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Introduction: A 2015 survey of the Japan Osteoporosis Society (JOS) on medication-related osteonecrosis of the jaw (MRONJ) revealed that cooperation between physicians and dentists was poor. Discontinuation of antiresorptive agents before tooth extraction was found to increase adverse events without preventing MRONJ. We compared this 2015 survey with a new survey conducted in 2022 to investigate cooperation between physicians and dentists for MRONJ. Materials and methods: A web-based structured questionnaire including 13 key queries was sent to 3813 physicians who were members of JOS, and 1227 (32.2%) responses were received. Results: Of the 1227 respondents, 909 (74.1%) had complied with a discontinuation request from a dentist before tooth extraction, although 25.4% of medications were not related to the incidence of MRONJ. Of these, 177 respondents reported 252 adverse events including 10 (1.3%) cases of MRONJ. The prevalence of fractures increased from 4.8% in 2015 to 8.2% in 2022. The rates of respondents who requested oral health care by a dentist before antiresorptive agent therapy and reported cooperation between physicians and dentists were 72.7% and 42.4% in 2022 compared with 32.9% and 24.8% in 2015, respectively. The rates of cooperation among the 47 prefectures in Japan were significantly different, ranging from 10.0 to 83.3% (p = 0.02). Conclusion: This study confirmed increased cooperation between physicians and dentists for MRONJ in Japan. However, a more equal distribution of cooperation across Japan is necessary to optimally manage MRONJ. Discontinuation of antiresorptive agents is no longer necessary because fractures during discontinuation continue to increase in Japan. [ABSTRACT FROM AUTHOR]

The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses. [ABSTRACT FROM AUTHOR]

Summary: We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents. Purpose: We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020. Methods: From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively. Results: The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3–41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8–801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant. Conclusion: We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue. [ABSTRACT FROM AUTHOR]

Since most of the reports of BRONJ onset are adults, in order to clarify the current situation of BRONJ onset in children, it is necessary to search for articles and report on the current status and actual conditions of surgical treatment of children with BP preparations who are being followed up in our clinic. In previous reports both inside and outside Japan, there was no mention of jaw bone necrosis during tooth extraction or surgery in children who were receiving or had a history of BP administration. There were 15 children with a history of BP administration who manage the oral cavity in our clinic. No unpleasant events in the extraction of deciduous teeth were confirmed in medical records. It is necessary to intervene early on oral management of pediatric BP-administered children, especially BP-and steroid-administered children, obtain plaque control to keep the oral cavity cleaner, respond early to infectious diseases, and manage to prevent inflammation from spreading to the jawbone. When surgical treatment is unavoidable, it is important to consider reducing the invasion as much as possible and to cooperate with the medical department such as administration of antibiotics to prevent infection. [ABSTRACT FROM AUTHOR]

Objectives: Osteonecrosis of the femoral head (ONFH) is a designated intractable disease (DID) in Japan. The Ministry of Health, Labour, and Welfare launched an online registry system for DIDs. We aimed to investigate the epidemiological characteristics of patients with ONFH using the DID database. Methods: Data of patients with ONFH registered in the DID database between January 2004 and December 2013 were extracted. The incidence of new cases and distributions of sex, age, and associated risk factors were investigated. The prevalence of the two categories, 'steroid-associated' and 'alcohol-associated' risk factors, was estimated for each prefecture. Results: New 15,049 cases of ONFH were investigated. The mean registration rate-corrected annual ONFH incidence per 100,000 individuals was 1.77. The male-to-female ratio was 1.33. Age distribution peaked in the 40s and 50s for male and 60s for female. The prevalence of steroid-associated ONFH was lower in males (28.6%) than in females (49.8%), while that of alcohol-associated ONFH was higher in males (47.2%) than in females (9.3%). No clear region was identified for the steroids. The incidence of alcohol-associated ONFH was significantly higher in Tokyo and Okinawa, regardless of sex. Conclusions: Alcohol-associated ONFH incidence varies geographically across Japan, suggesting that it has regional characteristics. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the epidemiological characteristics of osteonecrosis of the femoral head (ONFH) using the designated intractable diseases (DID) database in Japan. Methods: Data on patients who had received public subsidies for medical costs due to ONFH from 2012 to 2013 were extracted from the DID database. The incidence and prevalence of ONFH, distribution of gender, age, and the prevalence of associated risk factors were assessed. These epidemiological characteristics were compared with those of another nationwide ONFH survey conducted during a similar period. Results: Data on 3264 newly diagnosed patients (incident cases) and 20,042 patients registered until 2013 (prevalent cases) were evaluated. The corrected annual incidence and prevalence of ONFH per 100,000 were 3.0 and 18.2-19.2, respectively. The ratio of males to females was 1.4 in 2012 and 1.2 in 2013, respectively. Peak distribution was observed at ages 40s and 60s in males and females, respectively. The prevalence of the risk factors were steroid-associated: 39%, alcohol-associated: 30%, both: 4%, and none: 27%. Conclusions: The DID database data showed a similar distribution of gender and age to that in other nationwide surveys but lower incidence and prevalence of ONFH. Sampling bias may affect the epidemiological characteristics of ONFH. [ABSTRACT FROM AUTHOR]

Bone-modifying agents (BMA) such as bisphosphonates and denosumab are frequently used for the treatment of bone metastases, osteoporosis, and multiple myeloma. BMA may lead to anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). This study aimed to clarify the risk factors for and probabilities of developing ARONJ after tooth extraction in patients undergoing BMA therapy. In this study, the records of 505 target sites of 302 patients undergoing BMA who presented with mandibular fractures at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from March 2014 to January 2022, were retrospectively analyzed for the onset of ARONJ after tooth extraction. The following variables were investigated as attributes: anatomy, health status, and dental treatment. The correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and the factors related to the onset of ARONJ were identified. The incidence rate of ARONJ was found to be 3.2%. Hypoparathyroidism was an important factor associated with ARONJ development. Thus, systemic factors are more strongly related to the onset of ARONJ after tooth extraction than local factors. [ABSTRACT FROM AUTHOR]

