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We systematically reviewed the literature to identify comparative studies of core treatments (exercise, education, or weight management), adjunct treatments (e.g. electrotherapeutical modalities, bracing), or multimodal treatments (core plus other treatments), for treating osteoarthritis (OA) complaints, published between 1 March 2022 and 1 March 2023. We searched three electronic databases for peer-reviewed comparative studies evaluating core treatments, adjunct treatments, or multimodal treatments for OA affecting any joint, in comparison to other OA treatments. Two authors independently screened records. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. A narrative synthesis focusing on pain and function outcomes was performed in studies with a mean sample size of at least 46 participants per treatment arm. 33 publications (28 studies), 82% with PEDro ratings of good or excellent, were eligible for narrative synthesis: 23 studies evaluated knee OA; one knee OA or chronic low back pain; two knee or hip OA; one hip OA only; and one thumb OA. No studies identified a dose, duration or type of exercise that resulted in better pain or function outcomes. Core treatments generally showed modest benefits compared to no or minimal intervention controls. Rehabilitation research continues to be focused on the knee. Most studies are not adequately powered to assess pain efficacy. Further work is needed to better account for contextual effects, identify treatment responder characteristics, understand treatment mechanisms, and implement guideline care. [ABSTRACT FROM AUTHOR]

• 29 HoFH children were matched to 101 HeFH and 102 unaffected children. • Children with HoFH had the highest Lp(a) levels. • A gene-dose increase (zero, one, two pathogenic LDLR variants) in Lp(a) was found. • We recommend to measure Lp(a) in HoFH children to minimize (potential) ASCVD risk. Homozygous familial hypercholesterolaemia (HoFH) is a life-threatening disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, severe atherosclerotic cardiovascular disease (ASCVD), including aortic valve stenosis (AVS), may already occur in childhood. Another important genetic risk factor for ASCVD and AVS is elevated lipoprotein(a) [Lp(a)], which is highly prevalent in the general paediatric population. However, data on Lp(a) in children with HoFH are scarce. Therefore, we performed a cross-sectional study to evaluate Lp(a) levels in children with HoFH and compared them to children with heterozygous FH (HeFH) and unaffected children. Adjusted least-square mean (95% CI) Lp(a) levels in HoFH (n=29), HeFH (n=101) and unaffected children (n=102) were 18.7 (12.0-29.1), 15.3 (11.8-19.8) and 10.5 (8.3-13.2) mg/dL, respectively (p-for-trend=0.007). Lp(a) levels in children with HoFH were higher than in children with HeFH and in unaffected children. Given the very high ASCVD risk with HoFH, identifying other risk factors such as elevated Lp(a) in these children is important. Therefore, Lp(a) levels should be measured at least once in all children with HoFH. [ABSTRACT FROM AUTHOR]

• HoFH requires prompt diagnosis and intensive treatment to prevent CVD in childhood. • Couples both carrying an FH variant run a 25% chance of having a child with HoFH. • Prenatal genetic counseling for HoFH should be performed on a case-by-case basis. • Clinicians should discuss all available diagnostic and reproductive options. • Discuss treatment outlook considering FH genotype and weighing parental preferences. Homozygous familial hypercholesterolemia (HoFH) is a rare, potentially life-limiting, inherited disorder of lipoprotein metabolism characterized by extremely high low-density lipoprotein cholesterol levels. When both parents have heterozygous FH, there is a 25% chance they will conceive a child with HoFH. Here we describe our clinical experience with two such prospective parent couples who were counseled regarding reproductive options and prenatal testing for HoFH. These cases showcase how, in consultation with a molecular geneticist and pediatric cardiologist, parents may be informed of the prognosis and treatment outlook of HoFH based on the FH-variants carried, to ultimately make personal decisions on reproductive options. One couple opted for prenatal testing and termination of pregnancy in case HoFH was found, while the other accepted the risk without testing. We review the available literature on preconception counseling for HoFH and provide practical guidance to clinicians counseling at-risk couples. Optimal counseling of prospective parents may help prevent future physical and psychological problems for both parent and child. [ABSTRACT FROM AUTHOR]

