Nocturnal pain and fatigue in middle-aged persons with hip symptoms suspected to be osteoarthritis, is there a link in 10-year follow-up of the CHECK study?

Objective: To explore the prevalence of nocturnal pain and fatigue in participants with hip symptoms suspected to be early osteoarthritis (OA) and to test the mediating effect of nocturnal pain on the association between hip OA pain and fatigue. Methods: We included participants with hip pain but no knee pain at baseline, from the Cohort Hip and Cohort Knee (CHECK)-study. Severity of hip OA pain was determined using the Numeric-Rating-Scale-pain-score last week. Fatigue was assessed using the SF-36 Fatigue subscale. Nocturnal pain was determined using the WOMAC-question: "How much pain have you experienced in the last 48 â€‹h at night while in bed?". Hip OA pain, nocturnal pain and fatigue were measured repeatedly during 10-year follow-up. Path analysis were used per time point to determine the direct effect of OA pain on fatigue and the indirect effect through nocturnal pain. Results: In 170 participants (female: 76%; mean age: 55.7 years; mean BMI: 25.5 â€‹kg/m2) the prevalence of nocturnal pain varied between 22 and 35% and the prevalence of fatigue ranged between 14 and 18%. Hip OA pain was associated with nocturnal pain and fatigue. The direct effect of hip OA pain on fatigue was significant at all-time points. No significant mediating effect of nocturnal pain was found. Conclusion: In this cohort of participants suspected to have early hip OA, the prevalence of fatigue remained stable and the prevalence of nocturnal pain decreased slightly over 10-year follow-up. We did not find a mediating effect of nocturnal pain in the pathway between hip OA pain and fatigue.

A systematic review of the sex differences in risk factors for knee osteoarthritis.

OBJECTIVES: Previous systematic reviews focused on the evidence of common risk factors for knee OA (KOA); however, the effect and strength of association between risk factors and KOA might be different between the two sexes. The aim of the present systematic review was to determine the current evidence on sex differences in the association between risk factors and KOA and their prevalence. METHODS: We searched the following electronic bibliographic databases: MEDLINE (PubMed), EMBASE and Web of Science. A methodological quality assessment was conducted independently by two researchers according to an adapted version of the standardized set of criteria known as the Newcastle-Ottawa Quality Assessment Scale (NOS). The NOS, a star system, was converted to three categories of quality. RESULTS: In total, 27 studies reported sex-specific risk estimates on several risk factors for KOA. Out of the 22 longitudinal cohort studies (except one nested case-control), 12 were of good quality and 10 were of fair quality. The five cross-sectional studies consisted of one of good, three of fair and one of poor quality. There was an indication of sex differences in risk factors leading to higher risk of KOA: high BMI, alcohol consumption, atherosclerosis and high vitamin E levels in women, and high physical activity, soft drink consumption and abdominal obesity in men. Knee injury, high blood pressure and low step rate seem to affect both women and men. CONCLUSION: More good quality studies are needed to assess sex differences in risk factors for KOA, especially for symptomatic/clinical OA.

Course of pain and fluctuations in pain related to suspected early hip osteoarthritis: the CHECK study.

OBJECTIVES: To evaluate the prevalence during a 10-year follow-up of clinically relevant fluctuations in pain and the course of hip pain in participants with hip complaints suspected to be early stage hip osteoarthritis (OA). To distinguish between participants with relevant fluctuations in pain and those without based on baseline characteristics. METHODS: Data were collected at baseline and after 2, 5, 8, and 10 years on 495 participants from the Cohort Hip and Cohort Knee Study (CHECK) with hip pain at baseline. Baseline demographic, anamnestic, and physical-examination characteristics were assessed. The primary outcome was levels of pain in the past week (scored using 0-10 Numeric Rating Scale) at follow-up assessments. Relevant fluctuation was defined as average absolute residuals greater than 1 after fitting a straight line to the participant's pain scores over time. RESULTS: The majority of the participants (76%) had stable or decreasing pain. Relevant fluctuations were found in 37% of the participants. The following baseline variables were positively associated with the presence of relevant fluctuations: higher levels of pain in the past week, use of pain transformation as a coping style, higher number of comorbidities, use of pain medication, and higher levels of high-sensitivity C-reactive protein. No associations were found for baseline radiographic hip OA or clinical hip OA. CONCLUSION: During a 10-year follow-up, the majority of participants had stable or decreasing pain levels. In those participants with relevant fluctuation (37%), a limited number of baseline variables were associated with increased odds of having relevant fluctuations in pain.

Pain appears to be an important reason for consulting the general practitioner (GP) for hip osteoarthritis (OA) complaints. We know that hip pain remained quite stable over 10 years. Also is known that there is considerable variety between patients in pain. In this study, we found relevant pain fluctuations in 37% of primary care patients with hip complaints over a period of 10 years. The pain fluctuation was not associated with having osteoarthritis, neither radiographic hip OA (diagnosed based on a X-ray) or clinical hip OA (determined according to the American College of Rheumatology (ACR) criteria) at baseline. More research is needed to discover why some people experience fluctuations in time than others.

