Pamidronate treatment of pediatric fracture patients on chronic steroid therapy

Abstract

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.

Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome

“…Leonard et al recently reported that intermittent GC therapy resulted in similar spine and total-body BMC in children with SSNS compared with controls [6], suggesting that bone mass is relatively preserved. However, Acott et al [14] reported vertebral fractures among NS children within 3 months of receiving GCs. Our report further supports the observation that vertebral body strength can indeed be compromised with intermittent GC therapy for NS.…”

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

“…Similarly, reductions in lumbar spine areal bone mineral density (LS BMD) have been documented during the initial high-dose GC treatment phase in children with NS [9,10], and modest deficits in LS bone mineral content have been shown following years of intermittent GC therapy for steroid-sensitive disease [11]. Overt bone fragility manifesting as vertebral fractures has also been reported in children with NS following the initial GC treatment phase in the context of a treatment study [10], and later in the disease course [12].…”

“…Overt bone fragility manifesting as vertebral fractures has also been reported in children with NS following the initial GC treatment phase in the context of a treatment study [10], and later in the disease course [12]. However, the frequency and characteristics of vertebral deformities in pediatric NS as well as their relationship to clinical factors has not been well studied.…”

Optimizing Bone Health in Children and Adolescents

“…123,[125][126][127] Pilot studies have also been conducted in adolescents with anorexia nervosa. 128 In osteogenesis imperfecta, an openlabel study examining the use of cyclic administration of intravenous pamidronate reported reduced pain and fractures associated with dramatic increases in BMD.…”