Effect of Risedronate on Bone Morbidity in Fibrous Dysplasia of Bone (PROFIDYS)

• Intensity of bone pain, assessed by visual analogical scale ranging from 0 to 10, on the most painful site. [ Time Frame: one year ] [ Designated as safety issue: No ]
• Surface of osteolytic lesions at three years. Radiological improvement. [ Time Frame: Three years ] [ Designated as safety issue: No ]

• Bone pain at one year
• Surface of osteolytic lesions at three years

• Variation of biochemical markers of bone turnover at three years [ Time Frame: three years ] [ Designated as safety issue: No ]
• Number of painful sites [ Time Frame: one year ] [ Designated as safety issue: No ]
• Improvement in quality of life [ Time Frame: one to three years ] [ Designated as safety issue: No ]
• Variation in bone mineral density of the femoral neck at three years [ Time Frame: three years ] [ Designated as safety issue: No ]

• Variation of biochemical markers of bone turnover at three years
• Number of painful sites at one year
• Improvement in quality of life
• Variation in bone mineral density of the femoral neck at three years

This trial is intended to test the efficacy of an oral bisphosphonate (risedronate) to decrease bone pain and improve radiological aspect in fibrous dysplasia of bone.

In open pilot studies, it has been suggested that bisphosphonates may alleviate bone pain and help decrease the surface of osteolytic lesion in patients with fibrous dysplasia of bone (FD). So, in this randomized placebo controlled trial, we test the hypothesis that the bisphosphonate risedronate reduces bone pain in patients with FD (study I, one year duration) and decrease osteolytic lesions (study II, three years duration). Patients will take risedronate during 2 months courses, every 6 months or a matching placebo. Dosage will be : 30mg tablet/day for adults and 5mg tablet x 2,4 according to the age and weight of the child. All participants will receive calcium and vitamin D. All patients with renal phosphate wasting will receive an oral phosphate supplement.

• Drug: risedronate
  During two months courses, every 6 months : 30mg tablet/day for adults and 10mg/day or 20mg/day for children, according to the age and weight of the child.
• Drug: placebo
  placebo and risedronate have exactly the same aspect. During two months courses, every 6 months : 30mg tablet/day for adults and 10mg/day or 20mg/day for children, according to the age and weight of the child.

• Experimental: 1
  treatment duration: 1 year
  Intervention: Drug: risedronate
• Placebo Comparator: 2
  treatment duration: 1 year
  Intervention: Drug: placebo
• Experimental: 3
  duration treatment: 3 years
  Intervention: Drug: risedronate
• Placebo Comparator: 4
  treatment duration: 3 years
  Intervention: Drug: placebo

Inclusion Criteria:

• Study I: patients with FD, with bone pain intensity above 3 on visual analogical scale from 0 to 10
• Study II: patients with FD with at least one osteolytic lesion and no current bone pain

Exclusion Criteria:

• patients < 8 years old
• other diseases affecting bone metabolism
• patients with malignant diseases or other conditions likely to reduce their life expectancy to less than 3 years
• patients with history of significant upper gastrointestinal disorders
• renal failure (creatinine clearance < 25 ml/mn)
• severe liver disease
• history of iritis or uveitis
• rickets or osteomalacia
• allergy to bisphosphonates
• pregnancy or lactation
• prior treatment with a bisphosphonate
• laboratory abnormalities that may be considered as clinically significant by trial physicians

• ZonMw: The Netherlands Organisation for Health Research and Development
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Charite University, Berlin, Germany