Teriparatide-induced alleviation of medication-related osteonecrosis of the jaw: Potential molecular mechanisms

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a significant side effect of drugs such as bone modifying agents (BMA) or angiogenesis inhibitors. The incidence has been rising but the clinical prognosis is dismal. Teriparatide (TPTD), a synthetic derivative of parathyroid hormone (PTH), is occasionally demonstrated to efficiently reduced the clinical incidence of MRONJ in particular patients. However, the precise signaling mechanisms involved in TPTD-induced MRONJ repair are unknown. Currently, MRONJ progression is involved with decreased expression of the Wnt/β-catenin signaling pathway, inhibition of angiogenic function, and up-regulated inflammatory cytokines (IL-1β, TNF-α, and IL-6). Notably, in animal model experiments, TPTD increased β-catenin expression in alveolar bone and skeletal muscle; similarly, TPTD was able to reduce the area of cerebral infarction, restore cerebral blood flow, and improve neovascularization by increasing the number of blood vessels in bone tunnels and enlarging the diameter of blood vessels in the bone marrow. Furthermore, TPTD can also treat osteoarthritis in animals by suppressing inflammatory markers such as TNF- and IL-6. Thus, we propose that TPTD can cure MRONJ by dynamically modulating various signaling pathways (stimulation of the Wnt/β-catenin signaling pathway, promotion of angiogenesis, and down-regulation of inflammatory markers).