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  • Related letters  • Related articles  • Similar articles in JAMA  Topic Collections  • Rheumatology  • Osteoporosis  • Alert me on articles by topic  Social Bookmarking   What's this?

Results From the Fracture Intervention Trial

Steven R. Cummings, MD; Dennis M. Black, PhD; Desmond E. Thompson, PhD; William B. Applegate, MD; Elizabeth Barrett-Connor, MD; Thomas A. Musliner, MD; Lisa Palermo, MA; Ronald Prineas, MD; Susan M. Rubin, MA; Jean C. Scott, PhD; Thomas Vogt, MD, MPH; Robert Wallace, MD; A. John Yates, MD; Andrea Z. LaCroix, PhD; for the Fracture Intervention Trial Research Group

JAMA. 1998;280:2077-2082.

Context.— Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures.

Objective.— To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures.

Design.— Randomized, blinded, placebo-controlled trial.

Setting.— Eleven community-based clinical research centers.

Subjects.— Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm² or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).

Intervention.— All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.

Main Outcome Measures.— Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry.

Results.— Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects.

Conclusions.— In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

From the Departments of Epidemiology and Biostatistics (Drs Cummings and Black and Mss Palermo and Rubin) and Medicine (Dr Cummings), University of California, San Francisco; Merck Research Laboratories, Rahway, NJ (Drs Thompson, Musliner, and Yates); Department of Preventive Medicine, University of Tennessee, Memphis (Dr Applegate); University of California, San Diego (Dr Barrett-Connor); University of Miami, Miami, Fla (Dr Prineas); University of Maryland, Baltimore (Dr Scott); Cancer Research Center of Hawaii, Honolulu (Dr Vogt); Department of Preventive Medicine, University of Iowa, Iowa City (Dr Wallace); and the Center for Health Studies, Group Health Cooperative, Seattle, Wash (Dr LaCroix).

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

RELATED LETTERS

Alendronate and Fracture Prevention
Atle Klovning, Ole Frithjof Norheim, and Steven R. Cummings
JAMA. 1999;282(3):231.
EXTRACT | FULL TEXT  

Use of Alendronate After 5 Years of Treatment
Pierre D. Delmas
JAMA. 2007;297(18):1979-1980.
EXTRACT | FULL TEXT  

Use of Alendronate After 5 Years of Treatment—Reply
Dennis M. Black, Ann V. Schwartz, Steven R. Cummings, Jane A. Cauley, and Lisa Palermo
JAMA. 2007;297(18):1980-1981.
EXTRACT | FULL TEXT  

RELATED ARTICLES

Bone Mass, Bone Fragility, and the Decision to Treat
Robert P. Heaney
JAMA. 1998;280(24):2119-2120.
EXTRACT | FULL TEXT  

December 23/30, 1998
JAMA. 1998;280(24):2185-2186.
EXTRACT | FULL TEXT  

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  

Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data
Bell et al.
BMJ 2009;338:b2266-b2266.
ABSTRACT | FULL TEXT  

Women over 75 with fragility fractures should have DEXA
Ralston et al.
BMJ 2009;338:b2340-b2340.
FULL TEXT  

Success with Men's Educational Group Appointments (MEGA): Subjective Improvements in Patient Education
Campbell et al.
Am J Mens Health 2009;3:173-178.
ABSTRACT  

Breast cancer in young women and its impact on reproductive function
Hickey et al.
Hum Reprod Update 2009;15:323-339.
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  

A Markov Model Simulation of the Impact of Treatment Persistence in Postmenopausal Osteoporosis
Cotte et al.
Med Decis Making 2009;29:125-139.
ABSTRACT  

Osteoporosis Primer for the Vertebroplasty Practitioner: Expanding the Focus Beyond Needles and Cement
Kearns and Kallmes
Am. J. Neuroradiol. 2008;29:1816-1822.
ABSTRACT | FULL TEXT  

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

The effect of alendronate on progression of spinal osteophytes and disc-space narrowing
Neogi et al.
Ann Rheum Dis 2008;67:1427-1430.
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  

The Effect of Raloxifene Treatment in Postmenopausal Women with CKD
Ishani et al.
J. Am. Soc. Nephrol. 2008;19:1430-1438.
FULL TEXT  

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

Use of Alendronate and Risk of Incident Atrial Fibrillation in Women
Heckbert et al.
Arch Intern Med 2008;168:826-831.
ABSTRACT | FULL TEXT  

The U.S. National Osteoporosis Foundation (NOF) Guidelines: Recommendations for Pharmacologic Treatment
Cummings et al.
IBMS BoneKEy 2008;5:137-141.
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  

