Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials (CDM-J).

PURPOSE: Osteoporotic vertebral compression fracture (OVCF) is a common fragile fracture resulting from osteoporosis. We compared the efficacy and safety of romosozumab and commonly used osteoporosis drug treatments for the treatment of OVCF in postmenopausal women. METHODS: Through searching and screening five databases, we included randomized controlled trials (RCTs) published through June 18, 2021 comparing different treatments. Following the Preferred Reporting Items for Systematic Reviews statement, the main objective was to evaluate the mean difference and risk ratio of the treatment effect. The primary measures of romosozumab efficacy used in this study were vertebral, non-vertebral, and clinical fracture events, and secondary outcomes were bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck and the incidence of adverse events (AEs), RESULTS: Nine RCTs including 12 796 participants were included in the analysis, and romosozumab was compared with placebo, alendronate, and teriparatide in the treatment of osteoporosis in postmenopausal women. The incidence of fractures, low BMD, and AEs was analyzed. Compared with the controls, three doses of romosozumab were linked to evident advantages in the treatment of low BMD and fractures but associated with increased hypersensitivity and injection site reaction risks. Furthermore, fewer AEs were observed in the romosozumab arms (210 mg: risk ratio = 0.96, 95% confidence interval = 0.93-0.99; 140 mg: risk ratio = 0.28, 95% confidence interval = 0.08-0.98) than in the alendronate and placebo arms. CONCLUSIONS: Our meta-analysis revealed the evident advantages of romosozumab in the treatment of osteoporosis and low BMD in postmenopausal women and increased risks of hypersensitivity and injection site reactions.

Using the AllerSearch Smartphone App to Assess the Association Between Dry Eye and Hay Fever: mHealth-Based Cross-Sectional Study.

BACKGROUND: Dry eye (DE) and hay fever (HF) show synergistic exacerbation of each other's pathology through inflammatory pathways. OBJECTIVE: This study aimed to investigate the association between DE and HF comorbidity and the related risk factors. METHODS: A cross-sectional observational study was conducted using crowdsourced multidimensional data from individuals who downloaded the AllerSearch smartphone app in Japan between February 2018 and May 2020. AllerSearch collected the demographics, medical history, lifestyle and residential information, HF status, DE symptoms, and HF-related quality of life. HF symptoms were evaluated using the nasal symptom score (0-15 points) and nonnasal symptom score (0-12 points). HF was defined by the participants' responses to the questionnaire as HF, non-HF, or unknown. Symptomatic DE was defined as an Ocular Surface Disease Index total score (0-100 points), with a threshold score of 13 points. HF-related quality of life was assessed using the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire (0-68 points). We conducted a multivariable linear regression analysis to examine the association between the severity of DE and HF symptoms. We subsequently conducted a multivariable logistic regression analysis to identify the factors associated with symptomatic DE (vs nonsymptomatic DE) among individuals with HF. Dimension reduction via Uniform Manifold Approximation and Projection stratified the comorbid DE and HF symptoms. The symptom profiles in each cluster were identified using hierarchical heat maps. RESULTS: This study included 11,284 participants, classified into experiencing HF (9041 participants), non-HF (720 participants), and unknown (1523 participants) groups. The prevalence of symptomatic DE among individuals with HF was 49.99% (4429/9041). Severe DE symptoms were significantly associated with severe HF symptoms: coefficient 1.33 (95% CI 1.10-1.57; P<.001) for mild DE, coefficient 2.16 (95% CI 1.84-2.48; P<.001) for moderate DE, and coefficient 3.80 (95% CI 3.50-4.11; P<.001) for severe DE. The risk factors for comorbid symptomatic DE among individuals with HF were identified as female sex; lower BMI; medicated hypertension; history of hematologic, collagen, heart, liver, respiratory, or atopic disease; tomato allergy; current and previous mental illness; pet ownership; living room and bedrooms furnished with materials other than hardwood, carpet, tatami, and vinyl; discontinuation of contact lens use during the HF season; current contact lens use; smoking habits; and sleep duration of <6 hours per day. Uniform Manifold Approximation and Projection stratified the heterogeneous comorbid DE and HF symptoms into 14 clusters. In the hierarchical heat map, cluster 9 was comorbid with the most severe HF and DE symptoms, and cluster 1 showed severe HF symptoms with minimal DE-related symptoms. CONCLUSIONS: This crowdsourced study suggested a significant association between severe DE and HF symptoms. Detecting DE among individuals with HF could allow effective prevention and interventions through concurrent treatment for ocular surface management along with HF treatment.