Regeneron Pharmaceuticals, Inc. Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder caused primarily by mutations in the low-density lipoprotein (LDL) receptor gene and characterized by severely elevated levels of LDL cholesterol (LDL-C), leading to early-onset atherosclerotic cardiovascular disease. Currently, few treatments are available to lower LDL-C levels in pediatric patients with HoFH. In Part B of a three-part open-label study (NCT04233918), the addition of evinacumab, an angiopoietin-like-3 inhibitor, to background lipid-lowering therapies (LLTs) reduced LDL-C from baseline to Week 24 by 48% in patients with HoFH aged 5-11 years. Evaluate the long-term (up to 72 weeks) efficacy and safety of evinacumab in pediatric patients with HoFH. This open-label, three-part study enrolled patients aged 5-11 years with LDL-C >130 mg/dL on optimized LLT, including apheresis and lomitapide. Part A was a Phase 1b, single-dose, 16-week study including six patients who received intravenous (IV) evinacumab 15 mg/kg. Part B was a Phase 3, 24-week open-label treatment study including 14 patients who had not participated in Part A. Part C was a Phase 3, 48-week open-label extension study, with an optional 24-week follow-up period, which included all 20 patients from both Parts A and B. In Parts B and C, patients received IV evinacumab 15 mg/kg every 4 weeks. We report data pooled from Parts B and C that includes results from Part A patients who participated in Part C and had 48 weeks of evinacumab treatment, and Part B patients who participated in Parts B and C and had a total treatment duration of 72 weeks. All 20 patients completed Part C. Mean (standard deviation [SD]) LDL-C at baseline was 301.9 (149.1) mg/dL. Evinacumab reduced mean LDL-C by 44.6% (mean [SD] reduction of 131.1 [90.2] mg/dL) and 40.7% (mean [SD] reduction of 115.8 [101.2] mg/dL) from baseline to Weeks 48 (n=16) and 72 (n=14), respectively. Evinacumab reduced mean apolipoprotein B (Week 48: 38.3%; Week 72: 34.0%), non-high-density lipoprotein cholesterol (Week 48: 45.3%; Week 72: 41.6%), total cholesterol (Week 48: 44.7%; Week 72: 42.2%), and median lipoprotein(a) (Week 48: 17.3%; Week 72: 15.7%). Treatment-emergent adverse events (TEAEs) occurred in all 20 patients. Serious TEAEs occurred in two (10.0%) patients (tonsilitis [n=1]; aortic valve stenosis [n=1]), both were unrelated to the study drug. No treatment discontinuations or deaths were reported. In pediatric patients with HoFH, evinacumab demonstrated substantial and durable reductions in LDL-C and other atherogenic lipids, and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder predominantly caused by mutations in the low-density lipoprotein (LDL) receptor gene and characterized by severely elevated LDL cholesterol (LDL-C) levels, beginning in utero. Although cardiovascular events often occur during childhood and adolescence in HoFH, few treatments effectively lower LDL-C in pediatric patients with HoFH. To evaluate the efficacy and safety of evinacumab, a monoclonal antibody inhibitor of angiopoietin-like 3, in pediatric patients with HoFH. This open-label, three-part study (NCT04233918) enrolled 14 patients 5–11 years old with LDL-C >130 mg/dL on optimized lipid-lowering therapy, including apheresis. Part B, reported here, consisted of an ≤8-week run-in, a 1–2-week screening period, and a 24-week open-label treatment period. The primary endpoint was mean change in LDL-C. Intravenous evinacumab 15 mg/kg every 4 weeks. All patients completed Part B. At Part B baseline, the mean age (standard deviation [SD]) was 9.1 (1.9) years and the mean (SD) LDL-C was 263.7 (91.0) mg/dL. At week 24, the mean percent change in LDL-C from baseline was –48.3% (standard error [SE]: 10.4%). Mean (SE) percent changes in apolipoprotein B (–41.3% [9.0%]), non-high-density lipoprotein cholesterol (–48.9% [9.8%]), and total cholesterol (–49.1% [8.1%]) at Week 24 from baseline were also observed. Treatment-emergent adverse events (TEAEs) occurred in 10 (71.4%) patients. TEAEs were considered treatment-related only in two (14.3%) patients (nausea and abdominal pain; both ongoing). No treatment discontinuations due to TEAEs or deaths were reported. A serious TEAE of tonsilitis occurred in one patient but was not considered treatment related. In children with HoFH and inadequately controlled LDL-C despite pre-existing treatment (including apheresis), evinacumab effectively lowers LDL-C and other atherogenic lipid levels by an additional 40–50%. Evinacumab was generally well tolerated. Yes Regeneron Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a prognostic model for incident radiologic hip osteoarthritis (HOA) and determine the value of previously identified predictive factors.Design: We first validated previously reported predictive factors for HOA by performing univariate and multivariate analyses for all predictors in three large prospective cohorts (total sample size of 4548 with 653 incident cases). The prognostic model was developed in 2327 individuals followed for 10 years from the Rotterdam Study-I (RS-I) cohort. External validation of the model was tested on discrimination in two other cohorts: RS-II (n = 1435) and the Cohort Hip and Cohort Knee (CHECK) study (n = 786).Results: From the total number of 28 previously reported predictive factors, we were able to replicate 13 factors, while 15 factors were not significantly predictive in a meta-analysis of the three cohorts. The basic model including the demographic, questionnaire, and clinical examination variables (area under the receiver-operating characteristic curve (AUC) = 0.67) or genetic markers (AUC = 0.55) or urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) levels (AUC = 0.67) alone were poor predictors of HOA in all cohorts. Imaging factors showed the highest predictive value for the development of HOA (AUC = 0.74). Addition of imaging variables to the basic model led to substantial improvement in the discriminative ability of the model (AUC = 0.78) compared with uCTX-II (AUC = 0.74) or genetic markers (AUC = 0.68). Applying external validation, similar results were observed in the RS-II and the CHECK cohort.Conclusions: The developed prediction model included demographic, a limited number of questionnaire, and imaging risk factors seems promising for prediction of HOA. [ABSTRACT FROM AUTHOR]

