Tuberoplasty reduces resistance force in dynamic shoulder abduction for irreparable rotator cuff tears: a cadaveric biomechanical study.

BACKGROUND: Arthroscopic tuberoplasty is an optional technique for managing irreparable rotator cuff tears. However, there is a lack of studies investigating the resistance force during shoulder abduction in cases of irreparable rotator cuff tears and tuberoplasty. HYPOTHESES: In shoulders with irreparable rotator cuff tears, impingement between the greater tuberosity (GT) and acromion increases the resistance force during dynamic shoulder abduction. Tuberoplasty is hypothesized to reduce this resistance force by mitigating impingement. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric shoulders, with a mean age of 67.75 years (range, 63-72 years), were utilized. The testing sequence included intact rotator cuff condition, irreparable rotator cuff tears (IRCTs), burnishing tuberoplasty, and prosthesis tuberoplasty. Burnishing tuberoplasty refers to the process wherein osteophytes on the GT are removed using a bur, and the GT is subsequently trimmed to create a rounded surface that maintains continuity with the humeral head. Deltoid forces and actuator distances were recorded. The relationship between deltoid forces and actuator distance was graphically represented in an ascending curve. Data were collected at five points within each motion cycle, corresponding to actuator distances of 20 mm, 30 mm, 40 mm, 50 mm, and 60 mm. RESULTS: In the intact rotator cuff condition, resistance forces at the five points were 34.25 ± 7.73 N, 53.75 ± 7.44 N, 82.50 ± 14.88 N, 136.25 ± 30.21 N, and 203.75 ± 30.68 N. In the IRCT testing cycle, resistance forces were 46.13 ± 7.72 N, 63.75 ± 10.61 N, 101.25 ± 9.91 N, 152.5 ± 21.21 N, and 231.25 ± 40.16 N. Burnishing tuberoplasty resulted in resistance forces of 32.25 ± 3.54 N, 51.25 ± 3.54 N, 75.00 ± 10.69 N, 115.00 ± 10.69 N, and 183.75 ± 25.04 N. Prosthesis tuberoplasty showed resistance forces of 29.88 ± 1.55 N, 49.88 ± 1.36 N, 73.75 ± 7.44 N, 112.50 ± 7.07 N, and 182.50 ± 19.09 N. Both forms of tuberoplasty significantly reduced resistance force compared to IRCTs. Prosthesis tuberoplasty further decreased resistance force due to a smooth surface, although the difference was not significant compared to burnishing tuberoplasty. CONCLUSION: Tuberoplasty effectively reduces resistance force during dynamic shoulder abduction in irreparable rotator cuff tears. Prosthesis tuberoplasty does not offer a significant advantage over burnishing tuberoplasty in reducing resistance force. CLINICAL RELEVANCE: Tuberoplasty has the potential to decrease impingement, subsequently reducing resistance force during dynamic shoulder abduction, which may be beneficial in addressing conditions like pseudoparalysis.

Arthroscopic Resection for Extra-articular Ganglion Cysts of Gastrocnemius Near Vessels.

Extra-articular ganglion cysts arising from the gastrocnemius tendon near popliteal vessels can cause pain and claudication. Open resection of this kind of cyst has been described frequently because the vessels can be well protected with a retractor. However, it's a challenge to remove cysts that are near vessels under arthroscopy, because a retractor cannot be used in arthroscopic surgery. This article will report a method of arthroscopic resection for extra-articular ganglion cysts near popliteal vessels.

A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances In Vivo Cartilage Regeneration.

Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility in vitro, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, in vivo experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing.

BACKGROUND: Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. METHODS: RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. RESULTS: In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. CONCLUSIONS: We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair.

Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture. Nowadays, the application of various stem cell sources, including mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), for tendon repair has shown great potential, because these cells can differentiate into a tendon lineage and promote functional tendon repair. However, the mechanism underlying tenogenic differentiation remains unclear. Moreover, no widely adopted protocol has been established for effective and reproducible tenogenic differentiation because of the lack of definitive biomarkers for identifying the tendon differentiation cascades. This work is aimed at reviewing the literature over the past decade and providing an overview of background information on the clinical relevance of tendons and the urgent need to improve tendon repair; the advantages and disadvantages of different stem cell types used for boosting tendon repair; and the unique advantages of reported strategies for tenogenic differentiation, including growth factors, gene modification, biomaterials, and mechanical stimulation.

Patient-Reported Outcomes and Risk Factors for Decreased Improvement after Patellofemoral Arthroplasty.