Purpose: Survival time after bisphosphonate use has been increasingly recognized to be associated with the incidence of medication-related osteonecrosis of the jaw (MRONJ); however, this has not been elucidated sufficiently in the literature. This study aimed to clarify the incidence of MRONJ and the corresponding survival rate of patients treated with zoledronic acid (ZA) for each type of cancer and obtain useful information for the oral/dental supportive care of cancer patients. Methods: We evaluated 988 patients who were administered ZA at our hospital; among them, 862 patients with metastatic bone tumors or myeloma were included. Results: The median survival time (MST) after ZA initiation was 35, 34, 8, 41, 12, and 6 months for patients with breast, prostrate, lung, myeloma, renal, and other cancers, respectively. Patients with cancers that had a short survival time (lung and other cancers [MST = 8 and 6 months, respectively] and cancers with MST < 10 months) did not develop MRONJ; this could be attributed to the shorter duration of ZA administration. The cumulative incidence of MRONJ in breast cancer, prostate cancer, and multiple myeloma was related to the frequency of anti-resorptive drug use and the increased risk over time. In renal cancer, the cumulative incidence of MRONJ increased early, although the MST was 12 months. Conclusion: For the dentists in charge of dental management, it is essential to be aware of prognosis-related factors, predict MRONJ risk for each cancer treatment, and use risk prediction in dental management planning, particularly for cancers with non-poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Alcohol intake and smoking are modifiable lifestyle-related risk factors for osteonecrosis of the femoral head (ONFH). We investigated geographic differences in ONFH incidence in Japan and the correlation with alcohol intake and smoking to develop prevention strategies for ONFH in Japan. Methods: This ecological study was conducted in Japan primarily using the following data sources: nationwide epidemiological survey and national survey. We estimated the annual ONFH incidence and the prevalence of alcohol drinking and smoking in each prefecture. Prefectural incidence and prevalence were calculated by sex and age-standardization. Results: The mean annual ONFH incidence per 100,000 population was 3.08 in men and 1.63 in women, respectively. There was no significant correlation between ONFH incidence and the prevalence of any levels of alcohol intake, while smoking ≥20 cigarettes/day showed a significant and moderate correlation in men (r=0.47, p=.01). This correlation remained significant after adjustment for the prevalence of any levels of alcohol intake (standardized partial regression coefficient = 0.47-0.49, p=.009-.01). Conclusion: ONFH incidence is geographically variable in Japan, and this may be partly explained by the distribution of smoking prevalence. Smoking cessation may contribute to an effective decline in the overall ONFH incidence in Japan. [ABSTRACT FROM AUTHOR]

For patients with non‐traumatic osteonecrosis of the femoral head (ONFH), core decompression (CD) and bone grafts (BG) are mainly performed in the West, while osteotomy is found to be predominant in Japan. It is not well recognized how the surgical procedures for joint preservation in patients with ONFH are completely different between the United States and Japan. This paper identifies the contexts and the differences in treatment strategies for ONFH between the two countries. We compared the surgical trends of the two countries over three periods, 1997–2001, 2002–2006, and 2007–2011 (the US data for the third period was 2007–2008), based on a 2014 US paper and a 2013 national publication in Japan. We compared the details of surgery for non‐traumatic ONFH under the same conditions in the two reports. For the period 1997–2001, the rates of surgeries for ONFH in the US were as follows: total hip arthroplasty (THA), 86%; CD, 10%; and osteotomy, 0.4%. In Japan, THA was 61%, osteotomy 38%, and CD 0%. For the recent period, 2007–2011 (US 2007–2008), the rate of THA was 91%, CD 6%, and osteotomy 0.1%, in the US, compared to a THA rate of 73%, CD 0%, and osteotomy 26% in Japan. The results for the interim period (2002–2006) were between the old and new data. The use of joint‐preserving surgery for ONFH differs greatly between the US and Japan. The first‐line joint‐preserving surgery was CD in the US and osteotomy in Japan. Each procedure was rarely done in the other country. From about 2000 to 2010, the percentage of THA increased in both countries. The proportion of joint‐preserving surgery (CD in the US and osteotomy in Japan) declined. The decrease in joint‐preserving procedures may be largely attributed to improved long‐term outcomes of THA due to technological advances. There is also a reluctance for young ONFH patients to undergo joint‐preserving procedures, such as osteotomy, that require long‐term hospitalization. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the pathology of environmental lead (Pb) poisoning in Whooper swans (Cygnus cygnus). A number of 12 out 54 swans (22.2%) randomly collected from Honshu, Japan from June 2005 to July 2007 were affected with Pb poisoning. Affected swans showed stained vent with greenish watery diarrhoea and impacted crop. The presence of Pb shots in the gizzard (50%) was confirmed by X-ray, and all cases showed a dark greenish coloured liver. Microscopically, the pathology of Pb poisoning in swans was multisystemic. The severity of the lesions was the highest in the CNS followed by the liver, kidney, spleen, lungs, gizzard, heart, bone marrow respectively and was the least in the peripheral nervous system. CNS lesions were cerebral haemorrhage, malacia, and spongiosis with astrocytic activation and increased neurofilaments accumulations. In addition, there were hepatic and renal hemosiderosis and apoptosis, hepatic granuloma, interstitial pneumonia, gizzard and myocardial necrosis and bone marrow hypoplasia. Chemical analysis of the Pb content in liver and kidneys ranged from 8.18 to 60.6 μg/g, respectively. The extent and severity of lesions varied among individuals and were mostly dose-dependent. Finally, these findings improved the diagnostic procedure of Pb poisoning in free-living Whooper swans. [ABSTRACT FROM AUTHOR]

Purpose: Although several small-scale studies have reported risk factors for surgical site infection (SSI) after high tibial osteotomy (HTO), no study has collectively analysed risk factors in a large cohort. The present study aimed to clarify the risk factors for SSI after HTO using a national database.Methods: Data of inpatients who underwent HTO from 2010 to 2017 were obtained from the Diagnosis Procedure Combination database in Japan. Outcome measures were the incidence of SSI and deep SSI after HTO. Associations between SSI and patient data were examined with multivariable logistic regression analysis.Results: Among 12,853 patients who underwent HTO, 195 developed SSI (1.52%) and 50 developed deep SSI (0.39%). Univariate analysis showed that male sex, smoking, and longer anaesthesia duration were associated with higher incidences of SSI, whereas a primary diagnosis of osteonecrosis and use of natural bone grafts were associated with lower incidences. In multivariable analysis, SSI was positively associated with male sex, anaesthesia duration longer than 210 min (vs. 150-210 min), and use of artificial bone graft (vs. natural bone graft). SSI was negatively associated with age ≤ 49 years (vs. 50-59 years) and a primary diagnosis of osteonecrosis (vs. osteoarthritis).Conclusion: The present study revealed novel risk factors for SSI after HTO that previous studies have failed to find, including use of artificial bone graft and longer anaesthesia duration; primary diagnosis of osteonecrosis and younger age were novel protective factors. These findings will help surgeons assess risks of SSI after HTO in individual patients.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Purpose: The Clinical Practice Guidelines for Osteonecrosis of the Femoral Head (ONFH) 2019 Edition, written by the working group for ONFH guidelines of the Japanese Investigation Committee (JIC) for ONFH under the auspices of the Japanese Ministry of Health, Labour, and Welfare and endorsed by the Japanese Orthopaedic Association, were published in Japanese in October 2019. The objective of this guideline is to provide a support tool for decision-making between doctors and patients.Methods: Procedures for developing this guideline were based on the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014, which proposed an appropriate method for preparing clinical guidelines in Japan.Results: This clinical practice guideline consists of 7 chapters: epidemiology; pathology; diagnosis; conservative therapy; surgical treatment: bone transplantation/cell therapy; surgical treatment: osteotomy; and surgical treatment: hip replacement. Twelve background questions and 13 clinical questions were determined to define the basic features of the disease and to be addressed when deciding treatment in daily practice, respectively.Conclusions: The clinical practice guidelines for the ONFH 2019 edition will be useful for physicians, investigators, and medical staff in clinical practice, as well as for patients, during the decision-making process when defining how to treat ONFH. [ABSTRACT FROM AUTHOR]

