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

Rheumatoid Arthritis Clinical Trial

Official title:

Prevention of Glucocorticoid-Induced Osteoporosis in Patients With Rheumatic Diseases. The STOP-Study: a Randomized Placebo Controlled Trial With Alendronate Versus Alfacalcidol.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00138983
• Other study ID #: OG67-STOP-study
• Status: Completed
• Phase: Phase 3
• First received: August 29, 2005
• Last updated: November 28, 2006
• Start date: May 2000
• Est. completion date: November 2003

Study information

• Verified date: March 2000
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: November 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Giant Cell Arteritis
• Osteoporosis
• Polymyalgia Rheumatica
• Polymyositis
• Rheumatic Diseases
• Rheumatoid Arthritis
• Wegener Granulomatosis
• Wegener’s Granulomatosis

Intervention

Drug:
• Alendronate versus alfacalcidol (1-alpha OH vitamin D)

Locations

Country	Name	City	State
Netherlands	UMC Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Dutch Health Care Insurance Board

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

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. — View Citation

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 — View Citation

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in bone mineral density of the lumbar spine (lumbar vertebrae 2 to 4) at 18 months.
Secondary	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.