Publications by authors named "Shinya Ishizuka"

42 Publications

Comparison of vitamin D sufficiency between indoor and outdoor elite male collegiate athletes.

Nagoya J Med Sci 2021 May;83(2):219-226

Department of Orthopaedic Surgery, Asahi University Hospital, Gifu, Japan.

This study compared vitamin D sufficiency between indoor and outdoor elite athletes. We also evaluated the association between vitamin D level, body composition, and stress fractures incidence. 27 outdoor elite male collegiate athletes (field hockey players) and 21 indoor elite male collegiate athletes (fencing players) were enrolled. Participants' demographic information including past fractures were recorded. Furthermore, all the athletes' body compositions including percentage of body fat were measured. Blood samples were collected to test serum calcium, phosphorus, and 25(OH)D. levels. Participants were classified into three groups: vitamin D sufficiency (serum 25(OH)D levels of ≥30 ng/ml), vitamin D insufficiency (serum 25(OH)D levels of <30 ng/ml), and vitamin D deficiency (serum 25(OH)D levels of <20 ng/ml). The indoor athletes showed significantly higher mean percentage of body fat than outdoor athletes, 12.2 ± 3.2% and 9.7 ± 3.7%, respectively. The serum 25(OH)D levels of indoor athletes were significantly lower than those of outdoor athletes, 15.3 ± 3.3 ng/mL and 24.9 ± 4.5 ng/ml, respectively (P < 0.001). Furthermore, the indoor athletes showed a significantly higher rate of vitamin D deficiency than the outdoor athletes, 19 of 21 (90.5%) and 5 of 27 (18.5%), respectively (P < 0.001). The cohort of outdoor athletes with stress fractures' history had significantly lower serum 25(OH)D levels than those without history of any fractures, 21.1 ± 4.3 ng/ml and 26.4 ± 3.0 ng/ml, respectively (P < 0.05). In conclusion, a majority of the indoor elite athletes were vitamin D-deficient. The serum 25(OH)D levels were significantly higher in outdoor elite athletes. However, lower serum 25(OH)D levels might be associated with stress fractures among outdoor athletes.
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http://dx.doi.org/10.18999/nagjms.83.2.219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236685PMC
May 2021

Impact of Neck and Shoulder Pain on Health-Related Quality of Life in a Middle-Aged Community-Living Population.

Biomed Res Int 2021 8;2021:6674264. Epub 2021 Jun 8.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Japan.

Purpose: Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup.

Methods: This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool.

Results: Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76).

Conclusions: The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.
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http://dx.doi.org/10.1155/2021/6674264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208860PMC
June 2021

Human Nonmercaptalbumin Is a New Biomarker of Motor Function.

J Clin Med 2021 Jun 2;10(11). Epub 2021 Jun 2.

Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan.

The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group; f[HMA] ≥ 70%) and low (L group; f[HMA] < 70%) groups. There were 124 non-elderly (<65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.
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http://dx.doi.org/10.3390/jcm10112464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199584PMC
June 2021

Association Between Knee Alignment and Meniscal Tear in Pediatric Patients with Anterior Cruciate Ligament Injury.

J Bone Joint Surg Am 2021 Jun 18. Epub 2021 Jun 18.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: The present study aimed to evaluate the association between elapsed time from anterior cruciate ligament (ACL) injury to surgical treatment and the incidence of meniscal tears in a cohort of patients ≤16 years old with varus-aligned and non-varus-aligned knees.

Methods: The study cohort included 123 patients ≤16 years old who underwent primary ACL reconstruction between January 2016 and March 2020. Knee alignment was expressed as the hip-knee-ankle angle (HKAA), as measured preoperatively on an anteroposterior view of 3-dimensional computed tomography of the full length of the lower limb. Varus alignment was defined as an HKAA ≥181.0°, and non-varus alignment was defined as an HKAA <181.0°. Patients were divided into groups according to knee alignment and the elapsed time from injury to surgical treatment: early-treatment group (<60 days) and delayed-treatment group (≥60 days).

Results: A total of 64 varus-aligned and 59 non-varus-aligned knees were identified. Among patients with varus-aligned knees, those in the delayed-treatment group showed a significantly lower rate of lateral meniscal tears (6 of 30, 20%) compared with those in the early-treatment group (17 of 34, 50%; p = 0.015). Among patients with non-varus-aligned knees, there was no significant difference in meniscal tears of any type between the early and delayed-treatment groups. Among patients without medial meniscal injury identified on initial magnetic resonance imaging, those with varus-aligned knees in the delayed-treatment group showed a significantly higher rate of medial meniscal tears at the time of the surgical procedure (8 of 20, 40%) compared with those with non-varus-aligned knees (1 of 18, 6%; p = 0.015).

