Prevalence and treatment rates of osteoporosis among individuals with rotator cuff tears.

BACKGROUND: The relationship between osteoporosis and rotator cuff tears has been reported previously. However, the treatment rate of osteoporosis in individuals with rotator cuff tear is still unknown. The aim of this study was to investigate the prevalence and treatment rate of osteoporosis in individuals with rotator cuff tears. METHODS: In this cross-sectional study, we enrolled 207 participants. Participants underwent comprehensive assessments, including shoulder ultrasonographic examinations and quantitative ultrasound measurements for bone status evaluation. Osteoporosis diagnosis was predicated on a calcaneus ultrasound bone densitometry, and the cutoff value was set as a T score of -1.455, with reference to a previous report. RESULTS: One hundred fifty-six participants were classified as individuals without rotator cuff tears (group A), and 51 participants were classified as those with (group B). The mean age in group A was significantly lower than that in group B (63 ± 10 vs. 68 ± 9, respectively; P = .003). In terms of the T score examined by quantitative ultrasound, the mean T score in group A was significantly higher than that in group B (-1.4 ± 1.3 vs. -1.9 ± 1.6, respectively; P = .0412). The percentage of subjects with a T score of -1.455 or less in group B was 60.8% (31/51). The proportion of subjects with a T score of -1.455 or less undergoing osteoporosis treatment was 14.5% (12/83) in group A and 12.9% (4/27) in group B, showing no significant difference. CONCLUSIONS: Participants with a rotator cuff tear had relatively high prevalence of osteoporosis. Among those with both a rotator cuff tear and osteoporosis, the proportion receiving osteoporosis treatment was l2.9%, a very low rate.

Potential of patellar height measurement methods in predicting recurrent patellar dislocation incidence: a case-control study.

BACKGROUND: Recurrent patellar dislocation (RPD) is a multifactorial disease that affects young and active people. Patellar height measurements are used clinically to screen and diagnose knee conditions. However, there are no known studies that have assessed and compared the performance of patellar height indices for predicting the incidence of RPD, which could be used to recommend surgical treatment after primary patellar dislocation. This case-control study aimed to determine if the patellar height index could be used to predict the incidence of RPD, and to identify the optimal method in terms of its diagnostic ability for RPD. METHOD: Altogether, 133 patients (52 patients with RPD [Group R] and 81 sex- and age-matched controls [Group C]) were enrolled in this study. The Insall-Salvati (IS), Blackburne-Peel (BP), Caton-Deschamps (CD), and modified IS (mIS) methods were used to measure the patellar height index. The intra-observer and inter-observer reliabilities of these four methods were determined using intraclass correlation coefficients. A receiver operating characteristic curve analysis was performed to evaluate the predictive ability of each index and identify the cut-off values that indicated significantly increased risk of RPD. RESULTS: Patient demographics were similar between the two groups. The inter-observer and intra-observer reliabilities were good for all four methods. In patients with RPD, the mean index values for the four methods were significantly higher than those in the matched controls. The area under the curve (AUC) values for IS, BP, CD, and mIS were 0.91 (standard error [SE], 0.03; 95% confidence interval [CI], 0.84-0.96), 0.72 (SE, 0.05; 95% CI, 0.63-0.81), 0.86 (SE, 0.03; 95% CI, 0.79-0.92), and 0.96 (SE, 0.01; 95% CI, 0.94-0.99), respectively. CONCLUSION: Patellar height indices had high predictive performance for the incidence of RPD. The mIS method had the highest AUC.

Arthroscopic Bankart repair with peeling osteotomy of the anterior glenoid rim preserves glenoid morphology.