Patellofemoral arthroplasty (PFA) is acknowledged as the method for the treatment of isolated patellofemoral osteoarthritis (PFOA). Few previous studies have assessed the patient-reported outcomes (PROs) and risk factors of less improvement of PROs in patients undergoing PFA. A retrospective analysis was performed, including all patients who had undergone PFA. Pre- and postoperative PROs included the Oxford Knee Score (OKS) and Kujala score. Univariate and multivariate statistical analyses were performed to assess influencing factors of less improvement of PROs including the demographic factors (gender, age, body mass index, smoking, opioid usage, and duration of symptoms [DOSs]), surgical factors (concomitant surgery), and imaging factors (trochlear dysplasia [TD], patellar height, the degree of PFOA). A total of 46 PFAs were analyzed with a mean follow-up of 37 ± 7 months. The mean age at surgery was 61.1 ± 7.7 years. Patients showed significant improvement in all PROs (p < 0.001). Patients with TD preoperatively have greater improvement in OKS and Kujala score postoperatively (19.2 ± 5.0 vs. 23.1 ± 3.6, p = 0.038). Longer DOSs (≥1 year) had a greater mean improvement in OKS and Kujala score (p = 0.011 and p = 0.000). According to the measurement of patella height, patients with patella alta (Caton-Deschamps index [CDI] ≥1.3) showed less improvement in both OKS and Kujala score (p = 0.000 and p = 0.002). PFA is a safe and efficient surgery with good PROs. Patella alta with a CDI ≥1.3 and duration of preoperative symptoms ≤ 1 year were risk factors for decreased OKS and Kujala score improvement, while the preoperative presence of TD was significantly predictive factors for increased OKS improvement.

Tendon Stem/Progenitor Cell-Laden Nanofiber Hydrogel Enhanced Functional Repair of Patellar Tendon.

Functional repair of tendons remains a challenge to be overcome for both clinicians and scientists. We have previously reported a three-dimensional RADA peptide hydrogel that provides a suitable microenvironment for human tendon stem/progenitor cells (TSPCs) survival and tenogenesis. In this study, we explore the potential of in vivo patellar tendon repair by human TSPC-laden RADA hydrogel in rats, which were sacrificed at 4 and 8 weeks after operation. Hind limb function test, macroscopical and histological examination, tendon cell amount and alignment analysis, and radiographic assessments were performed at several time points. Our results demonstrated that human TSPC-laden RADA hydrogel (RADA+TSPC group) boosted in vivo patellar tendon repair with better ambulatory function recovery compared with the control groups, in which tendon defects were untreated (Defect group) or treated with RADA hydrogel alone (RADA group). In addition, better macroscopic appearance and improved matrix organization in the repaired tendon with less cell amount and reduced adipocyte accumulation and blood vessel formation were observed in the RADA+TSPC group. Moreover, tendon defect treated with TSPC-laden RADA hydrogel resulted in diminished heterotopic ossification (HO) at 8 weeks postoperation, which was indicated by both X-ray examination and micro-computed tomography scan. Taken together, the combination of TSPC and nanofiber hydrogel provide an optimistic alternative method to accelerate functional tendon repair with reduced HO. Impact statement Our study clearly demonstrates the combination of tendon stem/progenitor cell and nanofiber hydrogel provide a new and optimistic tissue engineering strategy to treat tendon injury by accelerating functional tendon repair with reduced heterotopic ossification. The clinical translation is also very promising, which can provide a minimally invasive, nonsurgical, or complementary treatment methods to treat human tendon injury.

Incidence of hip fracture among middle-aged and older Chinese from 2013 to 2015: results from a nationally representative study.

China is experiencing remarkable changes in people aging and migration. Therefore, the incidence and associated factors for hip fracture might differ from previous results. A nationally representative study of hip fracture enables policymakers to formulate preventive strategies and provide information on resource allocation. PURPOSE: To estimate the incidence of hip fracture, between 2013 and 2015, among the middle-aged and older Chinese population. METHODS: Individuals with hip fractures between 2013 and 2015 were identified from the China Health and Retirement Longitudinal Study. The sex-specific incidence and the associated factors of hip fracture were assessed. RESULTS: Among 19,112 individuals (51.4% women; mean age 60.5 years) included in the analysis, 408 (2.13%) had a hip fracture between 2013 and 2015. Moreover, the annual incidence of hip fracture for men and women were 1065 and 1069 per 100,000, respectively. The incidence of hip fracture increased with age (p < 0.001). A history of chronic disease, being unmarried, and individuals without insurance were associated with a higher incidence of hip fracture. Interestingly, the incidence of hip fracture was higher among individuals with fewer years of education (p = 0.002). The North-East regions of China had the lowest incidence of hip fracture (1022 per 100,000) between 2013 and 2015, followed by the North (1602 per 100,000), South-Central (2055 per 100,000), East (2173 per 100,000), and South-West (2537 per 100,000) regions. Finally, the incidence was highest among participants living in the North-West region (3244 per 100,000). CONCLUSION: Between 2013 and 2015, the incidence of hip fracture is high among the middle-aged and older Chinese population. Furthermore, it varied significantly according to sociodemographic and geographic factors. Therefore, the support of targeted health policies and cost-effective preventive strategies are warranted in China.

Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings From the Global Burden of Disease Study 2019.

OBJECTIVE: To estimate systematic and anatomic site-specific age-standardized prevalence rates (ASRs) and analyze the secular trends of osteoarthritis (OA) at global, regional, and national levels. METHODS: Data were derived from the Global Burden of Disease Study 2019. ASRs and their estimated annual percentage changes (EAPCs) were used to describe the secular trends of OA according to age group, sex, region, country, and territory, as well as the joints involved. RESULTS: Globally, prevalent cases of OA increased by 113.25%, from 247.51 million in 1990 to 527.81 million in 2019. ASRs were 6,173.38 per 100,000 in 1990 and 6,348.25 per 100,000 in 2019, with an average annual increase of 0.12% (95% confidence interval [95% CI] 0.11%, 0.14%). The ASR of OA increased for the knee, hip, and other joints, but decreased for the hand, with EAPCs of 0.32 (95% CI 0.29, 0.34), 0.28 (95% CI 0.26, 0.31), 0.18 (95% CI 0.18, 0.19), and -0.36 (95% CI -0.38, -0.33), respectively. OA prevalence increased with age and revealed female preponderance, geographic diversity, and disparity with regard to anatomic site. OA of the knee contributed the most to the overall burden, while OA of the hip had the highest EAPC in most regions. CONCLUSION: OA has remained a major public health concern worldwide over the past decades. The prevalence of OA has increased and diversified by geographic location and affected joint. Prevention and early treatment are pivotal to mitigating the growing burden of OA.

Measurement of the relative position of the femoral head center, greater trochanter, and lesser trochanter.

BACKGROUND: Understanding the relationship between the greater trochanter, the lesser trochanter, and the femoral head center is helpful to achieve satisfactory lower limb length in hip arthroplasty, and it may be more important when the contralateral side of the surgical hip cannot be referenced. This work aims to measure the relative position of the femoral head center, the greater trochanter, and the lesser trochanter, and analyze the relationship between these anatomical landmarks. METHODS: The femoral head diameter (D), the linear distance (G) from the femoral head center (C) to the greater trochanter, and the linear distance (L) from the femoral head center to the lesser trochanter were measured by pelvic X-ray. The basic information of the data was analyzed, the ratios of G to D and L to D were calculated, the functional relationship between the data was analyzed after the factors of gender and age were included, and the 95% reference intervals of the basic data and ratio data were calculated. RESULTS: A total of 97 patients with 194 hips were enrolled in this study. The diameter D was 5.08±0.43 cm, the distance G was 4.68±0.45 cm, and the distance L was 4.28±0.49 cm. The G/D ratio was 0.92±0.07, and the 95% reference range was 0.78-1.06. The L/D ratio was 0.84±0.08, and the 95% reference range was 0.68-1.00. Gender (g) was included in the regression analysis, and the regression equations G =1.890+0.536*D and L =1.129+0.620*D were obtained. Age was not related to the distances G and L. CONCLUSIONS: The basic data of G, D, and L was measured, and the relationship between these anatomical landmarks was analyzed.

Association of patellofemoral morphology and alignment with the radiographic severity of patellofemoral osteoarthritis.

