Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement.

UNLABELLED: Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength. INTRODUCTION: Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI. MATERIALS AND METHODS: This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg/m2/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg/kg/day for 6 days/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L1-L4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing. RESULTS: In the controlled phase, treated patients experienced a significant increase in L1-L4 DXA z score (p < 0.001) and increased L1-L4 mid-vertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases. CONCLUSIONS: A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment.

Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography.

The correlation between bone mineral density and vertebral strength is not based on mechanical principles and thus the method cannot reflect the effects of subtle geometric features and densitometric inhomogeneities that may substantially affect vertebral strength. Finite element models derived from quantitative computed tomography (QCT) scans overcome such limitations. The overall goal of this study was to establish that QCT-based "voxel" finite element models are better predictors of vertebral compressive strength than QCT measures of bone mineral density with or without measures of cross-sectional area. QCT scans were taken of 13 vertebral bodies excised from 13 cadavers (L1-L4; age: 37-87 years; M = 6, F = 7) and used to calculate bone mineral density (BMD(QCT)). The QCT voxel data were converted into linearly elastic finite element models of each vertebra, from which measures of vertebral stiffness and strength were computed. The vertebrae were biomechanically tested in compression to measure strength. Vertebral strength was positively correlated with the finite element measures of strength (r(2) = 0.86, P < 0.0001) and stiffness (r(2) = 0.82, P < 0.0001), the product of BMD(QCT) and vertebral minimum cross-sectional area (r(2) = 0.65, P = 0.0008), and BMD(QCT) alone (r(2) = 0.53, P = 0.005). These results demonstrate that highly automated "voxel" finite element models are superior to correlation-based QCT methods in predicting vertebral compressive strength and therefore offer great promise for improvement of clinical fracture risk assessment.

CTXA hip--an extension of classical DXA measurements using quantitative CT.

Bone mineral density (BMD) estimates for the proximal femur using Dual Energy X-ray Absorptiometry (DXA) are currently considered the standard for making a diagnosis of osteoporosis in an individual patient using BMD alone. We have compared BMD results from a commercial Quantitative CT (QCT) BMD analysis system, "CTXA Hip", which provides clinical data for the proximal femur, to results from DXA. We have also used CTXA Hip to determine cortical and trabecular contributions to total BMD. Sixty-nine patients were scanned using 3D QCT and DXA. CTXA Hip BMD measurements for Total Hip and Femoral Neck were compared to DXA results. Twenty-two women were scanned at 0, 1, 2 years and CTXA Hip and DXA results analyzed for long-term reproducibility. Long-term reproducibility calculated as root-mean-square averages of SDs in vivo was 0.012 g/cm2 (CV = 1.8%) for CTXA Total Hip and 0.011 g/cm2 (CV = 2.0%) for CTXA Femoral Neck compared to 0.014 g/cm2 (CV = 2.0%) and 0.016 g/cm2 (CV = 2.7%), respectively, for DXA. The correlation of Total Hip BMD CTXA vs. DXA was R = 0.97 and for Femoral Neck was R = 0.95 (SEE 0.044 g/cm2 in both cases). Cortical bone comprised 62±5% (mean ± SD) of total hipbone mass in osteoporotic women. CTXA Hip provides substantially the same clinical information as conventional DXA and in addition provides estimates of BMD in separate cortical and trabecular bone compartments, which may be useful in evaluation of bone strength.