BACKGROUND: A decrease in the glenoid size after arthroscopic Bankart repair (ABR) was common in shoulders without osseous fragments compared with those with osseous fragments. For cases of chronic recurrent traumatic anterior glenohumeral instability without osseous fragments, we have performed ABR with peeling osteotomy of the anterior glenoid rim (ABRPO) to make an intentional osseous Bankart lesion. The aim of this study was to compare the glenoid morphology after ABRPO with it after simple ABR. METHODS: The medical records of patients who underwent arthroscopic stabilization for chronic recurrent traumatic anterior glenohumeral instability were retrospectively reviewed. Patients with an osseous fragment, with revision surgery and without complete data were excluded. Patients were assigned to 1 of 2 groups: Group A, ABR without peeling osteotomy procedure or Group B, with ABRPO procedure. Computed tomography was performed preoperatively and 1 year after surgery. The size of the glenoid bone loss was investigated by the assumed circle method. The following formula was used to calculate the decreased size of the glenoid: (Δ) = (postoperative size of the glenoid bone loss) - (preoperative size of the glenoid bone loss). The size of the glenoid 1 year after surgery was assessed to determine if it had decreased (Δ > 0%) or not decreased (Δ ≤ 0%) relative to the preoperative size. RESULTS: This study evaluated 39 shoulders divided into 2 groups: 27 shoulders in Group A and 12 shoulders in Group B. In Group A, postoperative glenoid bone loss was significantly greater than preoperative glenoid bone loss (7.8 ± 6.2 vs. 5.5 ± 5.3, respectively, P = .02). In Group B, postoperative glenoid bone loss was significantly lower than preoperative glenoid bone loss (5.6 ± 5.4 vs. 8.7 ± 4.0, respectively, P = .02). The P value for the interaction of group (A or B) × time (preoperative or postoperative) was 0.001. The decreased size of the glenoid was significantly larger in Group A than in Group B (2.1 ± 4.2 vs. -3.1 ± 4.5, respectively, P = .001). The rate of shoulders in which the size of the glenoid decreased 1 year after surgery relative to the preoperative size was significantly higher in Group A than in Group B (63% [17/27] vs. 25% [3/2], respectively, P = .04). CONCLUSIONS: The study showed that ABRPO preserved the glenoid size better than simple ABR without a peeling osteotomy procedure.

Circulating miRNA-122 is associated with knee osteoarthritis progression: A 6-year longitudinal cohort study in the Yakumo study.

OBJECTIVE: The association between knee osteoarthritis (OA) and miRNAs has been widely reported. However, the utility of miRNAs as predictors of knee osteoarthritis (KOA) progression in longitudinal studies has not been reported. We aimed to identify circulating miRNAs (c-miRNAs) associated with KOA progression in the general population and to examine their potential use as predictors of KOA progression. METHODS: In 2012 and 2018, 66 participants (128 knees) took part in a resident health check-up in the Yakumo study. If the KL classification progressed two or more levels, the patient was classified as having progressive OA. Quantitative real-time polymerase chain reaction was used to screen 21 c-miRNAs. The expression levels of those c-miRNAs were compared between the progressive OA group and non-progressive OA group using student-t-test. Logistic analysis was performed in c-miRNAs less than p < 0.10 in univariate analysis. RESULTS: The progressive OA group consisted of 78 knees. The results of the comparison between the progressive OA group and the non-progressive OA group showed that six c-miRNAs as follows; let7d (p = 0.030), c-miRNA-122 (p < 0.001), 150 (p = 0.070), 199 (p = 0.078), 21 (p = 0.016) and 320 (p = 0.093) were extracted as factors related to the progression of knee OA. In addition, logistic regression analysis identified c-miRNA-122 as an independent factor involved in the progression of knee osteoarthritis (odds ratio: 1.510, 95% confidence interval: 1.060-2.140, p = 0.023). The ROC curve showed by c-miRNA-122 for the progression of OA risk had an area under the curve of 0.702 (95% CI: 0.609-0.795). The threshold of c-miRNA-122 was -4.609. CONCLUSION: The expression level of c-miRNA-122 was associated with the risk of KOA progression in community dwelling Japanese people.

The prevalence and characteristics of diffuse idiopathic skeletal hyperostosis in the community-living middle-aged and elderly population: The Yakumo study.