Projected numbers of knee and hip arthroplasties up to the year 2030 in Japan.

BACKGROUND: The aging population is a risk factor for an increase in osteoarthritis, leading to a potential increase in the number of arthroplasties worldwide. This study aimed to calculate the projected numbers of knee and hip arthroplasties in Japan until 2030 using national health insurance claim data. METHODS: Data on the numbers of knee and hip arthroplasties performed in Japan between 2014 and 2018 were obtained from the National Database of Health Insurance Claims and Specific Health Checkups of Open Data Japan. Demographic data were obtained from the National Institute of Population and Social Security Research. Collected data were categorized into three age subgroups (40-64, 65-74, and ≥75 years) for each sex. Projections were based on the Poisson regression model. RESULTS: The number of knee arthroplasties in Japan in 2030 was projected to be 4052 for men aged 40-64 years, 6942 for men aged 65-74 years, 14,986 for men aged ≥75 years, 7092 for women aged 40-64 years, 22,957 for women aged 65-74 years, and 58,340 for women aged ≥75 years. The number of hip arthroplasties in Japan in 2030 was predicted to be 8936 for men aged 40-64 years, 9005 for men aged 65-74 years, 5972 for men aged ≥75 years, 27,327 for women aged 40-64 years, 36,416 for women aged 65-74 years, and 37,011 for women aged ≥75 years. CONCLUSION: The numbers of knee and hip arthroplasties are expected to continue to increase over the next 10 years in Japan in most age groups. These findings are useful for future healthcare resource planning to meet the demand for knee and hip arthroplasties.

Individual characteristics and associated factors of hay fever: A large-scale mHealth study using AllerSearch.

BACKGROUND: The prevalence of hay fever, a multifactorial allergic disease, is increasing. Identifying individual characteristics and associated factors of hay fever is essential for predictive, preventive, personalized, and participatory (P4) medicine. This study aimed to identify individual characteristics and associated factors of hay fever using an iPhone application AllerSearch. METHODS: This large-scale mobile health-based cross-sectional study was conducted between February 2018 and May 2020. Individuals who downloaded AllerSearch in Japan and provided a comprehensive self-assessment (general characteristics, medical history, lifestyle habits, and hay fever symptoms [score range 0-36]) were included. Associated factors of hay fever (vs. non-hay fever) and severe hay fever symptoms were identified using multivariate logistic and linear regression analyses, respectively. RESULTS: Of the included 11,284 individuals, 9041 had hay fever. Factors associated with hay fever (odds ratio) included age (0.98), female sex (1.33), atopic dermatitis (1.40), history of dry eye diagnosis (1.36), discontinuation of contact lens use during hay fever season (3.34), frequent bowel movements (1.03), and less sleep duration (0.91). The factors associated with severe hay fever symptoms among individuals with hay fever (coefficient) included age (-0.104), female sex (1.329), history of respiratory disease (1.539), history of dry eye diagnosis (0.824), tomato allergy (1.346), discontinuation of contact lens use during hay fever season (1.479), smoking habit (0.614), and having a pet (0.303). CONCLUSIONS: Our large-scale mobile health-based study using AllerSearch elucidated distinct hay fever presentation patterns, characteristics, and factors associated with hay fever. Our study establishes the groundwork for effective individualized interventions for P4 medicine.

Living Anionic Addition Reaction of 1,1-Diphenylethylene Derivatives: One-Pot Synthesis of ABC-type Chain-End Sequence-Controlled Polymers.

In this study, a 1:1 addition reaction using 1,1-diphenylethylene (DPE) derivatives, referred to as the "living anionic addition reaction", was established to regulate the sequence of vinyl compounds having negligible homopolymerizability. The stoichiometric and successive addition reaction between a DPE anion and more reactive DPE derivatives proceeded quantitatively when the electrophilicity of the DPE derivatives was sufficiently enhanced by electron-withdrawing groups such as (trimethylsilyl)ethynyl and acyl groups. The relative electrophilicity of the DPE derivatives was predicted by Hammett's law and the ß-carbon chemical shifts of the carbon-carbon double bonds. AB- and ABC-type chain-end sequence-controlled polystyrenes with well-defined structures were synthesized by reacting two or three DPE derivatives with difunctional anionic living polystyrene in increasing order of their electrophilicity in a one-pot reaction.