Objective: No randomized controlled trial (RCT) has compared the high tibial osteotomy (HTO) with non-surgical treatment in patients with medial knee osteoarthritis (OA) and varus malalignment. The aim was to compare the effectiveness of an unloader brace treatment or a usual care program to the HTO regarding pain severity and knee function.Design: Surgical treatment (HTO) to two non-surgical options was compared by combining the data of two RCTs. One RCT (n = 117) compared an unloader brace to usual care treatment; the other RCT (n = 92) compared closing to opening wedge HTO. One-to-many propensity score matching was used to equalize patient characteristics. We compared clinical outcome at 1 year follow-up (VAS pain (0-10) and knee function (HSS, 0-100)) with mixed model analysis.Results: Propensity score matching resulted in a comparison of 30 brace patient with 83 HTO patients, and of 28 usual care patients with 71 HTO patients. Pain at 1 year after HTO (VAS 3.8) was lower than after valgus bracing (VAS 5.0) with a mean difference of -1.1 (95% CI -2.2; -0.1). Function showed a nonsignificant mean difference of 2.1 [95% CI -3.1; 7.3]. Comparing HTO to usual care a difference was seen in pain (-1.7 [95% CI -2.8; -0.6]) and function (6.6 [95% CI 0.2; 13.1]), in favor of the HTO.Conclusions: Our data suggest that HTO was more effective in pain reduction compared to both non-surgical treatments. Function improved only when HTO was compared to usual care treatment. These small differences question the benefits of surgical treatment over the brace treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T).Design: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC).Results: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC.Conclusion: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T. [ABSTRACT FROM AUTHOR]

