An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids

Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.

Time frame: Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Left posteroanterior (PA) hand/wrist X-ray were taken at Visit 1 and at the Month 12 visit to assess bone age and the between-treatment differences for change in 2nd metacarpal cortical width at Month 12 relative to baseline. If a fracture of the left upper extremity precluded radiographic imaging, then the right hand was evaluated for this purpose. In this case, the right hand was be imaged at both Visit 1 and at Month 12. The information was used in the assessment of bone density.

Time frame: Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Bone specific alkaline phosphatase (BSAP) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Lumbar Spine BMC was determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 6. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.

Time frame: Month 6

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Serum Cross linked N-telopeptide (NTX) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Total body BMC was all determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.

Time frame: Month 6, Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader.

Time frame: Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

New vertebral fractures were defined as fractures of Genant Grade 1 or higher that occurred at lumbar or thoracic spine from first dose infusion to the end of the study.

Time frame: Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Pain was evaluated at each visit (in office and telephone visit) at randomization, Months 3, 6, 9 and 12 using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'.

Time frame: Month 3, Month 6, Month 9 and Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.

Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis done.

Time frame: Baseline through Month 12

Population: The Safety population, which consisted of all patients who had been exposed to at least one infusion of study drug, was considered.

Urine was collected overnight or for at least 4 waking hours from all patients able to provide specimens, to measure urinary concentration of zoledronic acid at Month 12. Only descriptive analysis done.

Time frame: Month 12

Population: The Modified Intention-to-treat (MITT) population, which consisted of all randomized patients who had both baseline and at least one post-baseline lumbar spine BMD Z-score, was considered.