BACKGROUND: The incidence of diffuse idiopathic skeletal hyperostosis (DISH) is increasing with the aging of the population. Asymptomatic DISH can decrease the spinal range of motion (ROM) and cause fractures. However, the prevalence or physical function of patients with DISH before experiencing fractures and other serious conditions is unclear. This study aimed to investigate the prevalence of DISH in the community residents on the basis of age and sex and characterize their physical function, ROM, and bone fragility. METHODS: The subjects were community volunteers who attended a health checkup in 2018 and 2019. Overall, 455 subjects (mean age, 64.2 ± 9.7 years; 177 men) were included for analysis. We performed whole-spine lateral radiography for detecting DISH according to the criteria reported by Resnick. We compared the age, sex, body mass index (BMI), results of muscle strength and walking tests, ROM measured by SpinalMouse®, and quantitative ultrasound (QUS) of calcaneus with and without DISH. RESULTS: DISH was detected in 83 (18.2%) cases. The DISH group was older (69.8 y.o. vs. 63.0 y.o.; p < 0.05) and comprised more men (prevalence: men, 27.7%; women, 12.2%; p < 0.001). BMI was high in the DISH group (24.8 vs. 23.3 kg/m2, p < 0.05). SpinalMouse measurements showed the DISH group had a significantly decreased ROM in the lumbar spine (43.2°, 57.2°, p < 0.05). The DISH group had a significantly lower T-score on the QUS measurement in the calcaneus (-2.0, -1.5, p < 0.05). There were, however, no significant differences between groups in both muscle strength test and walking test. CONCLUSION: Subjects with DISH had decreased ROM in the lumbar spine and bone mineral density in calcaneal QUS. However, physical functions such as muscle strength and walking ability were similar among subjects with and without DISH without subjective symptoms.

Metabolic syndrome reduces spinal range of motion: The Yakumo study.

BACKGROUND: Excess visceral fat can accumulate owing to lack of exercise. The relationship between metabolic syndrome (MetS) and spinal range of motion (ROM) is not clear. The purpose of this study was to investigate the relationship between MetS and spinal alignment and ROM. METHODS: Orthopedic evaluation was prospectively performed in 544 participants. The participants were classified into two groups on the basis of the Japanese-specific MetS criteria proposed by the Japanese Committee of the Criteria for MetS (JCCMS). Lower back pain (LBP), knee joint pain with the visual analog scale (VAS), Kellgren-Lawrence (K-L) grade for knee osteoarthritis, body mass index (BMI), and spinal alignment and ROM were evaluated. RESULTS: Forty-four (8.1%) were diagnosed as having MetS. The prevalence rate of K-L grade 4 in the MetS group was significantly higher than that in the non-MetS group (p < 0.05). When sex, age, and BMI were evaluated as covariates, there were significant differences in the VAS score for knee pain (non-MetS group vs MetS group: 13.7 vs 23.3, p < 0.05), L1-S1 flexion spinal ROM (44.1° vs 38.1°, p < 0.001), flexion spinal inclination angle (SIA) ROM (107.6° vs 99.3°, p < 0.01), and SIA ROM (135.4° vs 124.0°, p < 0.05). CONCLUSIONS: Knee pain increased and flexion spinal ROM decreased significantly in the MetS group as compared with non-MetS group. Systemic factors associated with MetS may have a specific impact on spinal ROM while promoting knee osteoarthrosis and increased knee pain.

Effects of Unrestricted Kinematically Aligned Total Knee Arthroplasty with a Modified Soft-Tissue Respecting Technique on the Deformity of Limb Alignment in Japanese Patients.

Background and Objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft-tissue respecting technique (STRT) is a soft-tissue-dependent tibial resection entailing the restoration of the original soft-tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with the STRT. We modified the STRT, followed by an investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plotted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postoperative HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited a high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ±5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ±5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

Meclozine ameliorates skeletal muscle pathology and increases muscle forces in mdx mice.

