Head and neck cancer is among the top ten cancers worldwide, with most lesions in the oral cavity. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral malignancies and is a significant public health concern. Patients with OSCC are at increased risk for developing concomitant tumors, especially in the oral cavity, due to widely genetically susceptible mucosa to carcinogenic factors. Based on fulfilling specific criteria, these concomitant tumors can be called second primary tumors (SPTs), which can be further categorized into metachronous and synchronous tumors. This research reviews the literature that investigated the concurrent OSCC with second or multiple primaries to improve understanding of the definition, classification guidelines, and its effect on cancer survival. It also highlights the current investigation methods, the variation of standard treatment approaches due to such a phenomenon, and preventive measures discussed in the literature.

The aim of this in vivo study was to evaluate the efficacy of biphasic calcium phosphate (Maxresorb^®, BCP) used in combination with hyaluronic acid (Hyadent^®, HyA) gel for regeneration of osseous defects in a rat model. Bilateral femoral condylar bone defects (3 mm diameter and 3 mm depth) were created in 40 male Wistar rats. The defects were grafted as group I (BCP only), group II (BCP + HyA), group III (HyA only), and group IV (empty control). At four weeks and 10 weeks, the bone specimens were evaluated using histological and histomorphometrical analyses to identify the newly formed bone area (NF-BA (%)), as well as the remaining BCP particles (R-BCP (%)). Light microscopic examination indicated the absence of an inflammatory reaction within the bone defects after four weeks or 10 weeks of implantation. Significant new bone regeneration was present in the bone defects grafted with BCP or BCP + HyA biomaterials, as early as four weeks, compared to control groups. The addition of HyA to BCP did not significantly improve bone regeneration at four weeks or 10 weeks. Nevertheless, its role in bone healing and regeneration warrants further investigation.

Introduction: This meta-analysis of relevant animal studies was conducted to assess whether the use of porous-surface implants improves osseointegration compared to the use of non-porous-surface implants. Material and methods An electronic search of PubMed (MEDLINE) resulted in the selection of ten animal studies (out of 865 publications) for characterization and quality assessment. Risk of bias assessment indicated poor reporting for the majority of studies. The results for bone-implant contact (BIC%) and peri-implant bone formation (BF%) were extracted from the eligible studies and used for the meta-analysis. Data for porous-surface implants were compared to those for non-porous-surface implants, which were considered as the controls. Results: The random-effects meta-analysis showed that the use of porous-surface implants did not significantly increase overall BIC% (mean difference or MD: 3.63%; 95% confidence interval or 95% CI: −1.66 to 8.91; p = 0.18), whereas it significantly increased overall BF% (MD: 5.43%; CI: 2.20 to 8.67; p = 0.001), as compared to the controls. Conclusion: Porous-surface implants promote osseointegration with increase in BF%. However, their use shows no significant effect on BIC%. Further preclinical and clinical investigations are required to find conclusive evidence on the effect of porous-surface implants.

Studies in humans suggest that vitamin K is involved in the regulation of bone remodeling, but the precise mechanism at play remains unknown. In cells, vitamin K functions as a co-factor for the γ-glutamyl carboxylase (GGCX), an enzyme responsible for the conversion of glutamic acid residues (Glu) into γ-carboxyglutamic acid (Gla) residues in secreted proteins. We aim here at determining the role of γ-carboxylation in bone remodeling and at identifying the Gla protein(s) involved. We show that male mice lacking γ-carboxylation specifically in osteoblasts ( Ggcx ^flox/flox ; OCN-Cre ) have increased bone mass at 6 months of age due to a reduced number of multinucleated bone resorbing osteoclasts. In co-culture experiments, Ggcx -deficient osteoblasts were less effective than control osteoblasts at supporting osteoclast formation. Among known Gla proteins, we identify GAS6 as an osteoblast-secreted γ-carboxylated factor which signals to differentiating osteoclasts. The GAS6 receptors MerTK and AXL are expressed in pre-osteoclasts and pharmacological inhibitors of AXL and MerTK block osteoclast generation in co-culture. Conversely, recombinant γ-carboxylated GAS6 dose-dependently increases the size of osteoclasts and the number of nuclei per osteoclast in culture. GAS6 marginally affected the induction of osteoclast-specific genes during osteoclast differentiation but significantly increased pre-osteoclast fusion. Finally, increasing bone marrow GAS6 level in transgenic male mice was sufficient to increase the number and size of osteoclasts and to decrease bone mass. This work identifies GAS6 as a novel osteoblast-derived vitamin K-dependent protein regulating osteoclast maturation.