Higher fibular head is a risk for lateral hinge fracture in medial open wedge high tibial osteotomy.

PURPOSE: To examine the association between the hinge position, fibular head position, and type III lateral hinge fracture (LHF) in patients with knee osteoarthritis (OA) who underwent medial open wedge high tibial osteotomy (MOWHTO). METHODS: This retrospective study examined patients who underwent MOWHTO. Radiographically, the Kellgren-Lawrence (K/L) classification, distance between the articular surface and the tip of the fibular head (fibular head position), hinge point (hinge position), type of LHF, and safe zone (within the proximal tibiofibular joint) outlier were evaluated. To determine the cut-off value of the hinge position and fibular head position associated with type III LHF, a receiver operating characteristic (ROC) curve analysis was performed. The odds ratio (OR) was calculated from the obtained cut-off values using logistic regression, which was adjusted by age, gender, body mass index, and opening distance. RESULTS: Among 132 knees in 120 patients, the radiographic severity of knee OA was 19 (14%), 73 (55%), and 40 (30%) of K/L grades 2, 3, and 4, respectively. LHF was observed in 40 knees (30%), including types I, II, and III fractures in 21 (16%), 5 (4%), and 14 (11%) knees, respectively. Hinge and fibular head positions were 16 and 10 mm, respectively, with significant correlation. Safe zone outlier was observed in 38 knees (29%). The hinge and fibular head positions with type III LHF were significantly higher (more cranial) than those with no fracture or other LHF subtypes. The ROC curve revealed that the cut-off value for the hinge and fibular head positions was 13.3 and 8.6 mm, respectively. The OR of the hinge and fibular head positions was 22.42 and 13.86, respectively. CONCLUSIONS: A higher hinge position was a risk factor for type III LHF and was associated with a higher fibular head in patients with knee OA who underwent MOWHTO. The hinge position should be placed at a certain distance from the articular surface to avoid type III LHF, especially in participants with higher fibular head position, even if the hinge position is located in the safe zone. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

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.

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.

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.

Return to Play of Rugby Players After Anterior Cruciate Ligament Reconstruction Using Hamstring Autograft: Return to Sports and Graft Failure According to Age.

PURPOSE: To assess return to play and the frequencies of graft failure in rugby players after anterior cruciate ligament (ACL) reconstruction using a hamstring autograft augmented with an artificial ligament and to compare outcomes between rugby players aged <20 and ≥20 years over the long term. METHODS: A consecutive series of 146 rugby players who underwent ACL reconstruction with a hamstring autograft augmented with an artificial ligament were retrospectively reviewed. The study population was further divided into 2 groups aged <20 years and >20 years and compared. RESULTS: Twenty-five patients could not be followed up, and 121 (83%) were evaluated. Most patients (90%, <20 years; 92%, ≥20 years) returned to play after ACL reconstruction. At an average follow-up period of 56.5 months, 16% of the patients sustained an ACL graft rupture. Regarding age, <20 years (n = 58, 48%) and ≥20 years (n = 63, 52%), younger players had a significantly higher failure rate (23% vs 5%, respectively; P = .006) and a shorter time to failure (22.8 ± 13.2 vs 35.4 ± 15.4 months, respectively; P = .006) than older players. CONCLUSIONS: Rugby players were likely to return to play after ACL reconstruction with a hamstring autograft. However, there was a higher risk of graft failure in younger players than in older players. On the basis of this study, we conclude that the hamstring autograft may not be an appropriate graft source to use in a younger active population, including rugby players. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Application of shear wave elastography for the gastrocnemius medial head to tennis leg.

Muscle strain of the gastrocnemius medial head mainly occurs at the musculotendinous junction (MTJ), and stiffness is a risk factor. Shear wave elastography (SWE) measures elasticity by determining the propagation velocity. The aim of this study was to measure the elasticity of the normal muscle and aponeurosis in the MTJ of the gastrocnemius medial head using SWE, thus obtaining information relevant to muscle strain at this point. Forty-one volunteers (82 legs) were recruited and the gastrocnemius medial heads were examined at four points: three on the aponeurosis, namely at the center of the MTJ (Central), 10 mm proximal to it (Proximal) and 10 mm distal to it (Distal); and at one on the muscle belly (Muscle). The measurements were compared among the points, between males and females, and between younger and middle-aged subjects. Correlations between the elastic modulus and age were also examined. The elastic moduli at Proximal, Central, Distal, and Muscle were 2.82 ± 0.53 m/s, 3.43 ± 0.83 m/s, 4.83 ± 1.56 m/s, and 2.25 ± 0.43 m/s, respectively. These values differed significantly among the points of the aponeurosis, Distal having the highest modulus followed by Central. The elastic moduli were significantly greater in males than females at Distal and Muscle and in younger subjects than middle-aged subjects at Muscle. No significant correlations between elastic modulus and age were observed for any point. SWE could be a feasible method for quantifying the elasticity of muscle and aponeurosis in the MTJ of the gastrocnemius medial head. Clin. Anat. 30:114-119, 2017. © 2016 Wiley Periodicals, Inc.

