Bone Abstracts

Objectives: Children with osteogenesis imperfecta (OI) suffer fragility fractures due to altered bone mass, architecture and material quality. Management is multidisciplinary, often including bisphosphonates and physiotherapy. We wished to determine whether bisphosphonates altered the skeletal response to mechanical stimulation in OI. Short term exposure to whole body vibration (WBV) in apparently healthy children results in increases in bone formation and resorption markers, providing a dynamic test of the acute skeletal response to mechanical stimulation.

Methods: 12 children with OI, naïve to bisphosphonate treatment, stood on a high frequency low amplitude vibrating platform (LivMD) for 10 minutes daily (2.5 minutes × 4 with interspersed 1 minute rest periods) for 7 days, followed successively by five weeks ‘washout’, six weeks of risedronate treatment and one week of WBV. P1NP, alkaline phosphatase and CTX were measured at baseline and at intervals bracketing the periods of vibration and risedronate treatment.

Results: There were statistically significant increases in predicted P1NP (P=0.019) and CTX (P=0.013) but not alkaline phosphatase (P=0.11) by repeated measures ANOVA across the whole period of the study. Both P1NP and CTX rose after the initial WBV period (D1 –D8); P1NP from 442.8 to 529.1 ng/ml, P=0.016; CTX from 1.256 to 1.437 ng/ml, P=0.023. P1NP and CTX values decreased following treatment with Risedronate (D43 –D85); P1NP 534.9 to 438.2 ng/ml P=0.006 and CTX 1.507 to 1.253 ng/ml P=0.002. P1NP and CTX changed less after the second period of vibration; P1NP 438.2 to 454.2 ng/ml P=NS; CTX from 1.253 to 1.376 ng/ml P=NS. P1NP increased significantly more from D1-8 then from D85-92; %change 16.3 vs 3.5% P=0.016; there was no significant difference in the change in CTX between the two time periods.

Conclusions: The initial change in biomarkers following WBV shows bone tissue in children with OI is capable of responding to mechanical stimulation. Both P1NP and CTX fell following risedronate treatment, and increased less subsequently in response to mechanical stimulation. These data suggest there is some reduction in skeletal responsiveness to mechanical stimulation following bisphosphonate treatment that has implications for the management of these children.

Disclosure: NJB consults for Alexion, Mereo, UCB and Amgen, and receives grant support for clinical studies from Alexion and Amgen.