Conclusions: Delayed ACL reconstruction in patients ≤16 years old with varus-aligned knees might be associated with an increased incidence of secondary medial meniscal tears. Accordingly, earlier ACL reconstruction in patients with varus-aligned knees should be considered.

Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.01219DOI Listing
June 2021

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

J Orthop Sci 2021 May 31. Epub 2021 May 31.

Tokyo Sports & Orthopaedic Clinic, 4-29-9 Kami-ikebukuro, Toshima, Tokyo, 170-0012, Japan.

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.
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http://dx.doi.org/10.1016/j.jos.2021.04.012DOI Listing
May 2021

The impact of vitamin D supplementation on body fat mass in elite male collegiate athletes.

Nutr Metab (Lond) 2021 May 21;18(1):51. Epub 2021 May 21.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Background: Whether vitamin D supplementation has any effect on body fat percentage, especially among elite athletes, remains unclear. The aim of this study was to evaluate the effect of vitamin D supplementation on serum vitamin D level in elite male collegiate athletes and to analyze its effect on body fat percentage.

Methods: We enrolled a total of 42 elite male collegiate athletes in this prospective cohort study. In March 2020, body composition monitoring and blood test were performed. All athletes were provided with vitamin D3 supplement tablets of 25 μg/day. The use of the supplement was dependent on athletes' preference. During the study period, their club activities were stopped for 2 months due to the coronavirus disease 2019 outbreak. A second examination, similar to the first one, was performed after approximately 3 months. Supplement usage by each athlete was also confirmed. The participants were divided into a non-supplement group (without supplementation, n = 15) and a supplement group (with supplementation, n = 27).

Results: Regarding baseline data at initial examination, the non-supplement and supplement groups showed significant differences in the mean body fat percentage (9.0% and 12.1%, respectively; P = 0.03) and serum 25(OH)D level (22.7 and 18.5 ng/mL, respectively, P = 0.02). At the time of the second examination, there were no significant differences in the results of both the groups. In terms of mean change value from the first to the second examination, there were significant differences in body fat percentage (1.9 and 0.2%, respectively, P = 0.02) and serum 25(OH)D level (1.7 and 7.2 ng/mL, respectively, P < 0.001) between the two groups. A significant negative correlation was observed between the change ratio of body fat percentage and change value of serum 25(OH)D level (r =  - 0.37, P = 0.02).

Conclusions: Vitamin D supplementation of 25 μg/day significantly increased the serum 25(OH)D level in elite male collegiate athletes. Vitamin D supplementation may play a role in maintaining athletes' body fat percentage under circumstances where sports activity has decreased.
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http://dx.doi.org/10.1186/s12986-021-00578-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138511PMC
May 2021

Association between Low Muscle Mass and Inflammatory Cytokines.

Biomed Res Int 2021 27;2021:5572742. Epub 2021 Apr 27.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Sarcopenia is a multifaceted geriatric syndrome associated with the loss of muscle mass. We examined the relationship between low muscle mass and inflammatory cytokines in the context of aging. This study involved 299 participants (127 men and 172 women; mean age 63.3 ± 9.8 years) who underwent health checkups for body composition and inflammatory cytokine (TNF-alpha, IL-6, and MCP-1) levels. Muscle mass was determined using the skeletal muscle mass index. We divided the participants into the normal (N) and low muscle mass (L) groups and compared the levels of inflammatory cytokines in nonelderly (<65 years) and elderly (≥65 years) participants. Among the nonelderly subjects, C-reactive protein was significantly lower in the L group than in the N group ( < 0.05). However, there was no significant difference in the inflammatory cytokine levels between the groups. Among the elderly subjects, the TNF-alpha level was significantly lower in the L group than in the N group ( < 0.05), whereas there were no significant differences in the IL-6 and MCP-1 levels. Moreover, TNF-alpha was identified as a risk factor for the L group in the logistic regression analysis (Exp (B) 0.935, 95% CI: 0.876-0.997, = 0.04). Although a low TNF-alpha level is a risk factor for low muscle mass, inflammatory cytokine levels are not necessarily elevated in elderly individuals with the loss of muscle mass.
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http://dx.doi.org/10.1155/2021/5572742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099521PMC
May 2021

Bioelectrical Impedance Analysis and Manual Measurements of Neck Circumference Are Interchangeable, and Declining Neck Circumference Is Related to Presarcopenia.

Biomed Res Int 2021 29;2021:6622398. Epub 2021 Mar 29.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Japan.

Purpose: Preventive medicine is important in an aging society. Presarcopenia is the preliminary stage of sarcopenia. Recent advances in bioelectrical impedance analysis (BIA) devices have enabled automatic estimation of neck circumference (NC). However, the agreement between and interchangeability of NC measured manually and that calculated with BIA have not been evaluated. We performed these analyses in the context of health checkups and investigated their associations with presarcopenia.

