Pamidronate to Treat Osteogenesis Imperfecta in Children
Condition: Osteogenesis Imperfecta
MeSH terms: Osteogenesis Imperfecta
Intervention: Pamidronate (Aredia)
Intervention description: Patients receive a dose of 1mg/kg/cycle (3-day infusion = 1 cycle)
Intervention MeSH terms: Pamidronate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Bisphosphonates; Growth Hormone; Bone Density; Osteogenesis Imperfecta

Summary:

      This study will evaluate the effect of pamidronate a drug that decreases bone resorption
      (breakdown) on osteogenesis imperfecta. This is a genetic disorder of collagen, the major
      protein in bone. The abnormal collagen causes weak bones, and children with severe
      osteogenesis imperfecta sustain many fractures throughout their lives. They also have growth
      deficiency, curvature of the spine, crumbling teeth, hearing loss, easy bruising and heart
      and lung problems. The study will compare bone density, quality and strength, final adult
      height, trunk height, and functional ability in children who receive 1) pamidronate every 3
      months, 2) pamidronate every 3 months + growth hormone injections, 3) pamidronate every 6
      months, or 4) pamidronate every 6 months + growth hormone injections.

      Children 2 years of age and older with severe osteogenesis imperfecta (types III and IV) may
      be eligible for this study. Those enrolled will be randomly assigned to groups according to
      age; children two to four years of age will be randomly assigned to receive pamidronate every
      3 or every 6 months. Children four years of age and older may participate in the growth
      hormone treatment groups. These children will continue on growth hormone until they reach
      their adult height or fail to grow as much as would be expected for someone on growth
      hormone.

      Patients will be followed in the clinic every 3 months for a history, physical examination,
      X-rays, blood tests, and measurements (weight, head circumference, and bone lengths).
      Children will receive a 3 to 4 hour infusion of pamidronate through an intravenous catheter
      (thin flexible tube placed in a vein) once a day for 3 days each visit. (Once inserted, the
      catheter is left in place to avoid multiple needle sticks for administering the drug and
      collecting blood samples.) Children who are taking growth hormone will be given the drug at
      the first treatment visit. At that time, the accompanying parent will be instructed on how to
      mix the drug and give injections. The child receives an injection 6 days a week (Sunday off).
    

Eligibility criteria:

        INCLUSION CRITERIA:

        Children enrolled in this study will be limited to those with Sillence types III and IV OI,
        as determined by clinical and genetic criteria.

        Most of the children who will be included in this study are already enrolled in the
        protocols Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in
        Osteogenesis Imperfecta (97-CH-0064) and Growth Hormone Therapy in Osteogenesis Imperfecta
        (92-CH-0034).

        Screening of candidates will be based on telephone interviews with a parent, and referral
        records to include: AP and lateral radiographs of the lower extremities and spine, and
        family, developmental, fracture and medical history. An NIH clinical screening evaluation
        will be performed for those children who appear to have a history consistent with OI under
        protocol 04-CH-0077, Screening of and Diagnosis of Patients with Connective Tissue Disorder
        . Patients admitted for this screening visit who are less than four years of age as well as
        those older than 4 years of age but not meeting the criteria for inclusion in the growth
        hormone protocol, protocol 92-CH-0034, will be considered for enrollment in protocol
        97-CH-0064 (Evaluation and Intervention for Ambulation, Growth and Basilar Invagination in
        OI), those older than four years who meet the criteria will be considered for co-enrollment
        in protocol 92-CH-0034.

        The inclusion criteria for protocol 92-CH-0034 are as follows: patients must have a
        clinical/biochemical diagnosis of osteogenesis imperfecta types III or IV, height less than
        third percentile for age, and radiological evidence that long bone epiphyses have not yet
        fused.

        Patients are excluded from protocol 92-CH-0034 if they have scoliosis of greater than 40
        degrees unless scoliosis has been stable over the past two years, or evidence of severe
        basilar invagination.

        Patients with previous exposure to bisphosphonates in outside trials will be considered for
        participation in this trial.

        EXCLUSION CRITERIA:

        Inability to comply with the visit schedule, maintenance of the physical therapy program,
        and ability to administer and comply with GH injections are central to our analysis of the
        outcomes of this study. Failure to comply with these conditions will constitute exclusion
        criteria.

        Pregnancy.

        Patients that have had or will have surgery to place instrumentation in the spine (i.e.
        result of spine fusion).