Background: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis.Patients and Methods: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients.Results: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062).Conclusions: Teriparatide therapy has potential as an effective treatment option for MRONJ. [ABSTRACT FROM AUTHOR]

Background: Side-to-side variability in the femoral neck anteversion angle (FA) reportedly varies from 0.0° to 17.3°. To investigate the side-to-side variability in the FA and the relationship between the FA and the morphology of the acetabulum in the Japanese population, we performed a three-dimensional computed tomography (CT)-based study involving patients with osteonecrosis of the femoral head (ONFH)., Methods: CT data were obtained from 170 nondysplastic hips of 85 patients with ONFH. The FA and acetabular coverage parameters, including the acetabular anteversion angle, acetabular inclination angle, and acetabular sector angle in the anterior, superior, and posterior directions, were measured using three-dimensional CT. The distribution of the side-to-side variability in the FA was evaluated separately for each of the five degrees., Results: The mean side-to-side variability in the FA was 6.7° ± 5.3° (range, 0.2°-26.2°). The distribution of the side-to-side variability in the FA was 0.0°-5.0° in 41 patients (48.2%), 5.1°-10.0° in 25 patients (29.4%), 10.1°-15.0° in 13 patients (15.3%), 15.1°-20.0° in 4 patients (4.7%), and >20.1° in 2 patients (2.4%). There was a weak negative correlation between the FA and anterior acetabular sector angle (r = -0.282, P < 0.001) and a very weak positive correlation between the FA and acetabular anteversion angle (r = 0.181, P < 0.018)., Conclusions: The mean side-to-side variability in the FA was 6.7° ± 5.3° (range, 0.2°-26.2°) in Japanese nondysplastic hips, and about 20% of the patients had a side-to-side variability of >10°., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Since Marx reported on osteonecrosis of the jaw caused by the injectable bisphosphonates (BPs) pamidronate and zoledronate, there have been numerous reports not only in Western countries, but in Japan as well, of bisphosphonate-related osteonecrosis of the jaw (BRONJ) as a pathology similar to radiation-related osteonecrosis/osteomyelitis of the jaw, which is accompanied by exposure of the bone. Osteonecrosis of the jaw similar to that occurring with BPs is also produced with the anti-receptor activator of nuclear factor kappa-Β ligand (RANKL) antibody denosumab, a bone resorption inhibitor that has a different mode of action from BPs, and there is also a report of osteonecrosis of the jaw related to bevacizumab, an angiogenic inhibitor. Because of this, in its newest position paper (2014), the AAOMS changed the nomenclature from BRONJ to "medication-related osteonecrosis of the jaw" (MRONJ). This article presents an overview of the position paper on medication-related osteonecrosis of the jaw and the current status of the MRONJ in Japan. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaw (ONJ) associated with bisphosphonate therapy is a rare but severe side effect in osteoporosis patients. Recently, the number of osteoporosis patients with ONJ has dramatically increased in Japan. This has contributed to an increase in the number of patients avoiding extractions. However, there has been no prospective study providing definitive incidence data for ONJ in Japanese patients. The purpose of this study was to elucidate the true as well as suspected incidence of ONJ. A total of 3229 subjects (1612 subjects in the minodronic acid group and 1617 subjects in the raloxifene group) in the Japanese Osteoporosis Intervention Trial protocol number 4 participated in this study. ONJ was diagnosed by experienced dentists. Suspected Stage 0 and 1 (bone exposure of the jaw) ONJ was assessed by a structured questionnaire at baseline and at 6, 12, 18, and 24 months. No established ONJ cases were diagnosed during the study. The incidence of suspected Stage 0 and/or Stage 1 ONJ was 6.14 per 1000 patient-years in the minodronic acid group and 3.38 per 1000 patient-years in the raloxifene group [hazard ratio (95% confidence interval) = 1.82 (0.84-3.93), P = 0.13]. Approximately 50-60% of bone exposures that appeared during the study had disappeared at the next observation. Although the subjects in this study may have developed a greater interest in the health of the oral cavity, the incidence of ONJ after minodronic acid treatment would be lower than the expected incident rate. [ABSTRACT FROM AUTHOR]

Summary: In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ.Introduction: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ.Methods: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction.Results: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036).Conclusions: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years. [ABSTRACT FROM AUTHOR]

Background: There have been some reports of high tibial osteotomy combined with osteochondral autograft transfer for osteonecrosis of the medial femoral condyle of the knee. However, few of them have focused on the deep knee flexion needed to sit straight in the Japanese style.Purpose: To evaluate the clinical outcomes and the knee flexion of HTO combined with OAT for osteonecrosis of the medial femoral condyle of the knee, especially the ability to sit straight in the Japanese style.Methods: Between 1998 and 2012, valgus HTO combined with OAT was performed in 23 patients for stage IV osteonecrosis according to Koshino's radiological classification of the medial femoral condyle. The follow-up period was more than 2 years in all cases. The mean age at the time of the surgery was 65.8 years, and the mean follow-up period was 72.2 months. The function of the knee and the ability to sitting straight in the Japanese style were examined. Twenty-one knees were examined with second-look arthroscopy to assess the recipient and donor sites.Results: The JOA scale and IKDC subjective scores were significantly improved. Twelve patients were able to sit straight in the Japanese style after the surgery, compared to 3 patients who were able to do so before surgery. On second-look arthroscopy of 21 knees, the average ICRS score was 10.5 points. No patient needed additional surgery except for removal of the implants.Conclusion: Valgus HTO combined with OAT is one treatment option for osteonecrosis of the medial femoral condyle with osteoarthritis. In the present study, many of the patients regained good knee function, and 50% of the patients were able to sit straight in the Japanese style after surgery, which is a higher rate than after total knee arthroplasty and unilateral knee arthroplasty. [ABSTRACT FROM AUTHOR]