We screened pre-approved drugs for the survival of the Hu5/KD3 human myogenic progenitors. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, promoted the proliferation and survival of Hu5/KD3 cells. Meclozine increased expression of MyoD, but reduced expression of myosin heavy chain and suppressed myotube formation. Withdrawal of meclozine, however, resumed the ability of Hu5/KD3 cells to differentiate into myotubes. We examined the effects of meclozine on mdx mouse carrying a nonsense mutation in the dystrophin gene and modeling for Duchenne muscular dystrophy. Intragastric administration of meclozine in mdx mouse increased the body weight, the muscle mass in the lower limbs, the cross-sectional area of the paravertebral muscle, and improved exercise performances. Previous reports show that inhibition of phosphorylation of ERK1/2 improves muscle functions in mouse models for Emery-Dreifuss muscular dystrophy and cancer cachexia, as well as in mdx mice. We and others previously showed that meclozine blocks the phosphorylation of ERK1/2 in cultured cells. We currently showed that meclozine decreased phosphorylation of ERK1/2 in muscles in mdx mice but not in wild-type mice. This was likely to be one of the underlying mechanisms of the effects of meclozine on mdx mice.

Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears.

BACKGROUND: Recently, to treat the long head of the biceps tendon lesions in addition to rotator cuff repair has been recommended. However, the differences in clinical outcomes between biceps tenotomy and tenodesis for middle-aged and elderly females remains unclear. The purpose of this study was to compare the outcomes of biceps tenotomy and soft-tissue tenodesis that were performed concurrently with arthroscopic rotator cuff repair in ≥60-year-old females. METHODS: Female shoulders that underwent arthroscopic rotator cuff repair in our institute in 2016 were retrospectively reviewed. This study included 66 shoulders with concurrent biceps tenotomy or soft-tissue tenodesis: tenotomy group, 41 shoulders; soft-tissue tenodesis group, 25 shoulders. Clinical scores, biceps pain (visual analogue scale, VAS), Popeye deformity, and biceps strength (%contralateral side) were compared between the two groups. RESULTS: The mean age was significantly higher in the tenotomy group than the soft-tissue tenodesis group (72 ± 4 and 68 ± 6 years, respectively; P = 0.002). There were no significant differences in post-operative JOA and UCLA scores between the groups. VAS for biceps pain was significantly higher at postoperative 6 months in the tenotomy group than the soft-tissue tenodesis group (2.9 ± 2.5 and 1.7 ± 1.6, respectively, P = 0.03), though there were no significant differences at postoperative 3, 12, and ≥24 months. Subjective evaluation of Popeye deformity was not significantly different between the groups. Postoperative biceps strength was significantly lower in the tenotomy group than the soft-tissue tenodesis group (89.9% and 102.8%, respectively, P = 0.02). CONCLUSIONS: Both biceps tenotomy and soft-tissue tenodesis concurrent with rotator cuff repair in ≥60-year-old female patients resulted in good outcomes. Shoulders with soft-tissue tenodesis demonstrated earlier improvement in postoperative biceps pain and better postoperative biceps strength than those with tenotomy. There were no differences in objective and subjective Popeye deformity between tenotomy and soft-tissue tenodesis. The LHB procedures, tenotomy or tenodesis, can be selected depending on surgeons' preference.

Association between locomotive syndrome and fall risk in the elderly individuals in Japan: The Yakumo study.

