Pharmacological effects of PTH1R agonists on jaw bone fracture, periodontitis, orthodontic treatment and MRONJ: a view from dosing regimen settings

BACKGROUND: Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are endogenous ligands of PTH type I receptor (PTH1R), which are essential for skeletal development and homeostasis. Since the intermittent application of these molecules to organisms exerts bone anabolic effects, they are used pharmacologically to increase bone mass and stimulate bone formation. Teriparatide, an N-terminal 34 amino acid fragment of human PTH, and abaloparatide, a derivative of the N-terminal 34 amino acid of human PTHrP, have been pharmaceutically developed and clinically applied to treat severe osteoporosis and are categorized as PTH1R agonists. An increasing number of clinical and preclinical studies have demonstrated that PTH1R agonists can be used in dental medicine, including jaw bone regeneration and orthodontic treatment, periodontitis, and the management of medication-related osteonecrosis of the jaw (MRONJ). However, it is unclear whether the mandibular bone responds pharmacologically to PTH1R agonists in the same way as other trunk bones, such as the limb and axial bones. HIGHLIGHT: Compared with studies using long and vertebral bones, the beneficial effects of PTH1R agonists on the mandibular bone appear to require higher doses and longer treatment durations. CONCLUSION: Clinical application of PTH1R agonists in dental medicine may result in promising outcomes. However, dosing regimens and the timing of their application should be further investigated with knowledge of the biological uniqueness of the mandibular bone.