Shifting the focus in fracture prevention from osteoporosis to falls
Jarvinen et al.
BMJ 2008;336:124-126.
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  

Characteristics of males over 50 years who present with a fracture: EPIDEMIOLOGY AND UNDERLYING RISK FACTORS
Sharma et al.
J Bone Joint Surg Br 2008;90-B:72-77.
ABSTRACT | FULL TEXT  

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

Mechanism of Action, Pharmacokinetic and Pharmacodynamic Profile, and Clinical Applications of Nitrogen-containing Bisphosphonates
Kimmel
JDR 2007;86:1022-1033.
ABSTRACT | FULL TEXT  

Implications Of Expanding Disease Definitions: The Case Of Osteoporosis
Herndon et al.
Health Aff (Millwood) 2007;26:1702-1711.
ABSTRACT | FULL TEXT  

Prolonged Efficacy of a Single Dose of the Bisphosphonate Zoledronic Acid
Brown et al.
Clin. Cancer Res. 2007;13:5406-5410.
ABSTRACT | FULL TEXT  

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

The Effects of Combination of Alendronate and Human Parathyroid Hormone(1 34) on Bone Strength Are Synergistic in the Lumbar Vertebra and Additive in the Femur of C57BL/6J Mice
Johnston et al.
Endocrinology 2007;148:4466-4474.
ABSTRACT | FULL TEXT  

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

Cost-effectiveness of Bone Densitometry Followed by Treatment of Osteoporosis in Older Men
Schousboe et al.
JAMA 2007;298:629-637.
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  

Patient Assessment in the Diagnosis, Prevention, and Treatment of Osteoporosis
Lata and Elliott
Nutr Clin Pract 2007;22:261-275.
ABSTRACT | FULL TEXT  

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

Osteopenia
Khosla and Melton
NEJM 2007;356:2293-2300.
FULL TEXT  

Use of Alendronate After 5 Years of Treatment--Reply
Black et al.
JAMA 2007;297:1980-1981.
FULL TEXT  

Use of Alendronate After 5 Years of Treatment
Delmas
JAMA 2007;297:1979-1980.
FULL TEXT  

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

Alendronate and Atrial Fibrillation
Cummings et al.
NEJM 2007;356:1895-1896.
FULL TEXT  

The management of subcapital fractures in the elderly with an emphasis on economic aspects
Chaudhry
Trauma 2007;9:119-126.
ABSTRACT  

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  

Bisphosphonate Therapy: To Stop or Not to Stop?
McClung
IBMS BoneKEy 2007;4:78-82.
FULL TEXT  

Validation of a 4-Item Score Predicting Hip Fracture and Mortality Risk Among Elderly Women
Albertsson et al.
Ann Fam Med 2007;5:48-56.
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  

Ten vs Five Years of Bisphosphonate Treatment for Postmenopausal Osteoporosis: Enough of a Good Thing
Colon-Emeric
JAMA 2006;296:2968-2969.
FULL TEXT  

A 55-Year-Old Woman With Osteopenia
Cummings
JAMA 2006;296:2601-2610.
ABSTRACT | FULL TEXT  

Commentary: Statins and fracture--why the confusion?
Edwards and Arden
Int J Epidemiol 2006;35:1312-1313.
FULL TEXT  

A simple clinical score for estimating the long-term risk of fracture in post-menopausal women
van Staa et al.
QJM 2006;99:673-682.
ABSTRACT | FULL TEXT  

The Effect of Parathyroidectomy on Bone Fracture Risk in Patients With Primary Hyperparathyroidism
VanderWalde et al.
Arch Surg 2006;141:885-891.
ABSTRACT | FULL TEXT  

Preventing fragility hip fracture in high risk groups: an opportunity missed.
Peng et al.
Postgrad. Med. J. 2006;82:528-531.
ABSTRACT | 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  

HRT, osteoporosis and regulatory authorities Quis custodiet ipsos custodes?
Stevenson and on behalf of the International Consensus Group on
Hum Reprod 2006;21:1668-1671.
ABSTRACT | FULL TEXT  

How Can Osteoporosis Patients Benefit More from Their Therapy? Adherence Issues with Bisphosphonate Therapy
Gold et al.
The Annals of Pharmacotherapy 2006;40:1143-1150.
ABSTRACT | FULL TEXT  

Effects of Calcium Supplementation on Clinical Fracture and Bone Structure: Results of a 5-Year, Double-blind, Placebo-Controlled Trial in Elderly Women.
Prince et al.
Arch Intern Med 2006;166:869-875.
ABSTRACT | FULL TEXT  

The DXL Calscan heel densitometer: evaluation and diagnostic thresholds.
Thorpe and Steel
Br. J. Radiol. 2006;79:336-341.
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  