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.

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.

Disability for daily living is a predictor for joint replacement in patients with end-stage knee osteoarthritis.

The objective indicators which reflect the past results of end-stage knee osteoarthritis (OA) patients who have already received total knee arthroplasty (TKA) could be helpful for physicians to discuss with patients who are considering TKA. The aim of this prospective cohort study was to examine whether we could predict the knee OA patients who would receive TKA in advance based on baseline data, and to set cut-off points for receiving TKA. The two-hundred and forty end-stage medial-type knee OA patients were enrolled and followed up for 6 months while performing therapeutic exercises. Radiographic findings, visual analog scale for pain and a patient-oriented outcome measure, the Japanese Knee Osteoarthritis Measure (JKOM), were recorded at baseline. Relative risks (RRs) using the area under the curve (AUC) for a receiver operating characteristic (ROC) curve were calculated to evaluate several scores for receiving TKA. While 119 patients (55.3 %) did not undergo TKA, the remaining 96 patients (44.7 %) underwent TKA during this period. The AUCs of the ROC curve for the JKOM total score [0.71 (95 % CI 0.64-0.79)] were higher than those for radiographic parameters. Among the JKOM subcategories, JKOM category III, which indicates the condition in daily life, showed the highest AUC of 0.72 (0.65-0.80). The JKOM total score (65/100) and JKOM category III score (17/40) showed RRs of 2.20 (1.33-3.63) and 1.95 (1.18-3.22) for receiving TKA, respectively. The presence of disability in daily living was found to be an important factor determining whether the patient should undergo TKA.

Sympathetic control of bone mass regulated by osteopontin.

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the ß2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the ß2-adrenergic receptor/cAMP signaling system.

Conservative Treatment Using Platelet-Rich Plasma for Acute Anterior Cruciate Ligament Injuries in Highly Active Patients: A Retrospective Survey.

Background The recommended treatment for anterior cruciate ligament (ACL) injuries in active, sports-oriented patients is reconstructive surgery in order to regain stability and prevent secondary meniscal injuries. However, ACL reconstruction requires a long recovery period and poses issues such as decreased muscle strength due to tendon harvesting and postoperative osteoarthritis (OA) progression, thereby raising significant expectations for the advancement of conservative treatments. Recent studies have shown that platelet-rich plasma (PRP) therapy, which utilizes the tissue repair-promoting property of platelets, is effective for ACL injuries. Methods We administered PRP therapy within six weeks after ACL injury in patients who expressed the desire for an early return to sports through conservative care. After the treatment, patients wore a simple brace that limited deep flexion but placed no restrictions on weight bearing. Four months was the standard goal established for returning to pre-injury condition, and, depending on the target level, timing, and knee condition, we adjusted the additional PRP treatments and rehabilitation approach, gradually authorizing the patients' return to sport. We assessed the ligament repair status by magnetic resonance imaging (MRI) just before the full return to sports. A retrospective survey was conducted to evaluate the status of ligament repair and the condition of return-to-sport in patients with ACL injuries who underwent conservative treatment using PRP. Results The average patient age was 32.7 years and the average treatment was 2.8 PRP sessions. MRI evaluations confirmed that ligament continuity was regained in all cases. All the patients returned to their pre-injury level (Tegner Activity Scale 7.0) in an average of 139.5 days, but there was one instance of re-rupture following the return to sports. Conclusion All patients with ACL injury who underwent PRP therapy regained ligament continuity and returned to sport successfully with only one case of re-rupture.

Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage.

Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor ß (TGF-ß), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-ß and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p < 0.05), while the bFGF levels were higher in VFD than in the LR-PRP and LP-PRP groups (p < 0.01). In terms of anti-inflammatory cytokines, the TIMP-1 level was lower in VFD than that in the other groups (p < 0.01), whereas the IL-1ra levels were higher in VFD than those in LP-PRP (p < 0.05) and lower than those in LR-PRP (p < 0.01). In terms of inflammatory enzymes and cytokines, the IL-1ra level was higher in VFD than that in LP-PRP (p < 0.05) and lower than that in LR-PRP (p < 0.01), whereas the IL-6 levels did not differ among the groups. Furthermore, the TGF-ß, bFGF, TIMP-1, and IL-1ra levels were 5.61 â†’ 3.38 (x103 pg/µL), 61.0 â†’ 63.0 (pg/µL), 3.4 â†’ 2.7 (x105 pg/µL), and 14.9 â†’ 14.5 (x103 pg/µL) at baseline and 1 year later, respectively. No significant differences in the BS levels were observed between baseline and 1 year after storage. Conclusions: The VFD samples prepared in this study exhibited higher levels of anti-inflammatory cytokines than LP-PRP and contained growth factor levels similar to LP-PRP and LR-PRP. In addition, the BS levels in VFD samples were maintained after one year of storage. These results suggest that VFD can be prepared and stored and may serve as a novel treatment strategy for sports injuries in high-risk groups, such as athletes.

