Type 2 diabetes accelerates alveolar bone loss and weakens the bone anchoring teeth, yet bone anabolic agents restore this jaw structure in mice, according to a study published in the International Journal of Oral Science on Oct. 29, 2026.
Researchers at Indiana University School of Medicine and the University of Arkansas for Medical Sciences tested parathyroid hormone and abaloparatide in diabetic models.
Systemic effects of the metabolic disorder compromise skeletal health and worsen the loss of alveolar bone that anchors teeth, leading to tooth loosening and eventual tooth loss. Diabetic patients face a high risk of periodontitis, which disrupts bone homeostasis.
While parathyroid hormone analogs show promise for alveolar bone regeneration in preclinical models, researchers needed to explore whether they can restore bone in established type 2 diabetes and identify which cells mediate these effects.
To investigate these mechanisms, the team used a mouse model of established type 2 diabetes induced by a high-fat diet and streptozotocin. Using micro-computed tomography, histological staining, immunofluorescence, and conditional knockout mice lacking the parathyroid hormone receptor in DMP1-Cre-positive cells, scientists examined bone formation and resorption in the periodontium.
In non-diabetic mice, parathyroid hormone and abaloparatide stimulated both bone formation and resorption, resulting in no net change in alveolar bone mass.
In contrast, both agents increased bone volume and restored alveolar bone height toward non-diabetic levels in diabetic mice. Mechanistically, the drugs suppressed sclerostin and Dickkopf-1 in osteocytes, activating Wnt signaling and increasing RUNX2 expression in periodontal ligament cells. The drugs did not further increase the already elevated osteoclast numbers in diabetic mice, whereas they promoted osteoclastogenesis in non-diabetic animals.
Cellular mechanisms in remodeling
Using conditional knockout mice, the research team demonstrated that parathyroid hormone receptor signaling in DMP1-Cre-positive cells, primarily osteocytes, is essential for anabolic effects. This signaling pathway is dispensable for pro-resorptive effects, which are instead driven by receptor signaling in DMP1-Cre-negative marrow cells through the upregulation of receptor activator of nuclear factor kappa-B ligand and the suppression of osteoprotegerin.
This cell-type-specific duality explains why the drugs produce net bone gain only under diabetic conditions. The findings reveal a dual mechanism of receptor signaling in oral bone remodeling, where osteocytes drive bone formation while marrow cells drive resorption.
“Bone anabolic regimens using PTH1R ligands could help restore alveolar bone, enhance tooth stability, and promote oral health in diabetes,” the authors said, adding that further studies are needed to dissect these distinct regulatory pathways.
Parallel research indicates that type 2 diabetes mellitus also impairs tooth supraeruption following tooth loss by disrupting alveolar bone remodeling. That separate study observed reduced osteoblast numbers, decreased mRNA expression of transforming growth factor-beta, insulin-like growth factor-1, and periostin, alongside increased osteoclast numbers and elevated RUNX2 expression in diabetic mice.
hormone regimens may improve bone density in type 2 diabetes
Intermittent parathyroid hormone and abaloparatide regimens could help restore alveolar bone, improve tooth retention, and enhance dental implant osseointegration in patients with type 2 diabetes. Because the pro-resorptive effects of these agents are blunted under diabetic conditions, the therapeutic window for net bone gain may be wider in diabetic bone than in non-diabetic bone.
Identifying osteocytic receptor signaling as the key anabolic mediator and marrow cell signaling as the driver of resorption provides a foundation for optimizing targeted therapies. These strategies aim to maximize bone formation while limiting resorption in diabetic bone disease and other conditions marked by imbalanced bone remodeling.