The Role of Bone Turnover on the Development of Jaw Relationships

Objectives: The development of class II & III skeletal disharmonies is a significant problem in orthodontics. Skeletal malocclusions prolong treatment time, necessitate more chair time, often involve adjunctive mechanics, and may need orthognathic surgeryf or correction. Jaw relationships (such as maxillary and mandibular lengths) are not well understood, particularly molecular and cellular mechanisms. Our previous work shows bisphosphonate alendronate injection in ovo resulted in increased lower beak length by osteoclast inhibition. The purpose of this study was to determine whether osteoclast activity inhibition would lead to changes in mammalian lower jaw lengths.
Methods: To test our hypothesis, we performed 3 distinct experiments. First, 1mg/kg alendronate injected in Fvb mice in utero, litter examined. Second, osteoclasts were eliminated utilizing genetically modified mice. Ctsk^Cre;DTA (or cathepsin K Cre recombinase; diphtheria toxin fragment A)mice- cells expressing cathepsin K are killed(i.e., osteoclasts). Third, mice held on high calcium, low phosphorus diet for several generations to inhibit osteoclast activity. Samples collected at 3-6 weeks, and analyzed (histology and micro-computed tomography).
Results: Preliminary data suggests alendronate treated samples exhibited slightly longer mandibles vesus CtskCre;DTA show shorter mandibles(Co-Pg). Alendronate-treated mice trend: greater AP mandibular lengths and CtskCre;DTA mice shorter AP mandibular lengths(Go-Pg). Co-Go measurements were consistant except one CtskCre;DTA female mouse. Cranial base bones werenot found significant. Data is currently being analyzed for murine samples held on the high calcium, low phosphorus diet.
Conclusions: Altering osteoclast activity using alendronate resulted in larger mandibles measured in the Anterior-Posterior(AP) direction, consistent with findings from our previous quail model. CtskCre;DTA mice showed opposite result: shorter mandibles(AP) compared with controls. Vertical measurements were consistent between samples with one significantly different female CtskCre;DTA . Our preliminary data indicates osteoclasts and/or activity may be intricately linked to mandibular growth. Additional samples are currently being analyzed.