Safety and feasibility of locoregional platelet-rich plasma injection for iliopsoas impingement after total hip arthroplasty: A phase 1 prospective observational study.

Introduction: Although numerous studies have reported outcomes with various conservative approaches for the iliopsoas impingement after total hip arthroplasty (THA), reports on the use of locoregional autologous platelet rich plasma (PRP) injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA. Materials and methods: Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index, Japanese Hip Disease Evaluation Questionnaire, and Forgotten Joint Score-12. Results: Three patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male. All patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, or subcutaneous haemorrhage owing to the administration of locoregional PRP. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection. Conclusion: We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

Reference intervals of serum hyaluronic acid corresponding to the radiographic severity of knee osteoarthritis in women.

BACKGROUND: While serum levels of hyarulonic acid (sHA) is known to be useful for a burden of disease biomarker in knee OA, it is far from practical. The reference intervals must be established for biomarkers to be useful for clinical interpretation. The aim of this study was to establish the reference intervals of sHA corresponding to the radiographic severity of knee OA for elucidating whether sHA can be useful as a burden of disease marker for individual patient with knee OA. METHODS: 372 women with Kellgren & Lawrence grade (K/L) 1 through 4 painful knee OA were enrolled in this study. The patients included 54 with K/L 1, 96 with K/L 2, 97 with K/L 3, and 118 with K/L 4. Serum samples were obtained from all subjects on the day that radiographs taken. A HA binding protein based latex agglutination assay that employed an ELISA format was used to measure sHA. Age and BMI adjusted one way ANOVA was used to set the reference intervals of sHA. RESULTS: The reference intervals for sHA corresponding to the patients with K/L 4 (49.6 - 66.5 ng/ml) was established without any overlap against to those with K/L 1, 2 and 3, while those with K/L 1, 2 and 3 showed considerable overlap. CONCLUSIONS: These results indicate that sHA can be available as a burden of disease marker for the individuals with severe knee OA (K/L 4), while it is not for those with primary to moderate knee OA (K/L 1-3).

Plasma myoglobin indicates muscle damage associated with acceleration/deceleration during football.

BACKGROUND: Monitoring muscle damage in athletes assists not only coaches to adjust the training workload but also medical staff to prevent injury. Measuring blood myoglobin concentration can help evaluate muscle damage. The novel portable device utilized in this study allows for easy on-site measurement of myoglobin, providing real-time data on the player's muscle damage. This study investigated the relationship between external load (global positioning system parameters) and internal loads (myoglobin concentration and creatine kinase activity) in 15 male professional football players before and after a match. METHODS: Whole blood samples from participants' fingertips were collected before the match (baseline) and at 2, 16, and 40 h after the match. Myoglobin concentrations were measured using the IA-100 compact immunoassay system. Creatine kinase concentrations were measured in a clinical laboratory, and match loads were monitored using a global positioning system device. RESULTS: The mean myoglobin concentration was significantly higher at 2 h than at the other time points (P<0.05), and decreased to baseline levels within 16 h post-match. The mean creatine kinase concentration increased after the match but did not reach a significant level. Muscle damage monitored by myoglobin after football match-play was strongly associated with acceleration/deceleration metrics rather than the sprint/high-speed running distance. CONCLUSIONS: Our findings indicate that myoglobin is a more sensitive marker of muscle damage than creatine kinase after football match-play. Monitoring myoglobin in athletes can aid in determining their recovery status from the previous training load and help practitioners manage the training load.

Study protocol for a randomised placebo controlled trial of platelet-rich plasma injection to prevent post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction.

INTRODUCTION: The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction. METHODS AND ANALYSIS: This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20-49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index<35 and Kellgren Lawrence osteoarthritis grade<2. The primary outcome will include MRI-T2 values of knee cartilage at 6 months. The secondary outcomes will include pain assessment by Visual Analogue Scale, Knee injury and Osteoarthritis Outcome Score, blood and urine test, physical findings, measurements for muscle strength and joint stability. ETHICS AND DISSEMINATION: The study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTb030200391.