Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention. Children with symptomatic pathological fractures of the axial spine or ribs were treated with pamidronate 1 mg/kg/dose (n=17) IV at 60-day intervals for 1 yr (n=15) or 2 yr (n=2). Bone mineral density of L1-L4 (BMD) was assessed prior to treatment and at six-month intervals, and compared to 17 disease-age-gender-steroid dose-matched control patients. Alkaline phosphatase, calcium, phosphate, PTH, renal biochemistry, and 24-hr urine collections for CrCl, N-telopeptide/creatinine ratio, phosphate excretion, and calcium excretion were obtained every two months in the pamidronate population. Pamidronate caused a first exposure transient flu-like illness lasting <24 h in three patients and one patient had a new pathological fracture. No adverse events of hypocalcemia, allergic reaction or thrombophlebitis were noted. All patients reported improvement of skeletal pain. Despite ongoing steroid treatment, pamidronate significantly increased L1-L4 BMD Z-scores (mean+/-SE) relative to baseline (pamidronate vs control: 0-6 months: 0.27+/-0.14 vs -0.82+/-0.31; 0-12 months: 0.63+/-0.17 vs -0.46+/-0.27; 0-18 months: 0.55+/-0.32 vs 0.17+/-0.27; 0-24 months: 0.15+/-0.21 vs -0.23+/-0.22; 0-30 or 36 months: 0.77+/-0.71 vs -0.68+/-0.25) with repeated measures ANOVA assessment (F=11.27, p=0.0057). This study supports the safety and efficacy of pamidronate in steroid-induced fractures in pediatric nephrology and rheumatology patients.