Background: This multi‐institutional retrospective study focused on the clinical outcome of carbon‐ion radiotherapy (C‐ion RT) for non‐squamous cell malignant tumors of the nasopharynx. Methods: The Japan Carbon‐ion Radiation Oncology Study Group collected and analyzed data for 43 patients with non‐squamous cell malignant tumors of the nasopharynx treated with C‐ion RT at four institutions in Japan. Results: Twenty‐nine patients had adenoid cystic carcinomas, seven had malignant melanomas, three had adenocarcinomas, two had mucoepidermoid carcinomas, and two had other pathologies. Twenty‐six of the 43 patients (61%) had T4 tumors. The most common dose‐fractionation schedule was 64 Gy (relative biological effectiveness) in 16 fractions. The median follow‐up period was 30 months. The 2‐year local control (LC) and overall survival (OS) rates were 88% and 84%, respectively. For late toxicity, one patient developed grade 4 optic nerve disorder and two developed grade 5 pharyngeal hemorrhage. Actual incidence of grade 3 or higher late adverse events was 19%, and included cranial nerve dysfunction, jaw bone necrosis, central nervous system necrosis, and ear inflammation. Conclusions: C‐ion RT provided good LC and OS rates with acceptable toxicity for treatment of non‐squamous cell malignant tumors of the nasopharynx. This is the first study of 43 patients with non‐squamous cell malignant tumors of the nasopharynx treated with carbon‐ion radiotherapy. Carbon‐ion radiotherapy provided good LC and OS rates with acceptable toxicity even though non‐squamous cell malignant tumors of the nasopharynx often show refractoriness to the conventional therapy. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that multiple screw fixation is a common option of surgical treatment for femoral neck fractures, there is a paucity of precise morphological study of the femoral neck. To identify appropriate positions and spacing of hip screws for multiple-screw femoral neck fracture fixation, proximal femur morphology in Japanese patients was studied.Method: One hundred hips in fifty knee arthroplasty candidates were studied. Following full limb CT, defined slices were created and anatomical variables measured.Result: The average neck-shaft angle was 126.5° and the distance from the subcapital line to the subchondral bone on a line parallel to the femoral neck axis (FNA) was approximately 25 mm at the superior and inferior; borders of the femoral neck. The FNA was shown to run anterior to the femoral axis (FA). The cross section of the femoral neck forms a reverse right triangle. The height and width of the neck medullary canal were equal (approximately 25 mm), with the posterior wall closer to the femoral axis than the anterior wall.Conclusion: Based on these data, the anterior screw positioned just above the calcar femorale, 16 mm proximal and 27° anterior to the FA, and the posterior screw positioned 12 mm proximal and 5 mm posterior to the FA is recommended. For screws inserted with a fixed angle side-plate, ≤130° is recommended. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to examine the 10-year survivorship and clinical outcome after curved intertrochanteric varus osteotomy (CVO) for the osteonecrosis of the femoral head (ONFH), and to determine what factors predict the failure of this procedure. Materials and Methods: We retrospectively reviewed 102 consecutive CVOs in 93 patients diagnosed with ONFH. Mean follow-up duration was 10.1 years (3.0-23.2 years). Factors associated with radiographic failure (secondary collapse and/or osteoarthritic change), conversion to total hip arthroplasty (THA) and low Harris Hip Score (HHS), were assessed. The Kaplan-Meier method was used to estimate survival rate. Results: Radiographic failure occurred in 27 hips (26.5 %), and 11 hips (10.8 %) were converted to THA. The 10-year survival rate was 91.0 % [95 % confidence interval (CI) 83.4-95.2 %] with conversion to THA as the endpoint and 72.4 % (95 % CI 62.3-80.3 %) with radiographic failure as the endpoint. Mean HHS improved from 70.0 preoperatively to 88.1 at the final follow-up (p < 0.001). Multivariate Cox regression analysis showed that postoperative intact ratio <33.3 % [hazard ratio (HR), 11.17; 95 % CI 4.14-30.14] and center-edge (CE) angle <25° (HR 4.91; 95 % CI 1.92-12.55) were independent factors determining radiographic failure. In addition, the multivariate Cox regression analysis showed that postoperative intact ratio <33.3 % (HR 10.65; 95 % CI 2.24-50.53) and CE angle <25° (HR 7.81; 95 % CI 2.17-28.07) were also factors determining conversion to THA. Worse HHSs of <80 were seen in patients with postoperative intact ratio <33.3 % (p < 0.001), CE angle <25° (p < 0.001), and acetabular head index <75 % (p = 0.006). Conclusions: Postoperative intact ratio <33.3 % and CE angle <25° were identified as independent factors determining radiographic failure and conversion to THA. Therefore, these factors must be taken into consideration when selecting patients for CVO. [ABSTRACT FROM AUTHOR]

Background: Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (ONFH) in young adults has been a challenging disorder due to frequent incidence of collapse of the femoral head and resulting dysfunction of the hip joint and impairing quality of life. In Japan, the working group on ONFH in the Specific Disease Investigation Committee under auspices of the Japanese Ministry of Health, Labor and Welfare was founded in 1975, clinical and related basic research on ONFH have been continued for more than 40 years.Epidemiology and Clinical Course: A national epidemiologic survey in 2004 estimated that 2200 new patients per year would be diagnosed with ONFH in Japan. ONFH was associated with steroid intake (51%), heavy alcohol intake (31%), both (3%), and neither (15%). The male-to-female ratio was 5:4, and the peak decades of age at definitive diagnosis were the 40s in male patients and the 30s in females. MRI studies revealed that ONFH would have occurred in early phase after start of steroid administration and no expansion of necrotic lesion within the femoral head in spite of continued steroid use. To standardize ONFH diagnosis and treatment strategy, the Committee established validated diagnostic criteria, a radiological staging system, and type categorization.Treatment Options: Most symptomatic patients with collapse of the femoral head require various surgical procedures. Joint preserving surgery, such as transtrochanteric rotational osteotomy and curved varus osteotomy, should be the treatment choice for young patients with healthy areas without severe collapse of the femoral head.Clinical and Related Basic Research: Clinical and basic research has been performed to determine the pathogenesis of steroid-induced ONFH. Low hepatic CYP3A activity has been reported to significantly contribute to the risk of steroid-induced ONFH. Several gene polymorphisms related to steroid metabolism were shown to be associated with the occurrence of ONFH. [ABSTRACT FROM AUTHOR]

Objective: Our previous questionnaire-based survey suggested that discontinuation of antiresorptive agents before tooth extraction may increase adverse events and disturb osteoporosis treatment without completely preventing osteonecrosis of the jaw (O.N.J.). We also found little cooperation between physicians and dentists in Japan. However, limitations of our previous study included a survey of doctors belonging to small clinics and a small sample size. Our current study aimed to confirm the results of our previous survey in doctors mainly belonging to academia.Methods: A structured questionnaire including 14 key clinical queries was sent to 1812 physicians of the Japan Osteoporosis Society, and 629 responses were received.Results: Dentists requested discontinuation of many medications that were not associated with the incidence of O.N.J. A total of 523 respondents had received discontinuation requests from dentists. Of these, 97 respondents experienced 119 adverse events including 25 fractures and seven incidences of O.N.J. The ratios of valid responses for fractures were 3.6% and 5.3% in patients with a discontinuation of <3 and ≥3 months, respectively. Those for O.N.J. were 0.7% and 1.6%, respectively. Respondents who refused discontinuation requests reported no cases of O.N.J. Approximately 17% of respondents had patients who discontinued osteoporosis treatment following a requested drug discontinuation after tooth extraction. Approximately 62% of respondents did not request oral health care by a dentist before antiresorptive therapy, and 72% reported no cooperation between physicians and dentists in their region.Conclusions: This study reconfirms the results of our previous survey. Discontinuation of antiresorptive treatment may increase both fractures and O.N.J. Immediate development of a strategy for sharing information about O.N.J. among physicians, dentists, and patients is required to reduce the incidence of both O.N.J. and skeletal events in osteoporosis treatment. Study limitations were selection bias due to low response rate and possible inaccurate responses to the questionnaire. [ABSTRACT FROM AUTHOR]

