Osteoporosis
Conditions
Keywords
Fracture, Bone Mineral Density, DXA
Brief summary
We have previously evaluated the safety and efficacy of Alendronate in 10 patients with juvenile osteoporosis during a 12-month clinical trial. We have documented that Alendronate improved BMD of the spine and hip without any major side effects. There were no additional fractures during therapy. The present study is designed to further evaluate the safety and efficacy of Alendronate in 20 children with juvenile osteoporosis using a double-blind, randomized, placebo-controlled, cross-over protocol.
Detailed description
Osteoporosis is an uncommon disease in children and early adolescents. Patients have a low bone mineral density, develop fractures with minimal or no trauma, and frequently have a negative family history. The disease results from either diminished bone formation or increased bone removal (resorption). No specific drug therapy has been recommended for juvenile osteoporosis. Alendronate (Fosamax) is effective in inhibiting bone resorption, increasing BMD and reducing fractures in adults with postmenopausal osteoporosis, but have not become established therapies in children. In the present study, we plan to evaluate the safety and efficacy of Alendronate in 20 patients with juvenile osteoporosis in a two-year period. This is a randomized, double-blind, placebo-controlled protocol. In the year-1, 10 patients will be assigned to receive Alendronate and 10 patients placebo. In the year-2, patients will be crossed over to the second arm of the study. Those who received Alendronate in the year-1, will receive placebo in the second year and vice verse. The patients will have 5 visits, the initial screening visit followed by 4 post therapy visits in a six-month interval. Measurements include DXA bone density scan of spine and hip, urinalysis and blood work.
Interventions
DRUGAlendronate
Group-1/Year-1:Alendronate, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight, for 12 months. Group-1/Year-2:Placebo, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months. Group-2/Year-1:Placebo, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months. Group-2/Year-2: Alendronate, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months.
Sponsors
FDA Office of Orphan Products Development
Merck Sharp & Dohme LLC
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: * 5-15 yrs of age * Weighing 20 kg and more * History of multiple fractures * Tanner stage II or less * Osteoporosis by DXA. 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 percent). * Bone Mineral Density (BMD) determined by DXA sacn to confirm osteoporosis at a Z score greater than 2 SD (standard deviations) below the normal mean for age (Z score \< -2 SD). * 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 = 20 kg and more.
Exclusion criteria
* History of severe gastritis or reflux. * Abnormalities of the esophagus that delay emptying, such as strictures or achalasia * Marked kyphoscoliosis or the inability to sit or stand for at least 30 minutes * Hypersensitivity to bisphosphonates * Uncorrected hypocalcemia * History of gastric or duodenal ulcers * Renal dysfunction as indicated by serum Cr \>1.5 mg/dl. * Liver dysfunction as indicated by serum SGPT \> 2 times the upper limit for age or serum total bilirubin \> 2.0 mg/dl. * Diagnosis of osteogenesis imperfecta, a family history of osteogenesis imperfecta, blue sclerae or deafness. * Diagnosis of active rickets or osteomalacia or serum bone alkaline phosphatase 2 times greater than normal for age. * Pregnancy * Anorexia Nervosa
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy | 12 months therapy | Participants were screened for BMD of lumbar spine using DXA scan at visit 12 months after alendronate or placebo treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy | 12 months of therapy | — |
| Number of Participants With Improvement in BMD of Hip | 24 months of therapy | Analysis was done per protocol and intention to treat. |
| Participants With Atraumatic Fractures | 0 months | Number of Participants with Atraumatic fractures before therapy. |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment period:O5/27/2004 to 02/01/2006. Types of location:outpatient clinic, Clinical and Translational Research Center (CTRC), Medical University of South Carolina, Charleston, South Carolina.
Participants by arm
| Arm | Count |
|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D Group-1/Year-1, 11 participants will take Alendronate,(study medication) and calcium, and vitamin D (supplements) and in Year-2 they will crossover to placebo, calcium and vitamin D supplements. | 11 |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D Group-2/Year-1, 11 participants will take Placebo,and calcium, and vitamin D (supplements) and in Year-2 they will crossover to Alendronate (study medication), calcium and vitamin D (supplements). | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Months Treatment | Gr-1, lost followup; Gr-2, not compliant | 1 | 2 |
| 24 Months Treatment | Lost to Follow-up | 0 | 3 |
Baseline characteristics
| Characteristic | Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 11 Participants | 22 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 9.47 years STANDARD_DEVIATION 2.3 | 9.17 years STANDARD_DEVIATION 2.8 | 9.32 years STANDARD_DEVIATION 0.2 |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
Participants were screened for BMD of lumbar spine using DXA scan at visit 12 months after alendronate or placebo treatment.
Time frame: 12 months therapy
Population: Analysis was done per protocol and intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy | 10 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy | 9 participants |
Primary
Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
BMD of lumbar spine was measured using DXA scan at visit 24 months (Year-2)after alendronate or placebo treatment.
Time frame: 24 months therapy
Population: Analysis was done per protocol and intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy | 10 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy | 6 participants |
Secondary
Number of Participants With Improvement in BMD of Hip
Analysis was done per protocol and intention to treat.
Time frame: 24 months of therapy
Population: Analysis was done per protocol and intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Number of Participants With Improvement in BMD of Hip | 10 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Number of Participants With Improvement in BMD of Hip | 6 participants |
Secondary
Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy
Time frame: 12 months of therapy
Population: Analysis was done per protocol and intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy | 10 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy | 9 participants |
Secondary
Participants With Atraumatic Fractures
Number of Participants with Atraumatic fractures before therapy.
Time frame: 0 months
Population: Number of participants with fractures before therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Participants With Atraumatic Fractures | 11 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Participants With Atraumatic Fractures | 11 participants |
Secondary
Participants With Atraumatic Fractures
Number of participants with fractures at the completion of therapy.
Time frame: 24 months
Population: Number of participants with fractures at study completion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gr-1:Yr-1/Yr-2: Alendronate/Pbo, Calcium, Vitamin D | Participants With Atraumatic Fractures | 0 participants |
| Gr-2:Yr-1/Yr-2: Pbo/Alendronate, Calcium and Vitamin D | Participants With Atraumatic Fractures | 0 participants |