Methods: We enrolled 318 participants who underwent anthropometric measurements, including NC measured manually and by BIA; assessment of physical function; and blood testing. We used Bland-Altman analysis to calculate the agreement between and interchangeability of NC measurements by BIA and by the manual method. We then statistically compared normal participants and those with presarcopenia. Using multivariable analysis, we subsequently investigated significant risk factors for presarcopenia. We defined presarcopenia according to the appendicular skeletal muscle index (aSMI; the ratio of arm and leg skeletal muscle mass to height).

Results: Bland-Altman analysis showed that bias (BIA-manual) was negative overall (-1.07), for male participants (-1.23), and for female participants (-0.96). This finding suggests that BIA measurement is an underestimate in comparison with manual measurement. NC measurement by BIA was found to be interchangeable with that by manual methods, inasmuch as the percentage error was less than 5% overall (4.38%), for male participants (3.81%), and for female participants (4.58%). Univariable analysis revealed that NC was significantly smaller in the participants with presarcopenia than in those without. Multivariable analysis, adjusted for confounding factors, revealed that a decrease in NC was significantly correlated with presarcopenia.

Conclusions: BIA measurements of NC are interchangeable within about 95% with manual measurements. The decrease in NC measured by BIA was significantly associated with presarcopenia in both genders. NC measurement can be used for early detection of presarcopenia.
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http://dx.doi.org/10.1155/2021/6622398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024069PMC
May 2021

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

BMC Geriatr 2021 04 13;21(1):239. Epub 2021 Apr 13.

Department of Orthopedics, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showaku, Nagoya, Aichi, 466-8560, Japan.

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.
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http://dx.doi.org/10.1186/s12877-021-02187-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045267PMC
April 2021

The dual presence of frailty and locomotive syndrome is associated with a greater decrease in the EQ-5D-5L index.

Nagoya J Med Sci 2021 Feb;83(1):159-167

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Japan's aging society is facing an increase in the prevalence of frailty and locomotive syndrome (LS) among older adults. To evaluate the association of these age-related declines on health-related quality of life (QOL) in Japan, we investigated this relationship among Japanese middle-aged and older adults who underwent general checkups and examined whether LS or frailty has a stronger association with the Japanese version of EuroQol's five-level EQ-5D (EQ-5D-5L) index. Participants were 231 middle-aged and older Japanese adults receiving routine health checkups. The study utilized the 25-item Geriatric Locomotive Function Scale, the Japanese version of the Cardiovascular Health Study, and the Japanese version of the EQ-5D-5L. Univariate and multivariate analyses were performed to examine how frailty and LS are related to the EQ-5D-5L index. Patients with both frailty (p = 0.003) and LS (p < 0.001) had a significantly lower EQ-5D-5L index. After adjusting for age, gender, and body mass index, LS was significantly associated with a decrease in the EQ-5D-5L index (p < 0.001), whereas frailty had no significant association with the EQ-5D-5L index (p = 0.052). Further analysis showed no significant decrease in the EQ-5D-5L index among those with frailty but no LS, and a significant decrease among those with frailty and LS. The results suggest that frailty and LS are associated with a decrease in the EQ-5D-5L index, but LS has a more pronounced effect. In evaluating frailty's effects on health-related QOL, we determined the importance of separately assessing frailty both with and without LS, even within the same frailty group.
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http://dx.doi.org/10.18999/nagjms.83.1.159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938103PMC
February 2021

Outcomes of pediatric anterior cruciate ligament reconstructions in patients with and without bucket handle meniscus repairs.

J Pediatr Orthop B 2021 Mar 8. Epub 2021 Mar 8.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Asahi Department of Orthopaedic Surgery, Asahi University Hospital, Gifu, Japan.

To report the outcomes of concomitant bucket handle meniscal tear (BHMT) repair and anterior cruciate ligament (ACL) reconstruction and to compare the outcomes with those after isolated ACL reconstruction in patients aged ≤16 years. Patients in our database from 2013 to 2017 were retrospectively analyzed. Patients were assigned to one of two treatment groups based on the presence of BHMTs: no meniscal tear group (group A) and BHMT group (group B). All BHMTs were repaired using the combined inside-out with all-inside technique. This study included 64 knees divided into two groups: 47 knees in group A and 17 knees in group B. There was a significant difference in the interval between ACL injury and surgery between groups A and B (69 vs. 150 days, respectively; P < 0.001). Mean postoperative International Knee Documentation Committee and Lysholm scores in group A were slightly, although significantly, improved compared to those in group B (96.5 vs. 92.6, respectively; P < 0.05, and 98 vs. 95, respectively; P < 0.05). There were no significant differences in postoperative anteroposterior laxity and graft failure rate between the groups. In group B, four patients (23.5%) required surgery for incomplete meniscal healing. Postoperative International Knee Documentation Committee and Lysholm scores of patients with BHMTs were significantly lower than those of patients without any meniscal tear, although with significant improvement in the amount of instability. Level of evidence was Level III.
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http://dx.doi.org/10.1097/BPB.0000000000000857DOI Listing
March 2021

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

Mod Rheumatol 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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.
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http://dx.doi.org/10.1080/14397595.2021.1899890DOI Listing
March 2021

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

Mod Rheumatol 2021 Apr 12:1-8. Epub 2021 Apr 12.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, 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 ( < .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.
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http://dx.doi.org/10.1080/14397595.2021.1900030DOI Listing
April 2021

Spontaneous Pneumomediastinum in an Adolescent Soccer Player.

