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.

Brief assessment of motor function: reliability and concurrent validity of the Gross Motor Scale.

OBJECTIVE: The Brief Assessment of Motor Function (BAMF) is a series of 10-point ordinal scales developed for rapid description of gross motor, fine motor, and oral motor performance. We examined interrater and intrarater reliability and concurrent validity of the BAMF Gross Motor Scale. DESIGN: This validation study included 48 children (age, 5 mo to 17 yr) with a wide range of gross motor capability. Ten children with varied diagnoses participated in the reliability study. For concurrent validity, the BAMF performance of 38 children with osteogenesis imperfecta was compared with scores on the Peabody Developmental Motor Scales, laboratory gait analysis, and manual muscle testing. RESULTS: Reliability values for intraclass correlations were 0.996 (interrater) and 1.00 (intrarater). Significant relationships were identified between the BAMF and gait speed ( r = 0.68, P < 0.0001), stride length (r = 0.71, P < 0.0001), duration of double-limb support ( r = -0.40, P < 0.03), number of weak muscles (r = -0.74, P< 0.0001), and the Peabody Developmental Motor Scales (r = 0.95, P < 0.0001). Number of weak muscles was the strongest predictor of BAMF score R2 = 0.5080, F = 24.77, P < 0.0001). CONCLUSIONS: The BAMF demonstrates good reliability for children with a range of diagnoses and acceptable concurrent validity with gross motor development, muscle strength, and formal gait assessment in children with osteogenesis imperfecta.

Temperament and physical performance in children with osteogenesis imperfecta.

OBJECTIVE: Children with osteogenesis imperfecta (OI) must participate in therapy to achieve motor performance objectives. Their behavioral style may influence motor performance. For this reason, the temperament of children with types III or IV OI was assessed prospectively to 1) compare their temperament with that of nondisabled children, 2) investigate the relationship between temperament and gross motor performance, and 3) examine relationships among temperament, parental overprotection and coping, physical activity, muscle strength, and motor performance. METHODS: Age-appropriate Carey Temperament Scales, Brief Assessment of Motor Function (BAMF), and the Vulnerable Child/Overprotecting Parents Scale were completed for 35 children 1 to 12 years old. Additional measures included the Childhood Health Assessment Questionnaire, Parent Daily Hassles Scale, manual muscle testing, Pediatric Activity Record, and a Summed Severity Score. Spearman correlations and multiple regression were used to identify and predict significant relationships. RESULTS: Temperament of children with OI differed from age-based norms in only 1 domain: activity. Motor performance (BAMF) correlated significantly with 3 domains of temperament: persistence (r = -.48), approach (r = -.34), and activity (r =.40). Activity was also related to the ratio of head circumference to body length (r = -.45) and the number of fractures in the preceding year (r = -.35). Parents' reports of their daily hassles significantly correlated with several domains of the child's temperament. No significant relationships were identified between parental overprotection and temperament or motor performance. CONCLUSIONS: The temperament of children with types III and IV OI does not differ from that of their nondisabled peers, with the exception of lower activity scores. Although it is considered a biological attribute, the expression of temperament, specifically activity, may be influenced by learned behaviors. Because gross motor performance is related to activity, persistence, and approach/avoidance, knowledge of an individual's temperament may enhance the child's ability to benefit from interventions to improve motor skill and activity levels.