Remnant preservation provides good clinical outcomes after anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the association of remnant preservation (RP) and non-RP (NRP) with patient-reported outcome measures and subsequent graft rupture at a minimum 2-year follow-up after anterior cruciate ligament (ACL) reconstruction. METHODS: Patients in this retrospective study underwent primary isolated ACL reconstruction by the RP or NRP technique with a four- to five-strand hamstring tendon graft. Multivariate linear or logistic regression and Cox regression analyses were performed to compare the physical and psychological outcomes by the International Knee Documentation Committee subjective knee form (IKDC-SKF) and the Japanese Anterior Cruciate Ligament questionnaire 25 (JACL-25), respectively; satisfaction rate; and prognosticators of graft rupture. RESULTS: In total, 120 patients (mean age, 30.6 ± 12.7 years; 54 RP, 66 NRP) with a mean follow-up of 3.2 ± 1.6 years were enrolled in this study. At the latest postoperative follow-up, the RP group showed a mean IKDC-SKF score of 92.3 ± 8.5 and mean JACL-25 score of 13.2 ± 11.2, while these scores in the NRP group were 86.4 ± 12.2 and 24.4 ± 19.5, respectively (P = 0.016 and 0.007, respectively). No significant differences were found in the return-to-sports rate (RP vs. NRP, 79.5% vs. 67.5%) or satisfaction rate (RP vs. NRP, 89.2% vs. 74.4%) (n.s.); however, a significant difference was found in the rate of return to the preinjury sports level (RP vs. NRP, 64.1% vs. 37.5%; P = 0.014). The graft rupture rate was significantly higher in the NRP than RP group (9/66 vs. 1/54; hazard ratio 9.29; 95% confidence interval 1.04-82.81). Younger age (≤ 18 years) was the other important risk factor for graft rupture (hazard ratio 8.67; 95% confidence interval 2.02-37.13). CONCLUSION: Patients who underwent ACL reconstruction with the RP technique obtained somewhat better physical and psychological results than those who underwent ACL reconstruction with the NRP technique. With respect to clinical relevance, patients treated with the RP technique may obtain better outcomes in terms of graft rupture and return to the preinjury sports level than those treated with the NRP technique, but with no differences in overall return to sports or satisfaction. LEVEL OF EVIDENCE: IV.

Validation and defining the minimal clinically important difference of the Japanese version of the IKDC Subjective Knee Form.

BACKGROUND: This study aimed to validate and determine the minimal clinically important difference (MCID) in the Japanese version of the International Knee Documentation Committee Subjective Knee Form (Japanese IKDC-SKF) for patients with anterior cruciate ligament (ACL) injuries. METHODS: This prospective study was performed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guideline to assess the measurement properties of reliability, responsiveness, validity, and interpretability of the Japanese IKDC-SKF. RESULTS: A total of 152 patients were enrolled in the study. The Japanese IKDC-SKF had excellent internal consistency [Cronbach's alpha (95% confidence interval, CI) was 0.90 (0.88-0.92), and the test-retest reliability [intraclass correlation coefficient, ICC2,1 (95% CI)] was 0.97 (0.94-0.98). The content validity (r), which was interpretable between the Japanese IKDC-SKF and the Japanese Anterior Cruciate Ligament questionnaire 25 was -0.87 (P < 0.001). The construct validity for the IKDC-SKF was 86% (six of seven hypotheses were consistent with the results), also indicating high validity. Responsiveness of the Japanese IKDC-SKF was confirmed, with an acceptable area under the curve of 0.81 and a large effect size (Cohen's d of 0.8). There were no floor or ceiling effects. The MCID for the Japanese IKDC-SKF for ACL injury was 10.7. CONCLUSIONS: Our results indicate that the Japanese version of the IKDC-SKF is a reliable, valid, and responsive measurement instrument with which to evaluate the physical function of patients with ACL injuries.

Reliability assessment of the functional movement screen for predicting injury risk in Japanese college soccer players.