Dentists request a discontinuation of antiresorptive agents, such as bisphosphonate, before and after tooth extractions to prevent osteonecrosis of the jaw (ONJ). However, little is known about how this affects ONJ and osteoporosis treatment and how medical professionals and dentists cooperate to treat ONJ in patients with osteoporosis. This study aimed to clarify the impact of ONJ on osteoporosis treatment in Japan. A structured questionnaire including 14 key clinical queries was sent to 488 medical professionals as part of the Japanese Osteoporosis Intervention Trial (JOINT)-04, and 206 responses were received. A total of 173 respondents had received discontinuation requests from dentists. Of these, 28 respondents experienced 30 adverse events including ten fractures and one incidence of ONJ. The respondents who refused discontinuation requests observed no cases of ONJ. Approximately 16 % of respondents had patients who discontinued osteoporosis treatment, following a requested drug discontinuation, after tooth extraction. Dentists requested discontinuations for many medications that were not associated with the incidence of ONJ. Approximately 76 % of respondents had never requested oral health care from dentists before osteoporosis treatment and 72 % reported no cooperation between dentists and medical professionals in their region. Our results suggest that drug discontinuation may increase adverse events and disturb osteoporosis treatment without completely preventing ONJ. Currently, both medical professionals and dentists in Japan still continue to recommend their own treatment position. A forum to share information about ONJ among medical professionals, dentists, and patients is required. [ABSTRACT FROM AUTHOR]

Summary: There is no standard surgical protocol of bisphosphonate-related osteonecrosis of the jaws (BRONJ), because of the impossibility to visualize this feature intraoperatively. The aim of this study was to introduce how to provide preoperative labeling of the viable bone with minocycline bone fluorescence technique (MBFT) by using VELscope® and investigate histopathologically. Introduction: The American Association of Oral and Maxillofacial Surgeons (AAOMS) and the Japanese Society of Oral and Maxillofacial Surgeons (JSOMS) now recommend a more conservative treatment strategy. There is no standard surgical protocol of bisphosphonate-related osteonecrosis of the jaws (BRONJ) because of the impossibility to visualize this feature intraoperatively. The aim of this study was to introduce a mechanism providing preoperative labeling of a viable bone using minocycline bone fluorescence technique (MBFT) with VELscope® and to histopathologically investigate. Methods: This report describes a surgical technique used in six patients with BRONJ who underwent jawbone resection under minocycline bone fluorescence imaging using VELscope®. Subsequently, we investigated and compared the clinical findings using VELscope® and histopathological findings. Results: Histopathological examinations showed that the non-fluorescent moiety was consistent with the BRONJ lesions. Conclusions: The surgical treatments that were exactly performed using MBFT with VELscope® offered successful management of BRONJ. This bone fluorescence helped to define the margins of resection, thus improving surgical therapy for extended osteonecrosis. [ABSTRACT FROM AUTHOR]

Objectives. To elucidate the epidemiology of nontraumatic osteonecrosis of the femoral head (ONFH), and to estimate the annual incidence rate in Japan. Methods. We examined, over the course of 3 years, personal records and radiographic images from the national registry of documents used for the study of nontraumatic ONFH in patients in Aichi Prefecture, Japan (population: 7.4 million). Those patients not meeting the diagnostic criteria according to the Japanese Investigation Committee for nontraumatic ONFH were excluded from this study. Results. A total of 285 out of the 327 patients who applied for the national registration of nontraumatic ONFH during the 3-year study met the diagnostic criteria for personal records, radiographic images, and magnetic resonance images. Forty-two patients (12.8%) were not considered to have nontraumatic ONFH. The mean age of patients was 50.4 years, and the male-female ratio was 2.1:1. Nontraumatic ONFH was steroid-induced in 135 cases (47.4%), alcohol-associated in 87 cases (30.5%), steroid-induced and alcohol- associated in 14 cases (4.9%), and idiopathic in 49 cases (17.2%). Conclusions. The age-adjusted annual incidence of nontraumatic ONFH in Aichi Prefecture was estimated at 138.5 patients.Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare the levels of bone and cartilage metabolism markers in the synovial fluid of the hip joint between patients with secondary OA due to osteonecrosis of the femoral head (ONFH), rapidly destructive arthrosis (RDA) and developmental dysplasia of the hip (DDH).Methods. We studied 70 synovial fluid samples obtained from 57 patients with ONFH (mean age 46 years, 34 males, 23 females), 21 samples obtained from 21 patients with RDA (mean age 70 years, 2 males, 19 females) and 20 samples obtained from 20 patients with DDH (mean age 56 years, 2 males, 18 females). The levels of bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), as bone metabolism markers, and matrix metalloproteinase 3 (MMP-3) and keratan sulphate (KS), as cartilage metabolism markers, were analysed.Results. The levels of BAP, MMP-3 and KS were significantly higher in the ONFH group than in the RDA and DDH groups. The levels of TRACP-5b were highest in the RDA group. The levels of BAP in the ONFH group after the development of osteoarthritic changes were significantly lower than those observed in earlier stages. In comparisons between the samples obtained from each group with a terminal condition, the ONFH samples exhibited significantly higher MMP-3 and KS levels, while the TRACP-5 levels were highest in the RDA group.Conclusion. The ONFH patients showed a relatively bone formative condition before the osteoarthritic stage and maintained a higher rate of cartilage turnover throughout several stages compared with the RDA and DDH patients. RDA patients were characterized by a significantly high osteoclast activity. [ABSTRACT FROM PUBLISHER]

Objective. The purpose of this study was to evaluate cytokine level characteristics in the hip joint fluid, including rapidly destructive coxopathy (RDC), OA, osteonecrosis (ON) of the femoral head and RA.Methods. Thirty-three hips with RDC, 57 with OA, 36 with ON and 10 with RA were included in the study. OA hips were divided into two groups: 20 hips with early OA without joint space narrowing and 37 hips with terminal OA. ON hips were divided into three groups: 13 hips with <3 mm collapse, 14 hips with >3 mm collapse and 9 hips with terminal ON. Joint fluid was collected during surgery. Cytokine levels including IL-1β, IL-6, IL-8 and TNF-α were measured using homogeneous time-resolved fluorescence.Results. All measured cytokine levels in RDC were significantly higher than those in OA (P < 0.05). Terminal OA showed higher cytokine levels than those in early OA (P < 0.05). IL-6 and TNF-α levels in the ON group with >3 mm collapse were higher than those found in the ON group with <3 mm collapse. In comparing cytokine levels between RDC, terminal OA, RA and terminal ON, RDC showed significantly higher IL-8 levels than terminal OA and RA (P < 0.05).Conclusion. IL-8 levels in RDC were higher than in the other hip diseases. The IL-8 level may reflect the aggressiveness of joint destruction in RDC, and IL-6 and TNF-α levels may also reflect ongoing destruction in OA and ON. [ABSTRACT FROM PUBLISHER]

