Osteoporosis
Conditions
Keywords
arthritis & connective tissue diseases, idiopathic juvenile osteoporosis, rare disease
Brief summary
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
PROTOCOL OUTLINE: Patients receive oral alendronate sodium weekly for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGAlendronate
Pill, 35mg or 70mg weekly, depending upon the body weight for 12 months.
Sponsors
Merck Sharp & Dohme LLC
Medical University of South Carolina
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Increased Bone Mineral Density | at 12 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Before and 12 months after treatment with alendronate | 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. |
Countries
United States
Participant flow
Recruitment details
Dates of the recruitment period: 5/3/2001 to 7/23/2002. Types of location: Out-patient clinic, Clinical and Translational Research Center (CTRC, formerly General Clinical Research Center), Medical University of South Carolina.
Participants by arm
| Arm | Count |
|---|---|
| Alendronate Ten children will take alendronate 35mg or 70mg weekly depending upon the body weight for 12 months. Patients will also take calcium supplement daily. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Alendronate |
|---|---|
| Age, Categorical <=18 years | 10 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous Post Treatment | 10.6 years STANDARD_DEVIATION 2.3 |
| Age Continuous Pre-Treatment (Baseline) | 9.4 years STANDARD_DEVIATION 2.3 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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)
Time frame: at 12 months
Population: per protocol
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Alendronate | Number of Participants With Increased Bone Mineral Density | 10 participants | 0.11 |
Secondary
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.
Time frame: Before and 12 months after treatment with alendronate
Population: Per protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | 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 with fractures before therapy. | 9 participants |
| Alendronate | 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 with fractures after therapy. | 1 participants |
| Alendronate | 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. | Pts average MAR near normal after therapy | 9 participants |
| Alendronate | 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. | Pts av biomarker change insignificant aft. therapy | 9 participants |