Effects of Cerclage Cabling on Preventing Periprosthetic Femoral Fractures When Using Cementless Stems for Unstable Femoral Neck Fractures.

BACKGROUND: Periprosthetic femoral fractures (PFFs) are serious complications in hip arthroplasty for femoral neck fractures. The rates of intraoperative (iPFFs) and postoperative PFFs (pPFFs) are higher in cementless stem cases than in cemented cases. This study aimed to investigate the effects of cerclage cabling on PFF prevention in cementless arthroplasty for femoral neck fractures. METHODS: This retrospective study included 329 consecutive patients who underwent hip arthroplasty using a cementless stem for femoral neck fractures. A total of 159 and 170 patients were in the non-cabling and cabling groups, respectively. Patient characteristics were comparable in both groups. The PFF occurrence (iPFF and pPFF) rates, reoperation rates, operative time, and blood loss volume were compared between the groups. RESULTS: The iPFF rate was significantly higher in the noncabling group (6.3%) than in the cabling group (0%, P < .001). The rate of pPFF was significantly higher in the non-cabling group (5.1%) than in the cabling group (0.6%; P = .016). All patients in the non-cabling group required reoperation (5.1%), whereas the patient in the cabling group was an ambulatory case and required no reoperation (0%, P = .003). No significant difference in either operative time or blood loss volume was observed between the non-cabling (50 minutes, 133 mL) and cabling (52 minutes, P = .244; 149 mL, P = .212, respectively) groups. CONCLUSIONS: When a cementless stem is used to treat unstable femoral neck fractures, cerclage cabling effectively prevents iPPF and pPPF without increasing surgical time or blood loss volume.

The regenerative treatment of costal osteochondral graft implantation for partial growth arrest using a rabbit model.

PURPOSE: To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. METHODS: The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. RESULTS: Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. CONCLUSION: The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury.

Risk analysis of COVID-19 hospitalization and critical care by race and region in the United States: a cohort study.

BACKGROUND: This study aimed to identify the current risk factors for coronavirus disease 2019 severity and examine its association with medication use. METHODS: We used data from a large United States electronic health record database to conduct an anonymized cohort study of 171,491 patients with coronavirus disease 2019. The study was conducted from January 1, 2020, to August 27, 2021. Data on age, race, sex, history of diseases, and history of medication prescriptions were analyzed using the Cox proportional hazards model analysis to calculate hazard ratios for hospitalization and severe risk. RESULTS: Factors that increased the risk of hospitalization and critical care were age ≥ 65 years, male sex, type 2 diabetes, hypertension, interstitial pneumonia, and cardiovascular disease. In particular, age ≥ 65 years significantly increased the risk of hospitalization (hazard ratio, 2.81 [95% confidence interval, 2.58-3.07]; P < 0.001) and critical care (hazard ratio, 3.45 [2.88-4.14]; P < 0.001). In contrast, patients with hyperlipidemia had a reduced risk. However, patients with hyperlipidemia who were not taking statins had a significantly increased risk of hospitalization (hazard ratio, 1.24 [1.16-1.34]; P < 0.001). Sodium-glucose cotransporter-2 inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, glucocorticoids, and statins significantly reduced the risk of hospitalization and critical care. The risk of hospitalization and critical care increased in patients of all ethnicities with type 2 diabetes. The factors that significantly increased the risk of hospitalization in all regions were older age, hypertension, chronic obstructive pulmonary disease, and cardiovascular disease. CONCLUSION: This study identified factors that increase or reduce the risk of severe coronavirus disease. The provision of appropriate drug treatment and modification of lifestyle-related risk factors may reduce coronavirus disease severity.

Is There an Association Between Femoral Head Collapse and Acetabular Coverage in Patients With Osteonecrosis?