Cost-Effectiveness of Osteoporosis Screening and Treatment with Hormone Replacement Therapy, Raloxifene, or Alendronate
Mobley et al.
Med Decis Making 2006;26:194-206.
ABSTRACT  

Bone loss after stroke over 52 weeks at os calcis: influence of sex, mobility and relation to bone density at other sites
Bainbridge et al.
Age Ageing 2006;35:127-132.
ABSTRACT | FULL TEXT  

The Effect of Raloxifene after Discontinuation of Long-Term Alendronate Treatment of Postmenopausal Osteoporosis
Michalska et al.
J. Clin. Endocrinol. Metab. 2006;91:870-877.
ABSTRACT | FULL TEXT  

Three-Year Changes in Bone Mineral Density Around the Knee After a Six-Month Course of Oral Alendronate Following Total Knee Arthroplasty. A Prospective, Randomized Study
Wang et al.
JBJS 2006;88:267-272.
ABSTRACT | FULL TEXT  

Intervertebral disc height in treated and untreated overweight post-menopausal women
Baron et al.
Hum Reprod 2005;20:3566-3570.
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  

One Year of Alendronate after One Year of Parathyroid Hormone (1-84) for Osteoporosis
Black et al.
NEJM 2005;353:555-565.
ABSTRACT | FULL TEXT  

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

Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal Women
Schousboe et al.
ANN INTERN MED 2005;142:734-741.
ABSTRACT | FULL TEXT  

Osteopenia: To Treat or Not To Treat?
McClung
ANN INTERN MED 2005;142:796-7.
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  

Hip Fracture in Women without Osteoporosis
Wainwright et al.
J. Clin. Endocrinol. Metab. 2005;90:2787-2793.
ABSTRACT | FULL TEXT  

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

Effect of Folate and Mecobalamin on Hip Fractures in Patients With Stroke: A Randomized Controlled Trial
Sato et al.
JAMA 2005;293:1082-1088.
ABSTRACT | FULL TEXT  

Effect of Alendronate on Vertebral Fracture Risk in Women With Bone Mineral Density T Scores of -1.6 to -2.5 at the Femoral Neck: The Fracture Intervention Trial
Quandt et al.
Mayo Clin Proc. 2005;80:343-349.
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  

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

Interventions to Improve Osteoporosis Treatment Following Hip Fracture. A Prospective, Randomized Trial
Gardner et al.
JBJS 2005;87:3-7.
ABSTRACT | FULL TEXT  

Diagnosis of Osteoporotic Vertebral Fractures: Importance of Recognition and Description by Radiologists
Lenchik et al.
Am. J. Roentgenol. 2004;183:949-958.
FULL TEXT  

Nutrition and Physical Activity and Chronic Disease Prevention: Research Strategies and Recommendations
Prentice et al.
JNCI J Natl Cancer Inst 2004;96:1276-1287.
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  

Randomized controlled trial of alendronate in airways disease and low bone mineral density
Smith et al.
Chronic Respiratory Disease 2004;1:131-137.
ABSTRACT  

Prevalence of Prevention and Treatment Modalities Used in Populations at Risk of Osteoporosis
Rohr et al.
JAOA: Journal of the American Osteopathic Association 2004;104:281-287.
ABSTRACT | FULL TEXT  

Effect of Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Type 2 Diabetic Women: The Fracture Intervention Trial
Keegan et al.
Diabetes Care 2004;27:1547-1553.
ABSTRACT | 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  

Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal Women
Bone et al.
NEJM 2004;350:1189-1199.
ABSTRACT | FULL TEXT  

Principles of Diagnosing and Managing Postmenopausal Osteoporosis for the Podiatric Physician
McGarry and Cyr
J. Am. Podiatr. Med. Assoc. 2004;94:187-193.
ABSTRACT | FULL TEXT  

Time for (More Research on) Testosterone
Barrett-Connor and Bhasin
J. Clin. Endocrinol. Metab. 2004;89:501-502.
FULL TEXT  

An Investigation of the Predictors of Bone Mineral Density and Response to Therapy with Alendronate in Osteoporotic Men
Drake et al.
J. Clin. Endocrinol. Metab. 2003;88:5759-5765.
ABSTRACT | FULL TEXT  

Patient Self-Referral for Radiologic Screening Tests: Clinical and Ethical Concerns
Fenton and Deyo
J Am Board Fam Med 2003;16:494-501.
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  

The Effect of Alendronate on Bone Mineral Density in the Distal Part of the Femur and Proximal Part of the Tibia After Total Knee Arthroplasty
Wang et al.
JBJS 2003;85:2121-2126.
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