Objective: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content.Design: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-μCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-μCT X-ray attenuation, sGAG content and collagen content was assessed.Results: CTa X-ray attenuation correlated well with EPIC-μCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36).Conclusions: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA).Design: Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m(2) without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses.Results: 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome.Conclusions: In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted. [ABSTRACT FROM AUTHOR]

Summary Objective To investigate the association between urinary biomarker Coll2-1NO 2 (uColl2-1NO 2 ) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA). Design Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m 2 without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO 2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses. Results 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO 2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55–0.99 ) . The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome. Conclusions In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO 2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted. [ABSTRACT FROM AUTHOR]

Summary Objective Recently, the MRI Osteoarthritis Knee Score (MOAKS), a new semi-quantitative magnetic resonance imaging (MRI) scoring tool, was introduced by a panel of experienced researchers in osteoarthritis (OA). The MOAKS is primarily applicable to quantify OA status, since the interpretation of change in the MOAKS features was not described. In order to enable longitudinal evaluation, we propose definitions for progression and improvement of the main MOAKS features. Method Clear definitions for progression and improvement of the main MOAKS features are given in this brief report. 687 baseline and 30 months follow-up MRIs of the knees of 348 overweight and obese middle-aged women, free of OA at baseline, were scored using the MOAKS. Baseline prevalence and the change of MOAKS features after 30 months follow-up, based on our definitions for progression and improvement, are presented. Results The proposed definitions showed 3% to 23% progression and 0% to 11% improvement in the MOAKS features during the 30 months follow-up. Overall, progression rates were higher in the medial than in the lateral tibiofemoral (TF) joint. Progression of bone marrow lesions (BMLs) and cartilage defects was highest in the patellofemoral (PF) joint. Inter-rater reliability of the MOAKS scores was moderate to nearly perfect (PABAK 0.77–0.88), with high percentage of agreement overall (89–94%). Conclusion This brief report presents definitions for progression and improvement of the main MOAKS features for the longitudinal evaluation of knee OA features on MRI. We advocate uniform usage of the proposed definitions across studies, but welcome suggestions for optimization. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Cam impingement is characterized by abnormal contact between the proximal femur and acetabulum caused by a non-spherical femoral head, known as a cam deformity. A cam deformity is usually quantified by the alpha angle; greater alpha angles substantially increase the risk for osteoarthritis (OA). However, there is no consensus on which alpha angle threshold to use to define the presence of a cam deformity. Aim: To determine alpha angle thresholds that define the presence of a cam deformity and a pathological cam deformity based on development of OA. Methods: Data from both the prospective CHECK cohort of 1002 individuals (45–65 years) and the prospective population-based Chingford cohort of 1003 women (45–64 years) with respective follow-up times of 5 and 19 years were combined. The alpha angle was measured at baseline on anteroposterior radiographs, from which a threshold for the presence of a cam deformity was determined based on its distribution. Further, a pathological alpha angle threshold was determined based on the highest discriminative ability for development of end-stage OA at follow-up. Results: A definite bimodal distribution of the alpha angle was found in both cohorts with a normal distribution up to 60°, indicating a clear distinction between normal and abnormal alpha angles. A pathological threshold of 78° resulted in the maximum area under the ROC curve. Conclusion: Epidemiological data of two large cohorts shows a bimodal distribution of the alpha angle. Alpha angle thresholds of 60° to define the presence of a cam deformity and 78° for a pathological cam deformity are proposed. [Copyright &y& Elsevier]