BACKGROUND: Osteonecrosis of the femoral head (ONFH) classification systems are based on the size, volume, and location of necrotic lesions. Often-but not always-ONFH results in femoral head collapse. Because acetabular coverage is associated with mechanical stress on the femoral head, it might also be associated with femoral head collapse in patients with ONFH. However, the association between acetabular coverage and femoral head collapse in these patients has not been established. QUESTIONS/PURPOSES: (1) Is femoral head collapse associated with acetabular coverage or pelvic incidence (PI) in patients with ONFH? (2) Are established predictors of femoral head collapse in ONFH classification systems associated with acetabular coverage? METHODS: Between 2008 and 2018, we evaluated 343 hips in 218 patients with ONFH. We considered all patients with ONFH except for those with a traumatic etiology, a history of surgical treatment before collapse, or those with collapse at initial presentation as potentially eligible for this study. Of those, 101 hips with ONFH (50% [50] were in males with a mean age of 44 ± 15 years) met our inclusion criteria. These patients were subsequently divided into two groups: those with femoral head collapse within 12 months (collapse group, 35 hips) and those without femoral head collapse (noncollapse group, 66 hips). No differences in patient demographics were observed between the two groups. CT images were used to measure the PI and acetabular coverage in three planes: the lateral center-edge angle (LCEA) in the coronal plane, the anterior and posterior center-edge angle in the sagittal plane, and the anterior and posterior acetabular sector angle in the axial plane; in addition, the difference between these parameters was investigated between the groups. The thresholds for femoral head collapse in the parameters that showed differences were investigated. Necrotic location and size were evaluated using the Japanese Investigation Committee (JIC) classification and the Steinberg grade classification, respectively. We examined the relationship between these parameters and classifications. RESULTS: The mean LCEA was slightly greater in the noncollapse group than in the collapse group (32° ± 6° versus 28° ± 7°; mean difference 4° [95% CI 1.15° to 6.46°]; p = 0.005); the clinical importance of this small difference is uncertain. There were no differences in PI between the two groups. After accounting for sex, age, BMI, and etiology as confounding factors, as well as acetabular coverage parameters and PI, we found a lower LCEA to be independently associated with increased odds of collapse, although the effect size is small and of questionable importance (OR 1.18 [95% CI 1.06 to 1.33]; p = 0.001). The threshold of LCEA for femoral head collapse was 28° (sensitivity = 0.79, specificity = 0.60, area under the curve = 0.73). The percentage of patients with an LCEA less than 28° was larger in JIC Type C1 (OR 6.52 [95% CI 1.64 to 43.83]; p = 0.006) and C2 (OR 9.84 [95% CI 2.34 to 68.38]; p = 0.001) than in patients with both Type A and Type B. The acetabular coverage data for the excluded patients did not differ from those of the patients included in the analysis. CONCLUSION: Our findings suggest that acetabular coverage appears to have little, if any, association with the likelihood of collapse in patients with ONFH. We found a small association between a lower LCEA and a higher odds of collapse, but the effect size may not be clinically important. Factors other than acetabular coverage need to be considered, and if our findings are verified by other investigators, osteotomy is unlikely to have a protective role. As the patients in our study were fairly homogeneous in terms of ethnicity and BMI, these factors need to be further investigated to determine whether they are associated with femoral head collapse in ONFH. LEVEL OF EVIDENCE: Level III, prognostic study.

What Changes in Pelvic Sagittal Tilt Occur 20 Years After THA?