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is becoming common in Japan. Oral and maxillofacial radiologists must diagnose BRONJ in general practice. However, little information on how to recognise BRONJ is available. The purpose of this study, therefore, was to confirm the recognition of BRONJ among Japanese oral and maxillofacial radiologists. Methods: A questionnaire including 14 main queries and relevant branch queries was created and sent to 29 Japanese institutions employing oral and maxillofacial radiologists. Results: A large number of patients (705) with BRONJ during the last 3 years were reported by 23 institutions (25 responders) that participated in our survey. The rate of osteonecrosis of the jaw associated with intravenous bisphosphonates was almost identical to that associated with oral bisphosphonates. This finding was inconsistent with worldwide data. About half of the responders felt that the diagnosis of BRONJ based on imaging was difficult. No specific modality was selected for identifying the early signs of BRONJ, although 19 responders selected multi-detector computed tomography followed by magnetic resonance imaging as the best modality for determining the extent of BRONJ. Almost all responders felt that the detection of early signs and determination of lesion extent on imaging were important roles of oral and maxillofacial radiologists. Conclusions: Oral and maxillofacial radiologists recognised their roles in BRONJ diagnosis; however, insufficient evidence regarding the accomplishment of these roles is available. Japanese oral and maxillofacial radiologists must accumulate a large number of BRONJ images, analyse them in cooperation with one another and share the information obtained from their analysis. [ABSTRACT FROM AUTHOR]

Objective: To analyze the similarities and differences of bone microstructure and apoptosis phenotype of lateral column, middle column, and medial column in type L2 and L3 osteonecrosis of the femoral head (ONFH) specimens classified by China-Japan Friendship Hospital (CJFH) classification, so as to carry out a quantitative study of ONFH "three-columns structure theory" and to provide research support for the treatment of ONFH by rotational osteotomy through the base of femoral neck., Methods: Discarded femoral head specimens from 16 patients (16 hips) with CJFH type L2 and L3 ONFH undergone total hip arthroplasty between April 2020 and February 2021 were selected as the research objects. First, the "three-column structure" of the femoral head was three-dimensionally segmented by Micro-CT, and the bone volume to total volume (BV/TV), bone surface area to bone volume ratio (BS/BV), trabecular spacing/separation (Tb.Sp), trabecular thickness (Tb.Th), and trabecular number (Tb.N) in the lateral column, middle column, and medial column were analyzed to compare the similarities and differences of parameters related to bone mass and trabecular structure among the three columns. Then, the specimens were cut with a oscillating saw and made into paraffin sections for HE staining and immunohistochemical staining of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). The differences of apoptosis phenotype between the three columns of ONFH samples of CJFH type L2 and L3 were evaluated by comparing the rate of empty lacunae and the rate of positive cells of immunohistochemical staining., Results: There were significant differences in BV/TV, Tb.Th, and Tb.N among the three columns of CJFH type L2 ONFH femoral head ( P <0.05), with the largest in the medial column and the smallest in the lateral column; BS/BV and Tb.Sp of the lateral column were significantly greater than those of the medial column and middle column ( P <0.05), no significant difference was found between the middle column and medial column ( P >0.05). There was no significant difference in the bone parameters between the three columns of the CJFH type L3 ONFH femoral head ( P >0.05). There was no significant difference in the rate of empty lacunae between the three columns of the CJFH type L2 and L3 ONFH femoral head ( P >0.05). Immunohistochemical staining showed that a large number of tissue sections were detached, and only a small amount of non-specific staining was found in the sections without detachment, so the positive cell rate could not be calculated., Conclusion: The middle and medial columns of the CJFH type L2 ONFH has better trabecular structures than the lateral column, and there is no significant difference in trabecular structures among the three columns of the CJFH type L3 ONFH.

Abstract: Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25–0.66 to 0.69–1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0–0.17 to 0.022–0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38–0.39 to 0.80–0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9–12.9) to 6.0 (1.3–26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind. [Copyright &y& Elsevier]

Objective. To investigate the effects of an anti-platelet drug (clopidogrel) on the prevention of steroid-induced osteonecrosis (ON) in rabbits.Methods. Adult male Japanese white rabbits were divided into two groups and treated as follows: one group received daily clopidogrel mixed in normal saline (AP; n = 35), the other received only normal saline (NS; n = 30). One week after the administration, all rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. Three weeks after, both the femora and humeri were examined histopathologically for the presence of ON. The platelet aggregation assay and hematological examinations were performed before and after the steroid injection.Results. The incidence of ON in the AP group (48.5%) was significantly lower than that observed in the NS group (73.3%). The platelet aggregations in the AP group were significantly inhibited by the administration of clopidogrel. The levels of total cholesterol and triglycerides showed no significant differences between the AP and NS group.Conclusion. The present experimental study demonstrated that the administration of an anti-platelet drug prevented steroid-induced ON in rabbits and that platelet aggregation seems to be one of the possible factors involved in the pathogenesis of steroid-induced ON. [ABSTRACT FROM PUBLISHER]

Objective. The purpose of the study was to clarify the incidence of alcohol-associated osteonecrosis of the knee using MRI.Methods. A total of 131 patients (56 women and 75 men) with osteonecrosis of the femoral head were enrolled; 60 patients had a history of alcohol abuse and 71 had previously received steroids. All patients underwent MRI of the knee. The incidence of alcohol-associated osteonecrosis of the knee was compared with that of steroid-associated osteonecrosis of the knee. Predictive factors of alcohol- and steroid-associated osteonecrosis of the knee were also evaluated.Results. The incidence of alcohol-associated osteonecrosis of the knee was lower than that of steroid-associated osteonecrosis of the knee (18.3 vs 54.9%; P < 0.001, Fisher's exact probability test). No significant difference in weekly alcohol consumption was observed between patients with osteonecrosis of the knee and those without osteonecrosis of the knee. No significant difference in daily maximum steroid doses was observed between patients with osteonecrosis of the knee and those without osteonecrosis of the knee.Conclusion. The present study revealed that the incidence of alcohol-associated osteonecrosis of the knee is lower than that of steroid-associated osteonecrosis of the knee. [ABSTRACT FROM PUBLISHER]

Objectives. The purpose of this study was to clarify the incidence of (CS)-associated osteonecrosis among different underlying diseases and to evaluate the risk factors for steroid-associated osteonecrosis in a prospective MRI study.Methods. We prospectively used MRI to study 337 eligible underlying disease patients requiring CS therapy and succeeded in examining 1199 joints (hips and knees) in 302 patients with MRI for at least 1 year starting immediately after the onset of CS therapy (1-year follow-up rate of 90%). The underlying diseases included SLE in 687 joints (173 patients) and a variety of other rheumatological disorders in 512 joints (129 patients).Results. The incidence of osteonecrosis was significantly higher in SLE patients than in non-SLE patients (37 vs 21%, P = 0.001). Logistic regression analysis revealed that adolescent and adult patients had a significantly higher risk of osteonecrosis compared with paediatric patients [odds ratio (OR) = 13.2], that high daily CS dosage (>40 mg/day) entailed a significantly higher risk of osteonecrosis compared with the dosage of <40 mg/day (OR = 4.2), that SLE patients had a significantly higher risk of osteonecrosis compared with non-SLE patients (OR = 2.6) and that male patients had a significantly higher risk of osteonecrosis compared with female patients (OR = 1.6).Conclusion. These findings suggest that the incidence of CS-associated osteonecrosis varies among different underlying diseases. [ABSTRACT FROM PUBLISHER]