A prospective cohort study on cam morphology and its role in progression of osteoarthritis.

BACKGROUND: Cam morphology contributes to the development of hip osteoarthritis (OA) but is less studied in the general population. This study describes its associations with clinical and imaging features of hip OA. METHODS: Anteroposterior hip radiographs of 1019 participants from the Tasmanian Older Adult Cohort (TASOAC) were scored at baseline for α angle (cam morphology) in both hips. Using the Altman's atlas, radiographic hip OA (ROA) was assessed at baseline. Hip pain and right hip structural changes were assessed on a subset of 245 magnetic resonance images (MRI) at 5 years. Joint registry data for total hip replacement (THR) was acquired 14 years from baseline. RESULTS: Of 1906 images, cam morphology was assessed in 1016 right and 890 left hips. Cross-sectionally, cam morphology modestly associated with age (prevalence ratio [PR]: 1.02 P = .03) and body mass index (BMI) (PR: 1.03-1.07, P = .03) and strongly related to male gender (PR: 2.96, P < .001). Radiographically, cam morphology was prevalent in those with decreased joint space (PR: 1.30 P = .03) and osteophytes (PR: 1.47, P = .03). Longitudinally, participants with right cam and high BMI had more hip pain (PR: 17.9, P = .02). At the end of 5 years of follow-up these participants were also more likely to have structural changes such as bone marrow lesions (BMLs) (PR: 1.90 P = .04), cartilage defects (PR: 1.26, P = .04) and effusion-synovitis at multiple sites (PR: 1.25 P = .02). Cam morphology at baseline in either hip predicted up to threefold risk of THR (PR: 3.19, P = .003) at the end of 14 years. CONCLUSION: At baseline, cam morphology was linked with age, higher weight, male gender, early signs of radiographic OA such as joint space narrowing (JSN) and osteophytes (OST). At follow-up, cam predicted development of hip BMLs, hip effusion-synovitis, cartilage damage and THR. These findings suggest that cam morphology plays a significant role in early OA and can be a precursor or contribute to hip OA in later life.

Towards sex-specific osteoarthritis risk models: evaluation of risk factors for knee osteoarthritis in males and females.

OBJECTIVES: The aim of this study was to identify sex-specific prevalence and strength of risk factors for the incidence of radiographic knee OA (incRKOA). METHODS: Our study population consisted of 10 958 Rotterdam Study participants free of knee OA in one or both knees at baseline. One thousand and sixty-four participants developed RKOA after a median follow-up time of 9.6 years. We estimated the association between each available risk factor and incRKOA using sex stratified multivariate regression models with generalized estimating equations. Subsequently, we statistically tested sex differences between risk estimates and calculated the population attributable fractions (PAFs) for modifiable risk factors. RESULTS: The prevalence of the investigated risk factors was, in general, higher in women compared with men, except that alcohol intake and smoking were higher in men and high BMI showed equal prevalence. We found significantly different risk estimates between men and women: high level of physical activity [relative risk (RR) 1.76 (95% CI: 1.29-2.40)] or a Kellgren and Lawrence score 1 at baseline [RR 5.48 (95% CI: 4.51-6.65)] was higher in men. Among borderline significantly different risk estimates was BMI ≥27, associated with higher risk for incRKOA in women [RR 2.00 (95% CI: 1.74-2.31)]. The PAF for higher BMI was 25.6% in women and 19.3% in men. CONCLUSION: We found sex-specific differences in both presence and relative risk of several risk factors for incRKOA. Especially BMI, a modifiable risk factor, impacts women more strongly than men. These risk factors can be used in the development of personalized prevention strategies and in building sex-specific prediction tools to identify high risk profile patients.

Are pain coping strategies and neuropathic pain associated with a worse outcome after conservative treatment for Achilles tendinopathy? A prospective cohort study.

OBJECTIVES: To analyse whether (1) passive or active pain coping strategies and (2) presence of neuropathic pain component influences the change of Achilles tendinopathy (AT) symptoms over a course of 24 weeks in conservatively-treated patients. DESIGN: Prospective cohort study. METHODS: Patients with clinically-diagnosed chronic midportion AT were conservatively treated. At baseline, the Pain Coping Inventory (PCI) was used to determine scores of coping, which consisted of two domains, active and passive (score ranging from 0 to 1; the higher, the more active or passive). Presence of neuropathic pain (PainDETECT questionnaire, -1 to 38 points) was categorized as (a) unlikely (≤12 points), (b) unclear (13-18 points) and (c) likely (≥19 points). The symptom severity was determined with the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire (0-100) at baseline, 6, 12 and 24 weeks. We analysed the correlation between (1) PCI and (2) PainDETECT baseline scores with change in VISA-A score using an adjusted Generalized Estimating Equations model. RESULTS: Of 80 included patients, 76 (95%) completed the 24-weeks follow-up. The mean VISA-A score (standard deviation) increased from 43 (16) points at baseline to 63 (23) points at 24 weeks. Patients had a mean (standard deviation) active coping score of 0.53 (0.13) and a passive score of 0.43 (0.10). Twelve patients (15%) had a likely neuropathic pain component. Active and passive coping mechanisms and presence of neuropathic pain did not influence the change in AT symptoms (p=0.459, p=0.478 and p=0.420, respectively). CONCLUSIONS: Contrary to widespread belief, coping strategy and presence of neuropathic pain are not associated with a worse clinical outcome in this homogeneous group of patients with clinically diagnosed AT.