BACKGROUND: Cup orientation in THA in the supine, standing, and sitting positions is affected by pelvic sagittal tilt (PT). Patterns of PT shift between these positions may increase the risk of dislocation and edge loading. The PT has also been reported to change during the aging process; however, there is limited research regarding long-term changes in PT and PT shifts after THA. QUESTIONS/PURPOSES: (1) What changes occur in PT in the supine, standing, and sitting positions during 20 years of follow-up after THA in patients who have not had revision or dislocation? (2) What factors are associated with the differences between preoperative supine PT and postoperative sitting or standing PT (Δ sitting and Δ standing, respectively) 20 years postoperatively? METHODS: Between January 1998 and December 1999, 101 consecutive patients underwent THA for appropriate indications. AP radiographs of the pelvis in the supine, standing, and sitting positions preoperatively and at 1, 10, and 20 years after THA were longitudinally performed to evaluate changes in PT. Fifty-nine percent (60 of 101) of patients were lost before 20 years of follow-up or had incomplete sets of imaging tests, leaving 41% (41 of 101) eligible for analysis here. There were no patients who had recurrent dislocation or underwent revision arthroplasty in the cohort; therefore, this analysis regarding postoperative changes in PT indicates the natural course of the change in PT during follow-up of THA. PT was measured based on the anterior pelvic plane. PT shifts with positional changes, Δ standing, and Δ sitting during the follow-up period were calculated. Posterior changes and shifts are represented by negative values. To analyze the factors associated with Δ standing and Δ sitting after 20 years, the correlations between these parameters and preoperative factors (including sex, age, pelvic incidence [PI], lumbar lordosis [LL], preoperative PT, and preoperative PT shift) and postoperative factors (including the occurrence of new lumbar vertebral fractures, lumbar spondylolisthesis, contralateral THA performed during follow-up, and PI-LL 20 years after THA) were determined. RESULTS: Median (IQR) supine and standing PTs changed (moved posteriorly) by -5° (-11° to -2°; p < 0.01) and -10° (-15° to -7°; p < 0.01), respectively. Sitting PT did not change during the 20-year follow-up period. Median (IQR) PT shift from standing to sitting changed from -34° preoperatively (-40° to -28°) to -23° after 20 years (-28° to -20°). There were posterior changes in median (range) Δ standing (median -12° at 20 years [-19° to -7°]); Δ sitting did not change during the follow-up period (median -36° at 20 years [-40° to -29°]). Patients with a large preoperative posterior PT shift from supine to standing demonstrated larger posterior tilt of Δ standing at 20 years. Patients with lumbar vertebral fractures during follow-up demonstrated larger posterior tilt of Δ standing at 20 years. CONCLUSION: Patients who demonstrate a large preoperative posterior shift from supine to standing deserve special consideration when undergoing THA. In such circumstances, we recommend that the anteversion of the cup not be excessive, given that there is a relatively high risk of further posterior tilt in PT, which may lead to anterior dislocation and edge loading. Further longitudinal study in a larger cohort of patients with complications including postoperative dislocation and revision, as well as older patients, is needed to verify these assumptions on the potential risk for dislocation and edge loading after THA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Osteocompatibility of Si3N4-coated carbon fiber-reinforced polyetheretherketone (CFRP) and hydroxyapatite-coated CFRP with antibiotics and antithrombotic drugs.

This study used a rabbit model to investigate the osteocompatibility of Si3N4-coated carbon fiber-reinforced polyetheretherketone (CFRP) and hydroxyapatite (HA)-coated CFRP with antibiotics (vancomycin [VCM]) and antithrombotic drugs (polyvinylpyrrolidone [PVP]). HA-coated cylindrical CFRP implants were used as the controls (HA), and HA-coated implants treated with VCM and PVP were prepared (HA-VP) as the test groups; a cylindrical CFRP coated with Si3N4 was also prepared (SiN). Ten implants from each group were randomly inserted into the femoral diaphysis of rabbits. The pull-out test, radiological analysis using micro-computed tomography (µ-CT), and histological analysis were performed. The pull-out strength of the SiN group was lower than that of the HA group. µ-CT analysis revealed that the amount of bone formation around the implant in the SiN group was inferior to that in the HA group. Conversely, the HA-VP group had equivalent pull-out strength and bone formation as analyzed by µ-CT compared to the HA group. In conclusion, the additional surface treatment of the HA-coated CFRP with VCM and PVP provided sufficient bone fixation and formation.

Optimizing vancomycin release from novel carbon fiber-reinforced polymer implants with small holes: periprosthetic joint infection treatment.

Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty. A new drug-loaded carbon fiber-reinforced polymer (CFRP) prosthesis with a sustained drug-release mechanism is being developed for one-stage surgery. We aimed to examine the diffusion dynamics of vancomycin from vancomycin paste-loaded CFRP implants. The differences in the in vitro diffusion dynamics of vancomycin paste were investigated using the elution test by varying parameters. These included the mixing ratio of vancomycin and distilled water (1:0.8, 1:1.2, and 1:1.4) for vancomycin paste, and hole diameter (1 mm and 2 mm) on the container. The in vivo diffusion dynamics were investigated using a rabbit model with vancomycin-loaded CFRP implants placed subcutaneously. The in vitro experiments showed that the diffusion effect of vancomycin was highest in the parameters of vancomycin paste with distilled water mixed in a ratio of 1:1.4, and with a 2 mm hole diameter. The in vivo experiments revealed diffusion dynamics similar to those observed in the in vitro study. The drug diffusion effect tended to be high for vancomycin paste with a large water ratio, and a large diameter of holes. These results indicate that the drug diffusion dynamics from a CFRP implant with holes can be adjusted by varying the water ratio of the vancomycin paste, and the hole size on the CFRP implant.

Freeze-dried noncoagulating platelet-derived factor concentrate is a safe and effective treatment for early knee osteoarthritis.

PURPOSE: While a wide variety of platelet-rich plasma (PRP) solutions has been developed, innovation continues. In this case, the freeze-dried platelet factor concentrate (PFC-FD) represents another step in PRP refinement. The preparation of PFC-FD at a central laboratory with freeze drying for shelf stabilization should provide additional quality improvements if clinical effectiveness can be demonstrated. Therefore, this study was undertaken to assess the safety and effectiveness of PFC-FD in a prospective open-label trial of patients suffering from knee osteoarthritis (OA). METHODS: 312 consecutive knee OA patients (67% female, mean age 63 ± 10 years), were prospectively recruited in an outpatient knee clinic in Japan. Of these, 10 (3.2%) were lost to follow-up at < 12 months and 17 (5.5%) sought additional knee therapy during the follow-up period. The primary outcome of interest was achievement of the OMERACT-OARSI responder criteria with secondary outcomes of adverse events and PROMs scores 1, 3, 6, 12 months following a single PFC-FD injection. RESULTS: 285 patients (91%) completed 12 month PROMs. The 17 who sought additional therapy were considered failures leaving an effective sample size of 302 for our primary outcome in which 62% of patients achieved OMERACT-OARSI responder status by 12 months. This varied by OA class with Kellgren-Lawrence grade 4 patients 3.6 times less likely to be responders than grade 1-2 patients. 6% of patients experienced a non-serious adverse event, primarily pain or swelling at the injection site. CONCLUSIONS: PFC-FD provides an observable clinical improvement in 62% of knee OA patients at 12 months post-injection with very little risk of any clinically relevant adverse event. Of course, nearly 40% of patients did not experience an observable clinical improvement, primarily among those with worse KL grades. LEVEL OF EVIDENCE: Therapeutic, Level II.

Association between magnitude of femoral head collapse and quality of life in patients with osteonecrosis of the femoral head.

OBJECTIVES: The magnitude of femoral head collapse (MFHC) is one of the criteria for staging osteonecrosis of the femoral head (ONFH). The present study aimed to clarify the relationship between MFHC and hip pain or functional quality of life (QOL) scores in patients with ONFH. METHODS: Seventy patients with ONFH who had femoral head collapse without osteoarthritic changes were divided into four groups based on MFHC by 1 mm. Pain was assessed using the visual analogue scale (VAS). QOL was evaluated using patient-reported outcome measures such as the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), Oxford Hip Score (OHS), and Short Form-12 Health Survey, version 2 (SF-12v2). We also explored the relationship between MFHC and QOL. RESULTS: Pain score and satisfaction score in the VAS, JHEQ pain subscale, JHEQ movement subscale, and JHEQ total score were significantly associated with MFHC, and no significant differences were found between groups in any subscale or total score for OHS and SF-12v2. CONCLUSION: In patients with ONFH, differences in MFHC by 1 mm were associated with deterioration of some pain VAS and QOL outcomes.

Effect of hip flexion contracture on the pelvic sagittal tilt in the supine position: A retrospective case-series study.

