Increased mineralisation rate and bone formation after surgery or fracture is the regional acceleratory phenomenon (RAP), and its systemic impact is the systemic acceleratory phenomenon (SAP). The proportion of circulating osteoblast lineage cells, including osteocalcin-positive (OCN⁺) cells, in the peripheral blood is markedly higher during pubertal growth and in patients with bone fractures. This study aimed to elucidate the dynamic changes in bone metabolic activity after orthognathic surgery by longitudinal prospective observation. Peripheral venous blood samples were collected from patients who had undergone orthognathic surgery, and serum bone metabolic markers and the proportion of OCN⁺ cells were measured. Orthognathic surgery induces systemic dynamic changes in bone metabolic activity by targeting steps in the bone healing process and related proteins, such as surgical stress/inflammation (C-reactive protein), bone resorption (type I collagen C-telopeptide), and bone formation (alkaline phosphatase and bone-specific alkaline phosphatase). During the early post-operative period, the population of OCN⁺ cells significantly increased. Confocal microscopy revealed that OCN proteins were localised in the cytoplasm in Triton X-100-treated OCN⁺ cells. Furthermore, OCN, ALP, and COL1A1 gene expression was detected in OCN⁺ cells, suggesting the contribution of the local maturation of bone marrow-derived OCN⁺ cells at the site of bone healing.

Bisphosphonates (BPs) are classified into two groups, according to their side chain structures, as nitrogen-containing BPs (NBPs) and non-nitrogen-containing BPs (non-NBPs). In this study, we examined the effects of NBPs and non-NBPs on inflammatory responses, by quantifying the inflammatory mediators, prostaglandin E₂ (PGE₂) and nitric oxide (NO), in cultured neonatal mouse calvaria. All examined NBPs (pamidronate, alendronate, incadronate, risedronate, zoledronate) stimulated lipopolysaccharide (LPS)-induced PGE₂ and NO production by upregulating COX-2 and iNOS mRNA expression, whereas non-NBPs (etidronate, clodronate, tiludronate) suppressed PGE₂ and NO production, by downregulating gene expression. Additionally, [4-(methylthio) phenylthio] methane bisphosphonate (MPMBP), a novel non-NBP with an antioxidant methylthio phenylthio group in its side chain, exhibited the most potent anti-inflammatory activity among non-NBPs. Furthermore, results of immunohistochemistry showed that the nuclear translocation of NF-κB/p65 and tyrosine nitration of cytoplasmic protein were stimulated by zoledronate, while MPMBP inhibited these phenomena, by acting as a superoxide anion (O₂⁻) scavenger. These findings indicate that MPMBP can act as an efficacious agent that causes fewer adverse effects in patients with inflammatory bone diseases, including periodontitis and rheumatoid arthritis.