Abaloparatide and teriparatide enhance mandibular growth in adolescent rats with site- specific effects

Abstract Aims Teriparatide (TPTD) and abaloparatide (ABL) are two osteoanabolic drugs targeting PTH1R signaling. This study aimed to investigate the effects of TPTD and ABL on adolescent mandibular growth. Method Seventy 4-week-old male SD rats were randomly divided into 14 groups, treated with intermittent TPDT or ABL at various doses, accompanied by mandibular advancement (MA) or not. 3D printing was used to fabricate an innovative splint for MA. After 4-week treatment, morphological measurement, histological and immunohistochemical analysis were performed. Mandibular condylar chondrocytes (MCCs) were treated with TPTD or ABL, followed by CCK-8 assay, alcian blue staining, RT-PCR and immunofluorescent staining. Result In vivo, TPTD or ABL alone increased the condylar length and cartilage thickness, with up-regulated SOX9 and COL II, whilst down-regulated COL X; however, when combined with MA, the promotive effects were attenuated. TPTD or ABL alone increased the mandibular body height and mandibular angle width, whilst increased the mandibular body length and alveolar bone width when combined with MA. In vitro, TPTD or ABL enhanced the MCC proliferation, glycosaminoglycan synthesis, COL II and SOX9 expression, whilst down-regulated COL X, Ihh and PTH1R expression. Conclusion Abaloparatide or teriparatide alone increases the mandibular condylar length and cartilage thickness, mandibular body height and mandibular angle width. When combined with MA, they also increase the mandibular body length and alveolar bone width. In general, ABL seems more potent than TPTD. Clinical Relevance: Abaloparatide or teriparatide may be potential drugs for growth modification of the mandible, combined with functional appliance treatment or not.