OBJECTIVES: The functional pelvic plane, which adopts the natural pelvic sagittal tilt in the supine position, is a good reference for determining the cup angle in total hip arthroplasty. However, hip flexion contracture may change pelvic tilt postoperatively by the release of contracture. This study investigated the influence of hip flexion contracture on pelvic sagittal tilt in the supine position. METHODS: This study included 300 patients who underwent primary unilateral total hip arthroplasty. We divided the participants into two groups: with a preoperative hip extension angle of <0° (hip flexion contracture group) and without (non-contracture group). The pelvic sagittal tilt and femoral flexion angle were investigated using computed tomography or pelvic radiographs performed preoperatively and postoperatively. RESULTS: The femoral flexion angle had significantly reduced postoperatively in the hip flexion contracture group but remained unchanged in the non-contracture group. The preoperative and postoperative pelvic sagittal tilt showed no significant differences between the two groups up to 1 year postoperatively. CONCLUSIONS: The influence of hip flexion contracture on the pelvic sagittal tilt in the supine position was minimal. The functional pelvic plane in the supine position could be a good reference to ascertain the cup orientation, even in hip flexion contracture cases.

MRI screening for osteonecrosis of the femoral head after COVID-19.

OBJECTIVES: Systemic steroid administration has been suggested for the treatment of coronavirus disease 2019 (COVID-19), but the occurrence of osteonecrosis of the femoral head (ONFH) was one of the concerns for this treatment. This study aimed to use magnetic resonance imaging (MRI) to assess the incidence of ONFH after treatment COVID-19. METHODS: The study included 41 patients who were hospitalized and treated for pneumonia or other COVID-19-induced diseases. We conducted interviews with these patients regarding hip pain and performed MRI screenings for ONFH. The incidence and timing of ONFH after COVID-19 treatment were investigated. RESULTS: Of the 41 patients, one died of pneumonia, and the remaining patients did not complain of hip pain. MRI screening of 26 patients was performed, and asymptomatic ONFH was detected in one patient (3.8%) whose ONFH appeared 1 month after the COVID-19 infection. CONCLUSION: Our MRI screening of ONFH in post-COVID-19 patients revealed asymptomatic ONFH, which would not have been identified without active screening. Physicians should be aware that ONFH may occur in patients after treating COVID-19.

The Effect of Region of Interest on Measurement of Bone Mineral Density of the Proximal Femur: Simulation Analysis Using CT Images.

While accurate measurement of bone mineral density (BMD) is essential in the diagnosis of osteoporosis and in evaluating the treatment of osteoporosis, it is unclear how region of interest (ROI) settings affect measurement of BMD at the total proximal femur region. In this study, we performed a simulation analysis to clarify the effect on BMD measurement of changing the ROI using hip computed tomography (CT) images of 75 females (mean age, 62.4 years). Digitally reconstructed radiographs of the proximal femur region were generated from CT images to calculate the change in BMD when the proximal boundary of the ROI was altered by 0-10 mm, and when the distal boundary of the ROI was altered by 0-30 mm. Further, changes in BMD were compared across BMD classification groups. A mean BMD increase of 0.62% was found for each 1-mm extension of the distal boundary. A mean BMD decrease of 0.18% was found for each 1-mm alteration of the proximal boundary. Comparing BMD classification groups, patients with osteoporosis and osteopenia demonstrated greater BMD changes than patients with normal BMD for the distal boundary (0.68%, 0.64%, and 0.54%, respectively) and patients with osteoporosis demonstrated greater BMD changes than patients with osteoporosis and normal BMD for the proximal boundary (0.37%, 0.13%, and 0.03%, respectively). In conclusion, our study found that a consistent ROI setting, especially on the distal boundary, is necessary for the accurate measurement of total proximal femur BMD. Based on the findings, we recommend confirming that the ROI setting shown on the BMD result form is consistent with changes in serial BMD.

Long-term prediction of hepatocellular carcinoma using serum autotaxin levels after antiviral therapy for hepatitis C.