[Purpose] This study aimed to assess the reliability of the Functional Movement Screen and explore whether this evaluation tool can predict the risks of personal injuries in Japanese soccer players. [Participants and Methods] Seventy-five Japanese college soccer players who participated in our 1 year prospective cohort study underwent a Functional Movement Screen assessment. Demographic data, athletic characteristics, and types and frequency of injuries sustained, were analyzed with the assessment results. [Results] There was no significant difference in the mean Functional Movement Screen composite scores between genders. Although the Functional Movement Screen showed excellent inter-rater reliability (0.92), low overall internal consistency (0.35) was observed. A maximum score of 3 in straight leg raise occurred in 94% of the females and was considered a ceiling effect. None of the cut-off point scores of the Functional Movement Screen were associated with the number of overall injuries, lower limb injuries, and traumatic injuries, or time to return to play. The Functional Movement Screen composite score of ≤15 represented the maximum sensitivity of 76.92% and specificity of 34.78% with 0.56 in the area under the curve. [Conclusion] Functional Movement Screen composite scores do not have sufficient sensitivity and specificity for predicting injuries in Japanese college soccer players.

Reproducibility, responsiveness and validation of the Tampa Scale for Kinesiophobia in patients with ACL injuries.

BACKGROUND AND PURPOSE: Psychological factors including fear of pain, re-injury during movement (kinesiophbia) affect return-to-sport rates after anterior cruciate ligament (ACL) reconstructive surgery. Clinicians often encounter in the daily practice that athletes explain lack of self-confidence or psychological readiness during the sports activity. The Tampa Scale for Kinesiophobia (TSK) has been used to evaluate psychological outcomes in patients with ACL injuries in many countries and translated into Japanese version in 2013. However, no researchers validated its reliability, validity, and responsiveness of TSK for patients with ACL injury up to now. The purpose of this study was to evaluate the measurement properties of the Japanese version of the TSK (TSK-J) in patients with ACL injuries. STUDY DESIGN: Cohort study (Diagnostic); Level of evidence, 2. METHODS: This prospective study was performed in the department of orthopaedic surgery at the university hospital of Juntendo from Sep 2016 and Apr 2017. Patients who diagnosed with ACL injury with or without reconstruction surgery completed several patient-reported outcome measures (PROMs) were included in this study. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines were used to evaluate reliability, validity, responsiveness, and interpretability of the TSK-J. RESULTS: 222 patients were included in this study. The TSK-J for ACL injured patients showed good internal consistency (Cronbach's alpha = 0.79) and excellent test-retest reliability (intra-class correlation coefficient, ICC2,1 = 0.90, 95% CI = 0.81 to 0.95). In addtion, the TSK-J was significantly but moderately correlated with the IKDC-SKF (r = - 0.49, P <0.001), VAS-Sports (r = - 0.48, P <0.001), and JACL-25 (r = 0.48, P <0.001). The effect size (ES) was small with the Cohen's d = - 0.2. The minimal important difference (MID) was - 1.3 points. No significant TSK-J score change was observed over 1-year after ACL reconstruction (r = - 0.12, P <0.001). There were no floor or ceiling effects. CONCLUSIONS: Our study demonstrated that the Japanese version of TSK has good reliability. However, its low validity and responsiveness indicate that it may not the best way to assess psychological factors for patients with ACL injury.

Knee hyperextension and a small lateral condyle are associated with greater quantified antero-lateral rotatory instability in the patients with a complete anterior cruciate ligament (ACL) rupture.

