Methods: To participate in this study with a follow-up of 2 years the children with osteogenesis imperfecta (OI) had at least a restricted level of ambulation according to the criteria of Bleck and no history of prior bisphospho-nate use. Primary outcome measurements were BMD (L1-L4 and calcaneus), functional outcome (Bleck, Pediatric Disability Inventory (PEDI) and muscle strength) and quality of life (self-perception profile for children by Harter (CBSK)). Additional outcomes were sitting height, vertebral height (mean L1-L4) and fracture rate. Thirty-four children were included. Half of the children were treated with Olpadronate (dimethyl-APD, 10mg/m2/day), the others received placebo tablets. All children were supplied with calcium (500mg/m2/day) and vitamin D (400 I.U./day).

Results: Thirty-two children completed the two-year follow-up period of the study, 15 of them in the Olpadro-nate and 17 in the placebo group. The mean ages were 10.4 (SD 2.8) and 10.6 (SD 4.0) years, respectively, in both groups. In the complete study group, spinal BMD increased significantly during the two years of follow-up (p< 0.005), but the level of BMD accretion per year in the Olpadronate group was higher than in the placebo group (p< 0.0155). Increase of BMD at the os calcis was also seen in both groups (p< 0.05) with a borderline sig-nificant difference between the groups in favour of the Olpadronate group (p=0.085). Sitting height, vertebral height and muscle strength increased in both groups without a significant difference between the groups. No differences in changes in functional outcome (Bleck, PEDI) or self-perception (CBSK, Harter) were observed. Fracture rate and the percentage of children with 3 or more fractures during the 2 years follow-up were lower in the Olpadronate group compared to the placebo group. No side effects of the medication were noted during this study.

Conclusion: In this first double-blind randomized placebo-controlled study on the effects of bisphosphonates in children with OI, Olpadronate proved to be effective as demonstrated by a greater annual increase in BMD, independent from the effects of increase of age and calcium and vitamin D supplementation. Fracture risk seemed to decrease, however, given the interindividual variation in fracture rate within both groups, care must be taken in the wording of conclusions. The relationship between an increase in BMD and items such as functional outcome and quality of life remains unclear.

Introduction: The majority of collagen is found in connective tissues of the skeletal system. In diseases like Osteogenesis Imperfecta, the collagen synthesis is disturbed. The interest of this study is to determine if supplementation of amino acids can influence the Fractional Synthese Rate (FSR) of collagen I, especially in growing bone. We developed a method for direct measurement of collagen I s ynthesis in long bones.

Methods: Thirteen piglets were randomly divided into two groups. The animals were fed a standard diet. Group 1, was supplemented amino acids, counting for 150% of the normal protein intake, intravenously by constant infusion, starting 3 days prior to the experiment. Group 2 served as a control group. L-[1-13C]-valine was used as a tracer, and isotopic enrichment in plasma a-ketoisovalerate (KIV) was used as an indicator for intracellular valine enrichment. The tracer infusion rate was adapted to maintain a constant tracer to tracee ratio of the labeled amino acid precursor in the plasma blood samples were taken to measure the isotopic enrichment, P1CP, IGF1 and the amount of amino acids. At the end of the experiment the animals were killed and the femora were taken and new formed bone was collected just below the growth plate and collagen I was isolated, hydrolyzed, enrichment in valine with combustion mass spectrometry and FSR was calculated from the incorporation of the labeled valine in long bones.

Results: Although the amount of amino acids in blood in group I was much higher, there was no significant difference between the FSR of the amino acid group I (44.1% /day, SD 6.7) and the control group II (48.2%/day, SD 9.2). There was also no significant difference between the amount of P1CP and IGF between the groups.

Conclusion: Supplementation of a normal diet with amino acids doesn’t stimulate the collagen I synthesis in new formed bone.