BACKGROUND: Patients with locomotive syndrome (LS) are poor ambulatory status and a high risk of requiring nursing care. The purpose of this study is to investigate the relationship between LS and fall risk among community-dwelling elderly individuals. METHODS: The subjects were Japanese elderly individuals aged 65 and over who participated in Yakumo study 2019 (N = 189). We defined the fall risk index 5 items version (FRI-5) ≥6 points as the fall risk group. LS was evaluated by stand-up test, two-step test, and 25-Geriatric Locomotive Function Scale (GLFS-25). We divided the subjects into two groups according to the presence or absence of fall risk, and investigated factors associated with fall risk. RESULTS: The fall risk group (30 patients, 15.9%) had higher GLSF-25 (P = 0.001). The results of logistic regression analysis adjusted for age, sex, BMI, and knee osteoarthritis revealed that GLFS-25 (OR: 1.052; 95%CI: 1.009-1.097) was independent factor associated with fall risk. In the ROC analysis, the optimal cut-off value of the GLFS-25 to predict fall risk was 12, which is equivalent to LS stage 1 (AUC 0.688; 95% CI: 0.588-0.787; sensitivity: 0.467, specificity: 0.836). CONCLUSIONS: GLFS-25 was associated with fall risk among community-dwelling elderly individuals aged 65 and over.

The development of knee osteoarthritis and serum carotenoid levels among community-dwelling people in Japan.

OBJECTIVES: Carotenoids are plant pigments found in many vegetables, functioning as antioxidants scavenging singlet molecular oxygen and peroxyl radicals. No longitudinal study exists on the relationship between carotenoids and knee osteoarthritis (KOA) development. We aimed to determine the incidence of KOA development for 10 years in community-dwelling people in Japan and assess its association with serum carotenoids. METHODS: Data of 440 participants (174 men, 266 women) with health-screening records for at least 10 years were analysed. We defined KOA development as advancing from K/L grade 0/1 at the initial check-up to grade ≥2 in a unilateral knee during a 10-year follow-up period. Serum carotenoid levels were measured using high-performance liquid chromatography. We used the Cox hazard model for multivariate analysis and investigated each carotenoid's impact on KOA development. RESULTS: KOA developed in 33.4% of patients; the annual KOA development rate was significantly higher among women than among men (p < .01; 3.4% vs. 1.6%). Among the carotenoids measured, only retinol was associated with KOA development in women using multivariable analysis. KOA development was not associated with any carotenoids in men. CONCLUSION: The annual rate of KOA development was higher in women, and retinol was associated with KOA development in women.

Differences in the prevalence of locomotive syndrome and osteoporosis in Japanese urban and rural regions: The Kashiwara and Yakumo studies.

OBJECTIVES: To clarify whether the prevalence of locomotive syndrome (LS) and osteoporosis differed according to region, gender, and physical functions in Japan. METHODS: Data were collected in Kashiwara City (urban region) and Yakumo Town (rural region). Totally, 208 participants from the urban region and 782 participants from the rural region were included in this study. LS was assessed using the 25-item Geriatric Locomotive Function Scale and osteoporosis was assessed using a quantitative ultrasound. Physical functions were measured using grip strength and the 3-m timed up-and-go test. Differences between urban and rural regions were investigated using standardized incidence ratio and multivariate analysis. RESULTS: The prevalence of LS and osteoporosis was 24.5% and 42.8% in the urban region and 10.9% and 28.8% in the rural region, respectively. The standardized incidence ratio of the urban region versus the rural region was 1.80 (95% confidence intervals [CI] = 1.35-2.39) for LS and 1.21 (95% CI = 1.32-2.43) for osteoporosis, showing that the prevalence of LS was significantly higher in the urban region. Multivariate analysis indicated that LS was significantly associated with the urban sample and timed up-and-go was significantly longer in the urban sample. CONCLUSION: Regional differences may be considered when evaluating LS in health checkups. Understanding the results of this study may help reduce LS prevalence.

Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study.

BACKGROUND: For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia. METHODS: In total, 214 patients who were examined at our center during the study period (2016-2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia. RESULTS: Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = - 0.20) and CTV (r = - 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p < 0.01). Furthermore, CTV was significantly lower in women with poor-function and in both men and women with severe sarcopenia group (all p < 0.01). CONCLUSIONS: CSA mostly correlated with muscle strength, whereas CTV mostly correlated with physical performance. CT with measurements of CSA and CTV enables the evaluation of muscle mass and quality simultaneously. CT is believed to be useful in inferring evaluation of motor function and assessment of sarcopenia.