J Sports Sci Med 2021 03 1;20(1):52-55. Epub 2021 Mar 1.

Department of Orthopedic Surgery, Nagoya University, Nagoya, Japan.

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.
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http://dx.doi.org/10.52082/jssm.2021.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919345PMC
March 2021

The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people-the Yakumo study.

Clin Rheumatol 2021 Jul 11;40(7):2643-2649. Epub 2021 Jan 11.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan.

Objective: We aimed to investigate the relationship between high-sensitivity CRP (hs-CRP) levels and the knee osteoarthritis (KOA) status and whether high hs-CRP levels predict the progression of clinical KOA in community-dwelling people.

Methods: We enrolled 247 subjects (male, n = 99; female, n = 148) who participated in the "Yakumo study" at least twice from 2003 to 2008. The KOA was evaluated by knee X-ray using the knee osteoarthritis computer-aided diagnosis (KOACAD) measurement system to obtain the mJSW, the size of the osteophyte area (OPA), and femorotibial angle (FTA). The pain intensity of the knee joint was measured using a visual analog scale (VAS, 0-100). First, we performed a multiple regression analysis to assess the relationship between the initial hs-CRP and mJSW, OPA, FTA, and VAS. Second, we examined the correlated coefficients between the amount of change hs-CRP and radiographic progressions and VAS changes. Third, we divided into two groups. Group H elevated hs-CRP levels (> 0.1 mg/dl). We picked up the subject matched to Group H according to BMI, age, sex, and medial mJSW at baseline in a 1:1 ratio; these participants were classified as the control group (Group L). The Mann-Whitney U test was used to compare the demographic data between the two groups. P values of < 0.05 were considered to indicate statistical significance.

Results: The initial hs-CRP was a significant explanatory factor for mJSW and VAS change in multiple regression analysis. The change of VAS value negatively correlated with the change of hs-CRP. Besides, the change of hs-CRP did not correlate with the radiographical change. Among these subjects, 55 had elevated hs-CRP levels (> 0.1 mg/dl) (Group H). Among the 192 subjects whose hs-CRP levels were ≤ 0.1 mg/dl, 55 subjects were matched to patients in Group H according to the age, sex, BMI, and average minimum joint space width (mJSW) at baseline and were used as a control group (Group L). The narrowing of the medial mJSW and the amount of change in OPA in group H were significantly greater than group L. The amount of change in FTA and VAS scores did not differ between the two groups.

Conclusion: Hs-CRP levels would be significantly associated with the progression of knee osteoarthritis. Key Points • We investigated the relationship between hs-CRP levels and the progression and the pain of osteoarthritis knee. • We used a KOACAD system, which can measure the medial and lateral joint space narrowing, osteophyte, and femoral-tibia angle from plain radiographs automatically. • Hs-CRP levels were significantly associated with the progression of knee osteoarthritis.
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http://dx.doi.org/10.1007/s10067-020-05541-2DOI Listing
July 2021

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.

Arch Orthop Trauma Surg 2021 Jun 11;141(6):971-975. Epub 2021 Jan 11.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

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.
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http://dx.doi.org/10.1007/s00402-020-03745-4DOI Listing
June 2021

Incidence of Medial and Lateral Meniscal Tears After Delayed Anterior Cruciate Ligament Reconstruction in Pediatric Patients.

Orthop J Sports Med 2020 Nov 19;8(11):2325967120964603. Epub 2020 Nov 19.

Department of Orthopaedic Surgery, Asahi University Hospital, Gifu, Japan.

Background: The treatment of pediatric anterior cruciate ligament (ACL) injuries is controversial, and no clear management guidelines have been established.

Purpose: To evaluate the association between elapsed time from ACL injury to surgery and the incidence of meniscal tears and chondral injuries in patients aged ≤16 years.

Study Design: Cohort study; Level of evidence, 3.

Methods: Between December 2012 and April 2019, a total of 207 consecutive knees in 207 patients aged ≤16 years underwent primary ACL reconstruction and were included in this study. Patients were divided into 1 of 2 groups (early group [≤150 days] and delayed group [>150 days]) based on the time between injury and surgery. Patient records, including arthroscopic findings identified by 2 experienced knee surgeons at the time of surgery, were reviewed for demographic information, incidence and types of medial and lateral meniscal tears, and chondral injuries and their locations in each group.