PURPOSE: To identify factors associated with quantified rotatory stability (pivot-shift phenomenon) in the anterior cruciate ligament (ACL)-injured knee joint. METHODS: A consecutive sample of 54 patients who were diagnosed with an ACL injury and admitted to our hospital to undergo ACL reconstruction were enrolled in this study. Antero-lateral rotatory laxity of the knee joint was quantified using a Kinematic Rapid Assessment device (KiRA; Orthokey LTD) under spinal block before initiating reconstruction of the ACL. Univariate and multivariate regressions were performed assuming relationships between patient characteristics (independent variables) and quantified antero-lateral rotatory stability (a dependent variable). RESULTS: It was observed that a low BMI (t = - 1.659, n.s.), greater passive knee extension angle (t = 2.374, P = 0.023), and a narrower lateral femoral condyle width index (t = - 1.712, n.s.) could be candidates associated with the antero-lateral rotatory instability, using univariate analysis. Employing multivariate analysis controlling for these three variables, that the range of passive knee extension was found to be significantly associated with antero-lateral rotatory instability in the ACL-injured knee joint (t = 2.21, P = 0.035). Patients were then divided into two groups (pivot-shift negative versus positive groups) based on the KiRA-documented quantified pivot-shift test. Interestingly, 23.3% of patients were pivot-shift negative, even though their ACL was confirmed as a complete rupture by arthroscopic observations. The degree of passive knee extension was 2.3 ± 4.5 (mean ± SD) in the pivot-shift negative group, while it was 6.8 ± 6.6 in the pivot-shift positive group (n.s.). The lateral femoral condyle width index was 36.6 ± 2.0% in the pivot-shift negative group, and it was significantly wider than in the pivot-shift positive group (33.8 ± 2.6%, P = 0.0046). Finally, we estimated that the risk of positive pivot-shift depends on the degree of knee extension. The logistic regression analysis revealed that genu recurvatum significantly increased the odds ratio for positive pivot-shift (OR = 3.08, P = 0.047, 95% CI = 1.017-9.350). CONCLUSIONS: This study revealed that greater antero-lateral rotatory instability in patients with a complete ACL rupture was associated with genu recurvatum and small lateral femoral condyle. These factors should be considered as predictors of a poor outcome from an ACL reconstruction due to a higher load on the ACL graft, and therefore, the attending physicians should modify the treatment strategies accordingly. This study indicates that joint hyperlaxity and bone morphology contribute to the rotational stability of the knee joint, in addition to the ACL and antero-lateral complex (ALC). LEVEL OF EVIDENCE: IV.

High incidence of posterior glenoid dysplasia of the shoulder in young baseball players.

BACKGROUND: Rounding of the posterior glenoid rim is observed in young throwing athletes with internal shoulder impingement and is considered developmental dysplasia of the glenoid. The aim of our study was to determine the incidence rate of dysplastic changes of the glenoid within a group of 92 young baseball players. METHODS: The study group included 92 male baseball players, with a mean age of 14.63 years. Of these patients, 30 were diagnosed with Little Leaguer's shoulder and 62 with a painful baseball-throwing shoulder with no abnormal findings on x-ray. The posterior glenoid rim of the affected shoulder was compared with the contralateral nonpainful shoulder, with the 2 following outcomes measured on radiographs obtained using the modified Bernageau imaging method: the distance between the anterior and posterior glenoid rims and the presence or absence of dysplasia of the posterior glenoid rim. RESULTS: The mean distance between the anterior and posterior glenoid rims was significantly shorter in the painful shoulders (mean, 26 mm) than in the nonpainful shoulders (mean, 29 mm; P < .0001). Dysplasia of the posterior glenoid rim was identified in 89 painful shoulders (96.7%), with 9 cases (9.7%) identified on the unaffected contralateral side (P < .001). The presence of dysplasia was not correlated with the age at which baseball playing began. CONCLUSION: The incidence of dysplasia of the posterior glenoid rim is high (96.7%) among young baseball players with a painful shoulder. The identified dysplasia may be related to impaired development of the inferior peripheral secondary glenoid ossification center due to repetitive throwing.

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis.

OBJECTIVES: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD). METHODS: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were retrospectively analyzed. RESULTS: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p < .001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5-10.5 mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p = .02). While average sCa of the patients was 9.2 mg/dL before treatment, it increased time-dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike's information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3 mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3 mg/dL (0.8%, p = .038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed. CONCLUSION: sCa was associated with an increased LS-BMD by BPs with aVD.

Range limitation in hip internal rotation and fifth metatarsal stress fractures (Jones fracture) in professional football players.