Delayed anterior cruciate ligament reconstruction increases the incidence of medial meniscal bucket handle tears and medial compartment chondral injuries in patients aged 40 years and older.

INTRODUCTION: No widely accepted evidence-based indications exist for the initial surgical management of patients with anterior cruciate ligament (ACL) injuries ≥ 40 years old, and treatment for these patients remains controversial. This study aimed to evaluate the association between elapsed time from ACL injury to surgery and the incidence of meniscal tears and chondral injury in patients aged ≥ 40 years. MATERIALS AND METHODS: The patients who underwent primary ACL reconstruction were divided into two groups based on elapsed time from injury to surgery: early group, < 12 months; and delayed group, ≥ 12 months. Patient records were reviewed for incidence and types of meniscal tears and chondral injuries in each group. Chondral injury grades were evaluated with International Cartilage Regeneration and Joint Preservation Society (ICRS) Criteria. RESULTS: This study evaluated 67 knees in the early group and 33 knees in the delayed group. Mean ages in each group were 46.9 ± 6.5 and 46.9 ± 6.0. The delayed group showed significantly higher rates of medial meniscal tear [31 of 33, 93.9% vs 29 of 67, 43.3%; P < 0.0001; odds ratio (OR), 20.31; 95% confidence interval (CI), 4.49-91.9], medial femoral condyle chondral injuries ≥ ICRS grade II (15 of 33, 45.5% vs 8 of 67, 11.9%; P < 0.001; OR, 6.15; 95% CI 2.24-16.83), and medial tibial chondral injuries ≥ ICRS grade II (7 of 33, 21.2% vs 3 of 67, 4.5%; P < 0.05; OR, 5.74; 95% CI 1.38-23.9) compared with the early group. With respect to types of medial meniscal tear, the delayed group showed a significantly higher frequency of bucket handle tears (11 of 33, 33.3%) compared with the early group (2 of 67, 3.0%; P < 0.0001; OR, 16.25; 95% CI 3.34-79.1). CONCLUSIONS: Delayed ACL reconstruction was associated with increased incidence of chondral injuries and medial meniscal tears, particularly bucket handle tears in this cohort. LEVEL OF EVIDENCE: Level III.

Spontaneous Pneumomediastinum in an Adolescent Soccer Player.

Spontaneous pneumomediastinum (SPM) is an uncommon and usually benign self-limiting clinical disorder found in young people, often without apparent precipitating factors or diseases. A pressure gradient exists between the peripheral pulmonary alveoli and the hilum, and increased intra-alveolar pressure causes rupture of the terminal alveoli. We present the case of a 15-year-old male soccer player who presented with a complaint of anterior chest pain and dysphagia after stopping the strong ball with his chest. His symptom gradually progressed over hours. We can make the diagnosis of SPM using by chest X-ray and computed tomography (CT) scanning. His symptoms were gradually resolved over the course of approximately one week with no exercise and careful observation. We believe that our case provides very useful information to alert clinicians and coaches regarding this rare disease that may occur in anyone including adolescent soccer players.

Chondroprotective effects of 4-methylumbelliferone and hyaluronan synthase-2 overexpression involve changes in chondrocyte energy metabolism.