Results: There were 180 knees in the early group and 27 knees in the delayed group. The delayed group showed a significantly higher rate of medial meniscal tears than the early group: 16 of 27 (59.2%) and 46 of 180 (25.6%), respectively (odds ratio [OR], 4.24 [95% CI, 1.83-9.33]; = .0011). The delayed group had a significantly lower rate of lateral meniscal tears than the early group: 6 of 27 (22.2%) and 90 of 180 (50.0%), respectively (OR, 0.29 [95% CI, 0.11-0.70]; = .007). The delayed group had significantly higher rates of chondral injuries in the medial femoral condyle and the medial tibial plateau than the early group: 8 of 27 (29.6%) and 25 of 180 (13.9%), respectively (OR, 2.61 [95% CI, 1.03-6.62]; = .049), and 2 of 27 (7.4%) and 1 of 180 (0.6%), respectively (OR, 14.32 [95% CI, 1.58-208.10]; = .045).

Conclusion: Delayed ACL reconstruction was associated with an increased incidence of medial chondral injuries and medial meniscal tears but with a decreased incidence of lateral meniscal tears.
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http://dx.doi.org/10.1177/2325967120964603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686615PMC
November 2020

Influence of Global Spine Sagittal Balance and Spinal Degenerative Changes on Locomotive Syndrome Risk in a Middle-Age and Elderly Community-Living Population.

Biomed Res Int 2020 23;2020:3274864. Epub 2020 Sep 23.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.

Purpose: The aim of this study was to describe the characteristics of each locomotive syndrome (LS) risk stage, including global spine sagittal alignment, spinal degenerative changes evident on plain radiographs, low back pain (LBP), muscle strength, and physical ability in middle-aged and elderly people in a health checkup.

Methods: This study included 211 healthy Japanese volunteers (89 men and 122 women; mean age, 64.0 years) who underwent assessment with both radiographs and Spinal Mouse. Spinal sagittal parameters included thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sagittal vertical axis, and spinal inclination angle (SIA). Lumbar disc height (LDH) and lumbar osteophyte formation (LOF) at each level were evaluated as the spinal degenerative changes. The LS assessment comprised three tests: stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25). The subjects were divided into three groups (no risk, stage 1 LS, or stage 2 LS) according to LS risk test criteria. The prevalence of LBP was investigated with a visual analogue scale (VAS), and physical performances were also compared among the groups.

Results: Of the participants, 122 had no risk of LS, 56 had stage 1 LS risk, and 29 had stage 2 LS risk. With increasing LS risk stage, the prevalence of and VAS score for LBP increased significantly, and back muscle strength and physical abilities decreased significantly. The TKA did not differ among the three groups. The LLA decreased gradually with LS risk stage ( = 0.0001). At each level except L1-L2 and L5-S1, LDH decreased gradually with LS risk stage. The prevalence of LOF increased significantly with increasing LS risk stage. The SIA increased significantly with LS risk stage ( = 0.0167).

Conclusions: Participants with LS had higher prevalence of spinal degeneration, small LLA, and global spinal imbalance by anterior spinal inclination.
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http://dx.doi.org/10.1155/2020/3274864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532429PMC
May 2021

Associations of Serum MicroRNA with Bone Mineral Density in Community-Dwelling Subjects: The Yakumo Study.

Biomed Res Int 2020 30;2020:5047243. Epub 2020 Jul 30.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan.

Osteoporosis is a disease characterized by deterioration of bone tissue and mass, with an increasing global prevalence. Therefore, the discovery of biomarkers for osteoporosis would help to guide appropriate treatment. Circulating microRNAs (miRNAs) have become increasingly recognized as biomarkers for detecting diseases. However, few studies have investigated the association of circulating miRNA with osteoporosis in the general population. The aim of this study was to identify miRNA associated with osteoporosis in a general resident health check-up for potential use as an osteoporosis biomarker. We conducted a cross-sectional study as part of a health check-up program and recruited 352 volunteers (139 men, 213 women, mean age 64.1 ± 9.6 years). Osteoporosis was diagnosed according to the WHO classification. Twenty-two candidate microRNAs were screened through real-time quantitative PCR, and miRNAs associated with osteoporosis were analyzed using logistic regression analysis including other risk factors. In total, 95 females and 30 males were diagnosed with osteoporosis with bone mineral density tests (BMD: -score < -2.5). We found that miR195 was significantly lower in females, while miR150 and miR222 were significantly higher in males. The results of the logistic regression analysis indicated that in females, higher age and lower miR195 (odds ratio: 0.45, 95% confidential interval: 0.03-0.98) were significant risk factors for lower BMD, while the presence of a smoking habit and lower miR150 (odds ratio: 1.35, 95% confidential interval: 1.02-1.79) were significant risk factors for osteoporosis. Serum levels of miR195 and miR150 are independently associated with low bone mineral density in females and males, respectively.
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http://dx.doi.org/10.1155/2020/5047243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414326PMC
April 2021

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

BMC Musculoskelet Disord 2020 Jun 3;21(1):347. Epub 2020 Jun 3.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

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.
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http://dx.doi.org/10.1186/s12891-020-03383-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271481PMC
June 2020

Locomotive syndrome and the power spectral characteristics of body sway.