The aim of this study was to clarify the reproducibility of the Japanese Ministry of Health, Labor and Welfare (JMHLW) type classification for osteonecrosis of the femoral head. We performed inter-observer and intra-observer trials using 40 sets of magnetic resonance imagings, 20 of which were produced by a 0.5 Tesla (T) superconductive unit and the other 20 produced by a 1.5 T unit, in patients with non-collapsed and asymptomatic osteonecrosis of the femoral head (JMHLW stage 1 or 2). The JMHLW type classification (A, B, C1, or C2) was determined from T1-weighted coronal images at the center of the femoral head. Six orthopedic surgeons independently assessed all 40 images twice, with an interval of 4-5 weeks between sessions. Regarding inter-observer reliability, the percent agreement was 85% and weighted kappa was 0.709 for 0.5 T, versus a percent agreement of 82% and weighted kappa of 0.724 for 1.5 T. Regarding intra-observer reliability, the percent agreement was 82% and weighted kappa was 0.780 for 0.5 T versus a percent agreement of 80% and weighted kappa of 0.800 for 1.5 T. Inter-observer and intra-observer reliabilities did not differ significantly between the 0.5 and 1.5 T units. The JMHLW type classification provided high inter-observer and intra-observer reliabilities. [ABSTRACT FROM AUTHOR]

Objective To estimate the incidence rate of nontraumatic osteonecrosis of the femoral head (ONFH) in the Japanese population. Methods A survey was conducted to ascertain newly identified patients with nontraumatic ONFH in the Specified Disease Treatment Research Program of Fukuoka Prefecture (population 5 million) between 1999 and 2008. Distributions of age and sex in this population were investigated. Crude incidence rates of nontraumatic ONFH were calculated, and age-adjusted incidence rates were estimated by adjusting the crude values against those for the Japanese standard population in each year. Results In Fukuoka Prefecture, 1,244 newly identified patients with nontraumatic ONFH were recruited into the Japanese subsidy program over the span of 10 years. The ratio of men to women was 1.6, comprising 758 men (61%; mean age 48 years) and 486 women (39%; mean age 56 years). The crude incidence rate of nontraumatic ONFH in the 10-year period was 2.58 cases per 100,000 person-years (range 1.54-3.66). The mean age-adjusted incidence rate was 2.51 cases per 100,000 person-years. Conclusion This study showed that the incidence rate of nontraumatic ONFH was 2.51 cases per 100,000 person-years in the Japanese population. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The increased risk of fractures in patients with type 2 diabetes can partly be explained by poor bone quality and extra-skeletal factors. A retrospective study was conducted to compare the outcome of alendronate (ALN) treatment for 3 years in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Methods: One-hundred and fifty-one postmenopausal osteoporotic Japanese women (mean age at baseline: 67.8 years) who had been treated with ALN for more than 3 years in our outpatient clinic were analysed. The lumbar spine bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and the serum levels of alkaline phosphatase (ALP) were monitored during the 3-year treatment period. The incidence of osteoporotic fractures was also assessed. Results: Sixteen women had type 2 diabetes and were receiving pharmacological treatment, and 135 were non-diabetic. The urinary NTX and serum ALP levels significantly decreased and the lumbar spine BMD significantly increased, compared with the baseline values, without causing any severe adverse events including osteonecrosis of the jaw, femoral diaphysis atypical fractures, and atrial fibrillation, in a manner that was similar among women with type 2 diabetes and non-diabetics. However, the incidence of non-vertebral fractures was significantly higher among women with type 2 diabetes than among the non-diabetics. Conclusions: ALN treatment appeared to have the similar effect on surrogate markers in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Because of lacking in statistical power for fracture incidence due to the small sample size, further studies are warranted to confirm the results of the fracture incidence. [Copyright &y& Elsevier]

Objective To investigate the relationship between transient oxidative stress and the development of osteonecrosis in a rat model. Methods A total of 160 male Wistar rats (24 weeks old) were injected only once with the pro-oxidant [ABSTRACT FROM AUTHOR]

Background: Although numerous studies describe the clinical characteristics of idiopathic osteonecrosis of the femoral head (ONFH) in specific study populations, these have not been confirmed in countrywide studies. Questions/purposes: We therefore determined: (1) the annual number of patients seeking medical care and number of patients newly diagnosed; and (2) the distribution of the age and gender of the patients, potential causative factors, severity of the disease, and operative procedures performed. Patients and Methods: We conducted a nationwide epidemiologic survey in 2005. The survey included all orthopaedic departments in Japan by stratified random sampling according to the number of beds. Results: The number of patients who sought medical care for idiopathic ONFH during 2004 was estimated to be 11,400 (95% confidence interval, 10,100–12,800). We obtained clinical information from 1502 of these patients. The peak in age distribution occurred in the 40s. Potential causative factors were systemic steroid administration (51%) and habitual alcohol use (31%). Hip replacement was the most frequently performed procedure (65%). Among patients with a history of systemic steroid administration, systemic lupus erythematosus was reported most frequently (31%) as the underlying disease. Among patients younger than 40 years, steroid use was the most prominent potential causative factor (60%), and hip replacement frequently was performed (45%). A greater proportion of patients with no history of steroid or alcohol use was observed among patients 65 years or older (41%). Conclusions: In addition to the disease burden of idiopathic ONFH in Japan, our results confirmed the importance of developing preventive and treatment strategies, especially among the younger population. Level of Evidence: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study sought to examine the long-term outcomes of transtrochanteric anterior rotational osteotomy (ARO) as treatment for osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Twenty-one patients (33 hips), aged 20-40 years, underwent ARO between 1980 and 1988. We examined 16 patients (25 hips), a 76% follow-up rate. A Kaplan-Meier curve was used for survivorship analysis. Patients with surviving hips were evaluated by the modified Oxford hip score and Short Form 36 (SF-36). Twelve hips in eight patients had survived at the final follow-up. The average length of hip survival was 24.6 years (range: 20.1-27.2 years). Three patients (six hips) had died of unrelated causes without any subsequent operation. Based on Kaplan-Meier analysis with the endpoint defined as the need for a subsequent operation, the hip survival rate at 25 years was 73.7% (95% confidence interval, ±19.8%). Based on classification by the modified Oxford hip score, five hips were classified as excellent, two hips were good, and the remaining five hips were fair. The average SF-36 summary score for the physical and mental components was 38.7 and 47.2 points, respectively. The physical component summary scores for three patients exceeded the normal level of the Japanese population. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head (ONFH), occurring in children or adults, rarely shows familial aggregation. Recent reports from Taiwan and Japan, however, indicate that an inherited form of ONFH is associated with mutation of the type II collagen gene (COL2A1). These patients had not been exposed to known environmental risk factors, such as steroid medications, yet they presented with typical clinical and radiographic features of ONFH. Unlike other genetic disorders due to COL2A1 mutations, these ONFH cases have normal skeletal development before disease onset. The clinical manifestation of COL2A1-associated ONFH varies between pedigrees, and it appears that age of onset has a major effect on disease phenotype, reflecting different degrees of bone regeneration concurrent with bone damage in the hip joint. Although the inherited form of ONFH is rare, it provides an opportunity to study the natural history and pathogenetic mechanism of ONFH. Genetic approach for investigating ONFH is reviewed here, highlighting our current understanding of the many possible causes of ONFH, and at the end, casting a realistic projection on how genetics can advance the development for managing this debilitating disease. [ABSTRACT FROM AUTHOR]

