Mary McQuade

Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis

There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated with 3 monthly zoledronic acid for 2 years (annualised dose 0.1mg/kg/year). There was a significant improvement in lumbar spine (by 1.88 SD±1.24 over first 12 months, p<0.001) and total bone mineral density as assessed by dual energy absorptiometry (DXA) scans, with a similar increase in bone mineral content for lean tissue mass (mean increase 1.34 SD in first 12 months, p<0.001). Bone turnover was reduced with a suppression of both osteocalcin and alkaline phosphatase in the first 12 months of treatment. Skeletal architecture was improved, with increased second metacarpal cortical thickness from 2.44mm to 2.72mm (p<0.001) and improved vertebral morphometry, with 7 patients who had vertebral wedging at baseline showing improved anterior (p=0.017) and middle (p=0.001) vertebral height ratios. Aside from well reported transient side effects with the first dose, there were no adverse effects reported. No adverse effects on anthropometric parameters were seen over the course of the study. Despite all patients having sustained fragility fractures prior to treatment, no fractures were reported during the study period. Further evidence is required to confirm efficacy, with long term follow up required to assess the impact of treatment on fracture risk.

Systemic effects of zoledronic acid in children with traumatic femoral head avascular necrosis and Legg―Calve―Perthes disease

BACKGROUND Intravenous bisphosphonate therapy is associated with preservation of femoral head sphericity and congruence in 77% of children with traumatic avascular necrosis. The aim was to describe the systemic effects of intravenous zoledronic acid (ZA) on bone and mineral metabolism in otherwise normal children and adolescents with femoral head AVN. MATERIAL AND METHODS 37 children (age 10.8+/-2.76 years) diagnosed with avascular necrosis AVN (Slipped Capital Femoral Epiphysis (SCFE), N=20 or Legg-Calve-Perthes disease (LCPD), N=17) were treated with at least 12 months of ZA. Bone mineral density (BMD) by DXA, bone morphometry and mineral homeostasis were evaluated at baseline, 6, 12 and 18 months. Data was retrieved retrospectively. RESULTS All children maintained height SD during treatment. BMI SD increased in the SCFE subgroup during the first 12 month period. Bone age increased appropriately. Age adjusted total body BMD, lumbar spine BMD and lean tissue mass adjusted bone mineral content (BMC) Z-scores increased significantly over the 18 months of treatment. The LS.BMD increase was greater in LCPD than in SCFE leading to more individuals with LCPD having a LS.BMD((age))Z-score over 2 SD at 12 months follow-up. Biochemical markers of bone turnover were decreased and PTH increased during the first 12 months of treatment and bone modeling was reduced. All markers stabilised over the next 6 months. There were no incidences of fracture, spondylolisthesis or osteonecrosis of the jaw. CONCLUSION We here report that ZA in otherwise healthy children with femoral head AVN increases BMD - most pronounced in the LCPD group - and reduces bone modeling and turnover. Further efficacy and safety data are required before this therapy can be widely recommended.

The successful use of pamidronate in an 11-year-old girl with complex regional pain syndrome: Response to treatment demonstrated by serial peripheral quantitative computerised tomographic scans

Complex regional pain syndrome (CRPS) is a disorder that can cause significant functional morbidity. While it usually presents in adulthood, it has also been reported in children. Multiple treatment modalities have been reported with mixed success. Bisphosphonate therapy has been shown to be effective in adult patients, but there are limited data in children. We report the successful use of intravenous pamidronate therapy in diminishing pain, improving function, and restoring bone mass in an 11-year-old girl with CRPS of her left lower limb following a tibial fracture. Previous treatment with intense physiotherapy and regional sympathetic blockade had not improved her symptoms. Pain improved within weeks of the first pamidronate infusion, with subsequent improvement in function. The benefit in pain reduction and function was sustained during the 2-year treatment regime. Improvement in bone mass and density was demonstrated by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerised tomography (pQCT). pQCT scans showed marked improvement in bone size and geometry and muscle bulk on the affected side. No adverse affects were reported. We conclude that intravenous pamidronate was associated with reduced pain, a return of function, and recovery of bone and muscle parameters in a child with CRPS. Before definitive conclusions can be drawn, a randomised controlled trial similar to those undertaken in adults previously is required to fully validate this approach.

Zoledronic acid improves bone mineral density in pediatric spinal cord injury

Spinal cord injury (SCI) is associated with rapid and sustained bone loss and increase risk of fracture. Disuse is the primary cause for bone loss, although neural and hormonal changes may also contribute via different mechanisms. Bisphosphonates are used widely to treat osteoporosis in adults and are used increasingly for primary and secondary osteoporosis in children. Current data are insufficient to recommend routine use of bisphosphonates for fracture prevention in adult patients post‐SCI and there are no available data in pediatric SCI. We report a 12‐year‐old boy with non‐traumatic SCI who was treated with six monthly zoledronic acid (0.05 mg/kg/dose) for 18 months. The patient (AA) was diagnosed with transverse myelitis at 8.1 years of age, resulting in ventilator‐dependent incomplete C3 tetraplegia. Following a fragility fracture to the surgical neck of the right humerus at 9.5 years of age, he was started on zoledronic acid. Bone turnover decreased and bone densitometry data (dual‐energy X‐ray absorptiometry [DXA] and peripheral quantitative computed tomography [pQCT]) showed improvement in metaphyseal and diaphyseal bone mineral content (BMC), volumetric bone mineral density (vBMD), and size, after 18 months of treatment. In the growing skeleton post‐SCI, zoledronic acid potentially increases vertebral and long‐bone strength by preserving trabecular bone (increased BMC and vBMD) and increasing cortical vBMD and cross‐sectional area (CSA).