This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACT Treatment options for children with severe osteogenesis imperfecta (OI) are limited. There is no approved drug treatment for OI, and until recently treatment focused on fracture management and surgical correction of deformity. All medical therapies other than those directed at symptomatic pain relief, including fluoride, magnesium, calcitonin and anabolic steroids have been ineffective.Bisphosphonates, the synthetic analogs of pyrophosphate, have been widely used for the treatment of adults suffering from bone loss and bone fragility. Recent studies of the biophosphonate, pamidronate, in children with severe osteogenesis imperfecta show an increase in BMD evident as early as six weeks after the start of treatment. Without exception, this gain in BMD has been greater than the increase expected in healthy children. Signs of bone pain disappear within days of receiving the biophosphonate and a marked decrease in fracture rate is observed despite a higher risk of injury due to increased mobility.This is a one-year study extension to CZOL446H2202, a multicenter efficacy and safety trial which compared intravenous zoledronic acid to intravenous pamidronate in children with severe osteogenesis imperfecta. This study extension is an international, multicenter, randomized, open-label, safety and efficacy trial, evaluating the safety of continued treatment with two different dosing regimens of zoledronic acid: once yearly or twice yearly.The safety of zoledronic acid for the treatment of severe osteogenesis imperfecta in children will be shown through the monitoring of tolerability, renal safety, general safety and adverse events. Efficacy assessments will include bone mineral density measurements, x-rays of vertebral spine and left hand, specialized serum tests to evaluate bone resorption and formation, bone pain assessment, and grip strength measurements.HYPOTHESISZoledronic acid is safe and efficacious for the treatment of childrn with severe osteogenesis imperfecta.
SPECIFIC AIMS The primary aim of this extension study is to examine the long-term safety of two different dosage regiments of zoledronic acid over an additional 12 months in pediatric patients who have completed one-year of treatment of zoledronic acid in the core CZOL446H2202 study, with focus on general safety and renal safety.Secondary Aims are to assess continued safety and efficacy in pediatric patients with severe osteogenesis imperfecta at the time of randomization in the core as measured by:- the percentage change from baseline (visit 1 of the core study) in lumbar spine bone mineral density (BMD) at month 18 and 24 by core treatment stratum.- the change from baseline (visit 1 of the core study) in Z score of the lumbar spine at month 18 and 24 by core treatment stratum.- the number of clinical fractures per patient (sum of all anatomic sites) over the 12-month extension period and over the entire 24-month period (core and extension).- the change from baseline (visit 1 of core study) in base resorption and bone formation markers at month 15, 18, 21 and 24 by measuring the following bone markers: serum bone-specific alkaline phosphatase (formation), N-terminal propeptide of type I collagen (P1NP) (formation), c-telopeptide (resorption) by core treatment stratum.- the change from baseline (visit 1 of the core study) in supine length (or height) at months 15, 18, 21 and 24 by core treatment stratum.- the change from baseline (visit 1 of the core study) in bone pain, using the Wong-Baker FACES pain rating scale by core treatment stratum.- the change from baseline (visit 1 of the core study) in bone mineral content of the total body at month 18 and 24 by core treatment stratum.- the change from baseline (visit 1 of the core study) in cortical bone thickness at month 24 by core treatment stratum.- the change from baseline (visit 1 of the core study) in vertebral spine length at month 24 by core treatment stratum.- the change from baseline (visit 1 of the core study) in grip strength, measured by ahnd dynamometry relative at month 15, 18, 21 and 24 by core treatment stratum.- the percentage of patients who need treatment before the scheduled dosing visits during the extension by core treatment stratum.
Showing the most recent 10 out of 459 publications
