Risk factors for dental findings of the development of medication-related osteonecrosis of the jaw: Investigation of 3734 teeth in cancer patients receiving high dose antiresorptive agents.

Background/purpose: Local infection is a risk factor for medication-related osteonecrosis of the jaw (MRONJ), along with invasive dental treatment of the bone; the tooth that is the source of infection should be extracted prior to the administration of bone resorption inhibitors. However, which teeth should be extracted remains unclear. This study aimed to determine the relationship between dental findings prior to high-dose antiresorptive agent (ARA) administration and the subsequent development of MRONJ. Materials and methods: Patients with cancer who were scheduled to receive high-dose ARAs and referred to our hospital between 2011 and 2020 were included in this retrospective study. Apical lesions, enlargement of the periodontal space, thickening of the lamina dura, alveolar bone resorption of >1/3, periapical osteosclerosis, and local infection symptoms in each tooth were investigated using medical records and panoramic radiographs. Results: A total of 172 patients, 329 jaws, and 3734 teeth were registered. MRONJ developed in 68 teeth in 33 jaws of 32 patients. In tooth-by-tooth analysis, fewer teeth (P < 0.001), apical lesions (P < 0.001), periapical osteosclerosis (P < 0.001), local infection symptoms (P = 0.002), and one or more dental findings (P < 0.001) were significant factors for MRONJ development. In jaw-by-jaw analysis, old age, local infection symptoms, and number of radiographic abnormalities per tooth were significant. In patient-by-patient analysis, patients with diabetes and those with fewer teeth developed MRONJ. Conclusion: Patients with fewer teeth, apical lesions, periapical osteosclerosis, and local infection were more likely to develop MRONJ. Therefore, these teeth should be treated as much as possible before ARA administration.

Swallowing Functions after Sagittal Split Ramus Osteotomy with Loose Fixation for Mandibular Prognathism: A Retrospective Case Series Research.

Sagittal split ramus osteotomy (SSRO) is a standard surgical technique for patients with mandibular prognathism. However, the appropriate position of the proximal fragment is not strictly defined, and rigid fixation can induce early postoperative skeletal relapse and temporomandibular (TMJ) disorders. Loose fixation can be expected to seat the proximal bone fragments in a physiologically appropriate position, thereby reducing adverse events. Although long-term skeletal stability has been achieved using SSRO without fixation, the evaluation of preoperative and postoperative eating and swallowing functions remains unclear, and this study aimed to clarify this point. We evaluated mastication time, oral transfer time, and pharyngeal transfer time using videofluorography (VF) preoperatively, two months postoperatively, and six months postoperatively, and along with the position of anatomical landmarks using cephalometric radiographs, modified water swallowing test (MWST), food test (FT), and repetitive saliva swallowing test (RSST) were used to evaluate postoperative swallowing function. Four patients (one male, three females; mean (range) age 26.5 (18-51) years) were included, with a mean setback of 9.5 mm and 6.5 mm on the right and left sides, respectively. Postoperative eating and swallowing functions were good in VF, cephalometric analysis, MWST, FT, and RSST. In the present study, good results for postoperative eating and swallowing functions were obtained in SSRO with loose fixation of the proximal and distal bone segments.

A preliminary clinical study of segmental mandibulectomy on medication-related osteonecrosis of the jaw.

BACKGROUND/PURPOSE: Recently, many reports have recommended surgical treatment for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ is more likely to occur in older patients with poor general condition and often necessitates extensive surgery, such as segmental mandibulectomy. The purpose of this study was to investigate treatment outcome of patients with MRONJ undergoing segmental mandibulectomy. MATERIALS AND METHODS: This retrospective study included 137 patients with medication-related osteonecrosis of the lower jaw who underwent surgical treatment at our hospital between 2011 and 2019. A total of 168 surgeries (155 marginal mandibulectomies and 13 segmental mandibulectomies) were performed. The relationship between clinical and imaging factors and the treatment outcome was investigated in the segmental mandibulectomy cases. RESULTS: Preoperative computed tomography (CT) showed osteolytic lesions in 13/13, periosteal reaction (PR) in 12/13, and osteosclerosis in 12/13 cases of segmental mandibulectomy. On postoperative CT, no residual osteolytic lesion and PR were noted, and 9 cases showed osteosclerosis. Twelve patients (92.3%) undergoing segmental mandibulectomy had complete healing, whereas the cure rate of those undergoing marginal mandibulectomy was 104/155 (67.1%). One patient with relapse after segmental mandibulectomy showed healing after an additional resection. In the patients who underwent segmental mandibulectomy, clinical symptoms, such as pain and purulent discharge, disappeared, and oral intake was possible. CONCLUSION: Segmental mandibulectomy is a treatment option for end-of-life care of refractory MRONJ, because it can eliminate clinical symptoms early. When performing segmental mandibulectomy, the area of the osteolytic lesion and periosteal reaction needs to be included.

Surgical strategy for medication-related osteonecrosis of the jaw (MRONJ) on maxilla: A multicenter retrospective study.

BACKGROUND/PURPOSE: Because the anatomy and the nature of the bone tissue between the mandible and maxilla are largely different, more site-specific studies are required to improve the healing rate on medication-related osteonecrosis of the jaw (MRONJ). The present study assessed maxillary MRONJ that was treated by surgery to understand its clinical characteristics, and to identify critical factors that influenced outcomes. MATERIALS AND METHODS: The medical records of 54 patients with maxillary MRONJ who underwent surgery were retrospectively reviewed. Variables related to the prognosis of MRONJ were extracted from the medical records and imaging, and were statistically analyzed. We also evaluated the concomitant maxillary sinusitis (MS) after the surgical treatment of MRONJ, based on CT evaluation and change of symptoms. RESULTS: The healing rate of surgery for maxillary MRONJ was 85.2%, which suggested that surgical treatment is an effective strategy for treating maxillary MRONJ. Multivariate analysis revealed that postoperative residual necrotic bone was a poor prognosticator for maxillary MRONJ. Among 10 patients who did not obtain healing of MS postoperatively, 8 patients showed an improvement. CONCLUSION: Our results indicate that surgical treatment is an appropriate strategy for maxillary MRONJ and complete resection of necrotic bone (i.e., extensive surgery) is needed to obtain complete healing of maxillary MRONJ. Concomitant MS tends to be healed or improved clinically in combination with the healing of maxillary MRONJ.

Predisposing conditions for condylar sag after intraoral vertical ramus osteotomy.

Intraoral vertical ramus osteotomy (IVRO) is used to treat mandibular prognathism and temporomandibular disorders. However, the improvement of temporomandibular disorders after IVRO is considered to be due to the anterior and downward movement of the mandibular condyle, which may lead to condylar sag, and in the worst case, condylar luxation. In this retrospective cohort study, we examined factors potentially associated with condylar sag. Univariate analysis indicated that condylar sag was significantly associated with the following factors: magnitude of setback (P = 0.001), less than 3 mm setback (P < 0.001), presence of temporomandibular joint (TMJ) symptoms (P = 0.002), Wilkes classification (P = 0.039), occlusal cant correction ≥ 2 mm (P = 0.018), and mandibular condyle deformation (P < 0.001). Setback magnitude (P = 0.032) and TMJ symptoms (P = 0.007) remained significant in the multivariate analysis. In the receiver operating characteristic curve, the setback magnitude cut-off value for condylar sag after IVRO was 3.25 mm. Thus, the incidence of condylar sag after IVRO is increased with a smaller setback magnitude (≤ 3.25 mm) and the presence of TMJ symptoms. These factors should be evaluated by surgeons during treatment planning for IVRO to estimate condylar sag, and it may be possible to predict the risk of condylar luxation.

Inhibitory effect of topical antibiotics/antiseptics administration on bacterial growth in the open wound of the jawbone surgery: Randomized controlled, preliminary study.

BACKGROUND/PURPOSE: TThe bone cavities after extirpation of cysts or tumor of the jawbone requires the insertion of gauze containing various antibiotics/antiseptics to minimize the risk of pain, bleeding, and surgical site infection (SSI). However, there have been few reports on the efficacy of topical administration of antibiotics/antiseptics to an open wound of the jawbone. To compare the inhibitory effects of topical povidone-iodine gel and tetracycline ointment on the jawbone wound bacterial growth after extirpation of cyst or tumor. MATERIALS AND METHODS: This is a preliminary, randomized controlled, open-labeled trial. Eighteen patients were randomly assigned into two groups. In povidone-iodine (PI) group, gauze mixed with povidone-iodine gel was inserted into the bone cavity wound, and in tetracycline (TC) group gauze mixed with tetracycline ointment was inserted after extirpation of cyst or tumor of the jaw bone. In both groups, gauze was removed 48 h after surgery, and examined by bacterial culture and real-time polymerase chain reaction (PCR) using primers detecting total bacteria and MRSA. RESULTS: The topical application of tetracycline ointment was superior to that of povidone-iodine gel concerning inhibitory effects of total bacteria and methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: This preliminary study suggests that the insertion of gauze mixed with tetracycline ointment is recommended for bone wounds after extirpation of cyst or tumor of the oral cavity.

Effect of periosteal reaction in medication-related osteonecrosis of the jaw on treatment outcome after surgery.

INTRODUCTION: Surgical treatment in patients with medication-related osteonecrosis of the jaw (MRONJ) is superior to conservative treatment. However, treatment outcome in patients with periosteal reaction (PR) was significantly poorer than that of those without PR. The purpose of this retrospective study was to analyze the pathophysiology and clinical significance of PR in MRONJ. MATERIALS AND METHODS: Out of 181 patients with MRONJ undergoing surgery, 38 patients with PR were enrolled in the study. CT examinations, histological examinations, and bacteriological examinations using real-time polymerase chain reaction were performed, and the relationship among the opted surgical method, CT findings, and treatment outcome was investigated. RESULTS: The pattern of PR was classified into three types: type 1, new bone is formed parallel to the mandible, and no gap was evident between the mandible and new bone; type 2, new bone is formed parallel to the mandible, and a gap was evident between them; type 3, an irregular shape. Histological examinations revealed inflammatory tissue in the area visualized as a gap on CT. Bacteriological examination showed the presence of bacteria in the type 2 or type 3 PR. Complete cure was observed in 21 of 38 (55.3%) patients, which was lower than the cure rate of 73.4% in 143 patients without PR. The cure rate was significantly lower in cases with type 3 PR or with persistent osteolysis. CONCLUSIONS: It seems that complete resection of both osteolytic area and type 3 PR is necessary to obtain complete healing in patients undergoing marginal mandibulectomy.

Anterior relapse or posterior drift after intraoral vertical ramus osteotomy.

This study aimed to evaluate the factors contributing to postoperative anterior relapse or posterior drift of the distal segment after intraoral vertical ramus osteotomy. A retrospective cohort study was conducted which included 31 patients who underwent setback surgery for mandibular prognathism by the intraoral vertical ramus osteotomy technique. Uni- and multivariate analyses were performed to determine the association of potential explanatory variables (sex, age, magnitude of setback, differences in setback magnitude between sides (right/left), duration of splint use, Angle's classification of malocclusion, mandibular angle, and tightness of occlusion of the molars) with positional changes in the distal segment. The setback magnitude was only significant factor affecting (P = 0.015) for posterior drift, with significant posterior in setback magnitudes of less than 7.25 mm. Posterior drift after intraoral vertical ramus osteotomy is less likely if setback magnitude exceeds 7.25 mm. For setbacks less than 7.25 mm, posterior drift should either be carefully corrected postoperatively, or an alternative surgical technique should be used. The setback magnitude showed a significant association with the risk of posterior drift following intraoral vertical ramus osteotomy, and the determined cut-off value may serve as a predictor for postoperative outcomes.

Prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction on warfarin therapy: a multicenter retrospective study in Japan.

Postoperative hemorrhage after tooth extraction is a critical and clinically important issue for clinicians and patients receiving anticoagulants. The purpose of the present study was to investigate the prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction in Japanese patients receiving warfarin therapy. A total of 142 patients who underwent lower third molar extraction between January 2010 and December 2016 were included, and their medical records were retrospectively reviewed. The prevalence of and risk factors for postoperative hemorrhage were investigated. The prevalence of postoperative hemorrhage after lower third molar extraction was significantly higher in patients receiving warfarin than in healthy subjects (21.8% vs 0.7%, P < 0.001). The cutoff value for PT-INR was 2.11 based on a receiver-operating characteristic analysis. A multivariate analysis indicated that an elevated PT-INR value [hazard ratio (HR) 3.798, 95% confidence interval (CI) 1.400-10.467, P < 0.01], preoperative antibiotic administration (HR 4.434, 95% CI 1.591-14.775, P < 0.01), difficulties with intraoperative hemostasis (HR 16.298, 95% CI 2.986-110.677, P < 0.01), and higher serum creatinine levels (HR 7.465, 95% CI 1.616-39.576, P < 0.05) are significant predictors of postoperative hemorrhage after lower third molar extraction. Multivariate correlations were observed between risk factors including an elevated PT-INR value, preoperative antibiotic administration, and higher serum creatinine levels, and postoperative hemorrhage after lower third molar extraction in patients receiving warfarin therapy. Clinicians need to consider these risk factors for postoperative hemorrhage after the lower third molar extraction and monitor PT-INR in patients receiving warfarin therapy.

Effects of the changes in the condylar long axis angle and condylar position on temporomandibular symptoms after intraoral vertical ramus osteotomy: a preliminary study.

OBJECTIVE: This study was conducted to characterize the effects of the changes in the condylar long axis and position on temporomandibular symptoms with respect proximal segment position after intraoral vertical ramus osteotomy (IVRO). STUDY DESIGN: Twenty Japanese patients with diagnosed jaw deformity underwent IVRO without internal fixation. Long-term changes in condylar long axis and position were assessed during postoperative follow-up examinations by using computed tomography, and t tests were performed for comparison. In addition, changes in temporomandibular symptoms were examined. RESULTS: The degree of axial rotation of the proximal segment changed significantly when the proximal segment was located laterally. Downward changes in condylar position significantly differed when the proximal segment was located posterolaterally. Forward changes in condylar position significantly differed when the proximal segment was located laterally; moreover, when the proximal segment was located laterally, temporomandibular symptoms disappeared. CONCLUSIONS: Lateral location of the proximal segment may be an important factor in the positive effects of IVRO, with respect to temporomandibular symptoms.

Clinical complications in the application of polyglycolic acid sheets with fibrin glue after resection of mucosal lesions in oral cavity.

OBJECTIVES: Covering open wounds with a polyglycolic acid (PGA) sheet using fibrin glue after resection of oral mucosal lesions is reportedly useful. We focused on clinical complications of this procedure: development of marked granuloma-like neoplasm (GLN) and abnormal postoperative bleeding (APB) on the resected region. STUDY DESIGN: The characteristics of 100 cases with PGA sheet application after the resection of oral mucosal lesion were examined retrospectively by the medical records and/or oral photographs at our department between 2010 and 2016. RESULTS: Our retrospective analysis identified included 8 cases of GLN development and 7 cases of APB. There was a significantly higher risk of GLN development when the PGA sheet was applied to the raw surface of the tongue. There were no immediate APBs, but 4 APBs occurred several hours after surgery. All APB cases involved the tongue. CONCLUSIONS: Both GLNs and APBs are minor complications. Although all cases of GLNs did not involve the recurrence of a tumor, follow-up with incisional or excisional biopsy should be performed. APB in the oral cavity induced by the PGA sheet peeling due to fluctuating adhesive force of the PGA sheets and fibrin glue can sometimes induce life-threatening events.

Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence.

The aim of the present study was to identify the most useful markers for predicting recurrence of keratocystic odontogenic tumors (KCOTs). A total of 65 tumor samples from 63 patients diagnosed with typical parakeratinized cysts and KCOTs between 1992 and 2014 were retrospectively studied. Clinical and histopathological data and treatment modality were reviewed. In addition, the expression profiles of Ki-67, cluster of differentiation (CD)34 and podoplanin were assessed using immunohistochemistry. The association between these factors and the rate of KCOT recurrence was evaluated. The presence of daughter cysts, epithelial islands and high Ki-67, CD34 and podoplanin expression levels were revealed to be associated with tumor recurrence. In particular, univariate analysis revealed that high CD34 expression levels were significantly associated with tumor recurrence (P=0.034), as was conservative surgical treatment (P=0.003). Multivariate analysis revealed that conservative treatment was the greatest independent risk factor for tumor recurrence (odds ratio=13.337; P=0.018). These results suggest that overexpression of CD34 may be a potent predictor of tumor recurrence and radical treatment of the teeth that are in contact with the tumors is recommended in order to prevent tumor recurrence.

Multicenter Retrospective Study of the Risk Factors of Hemorrhage After Tooth Extraction in Patients Receiving Antiplatelet Therapy.

PURPOSE: To identify the risk factors affecting hemorrhage after tooth extraction in patients receiving antiplatelet therapy, this study investigated the relation between various factors and hemorrhage events after tooth extraction. PATIENTS AND METHODS: The records of 264 patients receiving antiplatelet therapy who underwent tooth extraction were retrospectively reviewed from 6 institutions belonging to the Japanese Study Group of Cooperative Dentistry with Medicine. Demographic information, hemorrhage events after tooth extraction, the presence or absence of comorbidities, antiplatelet agent, the use of preoperative antibiotics or nonsteroidal anti-inflammatory drugs, number of teeth extracted, serum creatinine level, estimated glomerular filtration rate, and alanine transaminase level were assessed. Risk factors for hemorrhage after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: The study population of 264 patients consisted of 153 men and 111 women with a mean age of 73.6 years (range, 24 to 96 yr). Six hundred ninety-four teeth were extracted (mean, 2.6 ± 2.3 teeth per patient). In patients receiving antiplatelet therapy, the frequency of hemorrhage after tooth extraction, including mild and self-controlled hemorrhages, was 17.4%. Univariate analysis showed that serum creatinine level and dual antiplatelet therapy were correlated with hemorrhage after tooth extraction (P = .001 and P = .049, respectively). Only serum creatinine was identified as an independent risk factor for hemorrhage after tooth extraction in patients receiving antiplatelet therapy (P = .037). CONCLUSIONS: The risk of hemorrhage after tooth extraction is increased in patients receiving dual antiplatelet therapy with or without chronic kidney disease. Local hemostatic treatments, such as at least suturing, are recommended.

Clinical Roles of Interleukin-6 and STAT3 in Oral Squamous Cell Carcinoma.

The effect inflammation has on cancer prognosis is marked by the presence of cytokines and chemokines. Interleukin-6 (IL-6) is one a multifunctional cytokine that regulates inflammatory responses. We investigated the roles of IL-6 and STAT3 and examined the relationship between IL-6 signaling and clinicopathological factors in patients with oral squamous cell carcinoma (OSCC). We retrospectively examined 116 patients who underwent radical surgery for OSCC. IL-6 and STAT3 expression were detected by immunohistochemistry. IL-6 and STAT3 positivity were detected by IHC, at 78.4 and 80.2 %, respectively. IL-6 expression was significantly associated with pattern of invasion (P = 0.004), vascular invasion (P = 0.003), and pathological nodal status (P = 0.019). Multivariate logistic regression analysis revealed that IL-6 expression was significantly associated with vascular invasion (P = 0.044). Meanwhile, there was no significant association between STAT3 expression and clinicopathological factors and no significant relationship between IL-6 and STAT3 expression. IL-6 expression was significantly associated with 5-year disease-free survival. These results suggest that IL-6 is involved in lymphangiogenesis and recurrence in OSCC.

Spindle cell variant of ameloblastic carcinoma: a case report and literature review.

Spindle cell variant of ameloblastic carcinoma is an extremely rare tumor. Severe dedifferentiated spindle cell variants are diagnostically challenging, particularly in small biopsy specimens. Here, we report a case of spindle cell variant of ameloblastic carcinoma in the mandible of a 69-year-old male patient and review the available literature. The tumor was surgically resected under general anesthesia. Histopathologic diagnosis of spindle cell carcinoma was made on incisional biopsy, and the final diagnosis was confirmed as spindle cell variant of ameloblastic carcinoma. Immunohistochemistry using cytokeratin and CK19 is helpful in determining the origin of spindle cell variant of ameloblastic carcinoma, particularly CK19 indicated that sarcomatoid spindle cells are derived from odontogenic epithelium. A review demonstrated higher mean age of patients compared with that of other types of ameloblastic carcinoma. The rates of mortality and local recurrence were concurrently 30%. No recurrence or metastasis was seen in the 23-month follow-up period in the present case.

Application of polyglycolic acid sheets and fibrin glue spray to bone surfaces during oral surgery: a case series.

PURPOSE: Previous studies have described the use of a combination of polyglycolic acid (PGA) sheets (a resorbable biomaterial) and fibrin glue spray to treat open soft tissue wounds during oral surgery, which have produced good results. However, there have not been any detailed investigations of the use of these materials to treat exposed hard tissue wounds. This study investigated the combination of PGA sheets and fibrin glue spray to treat exposed bone surfaces during oral surgery. MATERIALS AND METHODS: PGA sheets and fibrin glue spray were applied to exposed bone surfaces after lesion resection in 8 patients (10 sites) who had been diagnosed with malignant tumors. The sheets were cut into pieces (width, 5 to 10 mm) and applied to the exposed bone surface. RESULTS: PGA adhesion was confirmed for the final time on postoperative days 28 to 56 (mean, 35.8 days), and there were no cases in which the PGA sheets fell off the wound prematurely. Epithelialization of the wound surface occurred gradually and was complete by postoperative weeks 4 to 5, regardless of the size of the wound. CONCLUSION: This method was considered very effective at preventing postoperative bleeding, alleviating postoperative pain, and promoting epithelialization during the reconstruction of bone surfaces after tumor resection in the oral cavity.

Anti-tumor effect of the mammalian target of rapamycin inhibitor everolimus in oral squamous cell carcinoma.

The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC-2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P < 0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P < 0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC.

Lipomas of the oral cavity: clinicopathological and immunohistochemical study of 24 cases and review of the literature.

Although lipomas are common soft tissue tumors, few cases of lipoma or its variants have been reported in the oral cavity. We here described the clinical, histological, and immunohistochemical features of 24 cases of oral lipoma obtained from medical records at Nagasaki University Hospital between 1977 and 2010, and also retrospectively reviewed 603 cases of oral lipoma reported in the English literatures. The patients examined comprised 11 men and 13 women with a mean age of 59 years, ranging from 31 to 90 years. The main sites involved were the buccal mucosa (n = 9), followed by the tongue (n = 4), lip and retromolar area (n = 3), floor of the mouth (n = 2), and gingiva (n = 1). The mean tumor size was 2.0 cm, ranging from 0.2 to 5 cm. Histological analysis revealed 20 cases of lipoma, 2 cases of fibrolipoma, and one case each of intramuscular lipoma and spindle cell lipoma. Twenty-three cases were treated surgically while one case underwent biopsy and follow-up. Recurrence was not observed in any case. We reviewed the English literatures, and similar results were obtained. In immunohistochemical analysis, PCNA and ki-67 expression indices were higher in intramuscular lipoma cases than in its variants. Especially, it showed that a long time follow-up may be necessary in ki-67 positive cases.

Cbfb regulates bone development by stabilizing Runx family proteins.

Runx family proteins, Runx1, Runx2, and Runx3, play important roles in skeletal development. Runx2 is required for osteoblast differentiation and chondrocyte maturation, and haplodeficiency of RUNX2 causes cleidocranial dysplasia, which is characterized by open fontanelles and sutures and hypoplastic clavicles. Cbfb forms a heterodimer with Runx family proteins and enhances their DNA-binding capacity. Cbfb-deficient (Cbfb(-/-) ) mice die at midgestation because of the lack of fetal liver hematopoiesis. We previously reported that the partial rescue of hematopoiesis in Cbfb(-/-) mice revealed the requirement of Cbfb in skeletal development. However, the precise functions of Cbfb in skeletal development still remain to be clarified. We deleted Cbfb in mesenchymal cells giving rise to both chondrocyte and osteoblast lineages by mating Cbfb(fl/fl) mice with Dermo1 Cre knock-in mice. Cbfb(fl/fl/Cre) mice showed dwarfism, both intramembranous and endochondral ossifications were retarded, and chondrocyte maturation and proliferation and osteoblast differentiation were inhibited. The differentiation of chondrocytes and osteoblasts were severely inhibited in vitro, and the reporter activities of Ihh, Col10a1, and Bglap2 promoter constructs were reduced in Cbfb(fl/fl/Cre) chondrocytes or osteoblasts. The proteins of Runx1, Runx2, and Runx3 were reduced in the cartilaginous limb skeletons and calvariae of Cbfb(fl/fl/Cre) embryos compared with the respective protein in the respective tissue of Cbfb(fl/fl) embryos at E15.5, although the reduction of Runx2 protein in calvariae was much milder than that in cartilaginous limb skeletons. All of the Runx family proteins were severely reduced in Cbfb(fl/fl/Cre) primary osteoblasts, and Runx2 protein was less stable in Cbfb(fl/fl/Cre) osteoblasts than Cbfb(fl/fl) osteoblasts. These findings indicate that Cbfb is required for skeletal development by regulating chondrocyte differentiation and proliferation and osteoblast differentiation; that Cbfb plays an important role in the stabilization of Runx family proteins; and that Runx2 protein stability is less dependent on Cbfb in calvariae than in cartilaginous limb skeletons.