Zoledronate treatment duration is linked to bisphosphonate-related osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis.

OBJECTIVES: To determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissue-level features of BRONJ-like lesions in this model, and examine the specific anti-resorptive role of ZOL in BRONJ. MATERIALS AND METHODS: Rice rats (n = 228) consumed high sucrose-casein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 µg/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9-16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJ-like lesion prevalence and tissue-level features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling. RESULTS: Prevalence of BRONJ-like lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar dose-related plateau in the systemic anti-resorptive effect of ZOL. ZOL and BRONJ-like lesions also altered the structural and tissue-level features of the jaw. CONCLUSION: The relationship between BRONJ-like lesion prevalence and ZOL dose and duration varies depending on the co- or pre-existing oral risk factor. At clinically relevant doses of ZOL, BRONJ-like lesions are associated with anti-resorptive activity.

Proteomic Identification and Quantification of Basal Endogenous Proteins in the Ileal Digesta of Growing Pigs.

The accurate estimation of basal endogenous losses (BEL) of amino acids at the ileum is indispensable to improve nutrient utilization efficiency. This study used a quantitative proteomic approach to identify variations in BEL in the ileal digesta of growing pigs fed a nitrogen-free diet (NFD) or a casein diet (CAS). Eight barrow pigs (39.8 ± 6.3 kg initial body weight (BW)) were randomly assigned to a 2 × 2 crossover design. A total of 348 proteins were identified and quantified in both treatments, of which 101 showed a significant differential abundance between the treatments (p < 0.05). Functional and pathway enrichment analyses revealed that the endogenous proteins were associated with intestinal metabolic function. Furthermore, differentially abundant proteins (DAPs) in the digesta of pigs fed the NFD enriched terms and pathways that suggest intestinal inflammation, the activation of innate antimicrobial host defense, an increase in cellular autophagy and epithelial turnover, and reduced synthesis of pancreatic and intestinal secretions. These findings suggest that casein diets may provide a more accurate estimation of BEL because they promote normal gastrointestinal secretions. Overall, proteomic and bioinformatic analyses provided valuable insights into the composition of endogenous proteins in the ileal digesta and their relationship with the functions, processes, and pathways modified by diet composition.

Age-related periodontitis and alveolar bone loss in rice rats.

OBJECTIVE: To characterize in rice rats: (a) periodontitis (PD) progress with feeding of standard laboratory rat chow (STD) during ages 4-80 weeks; and (b) PD progress with feeding of a high sucrose-casein (H-SC) diet during young adulthood. METHODS: One group (N=12) was euthanized at age 4 weeks (Baseline). Four groups (N=8-16) consumed a STD diet from baseline and were necropsied at ages 22, 30, 52, and 80 weeks. Three groups (N=10-16) consumed an H-SC diet from baseline. Two were necropsied at ages 22 and 30 weeks, respectively. The third switched to the STD diet at age 22 weeks and was necropsied at age 30 weeks. All mandibles/maxillae were assessed by histometry for degree of periodontal inflammation (PD Score), alveolar crest height (ACH, mm), and horizontal alveolar bone height (hABH, mm2). RESULTS: In STD diet rats aged ≥30 weeks, all endpoints were worse (P<0.05) than at Baseline. In H-SC diet rats aged ≥22 weeks, all endpoints were worse than at Baseline (P<0.05). At age 22 weeks, all endpoints were worse in the H-SC group than in the STD group (P<0.05). By age 30 weeks, the STD and H-SC groups did not differ. CONCLUSIONS: 1) STD diet fed rice rats develop moderate/severe PD by age 30 weeks; 2) an H-SC diet accelerates moderate/severe PD development; and 3) switching to a STD diet does not halt/reverse PD that was accelerated by an H-SC diet. These data further clarify use of the rice rat as a PD model.