PURPOSE: To identify unknown risk factors associated with fifth metatarsal stress fracture (Jones fracture). METHODS: A case-controlled study was conducted among male Japanese professional football (soccer) players with (N = 20) and without (N = 40) a history of Jones fracture. Injury history and physical examination data were reviewed, and the two groups were compared. Univariate and multivariate logistic regression controlling for age, leg dominance and body mass index were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to describe the association between physical examination data and the presence or absence of Jones fractures. RESULTS: From 2000 to 2014, among 162 professional football club players, 22 (13.6%; 21 Asians and one Caucasian) had a history of Jones fracture. Thirteen out of 22 (60%) had a Jones fracture in their non-dominant leg. The mean range of hip internal rotation (HIR) was restricted in players with a history of Jones fracture [25.9° ± 7.5°, mean ± standard deviation (SD)] compared to those without (40.4° ± 11.1°, P < 0.0001). Logistic regression analyses demonstrated that HIR limitation increased the risk of a Jones fracture (OR = 3.03, 95% CI 1.45-6.33, P = 0.003). Subgroup analysis using data prior to Jones fracture revealed a causal relationship, such that players with a restriction of HIR were at high risk of developing a Jones fracture [Crude OR (95% CI) = 6.66 (1.90-23.29), P = 0.003, Adjusted OR = 9.91 (2.28-43.10), P = 0.002]. In addition, right HIR range limitation increased the risks of developing a Jones fracture in the ipsilateral and the contralateral feet [OR = 3.11 (1.35-7.16) and 2.24 (1.22-4.12), respectively]. Similarly, left HIR range limitation increased the risks in the ipsilateral or the contralateral feet [OR (95% CI) = 4.88 (1.56-15.28) and 2.77 (1.08-7.08), respectively]. CONCLUSION: The restriction of HIR was associated with an increased risk of developing a Jones fracture. Since the HIR range is a modifiable factor, monitoring and improving the HIR range can lead to prevent reducing the occurrence of this fracture. LEVEL OF EVIDENCE: III.

[Physical activity for knee osteoarthritis.]

Elder populations have been increasing in Japan and estimated 24 million people have knee osteoarthritis(OA). Recently, people have diverse sociological background and demand for participating sports has been growing. People may participate sports to prevent some diseases such as locomotive syndrome. According to the recent studies, excessive high impact sports increase the risk of OA, while daily life exercise decrease the risk. Epidemiological approach demonstrated that reduced knee extension muscle strength increases the risk of OA. We reviewed and discussed the recent topics including efficacy of physical therapy for knee OA and how much sports activities could be beneficial after knee surgery.

A novel patient-reported outcome measure for anterior cruciate ligament injury: evaluating the reliability, validity, and responsiveness of Japanese anterior cruciate ligament questionnaire 25.

PURPOSE: Despite objectively good results, up to 70 % of individuals may not return to their pre-injury level of sports activity after anterior cruciate ligament (ACL) reconstruction surgery. Although psychological responses have been shown to affect outcomes after ACL injury, an appropriate means of measuring their effects, in addition to functional status, has not been determined. The purpose of this study was to develop a patient-reported questionnaire for measuring psychological factors associated with outcomes after ACL injury and to evaluate its reliability, validity, and responsiveness. METHODS: After item analysis based on the results of two pilot studies and a short relevance assessment, 25 questionnaire items were selected for the Japanese Anterior Cruciate Ligament Injury Questionnaire 25 (JACL-25) and assessed for validity, reliability, and responsiveness in subjects with ACL injury. RESULTS: The JACL-25 had no floor or ceiling effects and no confounding factors. A Cronbach's alpha coefficient of 0.981 and a Guttman split-half coefficient of 0.983 indicated excellent reliability. Large standardized response means (1.30-1.62) and effect sizes (0.96-1.51) from the preoperative to postoperative period indicated good responsiveness. Construct structures were created, and these items were separated into three domains. Strong correlations between the JACL-25 and the International Knee Documentation Committee Subjective Knee Form (r s = -0.86), Lysholm Score (r s = -0.73), and Tegner Activity Scale (r s = -0.65) indicated good concurrent validity of the JACL-25. CONCLUSIONS: The present study demonstrated that the JACL-25 was valid, reliable, and responsive enough to evaluate psychological factors associated with outcomes in individuals with ACL injuries. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Leukocyte concentration and composition in platelet-rich plasma (PRP) influences the growth factor and protease concentrations.