BACKGROUND: Risk factors for the severity of patellofemoral osteoarthritis (PFOA) are poorly understood. This research aims to evaluate the association between patellofemoral joint (PFJ) morphology and alignment with the radiographic severity of PFOA. METHODS: A retrospective analysis of CT scan and lateral radiograph data were acquired in patients with PFOA. The radiographic grade of PFOA and tibiofemoral osteoarthritis (TFOA), lateral and medial trochlear inclination angle, sulcus angle, and the Wiberg classification of patella morphology, the congruence angle, patellar tilt angle, and lateral patellar angles, and tibial tubercle trochlear groove distance (TT-TG) and patella height (i.e., Caton-Deschamps index) were assessed using CT scans and sagittal radiographs of the knee. All the PFJ morphology and alignment data were divided into quarters, and the relationships between each of these measures and the severity of PFOA were investigated. RESULTS: By studying 150 patients with PFOA, we found a U-shaped relationship between the Caton-Deschamps index and the severity of PFOA (P < 0.001). A lower value of sulcus angle and lateral patellar angle, a higher value of congruence angle, and type III patella were associated with more severity of lateral PFOA. Compared with the highest quarter of each measure, the adjusted odds ratios (OR) of the severity of PFOA in the lowest quarter of sulcus angle, lateral patellar angle, and congruence angle; and type I patella was 8.80 (p = 0.043), 16.51 (P < 0.001), 0.04 (P < 0.001), and 0.18 (p = 0.048) respectively. CONCLUSIONS: Extreme value of patella height, a higher value of lateral patellar displacement and lateral patellar tilt, lower value of sulcus angle, and type III patella were associated with more severity of PFOA.

Association between changes in hip-knee-ankle angle and hindfoot alignment after total knee arthroplasty for varus knee osteoarthritis.

BACKGROUND: The change in hip-knee-ankle (HKA) angle after total knee arthroplasty (TKA) may cause an adjustment in hindfoot alignment (HFA). However, the relationship between the changes in HKA angle and HFA is still not well studied. This study aimed to investigate the association between HKA angle and hindfoot alignment changes after TKA for varus knee osteoarthritis. METHODS: A prospective study was carried out in which 108 patients with varus knee deformities were radiographically and clinically evaluated before and 3 months after TKA. The relationship of change in HFA with correction in HKA angle was investigated. RESULTS: The results showed that the HFA was adjusted significantly by 3 months after TKA (p < 0.001), along with improved American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score (p < 0.001). Next, a univariate correlation and linear regression analysis showed that the change in HFA was weakly correlated with the change in HKA angle (r=-0.262, ß=-0.14, 95 % CI: -0.23 to -0.04, P = 0.006). Further stratified analysis and interaction tests revealed that age has a distinct effect on the correlation between the changes in HFA and HKA angle. The correlation was dramatically greater in the group under 65 years (r=-0.474, ß=-0.26, 95 % CI: -0.41 to -0.12, P = 0.001), whilst, no correlation was observed in those above 65 years old (r=-0.036, ß=-0.02, 95 % CI: -0.14 to 0.11, P = 0.779). CONCLUSIONS: Our findings indicated that correction of HKA after TKA tend to promote adjustment in the hindfoot alignment toward re-balance of the whole lower limb weight-bearing axis. However, this mechanism obviously weakens in elderly patients. Therefore, if apparent hindfoot deformity exists in these patients before TKA, more perioperative intervention is required for hindfoot adjustment, and even HKA undercorrection may be considered.

A simple method to minimize leg length discrepancy in hip hemiarthroplasty.

PURPOSE: We developed a simple method to minimize leg length discrepancy (LLD) during hip arthroplasty. The purpose of this study is to evaluate the accuracy of the method. PATIENTS AND METHODS: A total of 47 patients who suffered from unilateral femoral neck fracture and underwent hip hemiarthroplasty between 2015 and 2018 were enrolled in this study. We measured the diameter of the contralateral femoral head (D) and the distance (L) between the center of the femoral head and the top of lesser trochanter in the antero-posterior pelvic X-ray view before the operation, the ratio (R) of D to L was calculated. During the operation, the diameter of the femoral head (d) was measured using a Vernier caliper. Then, the distance should be obtained from the center of the femoral head prosthesis to the lesser trochanter was calculated according to the contralateral ratio R. RESULTS: The mean LLD was 4.4±3.2 mm (-4.0 to 11.1 mm), 80.9% of the patients had LLD <6 mm, 93.6% of the patients with LLD <10 mm, only 6.4% ≥10 mm LLD. CONCLUSION: This method is a simple, cost-effective, fast and accurate way to reduce the postoperative leg length discrepancy.

Overexpression of FER1L4 promotes the apoptosis and suppresses epithelial-mesenchymal transition and stemness markers via activating PI3K/AKT signaling pathway in osteosarcoma cells.

Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been identified as a tumor suppressor in endometrial carcinoma, ovarian cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma. However, the function of FER1L4 in osteosarcoma has not been clear. The aim of the research was to explore the effects of FER1L4 in osteosarcoma. Results showed that FER1L4 was observed to be lowly expressed in osteosarcoma cell lines (US-O2, MG-63 and SaOS-2 cells), especially MG63 cells. Besides, overexpression of FER1L4 remarkably repressed the proliferation, migration and invasion of MG63 cells. FER1L4-induced apoptotic cell death leaded to the activation of caspase-3 and Bax/Bcl2. Moreover, epithelial-mesenchymal transition (EMT) was tremendously suppressed by increased FER1L4, evidences were the increased E-cadherin and reduced vimentin and fibronectin. Blocking FER1L4 expression by sh-FER1L4 treatment increased the expression of SOX9, CD44, ALDH1, Nanog and Oct4, indicating that FER1L4 could effectively decrease cell stemness in osteosarcoma. Furthermore, the protein levels of p-AKT and p-PI3K were remarkably suppressed when FER1L4 was knocked down. In conclusion, the study indicated that FER1L4 acted as a tumor suppressor in osteosarcoma via activating PI3K/AKT pathway may be a new prognostic biomarker and potential therapeutic target for osteosarcoma intervention.

Surgical therapy vs conservative therapy for patients with acute injury of lateral ankle ligament: A meta-analysis and systematic review.

The goal of this meta-analysis was to explore the overall safety and efficacy of surgical therapy vs conservative therapy for acute injury of the lateral ankle ligament based on eligible studies. Eligible studies were identified by searching PubMed, Cochrane, and Embase databases using appropriate updated index words to January 2018. We also searched relevant publication sources. Eligible studies included randomised controlled trials and comparative studies. Mean difference or relative risk (RR), along with 95% confidence interval (CI), was used to analyse the main outcomes. A total of 13 studies were eligible for this meta-analysis, with 834 patients in the surgical therapy group and 930 patients in the conservative therapy group. Compared with patients receiving conservative treatment, patients undergoing surgical treatment had a significant higher American Orthopedic Foot And Ankle Society (AOFAS) score (weighted mean difference(WMD): 10.33, 95% CI: 6.83-13.83) and an effective rate (RR: 1.15, 95% CI: 1.04-1.28). No significant differences were observed in the incidence of recurrent ankle injury (RR: 1.01, 95% CI: 0.62-1.65), limited range of motion (RR: 1.44, 95% CI: 0.83-2.50), deep vein thrombosis (RR: 1.33, 95% CI: 0.73-2.41), and wound infection or necrosis (RR: 3.99, 95% CI: 0.45-35.34). However, compared with patients receiving conservative treatment, patients undergoing surgical therapy had significantly increased rates of complications (RR: 3.31, 95% CI: 2.55-4.28), ankylosis (RR: 3.63, 95% CI: 2.16-6.08), scare tenderness (RR: 10.16, 95% CI: 3.89-26.52) and sensory loss (RR: 5.66, 95% CI: 2.76-11.59). The results demonstrated that surgical treatment increased the AOFAS score and effective rate compared with conservative treatment. Besides, surgical treatment increased the rate of complications. Nevertheless, more high-quality randomised controlled trials with a larger sample size conducted at multiple centres with a long-term follow up are needed to confirm our conclusions.

Effect of vitamin D supplementation on knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA). METHODS: A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials.gov and the reference lists of identified studies. A standardized mean difference (SMD) was used to assess effect sizes, as outcomes were reported on different scales. Depending on the degree of heterogeneity, random-effects or fixed-effects models were used to pool outcomes. RESULTS: Up to January 22, 2017, four clinical trials containing 570 subjects in the vitamin D supplementation group and 560 subjects in the placebo group were identified. All of the included studies were of high quality and had a low risk of bias for each domain. The results indicated that vitamin D supplementation had a statistically significant but small-to-moderate effect on pain control in patients with knee OA (SMD=-0.32, 95% CI: -0.63 to -0.02). However, no effects were observed for the change in tibial cartilage volume (SMD=0.12, 95% CI: -0.05 to 0.29) or joint space width (SMD=0.07, 95% CI: -0.08 to 0.23). The subgroup analysis indicated that vitamin D supplementation had no significant effect regardless of whether patients had sufficient or insufficient serum 25(OH)D levels at baseline. CONCLUSIONS: The results of this study indicate that vitamin D supplementation may not have a clinically significant effect on pain control or structure progression among patients with knee OA. Longer-term clinical trials with rigorous measurement of symptom and radiologic changes are required to further clarify the effect of vitamin D supplementation in patients with symptomatic knee OA and low serum 25(OH)D levels.