Summary: Objective: The pathophysiology of anterior cruciate ligament (ACL) rupture leading to knee osteoarthritis (OA) remains largely unknown. It seems that bone loss occurs after ACL rupture. The purpose of our study was to determine bone mineral density (BMD) changes in the knee after ACL rupture during 2-year follow-up period and to compare BMD changes between the injured and healthy contralateral knee. Design: Patients were included in an observational prospective follow-up study within 6 months after ACL trauma and evaluated for 2 years. Patients were treated operatively or non-operatively. At baseline and at the one- and 2-year follow-ups, BMD was measured in six regions of the tibia and femur for both knees (medial, central, lateral) using a Dual-energy X-ray Absorptiometry (DXA) scanner. Results: One hundred forty-one patients were included, with the following characteristics: 66% were male, median age at baseline was 25.3 (inter-quartile range 11.3) years, and 63% were treated operatively. After 1 year, BMD was significantly lower in all regions of the injured knee of the operatively treated patients compared to baseline. After 2 years, BMD was significantly increased, but remained lower than the baseline levels. In all regions for all measurements, the mean BMD was significantly lower in the injured knee than in the healthy contralateral knee. Conclusions: During a 2-year follow-up period after ACL rupture, the BMD level in the injured knee was found to be lower than in the healthy contralateral knee. In operatively treated patients, the BMD decreased in the first year and increased in the second follow-up year. [Copyright &y& Elsevier]

Summary: Background: A subset of patients with total hip arthroplasty (THA) or total knee arthroplasty (TKA) has suboptimal postoperative results in terms of Patient Reported Outcomes (PROs), and psychological factors could contribute to these suboptimal results. Objectives: To examine the prevalence of anxiety and depressive symptoms in patients undergoing primary THA or TKA preoperatively and postoperatively, and the relationship between preoperative anxiety and depressive symptoms on PROs of THA and TKA. Design: In this prospective study patients were measured preoperatively, and 3 and 12 months postoperatively. Patients filled in the Hospital Anxiety and Depression Scale, Knee injury and Osteoarthritis Outcome Score (KOOS) or Hip disability and Osteoarthritis Outcome Score (HOOS) and a satisfaction questionnaire. Results: Data were obtained from 149 hip and 133 knee patients. The prevalence of anxiety symptoms decreased significantly from 27.9% to 10.8% 12 months postoperatively in hip patients, and from 20.3% to 14.8% in knee patients. Depressive symptoms decreased significantly from 33.6% to 12.1% 12 months postoperatively in hip patients, and from 22.7% to 11.7% in knee patients. In hip and knee patients, preoperative depressive symptoms predicted smaller changes in different HOOS or KOOS subscales and patients were less satisfied 12 months postoperatively. Conclusions: Preoperatively, the prevalence of anxiety and depressive symptoms was high. At 3 and 12 months postoperatively, the prevalence of anxiety and depressive symptoms was decreased in both hip and knee patients. However, patients with preoperative anxiety and depressive symptoms had worse PROs 3 and 12 months after THA and TKA and were less satisfied than patients without anxiety or depressive symptoms. [Copyright &y& Elsevier]

Summary: Objective: Determining the relation between acetabular coverage, especially overcoverage which may lead to pincer impingement, and development of osteoarthritis (OA) of the hip. Design: From a prospective cohort study of 1,002 individuals with symptoms of early OA (Cohort Hip and Cohort Knee, CHECK), 720 participants were included. Standardized anteroposterior pelvic radiographs and false profile lateral radiographs were obtained at baseline and 5 years follow-up. Acetabular undercoverage (mild dysplasia) and overcoverage (pincer deformity) were measured by a centre edge angle of <25° and >40° respectively in both radiographic views. The strength of association between those parameters at baseline and development of incident OA (Kellgren and Lawrence (K&L) grade >2 or total hip replacement), or joint space narrowing within 5 years was expressed in odds ratio (OR) adjusted for K&L grade, age, body mass index (BMI), and sex using generalized estimating equations. Results: At baseline, 76% of the included hips had no signs of radiographic OA (K&L = 0) whereas 24% had doubtful OA (K&L = 1). Within 5 years, 7.0% developed incident OA. Acetabular dysplasia was significantly associated with development of incident OA with ORs between 2.62 (95% confidence interval (CI) 1.44–4.77) and 5.45 (95% CI 2.40–12.34), dependent on the radiographic view. A pincer deformity was not associated with any outcome measure, except for a significantly protective effect on incident OA when a pincer deformity was present in both radiographic views OR 0.34 (95% CI 0.13–0.87). Conclusion: Acetabular dysplasia was significantly associated with development of OA. However, a pincer deformity was not associated with OA, and might even have a protective effect on its development, which questions the supposed detrimental effect of pincer impingement. [Copyright &y& Elsevier]

