Bisphosphonate Therapy for Osteogenesis Imperfecta

Study Overview
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Brief Summary
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The study is designed to evaluate the efficacy and safety of Bisphosphonate Therapy for Osteogenesis Imperfecta (OI). We, the researchers at Indiana University School of Medicine, are characterizing the changes effected by oral bisphosphonate therapy and comparing them to a regimen of intravenous bisphosphonate therapy in a group of children with OI and also in children with other disorders that result in low bone mass and fractures.

Detailed Description
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The study is designed to evaluate the efficacy and safety of Bisphosphonate Therapy for Osteogenesis Imperfecta (OI). OI is an inherited disorder of collagen synthesis. Collagen is the major structural protein of the matrix of tendons, skin, and bones. Affected persons have low bone mineral density (and experience multiple fractures and progressive bony deformity). In its most severe form, the disorder is lethal in infancy. We plan to characterize the changes effected by oral bisphosphonate therapy and compare them to a regimen of intravenous bisphosphonate therapy in a group of children with OI. Additionally, we have begun to treat patients with OI and other conditions of low bone mineralization for age who are not eligible for the standard protocol (too young, history of abdominal pain, etc.) with bisphosphonate. We also plan to screen the parents and siblings of our patients diagnosed with osteogenesis imperfecta, in order to determine if they also have osteoporosis.

Official Title
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Bisphosphonate Therapy for Osteogenesis Imperfecta

Conditions
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Osteogenesis Imperfecta, Osteoporosis, Paget Disease of Bone

Intervention / Treatment
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* Drug: Alendronate
* Drug: Pamidronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of OI, as defined by genetic analysis revealing a defect of type I collagen, OR by bone mineral density (BMD) <2.5 standard deviations (SD) for age plus two of the following: Family history of OI Frequent fractures Blue sclerae Multiple wormian bones on skull x-ray Hearing disturbance Dentinogenesis imperfecta Age between 3 and 21 years at the start of the study period. Children must be able to swallow whole tablets Parents of children must be able to understand protocol and give informed consent. Exclusion Criteria: Therapy with bisphosphonates during the past 12 months. Other non-traditional therapy for OI in the last 6 months, such as growth hormone or anabolic steroids. Other chronic diseases besides OI that interfere with bone morphology or gastrointestinal absorption

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alendronate<br>1 mg/kg po qd rounded to nearest 10 or 20 mg dose | Drug: Alendronate<br> <br> * Other names: fosamax;|
| Active Comparator: Pamidronate<br>3 mg/kg IV q4 months | Drug: Pamidronate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density | By Dual-energy x-ray absorptiometry. Results were reported as z-scores as well as as absolute values. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome, or similar, as accurate and appropriate. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteogenesis Imperfecta, Fractures, Pediatric, Osteoporosis, Juvenile Pagets