INTRODUCTION AND OBJECTIVES: Continuous monitoring for hepatocellular carcinoma is necessary following treatment with direct-acting antivirals in patients with hepatitis C virus infection. We investigated whether the long-term follow-up of serum autotaxin levels could predict the development of hepatocellular carcinoma. PATIENTS AND METHODS: This prospective observational study enrolled adult patients with chronic hepatitis C virus infection who presented to the study center from January 2016 to March 2021. Among the patients who achieved a sustained viral response, the relationship between the development of hepatocellular carcinoma and serum autotaxin levels was assessed before treatment with direct-acting antivirals; at the end of therapy; at 12 and 24 weeks; and at 12, 24, 36, and 48 months after treatment. RESULTS: Data were analyzed for 139 patients. Thirteen patients developed hepatocellular carcinoma 48 months after treatment. The cut-off serum autotaxin values that predicted hepatocellular carcinoma after 24 weeks were 1.22 (men) and 1.92 (women) mg/L. The area under the curve for serum autotaxin was 0.83 (95% confidence interval [CI]:0.71-0.95) in men and 0.90 (95% CI: 0.82-0.99) in women. The positive predictive value of serum autotaxin was 0.208 (95% CI: 0.139-0.248), and the negative predictive value was 0.971 (95% CI: 0.939-0.990). The cumulative incidence of hepatocellular carcinoma was significantly higher when serum autotaxin levels were above the cut-off value after 24 weeks (p < 0.0001). CONCLUSIONS: Serum autotaxin is a candidate biomarker for predicting hepatocellular carcinoma during the long-term follow-up of patients with a sustained viral response following treatment with direct-acting antivirals.

Progressive Bone Destruction in Rapidly Destructive Coxopathy Is Characterized by Elevated Serum Levels of Matrix Metalloprotease-3 and C-Reactive Protein.

OBJECTIVE: Rapidly destructive coxopathy (RDC) is a rare condition characterized by rapid joint space narrowing; however, its pathology remains unclear. This study aimed to clarify the association of laboratory biomarkers with the radiological progression of RDC. METHODS: We examined 34 female and 4 male patients with RDC between October 2010 and April 2018. Patients were divided into 3 groups according to the progressive radiographic staging of RDC. Group 1 patients had progressive obliteration of the joint space without subchondral destruction (n = 11), group 2 had progressed subchondral destruction (n = 18), and group 3 had cessation of bone destruction observed for more than 6 months (n = 9). Clinical evaluation results were assessed using the Japanese Orthopedic Association hip score. Blood test results, including serum matrix metalloproteinase-3 (MMP-3), and C-reactive protein (CRP), were also evaluated. RESULTS: There were no significant differences in patient background or Japanese Orthopedic Association hip scores among the groups. However, there were significant differences in MMP-3 levels among groups, with MMP-3 levels in group 2 being significantly higher than those in group 3 (group 2, 118.4 ± 81.2 ng/mL; group 3, 42.5 ± 15.1 ng/mL, p < 0.001). The CRP levels in group 2 were also significantly higher than those in group 3 (group 2, 0.77 ± 0.92 mg/dL; group 3, 0.13 ± 0.07 mg/dL, p = 0.019), but elevated CRP levels in group 2 decreased back to the reference range. CONCLUSIONS: Matrix metalloproteinase-3 and CRP are the biomarkers of RDC progression but not of its occurrence. Severe inflammatory response may be associated with bone destruction in RDC.

Geographical distribution of the associated factors of osteonecrosis of the femoral head, using the designated intractable disease database in Japan.

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.

Geographic distribution of the incidence of osteonecrosis of the femoral head in Japan and its relation to smoking prevalence.

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.

Epidemiological study of osteonecrosis of the femoral head using the national registry of designated intractable diseases in Japan.

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.

Identification of CXCL12-abundant reticular cells in human adult bone marrow.