Summary: Background: An important goal of stem cell research in orthopaedics is to develop clinically relevant techniques that could be applied to heal cartilage or joint pathology. Stem cell treatment in orthopaedics for joint pathology is promising since these cells have the ability to modulate different processes in the various tissues of the joint simultaneously. The non life-threatening nature of musculoskeletal system disorders makes safety of stem cell therapy a necessary prerequisite. Objective: To systematically review the literature and provide an overview of reported adverse events (AEs) of intra-articular treatment with culture-expanded stem cells in humans. Design: A systematic literature search was performed in Pubmed, EMBASE, Web of Science and CINAHL in February 2013. AEs were reported into three categories: local/systemic, serious adverse event or AE (SAE/AE), related/unrelated. Results: 3039 Potentially eligible articles were identified of which eventually eight fulfilled our inclusion criteria. In total, 844 procedures with a mean follow-up of 21 months were analysed. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) were used for cartilage repair and osteoarthritis treatment in all included studies. Four SAEs were reported by the authors. One infection following bone marrow aspiration (BMA) was reported as probably related and resolved with antibiotics. One pulmonary embolism occurred 2 weeks after BMA and was reported as possibly related. Two tumours, both not at the site of injection, were reported as unrelated. Twenty-two other cases of possible procedure-related and seven of possible stem cell-product related adverse events (AEs) were documented. The main AEs related to the procedure were increased pain/swelling and dehydration after BMA. Increased pain and swelling was the only AE reported as related to the stem cell-product. Conclusions: Based on current literature review we conclude that application of cultured stem cells in joints appears to be safe. We believe that with continuous caution for potential side effects, it is reasonable to continue with the development of articular stem cell therapies. [Copyright &y& Elsevier]

Summary: Objectives: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. Design: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. Results: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R 2 = 0.60–0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R 2 = 0.07–0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. Conclusion: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline. [Copyright &y& Elsevier]

Summary: Objective: To investigate the association between baseline hip shape and both clinical hip osteoarthritis (OA) and total hip replacement (THR) at 5-year follow-up. Design: Individuals from the Cohort Hip and Cohort Knee (CHECK) study, with early symptomatic OA, having standardized anteroposterior pelvic radiographs at baseline and 5-year follow-up (n = 723) were included. Hip shape on the radiographs was assessed using statistical shape modeling (SSM). Hips fulfilling the American College of Rheumatology (ACR) criteria at follow-up were classified as clinical OA. The association between each mode of shape variation and both outcome measures was calculated by Generalized Estimating Equations (GEE). Results: The included individuals comprised 575 females and 148 males (mean age 55.9 ± 5.2 years). At baseline, 8% fulfilled the ACR criteria, 76% had no radiographic hip OA [Kellgren & Lawrence (K&L) = 0] and 24% had doubtful OA (K&L = 1). At follow-up, 147 hips (10.4%) fulfilled the ACR criteria and 35 hips (2.5%) had received THR. Five shape variants (modes) at baseline associated significantly with THR within 5 years. When combined in one GEE model, these shape variants resulted in a predictive power indicated by an area under the curve of 0.81. No shape variants associated with the presence of clinical OA at follow-up. Conclusion: The shape of the hip as quantified by an SSM has a good predictive value for THR, whereas variation in shape cannot predict clinical OA. Minor shape variants may be used as a radiographic biomarker to predict the future risk of THR. [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess a wide spectrum of biochemical markers (biomarkers) in a large cohort of individuals with (very) early symptomatic knee and/or hip osteoarthritis (OA). Secondly, to investigate associations between biomarkers and between biomarkers and demographics to demonstrate validity of the obtained dataset and further investigate the involvement and/or role of these biomarkers in OA. Design: Fourteen biomarkers (uCTX-II, uCTX-I, uNTX-I, sCOMP, sPIIANP, sCS846, sC1,2C, sOC, sPINP, sHA, sPIIINP, pLeptin, pAdiponectin, pResistin) were assessed by ELISA or RIA in CHECK (Cohort Hip and Cohort Knee), a 10-year prospective cohort of 1,002 individuals with early symptomatic knee and/or hip OA. Results: Quality controls revealed that gathered data were technically reliable. The majority of biomarkers showed relevant associations with demographic variables, which were expectedly different between genders and/or menopausal status for some. Principal component analysis enabled identification of five clusters, consecutively designated as ‘bone-CTX-II’, ‘inflammation’, ‘synovium’, ‘C1,2C-adipokines’, and ‘cartilage synthesis’ cluster. Notably, uCTX-II clustered with biomarkers of bone metabolism, while sCOMP clustered with biomarkers of synovial activity. Conclusions: The identified clusters extended knowledge on individual biomarkers from mostly smaller studies as did the observed associations between biomarker levels and demographics, from which validity of our data was deduced. uCTX-II may not only reflect articular cartilage but also bone metabolism and sCOMP may reflect synovial rather than cartilage metabolism. Major involvement of adipokines in joint metabolism was not identified. [ABSTRACT FROM AUTHOR]

