Residual ridge resorption (RRR) is a chronic and progressive
bone resorption following
tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a
tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied
ovariectomy to this model to elucidate the effects of
osteoporosis on RRR progression. As a result, the
alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Histological analysis indicated that
ovariectomy prolonged the activation of osteoclasts in the alveolar bone. Furthermore, the expressions of Tnfsf11 and
Sema4d kept increasing for a long time in OVX mice. Administration of neutralization
antibodies for receptor activator of NF-κB
ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of
Semaphorin 4D (
Sema4D) also improved
alveolar bone loss. This study demonstrated that reduced ovarian function may be a risk factor for RRR and that RANKL and
Sema4D suppression are potential treatments.