In this study, we performed a retrospective analysis of a cohort of Japanese paediatric patients with B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) treated with a Berlin-Frankfurt-Münster (BFM)95-based protocol, to clarify the incidence, clinical characteristics, and risk factors of osteonecrosis (ON) in comparison to the ALL-02 protocol. We identified a high frequency of ON with the BFM95-based protocol compared to the ALL-02 protocol. The incidence of symptomatic ON with the BFM95-based protocol is comparable to previous studies in Western countries. We believe that the type of treatment regimen has more impact on the incidence of symptomatic ON in paediatric ALL than ethnicity., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Aim: Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture., Materials and Methods: We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019., Results: Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between physicians and dentists., Conclusion: The behaviour of physicians and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study., Competing Interests: Conflict of interest None disclosed., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In this study, we aimed to elucidate the relationship between the duration from diagnosis to femoral head collapse and the collapse rate among patients with pre-collapse osteonecrosis of the femoral head (ONFH)., Methods: In this retrospective, observational, multicenter study, we analyzed 268 patients diagnosed with ONFH and classified them using the Japanese Investigation Committee classification. The primary endpoint was duration from the time of diagnosis to femoral head collapse for each type of ONFH., Results: The 12-, 24-, and 36-month collapse rates among participants were 0%, 0%, and 0% for type A, respectively; 0%, 2.0%, and 10.8% for type B, respectively; 25.5%, 40.8%, and 48.5% for type C-1, respectively; and 57.4%, 70.3%, and 76.7% for type C-2 ONFH, respectively. A comparison of unilateral and bilateral ONFH, using Kaplan-Meier survival curves demonstrated similar collapse rates., Conclusions: The lowest collapse rate was observed for ONFH type A, followed by types B, C-1, and C-2. Additionally, a direct association was observed between the collapse rate and location of the osteonecrotic lesion on the weight-bearing surface.

Aims: We compared the clinical outcomes of curved intertrochanteric varus osteotomy (CVO) with bone impaction grafting (BIG) with CVO alone for the treatment of osteonecrosis of the femoral head (ONFH)., Methods: This retrospective comparative study included 81 patients with ONFH; 37 patients (40 hips) underwent CVO with BIG (BIG group) and 44 patients (47 hips) underwent CVO alone (CVO group). Patients in the BIG group were followed-up for a mean of 12.2 years (10.0 to 16.5). Patients in the CVO group were followed-up for a mean of 14.5 years (10.0 to 21.0). Assessment parameters included the Harris Hip Score (HHS), Oxford Hip Score (OHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), complication rates, and survival rates, with conversion to total hip arthroplasty (THA) and radiological failure as the endpoints., Results: There were no significant differences in preoperative and postoperative HHS or postoperative OHS and JHEQ between the BIG group and the CVO group. Complication rates were comparable between groups. Ten-year survival rates with conversion to THA and radiological failure as the endpoints were not significantly different between groups. Successful CVO (postoperative coverage ratio of more than one-third) exhibited better ten-year survival rates with radiological failure as the endpoint in the BIG group (91.4%) than in the CVO group (77.7%), but this difference was not significant (p = 0.079)., Conclusion: Long-term outcomes of CVO with BIG were favourable when proper patient selection and accurate surgery are performed. However, this study did not show improvements in treatment results with the concomitant use of BIG. Cite this article: Bone Joint J  2021;103-B(4):665-671.

Introduction: The purpose of this study was to investigate the incidence of necrosis and insufficiency fracture of the hip and knee using magnetic resonance imaging (MRI) in renal transplant patients., Methods: We examined 300 consecutive renal transplant patients using MRI of the hips and knees (T1-weighted coronal MRI) preoperatively and at 3 and 6 months postoperatively. Oblique axial-plane T1-weighted MRI and short-tau inversion-recovery T2-weighted MRI were performed parallel to the femoral neck when distinguishing the osteonecrosis of the femoral head (ONFH) from subchondral insufficiency fracture (SIF) of the femoral head was difficult., Results: ONFH was observed in 3 hips (3 cases, 1.0%). Osteonecrosis of the knee was observed in 2 knees (1 case, 0.3%). SIF of the femoral head was observed in 5 hips (3 cases, 1.0%). Bilateral simultaneous onset of SIF of the femoral head was observed in 2 cases (0.7%). Insufficiency fracture of the knee was observed in 2 knees (1 case, 0.3%)., Conclusions: When it was difficult to distinguish ONFH from SIF of the femoral head, oblique axial-plane T1-weighted MRI and the short-tau inversion-recovery T2-weighted MRI parallel to the femoral neck were useful to establish the correct diagnosis.

Past reports showed good mid-term results of RHA for Japanese patients. However, few reports have compared the mid- to long-term results for RHA in Japanese patients with and without osteoarthritis. Therefore, this study investigated the mid- to long-term results of RHA in Japanese patients with osteoarthritis compared to those without. We conducted a retrospective review of a consecutive series of 92 hips in 80 patients (59 men and 21 women). The minimum follow-up period was 5 years. The JOA hip scoring system was used to clinically evaluate hip function. In the radiological assessment, stem-shaft angle, inclination of the acetabular component, postoperative complications, and adverse reactions around RHA were evaluated. The 10-year survival rate using the Kaplan-Meier method was investigated to compare patients with and without osteoarthritis. A significant difference was observed between the preoperative and postoperative JOA hip scores of either group. Also, the radiological assessment revealed no significant changes in either group. All three revision THAs were performed on patients in the only non-osteoarthritis group. In the osteoarthritis group, the 10-year survival rate was 94% (95% CI 81.8-100) in males and 100% (95% CI 100) for females; in the non-osteoarthritis group, the rate was 80% (95% CI 55.1-100) in males and 66.7% (95% CI 13.3-100) for females. In conclusion, this study showed good mid- to long-term clinical results for young Japanese osteoarthritis patients, with less satisfactory mid- to long-term results in patients without osteoarthritis.