BACKGROUND: Platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for orthopaedics and sports-related injuries, and various clinically available PRP preparation methods exist. However, the differences in PRP quality among numerous preparation methods remain unclear. Specifically, the benefit of including leukocytes in the PRP product remains controversial, and few studies have been conducted to evaluate the effects of the interaction between platelets and leukocytes on the growth factor concentrations. The aim of the present study was to compare the biological characteristics of PRPs focusing on the leukocyte concentration and composition. METHODS: Leucocyte rich (LR)-PRP, leucocyte poor (LP)-PRP, and pure-PRP were prepared from the peripheral blood of 6 healthy male volunteers (mean age: 31.3 years). The concentrations of platelets, leukocytes, erythrocytes, growth factors (transforming growth factor-beta 1: TGF-ß1; fibroblast growth factor-basic: FGF-b; platelet-derived growth factor-BB: PDGF-BB; vascular endothelial growth factor: VEGF) and matrix metalloproteinase-9 (MMP-9) from each of the PRP samples were measured. Considering the interaction between platelets and leukocytes, correlations between platelets/leukocytes and growth factors/MMP-9 were analyzed using partial correlation coefficients. RESULTS: The platelet concentration did not differ among the three PRP preparation methods. Conversely, the leukocyte concentration was dramatically different: 14.9 ± 4.5 (10(3)/µl) in LR-PRP, 2.4 ± 1.3 (10(3)/µl) in LP-PRP, 0.2 ± 0.2 (10(3)/µl) in pure-PRP. The platelet concentration positively correlated with all growth factors. On the other hand, the leukocyte concentration positively correlated with PDGF-BB and the VEGF concentration, while it negatively correlated with FGF-b. Regarding catabolic factors, the MMP-9 concentration strongly correlated with the leukocyte concentration, while there was no correlation between the platelet and MMP-9 concentrations. CONCLUSIONS: These findings demonstrate that leukocytes strongly influence the quality of PRPs. Therefore, modifying the PRP preparation method according to the pathology is essential to achieve better clinical results with PRP therapy.

Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.

Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.

The incidence of and risk factors for developing atypical femoral fractures in Japan.

The long-term treatment with anti-resorptive drugs for osteoporotic patients is suggested to be associated with an increase in atypical femoral fractures (AFFs). However, their incidence, patient characteristics, and risk factors have not been fully elucidated especially in Asian countries. This retrospective observational cohort study found fourteen AFFs in ten patients (four bilateral fractures) among 2,238 hip and femoral shaft fractures treated in our associated hospitals between 2005 and 2010; this incidence (0.63%) was similar to Caucasians. Of the ten patients with AFFs, nine (90%) and six (60%) were using bisphosphonates (BPs) and glucocorticoids (GCs), respectively, compared to 14.3 and 8.6% for patients with typical femoral fractures who were using these agents. As comorbid conditions, five patients had collagen disease (CD) and two had diabetes. A fracture location-, age- and gender-matched (1:3) case-control study revealed that administration of BPs, GCs, and suffering from collagen disease (CD) were significant risk factors for developing AFFs [odds ratios 36.0 (95% confidence intervals 3.8-342.2), 13.0 (2.3-74.1) and 9.0 (1.6-50.3), respectively]. Interestingly, all of the patients with atypical subtrochanteric femoral fractures, defined as those within 5 cm of the lesser trochanter, were taking GCs due to CD, and the age of these patients (average of 54.8 years) was significantly younger than those with atypical diaphyseal femoral fractures (average of 77.2 years, p < 0.05). In conclusion, the incidence of AFFs in the Japanese population was similar to that of Caucasians, and taking BPs and GCs and suffering from CD were risk factors for developing AFFs.

Anabolic action of parathyroid hormone regulated by the ß2-adrenergic receptor.

Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the ß(2)-adrenergic receptor (ß(2)AR), respectively. These receptors activate a common cAMP/PKA signal transduction pathway mediated through the stimulatory heterotrimeric G protein. Activation of ß(2)AR via the sympathetic nervous system decreases bone formation and increases bone resorption. Conversely, daily injection of PTH (1-34), a regimen known as intermittent (i)PTH treatment, increases bone mass through the stimulation of trabecular and cortical bone formation and decreases fracture incidences in severe cases of osteoporosis. Here, we show that iPTH has no osteoanabolic activity in mice lacking the ß(2)AR. ß(2)AR deficiency suppressed both iPTH-induced increase in bone formation and resorption. We showed that the lack of ß(2)AR blocks expression of iPTH-target genes involved in bone formation and resorption that are regulated by the cAMP/PKA pathway. These data implicate an unexpected functional interaction between PTHR and ß(2)AR, two G protein-coupled receptors from distinct families, which control bone formation and PTH anabolism.