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Friday, 15 June 2018

Low-Dose Pamidronate Therapy for Pediatric Osteoporosis: Influence of Diagnosis on Changes in Fracture Rate and Bone Mineral Density

                                http://austinpublishinggroup.com/pediatrics-child-health-care/




Controversy surrounds the optimal agent, dose and duration of bisphosphonate therapy for pediatric osteoporosis. We conducted a prospective, observational study of low-dose (4 mg/kg/year) intravenous pamidronate in 31 children with Osteogenesis Imperfecta (OI) or non-OI osteoporosis treated for a median of 39 months (range 6.5-164). Subjects in both diagnostic groups showed significant gains in spine areal Bone Mineral Density (aBMD) during the first year of therapy (29% median gain in children with OI and 15% in children with non-OI osteoporosis). Fracture frequency also declined significantly in both patient groups during the first year of treatment, including for two patients who had <10% improvement in spine aBMD over this time frame. The correlation between % change in aBMD and % change in fracture rate for our study population was weak, as demonstrated by a Spearman’s rank correlation coefficient (rho) of 0.13 (p-value 0.32, 95% confidence interval -0.32 to 1.00). Minor side effects of bisphosphonate therapy were self-limited, and no osteopetrosis, jaw osteonecrosis, or atypical femur fractures occurred during treatment for up to 13.6 years. These data suggest that low dose pamidronate is safe and effective for long-term use in pediatric osteoporosis, and that change in aBMD is an imperfect predictor of reduction in fracture risk.

Bone fragility and osteoporosis (OP) are common complications of several genetic and acquired disorders of childhood. Pediatric patients with Osteogenesis Imperfecta (OI), inflammatory bowel disease, rheumatologic disorders, cerebral palsy, muscular dystrophy, cystic fibrosis, or a history of transplantation may develop low bone mass and fragility fractures. Treatment of pediatric osteoporosis begins with optimizing nutrition, vitamin D stores, endocrine function, and weight-bearing physical activity. When these measures are insufficient to prevent bone loss and fracture, use of pharmacologic therapies is considered.

Pharmacologic options for treating OP in adults include bisphosphonates to reduce bone resorption and anabolic agents to stimulate bone formation. The safety and efficacy of these medications in older patients have been established in large randomized controlled trials (RCTs), but data are limited in pediatrics. The best studied anabolic agent, synthetic parathyroid hormone, should not be used in children due to a black box warning about the risk of osteosarcoma. The anti-resorptive bisphosphonates have been used to treat primary and secondary osteoporosis in children, but the optimal agent, dose and duration of therapy remain controversial due to a lack of RCTs comparing different drugs and dosing regimens.

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