Prevention of Glucocorticoid-Induced Osteoporosis in Rheumatic Diseases: Alendronate Versus Alfacalcidol. - Full Text View

Sponsor:	UMC Utrecht
Collaborator:	Dutch Health Care Insurance Board
Information provided by:	UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00138983

Purpose

The purpose of this study is to determine wich treatment is the most effective in prevention of glucocorticoid-induced osteoporosis in patients with rheumatic diseases. The STOP-study: a randomized placebo controlled trial with alendronate versus alfacalcidol.

Condition	Intervention	Phase
Rheumatoid Arthritis Polymyalgia Rheumatica Giant Cell Arteritis Polymyositis Wegener’s Granulomatosis	Drug: Alendronate versus alfacalcidol (1-alpha OH vitamin D)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Prevention
Official Title:	Prevention of Glucocorticoid-Induced Osteoporosis in Patients With Rheumatic Diseases. The STOP-Study: a Randomized Placebo Controlled Trial With Alendronate Versus Alfacalcidol.

Resource links provided by NLM:

Genetics Home Reference related topics: idiopathic inflammatory myopathy

MedlinePlus related topics: Bone Density Giant Cell Arteritis Minerals Osteoporosis Polymyalgia Rheumatica Rheumatoid Arthritis Vitamin D Wegener's Granulomatosis

Drug Information available for: Alfacalcidol Alendronate Alendronate sodium Fosamax Vitamin D

U.S. FDA Resources

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:

Percent change in bone mineral density of the lumbar spine (lumbar vertebrae 2 to 4) at 18 months.

Secondary Outcome Measures:

Percent change in bone mineral density of the femoral neck and total hip at 18 months and incidence of morphometrical vertebral deformities, symptomatic vertebral fractures and non-vertebral fractures.

Estimated Enrollment:	200
Study Start Date:	May 2000
Estimated Study Completion Date:	November 2003

Detailed Description:

Treatment with glucocorticoids (GCs) is associated with bone loss initiated already early in therapy, causing increased (vertebral) fracture risk. Bone loss is caused by inhibition of bone formation by GCs. Active vitamin D analogues like alfacalcidol directly stimulate osteoblasts leading to an increase in bone formation. Bisphosphonates like alendronate induce apoptosis of osteoclasts leading to inhibition of bone resorption.

We performed a randomized, double-placebo, double-blind clinical trial of 18 months duration in patients with a rheumatic disease, starting GCs in a dosage of 7.5 mg prednisone equivalent daily or higher. Two hundred one patients were allocated to receive either alendronate 10 mg and alfacalcidol-placebo daily or alfacalcidol 1 microgram and alendronate-placebo daily. Primary outcome was change in bone mineral density of the lumbar spine in 18 months, secondary outcome incidence of (symptomatic) morphometric vertebral deformities.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with a rheumatic disease.
Starting treatment with glucocorticoids in a dosage of 7.5 mg prednisone equivalent daily or higher.
All ethnic groups and races.

Exclusion Criteria:

Glucocorticoid treatment in the past 12 months (except for 12 weeks preceding the study)
Primary hyperparathyroidism, hyperthyroidism or hypothyroidism in last year
Metabolic bone disease
Creatinine clearance of < 50 ml/min
Documented hypercalcemia or hypercalciuria, nephrolithiasis in the last 5 years
Pregnancy or lactation
Treatment in the last 12 months with hormone-replacement therapy
Anabolic steroids, calcitonin, active vitamin D3 analogues, fluoride or bisphosphonates.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00138983

Locations

Netherlands
UMC Utrecht
Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

UMC Utrecht

Dutch Health Care Insurance Board

Investigators

Principal Investigator:	J.W.J. Bijslma, Prof.	UMC Utrecht
Study Director:	R.N.J.T.L. de Nijs, MD	UMC Utrecht

More Information

Publications:

de Nijs RN, Jacobs JW, Lems WF, Laan RF, Algra A, Huisman AM, Buskens E, de Laet CE, Oostveen AC, Geusens PP, Bruyn GA, Dijkmans BA, Bijlsma JW; STOP Investigators. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med. 2006 Aug 17;355(7):675-84.

Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990 Mar 1;112(5):352-64. Review.

de Nijs RN, Jacobs JW, Algra A, Lems WF, Bijlsma JW. Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D3 analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies. Osteoporos Int. 2004 Aug;15(8):589-602. Epub 2004 May 7. Review.

Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998 Jul 30;339(5):292-9.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Nijs RN, Jacobs JW, Lems WF, Laan RF, Algra A, Huisman AM, Buskens E, de Laet CE, Oostveen JC, Geusens PP, Bruyn GA, Dijkmans BA, Bijlsmat JW. [Alendronate more effective than alfacalcidol in the prevention of osteoporosis in patients with rheumatic disease who are starting glucocorticoid therapy] Ned Tijdschr Geneeskd. 2007 May 26;151(21):1178-85. Dutch.

ClinicalTrials.gov Identifier:	NCT00138983 History of Changes
Other Study ID Numbers:	OG67-STOP-study
Study First Received:	August 29, 2005
Last Updated:	November 28, 2006
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:

glucocorticoid-induced osteoporosis
rheumatic diseases
prevention
randomized double-blind, double placebo controlled trial
alendronate versus alfacalcidol

Additional relevant MeSH terms:

Arteritis
Arthritis
Arthritis, Rheumatoid
Osteoporosis
Polymyalgia Rheumatica
Giant Cell Arteritis
Rheumatic Diseases
Wegener Granulomatosis
Polymyositis
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Joint Diseases
Musculoskeletal Diseases
Connective Tissue Diseases

Autoimmune Diseases
Immune System Diseases
Bone Diseases, Metabolic
Bone Diseases
Muscular Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Lung Diseases, Interstitial
Lung Diseases

ClinicalTrials.gov processed this record on February 13, 2012