Hyaluronan is a critical component of articular cartilage and partially helps retain aggrecan within the extracellular matrix of this tissue. During osteoarthritis, hyaluronan and aggrecan loss are an early sign of tissue damage. However, our recent attempts to mimic hyaluronan loss with the hyaluronan inhibitor 4-methylumbelliferone (4MU) did not exacerbate arthritis-like features of in vitro models of arthritis, but surprisingly, caused the reverse (i.e. provided potent chondroprotection). Moreover, the protective effects of 4MU did not depend on its role as a hyaluronan inhibitor. To understand the molecular mechanism in 4MU-mediated chondroprotection, we considered recent studies suggesting that shifts in intracellular UDP-hexose pools promote changes in metabolism. To determine whether such metabolic shifts are associated with the mechanism of 4MU-mediated pro-catabolic inhibition, using molecular and metabolomics approaches, we examined whether bovine and human chondrocytes exhibit changes in the contribution of glycolysis and mitochondrial respiration to ATP production rates as well as in other factors that respond to or might drive these changes. Overexpression of either HA synthase-2 or 4MU effectively reduced dependence on glycolysis in chondrocytes, especially enhancing glycolysis use by interleukin-1ß (IL1ß)-activated chondrocytes. The reduction in glycolysis secondarily enhanced mitochondrial respiration in chondrocytes, which, in turn, rescued phospho-AMP-activated protein kinase (AMPK) levels in the activated chondrocytes. Other glycolysis inhibitors, unrelated to hyaluronan biosynthesis, namely 2-deoxyglucose and dichloroacetate, caused metabolic changes in chondrocytes equivalent to those elicited by 4MU and similarly protected both chondrocytes and cartilage explants. These results suggest that fluxes in UDP-hexoses alter metabolic energy pathways in cartilage.

Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan.

Osteoarthritis (OA) is a progressive degenerative disease of the joints caused in part by a change in the phenotype of resident chondrocytes within affected joints. This altered phenotype, often termed proinflammatory or procatabolic, features enhanced production of endoproteinases and matrix metallo-proteinases (MMPs) as well as secretion of endogenous inflammatory mediators. Degradation and reduced retention of the proteoglycan aggrecan is an early event in OA. Enhanced turnover of hyaluronan (HA) is closely associated with changes in aggrecan. Here, to determine whether experimentally increased HA production promotes aggrecan retention and generates a positive feedback response, we overexpressed HA synthase-2 (HAS2) in chondrocytes via an inducible adenovirus construct (HA synthase-2 viral overexpression; HAS2-OE). HAS2-OE incrementally increased high-molecular-mass HA >100-fold within the cell-associated and growth medium pools. More importantly, our results indicated that the HAS2-OE expression system inhibits MMP3, MMP13, and other markers of the procatabolic phenotype (such as TNF-stimulated gene 6 protein (TSG6)) and also enhances aggrecan retention. These markers were inhibited in OA-associated chondrocytes and in chondrocytes activated by interleukin-1ß (IL1ß), but also chondrocytes activated by lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), or HA oligosaccharides. However, the enhanced extracellular HA resulting from HAS2-OE did not reduce the procatabolic phenotype of neighboring nontransduced chondrocytes as we had expected. Rather, HA-mediated inhibition of the phenotype occurred only in transduced cells. In addition, high HA biosynthesis rates, especially in transduced procatabolic chondrocytes, resulted in marked changes in chondrocyte dependence on glycolysis versus oxidative phosphorylation for their metabolic energy needs.

Impact of pelvic incidence on lumbar osteophyte formation and disc degeneration in middle-aged and elderly people in a prospective cross-sectional cohort.

PURPOSE: Pelvic incidence (PI) is unique to each individual and does not change throughout life. High PI is related to lumbar spondylolisthesis, but associations of PI with lumbar osteophyte formation and disc degeneration are unclear. The objective was to evaluate relationships of PI with lumbar osteophyte formation and disc degeneration, as well as spinal sagittal alignment and geriatric diseases, in middle-aged and elderly people. METHODS: A total of 1002 volunteers (male: 434, female: 568, average age: 63.5) were prospectively examined for lumbar osteophyte formation (Nathan class ≥ 2) and disc degeneration (disc score ≥ 3). High (PI > 51, n = 501) and low (PI ≤ 51, n = 501) PI groups were defined. Clinical factors, frailty, sarcopenia, and physical quality of life (QOL) were compared between these groups, and risk factors for lumbar osteophyte formation and disc degeneration were identified in multivariate logistic regression analysis. RESULTS: Physical QOL was poorer in people with lumbar osteophyte formation (54.8%) and disc degeneration (33.6%). Age, male gender, spinal parameters including PI, bone mineral density, back muscle strength, and gait ability differed significantly between the groups, whereas frailty and sarcopenia were not significantly different. Low PI, low lumbar lordosis, elder age, male gender, high BMI, and weak back muscle strength were significant risk factors for lumbar osteophyte formation and disc degeneration. CONCLUSIONS: Low PI was identified as a risk factor for lumbar osteophyte formation and disc degeneration, both of which reduce physical QOL in middle-aged and elderly people. These slides can be retrieved under Electronic Supplementary Material.

