  

Pharmaceutical treatment of symptomatic vertebral fractures in primary care
Torgerson et al.
Ann Rheum Dis 2004;63:853-856.
ABSTRACT | FULL TEXT  

Osteoporosis Screening: Time to Take Responsibility
Mazanec
Arch Intern Med 2004;164:1047-1048.
FULL TEXT  

Bone Mineral Density Thresholds for Pharmacological Intervention to Prevent Fractures
Siris et al.
Arch Intern Med 2004;164:1108-1112.
ABSTRACT | FULL TEXT  

A Comparison of the Effects of Raloxifene and Conjugated Equine Estrogen on Bone and Lipids in Healthy Postmenopausal Women
Reid et al.
Arch Intern Med 2004;164:871-879.
ABSTRACT | FULL TEXT  

Clinical Considerations in Premenopausal Osteoporosis
Gourlay and Brown
Arch Intern Med 2004;164:603-614.
ABSTRACT | FULL TEXT  

Parathyroid Hormone
Madore et al.
J Am Acad Orthop Surg 2004;12:67-71.
FULL TEXT  

Acute and long-term management of patients with vertebral fractures
Francis et al.
QJM 2004;97:63-74.
ABSTRACT | FULL TEXT  

The patient with a fragility fracture: an evolving role for the orthopaedic surgeon
Schnitzer and Wehren
QJM 2004;97:101-104.
ABSTRACT | FULL TEXT  

Underreporting of Vertebral Fractures on Routine Chest Radiography
Kim et al.
Am. J. Roentgenol. 2004;182:297-300.
ABSTRACT | FULL TEXT  

Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables
Orstavik et al.
Ann Rheum Dis 2004;63:177-182.
ABSTRACT | FULL TEXT  

A randomised controlled trial of standing programme on bone mineral density in non-ambulant children with cerebral palsy
Caulton et al.
Arch. Dis. Child. 2004;89:131-135.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Human Parathyroid Hormone-(1-84) in Increasing Bone Mineral Density in Postmenopausal Osteoporosis
Hodsman et al.
J. Clin. Endocrinol. Metab. 2003;88:5212-5220.
ABSTRACT | FULL TEXT  

Aging Bone and Osteoporosis: Strategies for Preventing Fractures in the Elderly
Ettinger
Arch Intern Med 2003;163:2237-2246.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Oral Weekly Ibandronate in the Treatment of Postmenopausal Osteoporosis
Cooper et al.
J. Clin. Endocrinol. Metab. 2003;88:4609-4615.
ABSTRACT | FULL TEXT  

Effects of Estrogen Plus Progestin on Risk of Fracture and Bone Mineral Density: The Women's Health Initiative Randomized Trial
Cauley et al.
JAMA 2003;290:1729-1738.
ABSTRACT | FULL TEXT  

Painful Osteoporotic Vertebral Fracture: Pathogenesis, Evaluation, and Roles of Vertebroplasty and Kyphoplasty in Its Management
Rao and Singrakhia
JBJS 2003;85:2010-2022.
FULL TEXT  

Management of Postmenopausal Osteoporosis
Murphy et al.
JAOA: Journal of the American Osteopathic Association 2003;103:S6-S11.
ABSTRACT | FULL TEXT  

The Effects of Parathyroid Hormone and Alendronate Alone or in Combination in Postmenopausal Osteoporosis
Black et al.
NEJM 2003;349:1207-1215.
ABSTRACT | FULL TEXT  

Osteoporosis: What a Clinician Expects to Learn from a Patient's Bone Density Examination
Lentle and Prior
Radiology 2003;228:620-628.
ABSTRACT | FULL TEXT