Geriatr Gerontol Int 2020 Jul 1;20(7):691-696. Epub 2020 Jun 1.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Aim: In Japan, nursing care is advised for patients with locomotive syndrome (LS) because of musculoskeletal disorders. Balance tests have indicated an association between LS risk and sway size related to center of pressure (COP) movement. Here, the power spectrum represents the energy contained in each frequency of COP sway. Although balance tests are often performed during health checkups, no studies have investigated the relationship between the power spectrum and LS. This study investigated this relationship.

Methods: In total, 605 recipients of health checkups were evaluated for LS using the 25-item Geriatric Locomotive Function Scale. Power spectrums were calculated by applying fast Fourier transform to COP sway time-series data. These were classified into three sections (0.02-0.2 Hz [low-frequency band; LFB], 0.2-2 Hz [mid-frequency band], and 2-10 Hz [high-frequency band; HFB]). Power spectrums were evaluated in left-right and front-back directions.

Results: LS was associated with significantly lower ratios for both the HFB (P = 0.001) in the left-right direction and LFB (P = 0.007) in the front-back direction. In addition, men had significantly lower HFB ratios in the left-right direction (P = 0.032) and LFB ratios in the front-back (P = 0.013), whereas women had significantly lower HFB ratios in the left-right direction (P = 0.007).

Conclusions: LS was associated with significantly lower ratios for both the HFB in the left-right direction and LFB in the front-back direction. This understanding of the power spectral characteristics of LS may be useful in the context of pathology and therapeutic intervention. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.
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http://dx.doi.org/10.1111/ggi.13937DOI Listing
July 2020

Higher extracellular water-to-total body water ratio more strongly reflects the locomotive syndrome risk and frailty than sarcopenia.

Arch Gerontol Geriatr 2020 May - Jun;88:104042. Epub 2020 Mar 7.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address:

Objective: Among body composition parameters measured by bioelectrical impedance analysis, the extracellular water-to-total body water (ECW/TBW) ratio is a known prognostic or related factor for various diseases. While concepts such as locomotive syndrome risk, frailty, and sarcopenia are gaining popularity in Japan, their relationship with the ECW/TBW ratio has not been examined in detail. This study aimed to investigate the relationships between them.

Methods: Of 1081 individuals who underwent health checkups, 550 were included in this study. The evaluations included a two-step test, stand-up test, and a 25-question geriatric locomotive function scale questionnaire. Frailty was diagnosed based on the Japanese version of the Cardiovascular Health Study criteria. Sarcopenia was evaluated according to the Asian Working Group for Sarcopenia criteria. The aforementioned ratio was measured using bioelectrical impedance analysis.

Results: The ECW/TBW ratio significantly increased with locomotive syndrome risk, frailty, and sarcopenia (p < 0.001 each). Nevertheless, no significant difference was found between robust and pre-frailty groups (p = 0.71) and normal and pre-sarcopenia groups (p = 0.93). Furthermore, after correcting for age, sex, and body mass index, multiple regression analysis revealed that locomotive syndrome risk (p < 0.001) and frailty (p = 0.001) were significantly associated with an increase in the ECW/TBW ratio, whereas sarcopenia was not (p = 0.97).

Conclusions: An increase in the ECW/TBW ratio may reflect locomotive syndrome risk and frailty, but not sarcopenia. In bioelectric impedance analysis, this ratio is an important indicator; if it is high, it is necessary to consider locomotive syndrome risk and frailty.
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http://dx.doi.org/10.1016/j.archger.2020.104042DOI Listing
November 2020

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

Eur Spine J 2020 09 4;29(9):2262-2271. Epub 2020 Mar 4.

Department of Rehabilitation, Kansai University of Welfare Sciences, 3-11-1, Asahigaoka, Kashiwara, Osaka, 582-0026, Japan.

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.
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http://dx.doi.org/10.1007/s00586-019-06204-wDOI Listing
September 2020

Differences of lumbopelvic sagittal parameters among community-dwelling middle-age and elderly individuals: Relations with locomotor physical function.