Recurrent fifth metatarsal stress fractures in a professional soccer player with hypoparathyroidism: a case report.

BACKGROUND: Hypoparathyroidism is characterized by low or inappropriately normal levels of parathyroid hormone leading to hypocalcemia. In this report, a case of recurrent fifth metatarsal stress fractures in a professional soccer player with hypoparathyroidism is presented. CASE PRESENTATION: A 23-year-old male professional soccer player developed left foot pain. He had no specific medical or family history. He was diagnosed with a fifth metatarsal stress fracture and underwent osteosynthesis with a cannulated cancellous screw 3 days after the injury. After three and a half months, the X-ray showed bone union, and he returned to full sports activity. However, he felt pain in his left foot again, and a re-fracture was found on X-ray a week later. Osteosynthesis was performed again. Two months after re-operation, the cause of re-fracture was investigated. Laboratory results showed abnormally low levels of serum calcium (8.4 mg/dL) and intact parathyroid hormone (i-PTH: 19.0 pg/mL). However, other laboratory examinations were normal. Therefore, he was diagnosed with primary hypoparathyroidism according to the diagnostic criteria. Medical treatment was started with alfacalcidol 1.0 µg/day. One month after starting medication, the serum calcium improved to 9.4 mg/dL. Four months after the re-operation, the X-ray showed bone union, and he was therefore allowed to play soccer. While he played professional soccer, there were no new subjective complaints. CONCLUSIONS: Hypoparathyroidism may be one of the risk factors for stress fractures. We believe that serum calcium levels should be checked in patients with stress fractures, and if the serum calcium is low, hypoparathyroidism should be considered.

Relationship between lumbopelvic discordance and locomotive syndrome in a middle-aged community-living population: The Yakumo study.

BACKGROUND: Locomotive syndrome (LS) affects the quality and activities of daily living. Although spinal sagittal balance influences LS, no report elucidated the relationship between LS risk and lumbopelvic discordance. This study aimed to investigate the relationship between lumbopelvic discordance and LS in a middle-aged community. METHODS: The subjects (n = 135) were divided into three groups based on the LS risk stage, which was evaluated through spinopelvic sagittal alignment and lumbopelvic mismatch prevalence (Pelvic incidence-Lumbar lordosis >10°:PI-LL mismatch).Then, the subjects were divided into two groups (lumbopelvic matched and mismatched groups) and analyzed based on the demographic data, physical test, stabilometry, and body pain using the visual analog scale. RESULTS: There were 76, 37 and 22 subjects in stages 0, 1, and 2, respectively. The pelvic incidence-lumbar lordosis (PI-LL) mismatched group had a higher prevalence in LS risk stage 2 than in LS risk stage 0. The prevalence of PI-LL mismatch was significantly different among the groups. Post hoc test revealed the differences in spinopelvic alignment among the stages. In each LS risk stage, the degree of PI-LL was significantly higher in stage 2 than that in stages 0 and 1. On comparing the PI-LL matched (n = 67) and mismatched groups (n = 68) with a stabilometer, the envelopment area tracing by the movement of the center of pressure and locus length/second was greater in the PI-LL mismatched group than that in the PI-LL matched group with/without eyes opened. CONCLUSIONS: The prevalence of LS risk stage 2 was more frequently observed in the PI-LL mismatched group. The degree of PI-LL was evaluated through the LS risk stages. Physical dysfunction in the PI-LL mismatched group was related to trunk imbalance based on stabilometry. These findings will help manage LS and PI-LL mismatched subjects.