Histological and anatomical assessment of the effect of teriparatide treatment on mandibular bone defect healing in rats

Abstract

Objective: To determine the effect of systemic teriparatide on the potential to heal critical-size mandibular defects in Wistar rats, histologically.

Methods: 45 adult male Wistar rats were randomly divided into three groups (n=15 each): control (saline), teriparatide 10 µg/kg/day (T10), and teriparatide 40 µg/kg/day (T40). A critical-size defect that was 2 mm long was formed in the left mandibular body. Animals (n=5 animals/group/timepoint) were euthanised at 2,4 and 6 weeks. Specimen decalcification, sectioning and staining were done using H&E and Masson's trichrome. New bone formation, osteoblast activity, inflammatory infiltrate and collagen maturity were scored with semi-quantitative scoring (03), and osteoblast density was counted (cells/mm 2). ANOVA was used to compare treatment and time effects; Tukey was used in the form of post-hoc to compare treatment and time.

Results: All animals survived through the study. There was an increase in scores based on the new bone formation and osteoblast density on a dose and time basis. Mean bone formation scores at 6 weeks, C 1.5 + 0.4, T10 2.5 + 0.3, T40 3.0 + 0.2 (T40 vs C, p<0.001). The bone density 6 weeks was 40 +/-8 (C), 85 +/-10 (T10) and 110 +/-13 cells/mm 2 (T40) (p<0.001). Teriparatide groups experienced a faster reduction in inflammatory scores, and T40 had more collagen maturity (p<0.01).

Conclusion: Dose-related histological curing was attained by systemic teriparatide in the repair of mandibular defects in rats. Such preclinical evidence justifies additional effort, such as mechanical testing, local delivery plans, and translational testing to assess clinical relevance.