A population of mesenchymal stem cells, termed CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells or leptin receptor-expressing cells, are the major cellular component of niches for haematopoietic stem cells (HSCs) in murine bone marrow. CAR cells are characterized by several salient features, including much higher expression of CXCL12, stem cell factor (SCF), forkhead box C1 (FOXC1) and early B-cell factor 3 (EBF3), which are essential for HSC maintenance, than other cells. However, the human counterpart of CAR cells has not been fully described. Here, we show the presence of cells expressing much higher CXCL12 than other cells in human adult bone marrow using a flow cytometry-based in situ technique that enables high-throughput detection of mRNA at single-cell resolution. Most CXCL12hi cells expressed high levels of SCF, FOXC1 and EBF3 and had the potential to differentiate into adipocytes and osteoblasts. Histologically, the nuclei of CXCL12hi cells were identified and quantified by EBF3 expression in fixed marrow sections. CXCL12hi cells sorted from residual bone marrow aspirates of chronic myeloid leukaemia patients expressed reduced levels of CXCL12, SCF, FOXC1 and EBF3 in correlation with increased leukaemic burden. Together, we identified the human counterpart of CAR cells, enabling the evaluation of their alterations in various haematological disorders by flow cytometric and histological analyses.

Plasmalemmal Vesicle-Associated Protein Is Associated with Endothelial Cells Sprouting from the Peribiliary Capillary Plexus in Human Cirrhotic Liver.

INTRODUCTION: Plasmalemmal vesicle-associated protein (PLVAP) is an endothelial-specific integral membrane glycoprotein that localizes to caveolae and fenestrae in animal models; however, little is known about PLVAP in endothelial cells (ECs) in hepatic sinusoids during liver cirrhosis (LC). Here, we aimed to elucidate PLVAP localization and expression in the human liver during LC progression. METHODS: PLVAP protein expression was detected in specimens from normal control livers and hepatitis C-related cirrhotic livers using immunohistochemistry, Western blotting, and immunoelectron microscopy. RESULTS: PLVAP mainly localized to the peribiliary capillary plexus (PCP) and was rarely observed in hepatic artery branches and portal venules in control tissue, but was aberrantly expressed in capillarized sinusoids and proliferated capillaries in fibrotic septa within cirrhotic liver tissue. Ultrastructural analysis indicated that PLVAP localized to thin ECs in some caveolae, whereas PLVAP localized primarily to caveolae-like structures and proliferative sinusoid capillary EC vesicles in cirrhotic liver tissue. Western blot analysis confirmed that PLVAP was overexpressed at the protein level in advanced cirrhotic liver tissue. CONCLUSION: PLVAP was strongly expressed in the caveolae of proliferated capillaries directly connected with sinusoids linked with the PCP, suggesting that it plays a role in angiogenesis and sinusoidal remodeling in LC.

Gamma-Glutamyl Transferase: A Useful Marker of Habitual Drinking in Cases of Alcohol-Associated Osteonecrosis of the Femoral Head.

AIMS: Alcohol intake is one of the factors associated with the occurrence of osteonecrosis of the femoral head (ONFH), and its epidemiological information regarding alcohol intake depends on patients' self-reports. Therefore, we analysed the efficacy of laboratory tests as an objective diagnostic tool to indicate habitual drinking in patients with alcohol-associated ONFH. METHODS: This study included 109 consecutive patients diagnosed with ONFH who underwent primary hip surgery in our institution between 2010 and 2018. The patients were classified into group AL (alcohol-associated ONFH; n = 26) and group NO (alcohol-unassociated ONFH; n = 83), based on their self-reported information. Serum levels of gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol and triglycerides were compared between both groups. The sensitivities and specificities with the optimal cut-off values for detecting alcohol-associated ONFH were compared among these markers. RESULTS: The median serum levels of GGT, AST and ALT were significantly higher in the AL group than in the NO group. The receiver operating characteristic curve analysis demonstrated an area under the curve of 0.795 for GGT, 0.731 for AST and 0.709 for ALT. The optimal cut-off level of GGT as a marker for alcohol-associated ONFH was 36.5 units/L, with a sensitivity of 76% and specificity of 80%, and it was found to be the best marker among the other examined laboratory markers. CONCLUSION: Serum GGT level is a useful laboratory marker with moderate accuracy that indicates habitual drinking in patients with alcohol-associated ONFH.