Abstracto

Orthodontic Tooth movement in Osteogenesis Imperfecta: A Bisphosphonate model

Shivam Mehta

Statement of the Problem: Osteogenesis Imperfecta (OI) is characterized by low bone mass that predisposes affected individuals to musculoskeletal fragility due to genetic mutations in type I collagen (Col1A1 and Col1A2). The most common therapeutic treatment for OI patients is the administration of Bisphosphonates. 50% of patients with OI have skeletal class III malocclusion with an open bite and require orthodontic treatment. Previous studies have found that the Index of Orthodontic Treatment Need for OI patients are 88.5% compared to 24.8 % in the control patients. Thus, OI patients have multitude of dental problems and they require orthodontic treatment to achieve proper function, stability and esthetics. However, literature lacks the evidence regarding the nature of Orthodontic Tooth Movement (OTM) in an OI individual. Additionally, how the treatment with bisphosphonates affect the OTM is yet to be studied. Thus, the aim of this study was to decipher the cellular and molecular mechanisms behind the OTM and the rate of OTM with Alendronate treatment in an OI mice model.

Methodology: All procedures were approved by the UConn Health IACUC. The animals (Col1a2 oim/J OI mice) were injected with saline or Alendronate for 2 weeks giving rise to four groups (age:10 weeks; n=8 in each group). (i) Alendronate male (AM), (ii) Saline male (SM), (iii) Alendronate female, (AF) and (iv) Saline female (SF). OTM was performed by tying maxillary right first molar to the NiTi closed coil spring applying 3 cN to 5 cN of force. After OTM, the maxilla was harvested and stored at 40 C in 10% formalin for microCT (Bone volume fraction (BVF) and Tissue Density) and histological evaluation.

Findings: AM and Female AF showed significantly decreased OTM compared to SM and SF (P<0.05). Alendronate treatment resulted in decreased number of osteoclasts than saline. Female OI treated with saline exhibited more rapid resorption than males. The PicroSirius Red staining showed the higher intensity and thickness of collagen fibers in the Alendronate groups.

Conclusion & Significance: Alendronate results in decreased rate of OTM in OI mice. There is an increase in the hyalinization zone and decrease in the number of osteoclasts in the Alendronate mice after OTM compared to saline groups. There is significantly rapid resorption of hyalinized zones in the female OI mice compared to the male OI mice treated with saline. Alendronate might be helpful in restoring the integrity and quality of collagen fibers in OI.