J Clin Neurosci 2020 Mar 16;73:80-84. Epub 2020 Jan 16.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine 65, Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address:

This study aims to establish radiographic parameters of lumbopelvic sagittal alignment, gender related differences, and age-related changes in a middle-aged community, to investigate whether age-related changes of lumbopelvic alignment reflect the risk of locomotive syndrome (LS). This study included 448 healthy Japanese volunteers who attended a basic health checkup supported by the local government. The subjects (184 males and 264 females, mean age: 62.7 years) were grouped according to their age by decade. Sagittal lumbopelvic parameters were collected by lateral spine radiographs including lumbar lordosis (L1-S1, LL), lower lumbar lordosis (L4-S1, LLL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). The three tests (stand-up test, two-step test, and 25-question geriatric locomotive function scale [GLFS-25]) composing the LS risk test were performed. LL was significantly lower in males than in the females. A significant decrease of LL and LLL was observed from 60 s to 70 s in the females. PI did not markedly change with aging in either gender but was lower in males. A remarkable increase of PT was seen from 60 s to 70 s in the females. SS did not markedly change with aging and was lower in males in all decades. The prevalence of LS risk in males and females increased gradually with age and was greater in females in any decade. 70 s females with LS risk had significantly lower LL and higher PT compared to them without LS risk. Radiographic parameters of lumbopelvic sagittal alignment were established in community-dwelling middle-age and elderly individuals.
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http://dx.doi.org/10.1016/j.jocn.2020.01.033DOI Listing
March 2020

Musculoskeletal Factors and Geriatric Syndromes Related to the Absence of Musculoskeletal Degenerative Disease in Elderly People Aged over 70 Years.

Biomed Res Int 2019 18;2019:7097652. Epub 2019 Nov 18.

Department of Rehabilitation, Kansai University of Welfare Sciences, 3-11-1 Asahigaoka, Kashiwara, Osaka 582-0026, Japan.

Purpose: To investigate factors with a significant relationship with the absence of musculoskeletal disease (MSD: osteoporosis, knee osteoarthritis (K-OA), and lumbar spondylosis (L-OA)) in elderly people ≥70 years old.

Methods: The subjects were 279 people (134 males, 145 females, mean age: 75.2 years) who attended an annual health checkup and were prospectively included in the study. Osteoporosis was defined as %YAM ≤70%, K-OA as Kellgren-Lawrence grade ≥2, and L-OA as osteophytes of Nathan class ≥3. Subjects were divided into those with (group D) and without (group N) any MSD. Clinical variables including locomotive syndrome (LS), frailty, sarcopenia, and QOL (SF-36) were compared between the groups.

Results: There was no significant difference in age or gender between group N ( = 54) and group D ( = 225). Lower BMI and pain, including neuropathic pain; greater back muscle strength, physical ability, and balance with eyes closed; larger lumbar lordosis, sacral inclination, and lumbar ROM; and smaller spinal inclination were found in group N. The rates of LS and sarcopenia were significantly lower and QOL was significantly higher in group N.

Conclusions: This study firstly revealed the significant musculoskeletal factors and geriatric syndromes related to an absence of MSD, which may form the basis of interventions to improve QOL in elderly people ≥70 years old.
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http://dx.doi.org/10.1155/2019/7097652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925682PMC
May 2020

Suppression of murine osteoarthritis by 4-methylumbelliferone.

J Orthop Res 2020 05 8;38(5):1122-1131. Epub 2019 Dec 8.

Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, 27834.

Using in vitro models, we previously reported that 4-methylumbelliferone (4-MU) blocked many of the pro-catabolic features of activated chondrocytes. 4-MU also blocked safranin O loss from human cartilage explants exposed to interleukin 1β (IL1β) in vitro. However, the mechanism for this chondroprotective effect was independent of the action of 4-MU as a hyaluronan (HA) inhibitor. Interestingly, overexpression of HA synthase 2 (HAS2) also blocked the same pro-catabolic features of activated chondrocytes as 4-MU via a mechanism independent of extracellular HA accumulation. Data suggest that altering UDP-sugars may be behind these changes in chondrocyte metabolism. However, all of our previous experiments with 4-MU or HAS2 overexpression were performed in vitro. The purpose of this study was to confirm whether 4-MU was effective at limiting the effects of osteoarthritis (OA) on articular cartilage in vivo. The progression of OA was evaluated after destabilization of the medial meniscus (DMM) surgery on C57BL/6 mice in the presence or absence of 4-MU-containing chow. Mice fed 4-MU after DMM surgery exhibited significant suppression of OA starting from an early stage in vivo. Mice fed 4-MU exhibited lower OARSI scores after DMM; reduced osteophyte formation and reduced MMP3 and MMP13 immunostaining. 4-MU also exerted pronounced chondroprotective effects on murine joint cartilage exposed to IL1β in vitro and, blocked IL1β-enhanced lactate production in cartilage explants. Therefore, 4-MU is effective at significantly reducing the loss of proteoglycan and reducing MMP production both in vitro and in vivo as well as cartilage damage and osteophyte formation in vivo after DMM. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. 38:1122-1131, 2020.
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http://dx.doi.org/10.1002/jor.24541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162708PMC
May 2020

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

J Orthop Sci 2020 Jul 20;25(4):693-699. Epub 2019 Nov 20.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jos.2019.09.016DOI Listing
July 2020

Multivariate analysis of factors related to the absence of musculoskeletal degenerative disease in middle-aged and older people.

