Pamidronate Treatment of Severe Osteogenesis Imperfecta in Children under 3 Years of Age*

Abstract

Severe osteogenesis imperfecta (OI) is a hereditary disorder characterized by increased bone fragility and progressive bone deformity. Cyclical pamidronate infusions improve clinical outcome in children older than 3 yr of age with severe OI. Because earlier treatment may have potential to prevent deformities and improve functional prognosis in young children, we studied nine severely affected OI patients under 2 yr of age (2.3-20.7 months at entry) for a period of 12 months. Pamidronate was administered i.v. in cycles of 3 consecutive days. Patients received four to eight cycles during the treatment period, with cumulative doses averaging 12.4 mg/kg. Clinical changes were evaluated regularly during treatment, and radiological changes were assessed after 6-12 months of treatment. The control group consisted of six age-matched, severely affected OI patients, who had not received pamidronate treatment. During treatment bone mineral density (BMD) increased between 86-227%. The deviation from normal, as indicated by the z-score, diminished from -6.5 +/- 2.1 to -3.0 +/- 2.1 (P < 0.001). In the control group the BMD z-score worsened significantly. Vertebral coronal area increased in all treated patients (11.4 +/- 3.4 to 14.9 +/- 1.8 cm2; P < 0.001), but decreased in the untreated group (P < 0.05). In the treated patients, fracture rate was lower than in control patients (2.6 +/- 2.5 vs. 6.3 +/- 1.6 fractures/year; P < 0.01). No adverse side-effects were noted, apart from the well known acute phase reaction during the first infusion cycle. Pamidronate treatment in severely affected OI patients under 3 yr of age is safe, increases BMD, and decreases fracture rate.

Efficacy and Safety of Bisphosphonate Therapy in Children with Osteogenesis Imperfecta: A Systematic Review

“…Similar results have also been seen in several uncontrolled trials reporting a reduction in (bone) pain [45,46,47,48]. However, our results in children deviated from the review of Dwan et al [39] in which a reduction in bone pain was found in merely 1 out of 6 studies; however, they included adult studies and studies comparing different doses of BP without control groups [39].…”

Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists

“…The effect of this on bone fragility is not known. Reassuringly, at least in the paediatric population with OI, IV pamidronate can decrease fracture incidence [6,12,33,34], and a reduction in fracture has also been observed with oral bisphosphonates in some [13,27,35] but not all [14,15,36] studies. There have been only two controlled trials of bisphosphonates in adults with OI type I.…”

Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone

“…Patients with severe OI have numerous painful fractures, progressive skeletal deformities, and retarded bone growth, resulting in short stature (15)(16)(17). There is no cure for OI, and only one class of drugs, the bisphosphonates, has shown therapeutic potential (18)(19)(20). We previously demonstrated the feasibility of allogeneic bone marrow transplantation (BMT) for children with severe OI (21).…”