Objective: Osteogenesis imperfecta is an inherited disorder characterised by bone fragility. Antiresorptive treatment with bisphosphonates is a well-established first line medical treatment in OI types III/IV. Nevertheless, there is no consensus on treatment modalities, like which bisphosphonate to use in which dose and when to initiate treatment. The objective of this work was to evaluate the therapeutic effect of a one-year treatment period with bisphosphonates (neridronate i.v., 2mg/kg body weight every 3 months) on vertebral shape, bone mineral density and mobility in infants with severe OI, depending on the onset of treatment.
Methods: We analysed twelve infants with OI type III or IV receiving bisphosphonates (neridronate) within the first 6 month of life and subanalysed the results in respect of the time of treatment initiation. Areal Bone mineral density (BMD) of the lumbar spine (L2-L4) was assessed via DXA (GE Lunar iDXA). Vertebral shape was assessed by x-ray of the lateral spine (Morphometry COIN score). Mobility progress was analysed by age, when children reached certain defined motor milestones, based on parent's questionnaires.
For subanalysis we set up matched pairs, to control for severity: early initiation, meaning age of first bisphosphonate treatment within the first month of life and late initiation, meaning age of first bisphosphonate treatment at 3.8 +/- 1.7 months.
Results: All patients presented with a reduced mean lumbar spine aBMD at start of treatment and after one year (early initiation: 0.231 g/cm2 vs 0.244 g/cm2 (Z-score 1,4 SD vs. -2,9 SD); late initiation 0.131 g/cm2 vs. 0.236 g/cm2 (Z-score -7,76 SD vs. - 3,2 SD)). Vertebral morphometry score changed from 1 to 24.8 in the early treatment group and from 57.25 to 53.8 in patients which started later with treatment. Motor function assessment revealed "turning head" was reached within 1,1 months vs. 2 months and "first supported steps" within 17.0 vs 22.5 months.
Conclusion: OI patients starting intravenous neridronate within the first month of life showed less postnatal bone loss. Early treatment seems to preserve the prenatally gained bone mass. We found less deterioration of vertebral shape in patients started early. Those patients also tended to reach motor milestones earlier, than children starting at the mean age of 3.8 months. Therefore, one can assume that an early antiresorptive treatment might be beneficial for the development of the affected children.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology