Akira Taguchi

Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons.

Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of osteoporosis, malignant hypercalcemia, bone metastasis of solid cancers, and multiple myeloma bone diseases. Accumulating recent reports describe that surgical dental treatments in patients with cancer or osteoporosis who have been receiving intravenous or oral BPs are associated with osteonecrosis of the jaw (bisphosphonate-related osteonecrosis of the jaw, BRONJ). The accurate incidence, clinical backgrounds, and pathogenesis of BRONJ have been unclear and appropriate approaches for prevention and treatment have not been established to date. To address the current situation of BRONJ in Japan, the “Allied Task Force Committee of Bisphosphonate-Related Osteonecrosis of the Jaw,” consisting of physicians specializing in bone biology, orthopedic surgery, rheumatology, obstetrics/gynecology, and medical oncology and dentists specializing in oral surgery, periodontology, dental radiology, and oral pathology, was organized. The committee attempted to propose a standard position paper for the treatment of BRONJ. The committee expects that this proposal will provide objective and correct scientific information on BRONJ and will serve as a reference for conducting dental procedures for patients receiving BPs and in designing prevention and treatment of BRONJ. However, because this position paper is not based on direct clinical evidence, it should be used as a reference, and a decision on treatment in each case should be made after an extensive discussion among physicians, dentists/oral surgeons, and the patients.

Oral infection-inflammatory pathway, periodontitis, is a risk factor for endothelial dysfunction in patients with coronary artery disease

OBJECTIVEnSeveral studies have shown that periodontitis is a risk factor for cardiovascular diseases. There is an association between inflammation and endothelial dysfunction. The purpose of this study was to evaluate endothelial function in patients with coronary artery disease (CAD) who had periodontitis.nnnMETHODS AND RESULTSnWe evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients with periodontitis (37 men and 11 women, 63+/-12 yr) and without periodontitis (36 men and 17 women, 62+/-13 yr). FBF was measured by using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the non-periodontitis group. FBF response to ACh was significantly smaller in the periodontitis group than in the non-periodontitis group. SNP-stimulated vasodilation was similar in the two groups. Periodontal therapy reduced serum concentrations of C-reactive protein from 2.7+/-1.9 to 1.8+/-0.9mg/L (P<0.05) and interleukin-6 from 2.6+/-3.4 to 1.6+/-2.6ng/L (P<0.05) and augmented ACh-induced vasodilation from 14.7+/-5.2 to 20.1+/-6.1mL/(min100mL) tissue (P<0.05) in patients with periodontitis. The SNP-stimulated vasodilation was similar before and after treatment. After administration of N(G)-monomethyl-l-arginine, a nitric oxide synthase inhibitor, FBF response to ACh was similar before and after treatment.nnnCONCLUSIONnThese findings suggest that periodontitis is associated with endothelial dysfunction in patients with CAD through a decrease in nitric oxide bioavailability. Systemic inflammation may be, at least in part, a cause and predictor of progression of endothelial dysfunction.

Relationship between dental panoramic radiographic findings and biochemical markers of bone turnover

We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs.

Autologous Bone-Marrow Mononuclear Cell Implantation Reduces Long-Term Major Amputation Risk in Patients With Critical Limb Ischemia A Comparison of Atherosclerotic Peripheral Arterial Disease and Buerger Disease

Background— Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI.nnMethods and Results— We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels.nnConclusions— These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease.nnClinical Trial Registration— URL: . Unique identifier: 001769.Background—Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI. Methods and Results—We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels. Conclusions—These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease. Clinical Trial Registration—URL: http://home.hiroshima-u.ac.jp/angio/. Unique identifier: 001769.

Triage screening for osteoporosis in dental clinics using panoramic radiographs

Many patients with osteoporosis go undiagnosed because typically no symptoms are present before a fracture. Triage screening to refer patients to appropriate medical professionals for further investigation would be useful to address the increase in the incidence of osteoporotic fractures. Dental clinics may offer a new triage screening pathway because dentists frequently take radiographs of bones in the course of dental treatment. A major premise for such triage screening in dental clinics is that dentists can readily use a screening tool in their dental practice. For example, cortical width and shape of the mandible detected on panoramic radiographs may be appropriate indices for triaging individuals with osteoporosis. To date, several investigators have demonstrated significant associations between cortical indices on panoramic radiographs and bone mineral density of the skeleton generally, such as the spine and femur, biochemical markers of bone turnover and risk of osteoporotic fractures. Further, in two recent Japanese clinical trials, approximately 95% of women who were identified by trained dentists in their clinics using cortical shape findings did have osteopenia or osteoporosis. These findings support the possibility that dental clinics may offer a new triage platform to identify individuals with otherwise undetected osteoporosis.

Diagnosis of osteoporosis from dental panoramic radiographs using the support vector machine method in a computer-aided system

BackgroundEarly diagnosis of osteoporosis can potentially decrease the risk of fractures and improve the quality of life. Detection of thin inferior cortices of the mandible on dental panoramic radiographs could be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The aim of our study was to assess the diagnostic efficacy of using kernel-based support vector machine (SVM) learning regarding the cortical width of the mandible on dental panoramic radiographs to identify postmenopausal women with low BMD.MethodsWe employed our newly adopted SVM method for continuous measurement of the cortical width of the mandible on dental panoramic radiographs to identify women with low BMD or osteoporosis. The original X-ray image was enhanced, cortical boundaries were determined, distances among the upper and lower boundaries were evaluated and discrimination was performed by a radial basis function. We evaluated the diagnostic efficacy of this newly developed method for identifying women with low BMD (BMD T-score of -1.0 or less) at the lumbar spine and femoral neck in 100 postmenopausal women (≥50 years old) with no previous diagnosis of osteoporosis. Sixty women were used for system training, and 40 were used in testing.ResultsThe sensitivity and specificity using RBF kernel-SVM method for identifying women with low BMD were 90.9% [95% confidence interval (CI), 85.3-96.5] and 83.8% (95% CI, 76.6-91.0), respectively at the lumbar spine and 90.0% (95% CI, 84.1-95.9) and 69.1% (95% CI, 60.1-78.6), respectively at the femoral neck. The sensitivity and specificity for identifying women with low BMD at either the lumbar spine or femoral neck were 90.6% (95% CI, 92.0-100) and 80.9% (95% CI, 71.0-86.9), respectively.ConclusionOur results suggest that the newly developed system with the SVM method would be useful for identifying postmenopausal women with low skeletal BMD.

Autologous Bone-Marrow Mononuclear Cell Implantation Reduces Long-Term Major Amputation Risk in Patients With Critical Limb Ischemia

Background— Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI.nnMethods and Results— We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels.nnConclusions— These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease.nnClinical Trial Registration— URL: . Unique identifier: 001769.Background—Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI. Methods and Results—We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels. Conclusions—These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease. Clinical Trial Registration—URL: http://home.hiroshima-u.ac.jp/angio/. Unique identifier: 001769.

Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10xa0years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.

Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the Task Force) recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.

COMPUTER-AIDED MEASUREMENT OF MANDIBULAR CORTICAL WIDTH ON DENTAL PANORAMIC RADIOGRAPHS FOR IDENTIFYING OSTEOPOROSIS

AIMnTo develop a computer-aided diagnosis system to continuously measure mandibular inferior cortical width on dental panoramic radiographs and evaluate the systems efficacy in identifying postmenopausal women with low-skeletal bone mineral density.nnnMETHODSnMandibular inferior cortical width was continuously measured by enhancing the original X-ray image, determining cortical boundaries, and evaluating all distances between the upper and lower boundaries in the region of interest. The systems efficacy in identifying osteoporosis at the lumbar spine and the femoral neck was evaluated for 100 women (≥50 years): 50 in the development of the tool and 50 in its validation.nnnRESULTSnThe sensitivity and specificity of the cortical measurements for identifying the development patients were 90% (95% confidence interval shown in parentheses) (63.0-87.0) in women with low spinal bone mineral density, and 81.8% (70.1-91.8) and 69.2% (56.2-81.8) in those with low femoral bone mineral density, respectively. Corresponding values in the validation patients were 93.3% (85.9-100) and 82.9% (71.4-92.7) at the lumbar spine, and 92.3% (84.5-99.5) and 75.7% (63.0-87.0) at the femoral neck, respectively.nnnCONCLUSIONnOur new computer-aided diagnosis system is a useful procedure in triage screening for osteoporosis.