Geriatr Gerontol Int 2019 Nov;19(11):1141-1146

Department of Rehabilitation, Kansai University of Welfare Sciences, Kashiwara, Osaka, Japan.

Aim: Musculoskeletal degenerative disease (MSD; osteoporosis, knee arthritis and lumbar spondylosis) decreases the quality of life (QOL) of older people. The objective of the present study was to identify the factors related to the absence of MSD in multivariate logistic regression analysis.

Methods: The participants were 1034 volunteers (444 men, 590 women, mean age 63.5 years) in the Yakumo study. Osteoporosis (percentage of young adult mean ≤70%), knee arthritis (Kellgren-Lawrence grade ≥2), and lumbar spondylosis (Nathan class ≥3) were prospectively examined. Participants were divided into those with and without MSD. Age, sex, body mass index, muscle strength, gait ability, pain, body balance, spinal sagittal alignment, geriatric syndrome (locomotive syndrome, frailty and sarcopenia) and QOL (Short Form Health Survey) were compared between these groups to identify the factors associated with the absence of MSD.

Results: Significantly lower age, body mass index and pain; higher gait speed, grip and back muscle strength; more stable body balance; better sagittal spinal alignment; and lower rates of locomotive syndrome, frailty and sarcopenia were observed in the group without MSD (n = 445, 43%), with significantly better QOL (P < 0.0001). In multivariate logistic regression analysis adjusted for age and sex, lower body mass index (odds ratio [OR] 1.10, P < 0.001), lower spinal inclination (OR 1.08, P < 0.01), higher back muscle strength (OR 1.01, P < 0.05), no locomotive syndrome (OR 1.80, P < 0.05) and good body balance (OR: 1.12, P < 0.05) were significant factors for the absence of MSD.

Conclusions: Factors related to an absence of MSD are also related to good QOL, and should be a focus of health interventions in healthy middle-aged and older people. Geriatr Gerontol Int 2019; 19: 1141-1146.
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http://dx.doi.org/10.1111/ggi.13786DOI Listing
November 2019

Waist Circumference Measured by Bioelectrical Impedance Analysis Is Interchangeable with Manual Measurement: Increased Waist Circumference Is Associated with Locomotive Syndrome Risk.

Biomed Res Int 2019 25;2019:5971030. Epub 2019 Sep 25.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Objectives: The importance of preventive medicine in an aging society is increasing. Locomotive syndrome (LS) is attracting increasing attention. Recently, advances in bioelectrical impedance analysis (BIA) devices have made it possible to automatically measure waist circumference (WC). Nevertheless, there have been no reports evaluating the agreement or interchangeability between WC measured manually and using BIA. Therefore, we aimed to perform these analyses in the context of health checkups and investigated the associations with LS risk.

Methods: We enrolled 597 participants who underwent the following: two-step tests and stand-up tests; evaluations using a 25-question geriatric locomotive function scale for the LS risk test; anthropometric marker measurements including WC measured by manual and BIA; and measurements of total cholesterol and triglycerides. We used Bland-Altman analysis to calculate agreement and interchangeability of the WC measurement using BIA and the manual method. A statistical comparative study was then conducted between normal and LS risk groups. Subsequently, significant risk factors for LS were investigated using multivariate analysis.

Results: The Bland-Altman analysis showed that bias (BIA-manual) was negative overall (-2.024), for males (-1.418) and for females (-2.460), suggesting underestimation using BIA compared with manual measurements. Interchangeability was found between WC measurement by BIA and by manual methods, because the percentage error was less than 15% overall (12.3%), for males (10.2%) and for females (13.8%). Univariate analysis showed that WC was significantly higher in the LS risk group than in the normal group. Multivariate analysis adjusted for confounding factors showed that increase in WC significantly correlated with LS risk.

Conclusions: BIA and manual methods for measuring WC are interchangeable. The increase in WC measured by BIA was significantly associated with LS risk. It is important to continue focusing on increased WC and early detection of LS risk.
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http://dx.doi.org/10.1155/2019/5971030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778908PMC
March 2020

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

J Biol Chem 2019 11 16;294(47):17799-17817. Epub 2019 Oct 16.

Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834

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 models of arthritis, but surprisingly, caused the reverse ( 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-1β (IL1β)-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.
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http://dx.doi.org/10.1074/jbc.RA119.009556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879347PMC
November 2019
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