Trabecular Bone Microarchitectural Outcomes of the Mandible and Tibia or Lumbar Vertebrae are Correlated in SHAM but not the OVX Rat Model of Postmenopausal Osteoporosis
Authors: Longo Amanda , Ward Wendy 
Published: November 2023

In postmenopausal (PM) women, tooth loss and/or low bone mineral density (BMD) of the jaw is correlated with low BMD (i.e. osteoporosis) at other skeletal sites. Moreover, tooth loss, in general, makes it more difficult to consume healthy foods that often require more forceful mastication. Thus, there is a cyclic relationship among oral health, consumption of a nutritious diet, and the risk of osteoporosis. The ovariectomized (OVX) rat model is the FDA‐approved model of PM osteoporosis, and is commonly used to investigate how diet can attenuate the development of osteoporosis. OVX causes a skeletal‐site specific response, such that loss of bone quantity and quality in the long bones is greater than in the lumbar vertebrae (LV) and mandible. However, few studies have evaluated the correlation of trabecular microarchitectural outcomes, as measured by micro‐computed tomography (mCT), between mandible and tibia or LV to determine the fitness of the mandible as a predictor of overall bone health. The objective of this study was to determine if trabecular microarchitectural outcomes of the mandible and the tibia or LV are correlated in this widely used pre‐clinical model of PM osteoporosis, to understand how closely this model mimics changes observed in PM women. Three‐month old Sprague‐Dawley rats were randomized to SHAM (n=47) or OVX (n=49) and were maintained on an ad libitum diet until 6 months of age. Ex vivo mCT imaging of the mandible (alveolar bone) and LV, and in vivo mCT imaging of proximal tibia was conducted. Trabecular microarchitectural measurements, including percent bone volume (BV/TV), trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular separation (Tb.Sp.), and degree of anisotropy were quantified at each bone site. Correlation between these outcomes (mandible vs. tibia; mandible vs. LV) within SHAM or OVX rats was conducted using a Pearson's correlation test. Within rats randomized to SHAM, positive correlations exist between all bone sites for the outcomes BV/TV (p<0.001), Tb.N. (p<0.001), and Tb.Sp. (p<0.05). A negative correlation was observed between the mandible and LV for the outcome Tb.Th. (p<0.05). Within rats randomized to OVX, the sole positive correlation was between the mandible and tibia for Tb.Sp. (p<0.05). As expected, when the percent change between SHAM and OVX groups was assessed at 6 months of age, the most dramatic effect was seen at the tibia (−71% BV/TV), followed by the LV (−36% BV/TV) and mandible (−8% BV/TV). These results demonstrate that OVX has skeletal‐site specific effects on trabecular microarchitecture, and these relative responses may at least partially explain the lack of correlations among mandible and tibia or LV after OVX. In conclusion, positive correlations between BMD and trabecular bone microarchitecture of mandible and tibia or LV are observed in SHAM rats but not after OVX. Therefore, the alveolar bone of the mandible of OVX rats does not closely mimic the bone loss that occurs in PM women and does not reliably predict changes at other skeletal sites in the time frame studied.Support or Funding InformationThe authors acknowledge funding provided by the Natural Sciences and Engineering Research Council of Canada and the Canada Research Chairs program as well as infrastructure support from the Canada Foundation for Innovation.