Bone anabolic agents repair alveolar bone damaged by diabetes in mice

Type 2 diabetes (T2D) is a chronic metabolic disorder that significantly impacts skeletal health, including bones of the oral cavity, where alveolar bone is particularly susceptible due to its high remodeling rate and sensitivity to systemic metabolic changes. Using a mouse model of established T2D induced by high-fat diet and streptozotocin, we investigated the effects of the FDA-approved bone anabolic agents parathyroid hormone (PTH) and abaloparatide (ABL) on alveolar bone. In non-diabetic mice, PTH and ABL stimulated both bone formation and resorption, resulting in no net change in alveolar bone mass. In contrast, these agents selectively increased bone formation in T2D mice without further enhancing the already elevated resorption, leading to net alveolar bone gain. This anabolic effect involves suppression of sclerostin and Dickkopf-1 (Dkk-1) in osteocytes and activation of Wnt signaling in periodontal ligament cells. Studies using DMP1-Cre;PTH1R^fl/fl mice demonstrated that osteocytic PTH1R is essential for the anabolic effects but not for the bone resorption-promoting effects of PTH and ABL. These findings reveal a dual mechanism of PTH1R signaling in oral bone remodeling and suggest therapeutic strategies to restore alveolar bone and improve tooth retention and implant osseointegration in diabetic patients.