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

Further Study Details: 

Primary Outcomes: Percent change in bone mineral density of the lumbar spine (lumbar vertebrae 2 to 4) at 18 months.
Secondary Outcomes: 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.
Expected Total Enrollment:  200

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.

Ages Eligible for Study:  18 Years   -   90 Years,  Genders Eligible for Study:  Both

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.

Netherlands
      UMC Utrecht, Utrecht,  3584 CX,  Netherlands

Study chairs or principal investigators

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

Study ID Numbers:  OG67-STOP-study
Last Updated:  August 29, 2005
Record first received:  August 29, 2005
ClinicalTrials.gov Identifier:  NCT00138983
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
ClinicalTrials.gov processed this record on 2005-08-30