Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis

Study Overview
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Brief Summary
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OBJECTIVES: I. Determine the effects of alendronate sodium on skeletal remodeling and bone mineral density of the hip and spine in children with high-turnover idiopathic juvenile osteoporosis.

Detailed Description
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PROTOCOL OUTLINE: Patients receive oral alendronate sodium weekly for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Official Title
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A Non-Randomized, Open-Label, Prospective, Non-Controlled, 12-Month Clinical Trial to Determine the Effects of Alendronate 35 or 70 mg/Week Depending Upon Body Weight, in Children and Adolescent With IJO

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Alendronate


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: 5-14 years of age Weight 20 kg or greater History of one or more atraumatic fracture Sexual development no greater than Tanner II Osteoporosis by DXA (Diagnosis of high-turnover osteoporosis with no underlying cause (e.g., malignancy, hyperthyroidism, hyperparathyroidism, or vitamin D intoxication) Inclusion Criteria: Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20%). Bone mineral density by DXA at 2 standard deviations (SD) below normal mean for age (Z-score at least 2 SD below normal mean at the lumbar spine or hip) Parental consent (and patient assent after age 12 years) to participate in the study. Sexual development at Tanner stage II or less (Prepubertal stage) Weight 20kg and more Exclusion Criteria: History of severe gastritis or reflux Marked kyphoscoliosis or inability to sit or stand for at least 30 minutes. Abnormalities of the esophagus that delay emptying (e.g., strictures or achalasia) Hypersensitivity to bisphosphonates Uncorrected hypocalcemia History of gastric or duodenal ulcers Renal dysfunction as indicated by serum Creatinine greater than 1.5 mg/dL Liver dysfunction as indicated by serum SGPT greater than 2 times upper limit of normal for age or serum total bilirubin greater than 2.0 mg/dL Diagnosis of osteogenesis imperfecta (including family history) or blue sclerae or deafness Diagnosis of active rickets, osteomalacia, or bone alkaline phosphatase > 2 times normal for age Severe gastritis or reflux Pregnancy Anorexia Nervosa Prior/Concurrent Therapy- Prior course of prednisone allowed No concurrent prednisone except inhaled steroids No concurrent high-dose glucocorticoids No concurrent salmon calcitonin No other concurrent bisphosphonates No concurrent long-term anti-seizure medication

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Alendronate for 12 months<br>Ten children will take alendronate 35mg or 70mg weekly depending upon the body weight for 12 months. Patients will also take calcium supplement daily. | Drug: Alendronate<br>* Pill, 35mg or 70mg weekly, depending upon the body weight for 12 months.<br>* Other names: Fosamax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Increased Bone Mineral Density | Number of participants with increase in bone mineral density at Lumbar Spine and/or Hip at 12 months as compared to the bone mineral density at Lumbar Spine and/or Hip obtained before therapy (baseline values) | at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants (1) With Fractures Before and After Therapy,(2)Analysed for Average Changes From High to Near Normal Mineral Apposition Rate (MAR) After Therapy,(3)Analysed for Average Insignificant Changes in Biochemical Markers After Therapy. | Participants (pts) with fractures bef.and aft.therapy; pts analysed for average changes in mineral apposition rate (MAR) (high (1.9um/day) to near normal (1.2 um/day)as revealed in bone biopsies. MAR is the distance between the two tetracycline labels (um/day). The data represent the average of 10-17 measurements of the disltance obtained by reading 2-7 individual slides of bone biopsy and pts analysed for average insignificant biochemical markers (serum bone specific alkaline phosphatase for bone formation and urinary N-telopeptide for resorption)to determine the effect of therapy. | Before and 12 months after treatment with alendronate | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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idiopathic juvenile osteoporosis, rare disease, arthritis & connective tissue diseases