Summary: Objective: An earlier study showed that 6 months after total hip arthroplasty (THA) patients’ overall daily activity level had not increased, despite significant improvement in their perceived physical functioning. This discrepancy might be because postoperative recovery is not expressed by a more overall active lifestyle, but by the fact that patients could perform the individual activities of daily living (ADL) faster and/or for a longer period of time. The aim of this study was to assess whether patients perform ADL faster and/or for a longer period of time 6 months post-THA compared to baseline. Also examined was whether patients perform activities on the level of healthy matched controls. Method: Thirty patients were measured at home with an accelerometry-based Activity Monitor, pre-operatively and 6 months post-THA. Patients were matched with healthy controls on gender and age (±2 years). Results: Compared with baseline, 6 months post-THA the stride frequency and body motility during walking of patients had increased [56.1 (54.3, 57.8)strides/min vs 52.1 (50.3, 54.1)strides/min; P-value<0.0001, and 0.265 (0.245, 0.286)g vs 0.219 (0.197, 0.240)g; P-value<0.0001], and they rose faster from a chair [2.6 (2.5, 2.8)s vs 3.0 (2.8, 3.2)s; P-value<0.0001]. Compared with controls, preoperative all patients had lower values for these parameters. Six months post-THA the stride frequency and body motility during walking were similar to that of controls, but patients rose slower from a chair than controls. Conclusion: Six months post-THA patients walked faster and rose from a chair faster compared to baseline. Patients walked as fast as healthy controls but took longer rising from a chair. [ABSTRACT FROM AUTHOR]

Introduction: The Hip disability and Osteoarthritis Outcome Score (HOOS) was constructed in Sweden; this questionnaire has proved to be valid for persons with hip disability with or without hip osteoarthritis (OA) and with high demands of physical function.Objective: The objective of this study was to evaluate the internal consistency, reliability, construct validity, and floor and ceiling effects of the Dutch version of the HOOS questionnaire.Patients and Methods: After translation with a forward/backward protocol, 74 hip arthroplasty patients and 88 hip OA patients filled in the Dutch HOOS, as well as a Short Form-36 (SF-36), an Oxford Hip Score (OHS) and a VAS-pain questionnaire.Results: The Dutch version of the HOOS questionnaire achieved excellent scores in all of the clinimetric properties.Conclusion: The Dutch HOOS questionnaire has a good internal consistency and reliability. Moreover, the construct validity is good and no floor and ceiling effects were found. The HOOS is a good instrument for patients with different stadia of hip OA. [ABSTRACT FROM AUTHOR]