Differences in Knee Shape between ACL Injured and Non-Injured: A Matched Case-Control Study of 168 Patients.

OBJECTIVE: Anterior cruciate ligament (ACL) injury prevention programs could be more effective if we could select patients at risk for sustaining an ACL rupture. The purpose of this study is to identify radiographic shape variants of the knee between patients with and patients without an ACL rupture. METHODS: We compared the lateral and Rosenberg view X-rays of 168 prospectively followed patients with a ruptured ACL to a control group with intact ACLs, matched for gender, after knee trauma. We used statistical shape modeling software to examine knee shape and find differences in shape variants between both groups. RESULTS: In the Rosenberg view X-rays, we found five shape variants to be significantly different between patients with an ACL rupture and patients with an intact ACL but with knee trauma. Overall, patients who had ruptured their ACL had smaller, flatter intercondylar notches, a lower lateral tibia plateau, a lower medial spike of the eminence, and a smaller tibial eminence compared to control patients. CONCLUSION: Patients with an ACL rupture have smaller intercondylar notches and smaller tibial eminences in comparison to patients with an intact ACL after knee trauma.

Characteristics associated between the incidence of hip osteoarthritis and early hip complaints (CHECK study) within 10 years.

OBJECTIVE: To determine which baseline characteristics, especially clinically variables like pain, stiffness, physical functioning and disease variables, are associated with incident hip OA within 10 years in first presenters with hip complaints. Rheumatology key messages History taking and not physical exam variables are associated with incident hip osteoarthritis. Specific questions about daily life activities are associated with incident hip OA. These questions are about pain while walking/shopping, difficulties putting socks on/off and rising from bed. METHODS: Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study (n = 1002). Incident hip OA was defined as fulfilling the clinical ACR criteria for hip OA, a Kellgren and Lawrence score ≥2 with hip pain, or received a hip replacement during follow-up. Baseline measurements were used of participants with hip complaints and without hip OA. Principal component analysis (PCA) was used to reduce the number of correlated variables. Associations between baseline characteristics (including PCA components) and incident hip OA were investigated using logistic regression analysis, adjusted for age, sex and BMI. RESULTS: In total, 312 participants (85% female and 98% Caucasian) were included, 181 developed hip OA. PCA resulted in four components. Incident hip OA was associated with (i) component 1 (general presence of pain and symptoms) [odds ratio (OR) = 1.46 (95%CI: 1.08, 1.98)], (ii) component 3 (relatively high levels of pain during shopping/walking combined with less difficulty with putting socks on/off and rising from bed) [OR = 1.58 (95%CI: 1.18, 2.12)] and (iii) knee pain [OR = 0.34 (95% CI: 0.17, 0.66)]. CONCLUSION: In first presenters with hip complaints, use of a few history-taking variables might allow better recognition of those at higher odds for incident hip OA within 10 years.

10-Year natural course of early hip osteoarthritis in middle-aged persons with hip pain: a CHECK study.

OBJECTIVE: To explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints. METHODS: Data were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features. RESULTS: In total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years. CONCLUSION: One out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.

Relationship between cam morphology, hip symptoms, and hip osteoarthritis: the Musculoskeletal pain in Ullersaker STudy (MUST) cohort.

BACKGROUND: The primary aim of this study was to determine the prevalence of cam morphology in a cohort of people aged 40-55 years. Secondary aims were to: (1) determine differences in participant characteristics, physical impairments, radiographic and ultrasound appearances of people with and without cam morphology; and (2) explore associations between cam morphology and radiographic measures of hip osteoarthritis (OA). METHODS: 107 people (68% women; 49 ± 4 years) from the Musculoskeletal pain in Ullensaker (MUST) Study underwent the clinical and imaging examinations. Examinations included questionnaires, hip range, functional task performance, pelvic radiographs and ultrasound. Alpha angle and radiographic hip OA (Kellgren Lawrence (KL) and minimal joint space (MJS)) were determined. RESULTS: The prevalence of cam morphology was 42% and was bilateral in 47%. People with cam morphology were 6 times more likely to have a KL score ⩾2 (adjusted odds ratio [95% confidence intervals, p-value]) 6.386 [1.582-37.646, p = 0.012]) and 4 times more likely to have MJS <2.0 mm (adjusted odds ratio 4.032 [1.031-12.639, p = 0.045]). The prevalence of radiographic OA features ranged from 4-13% in people with cam morphology, and 0-3% in those without. Those with cam morphology also demonstrated reduced hip flexion and rotation range (p = 0.018-0.036) compared with those without. There was no association between ultrasonic features and patient reported outcomes, and cam morphology. CONCLUSIONS: In a cohort aged 40-55 years, the prevalence of cam morphology was high (42%), with a significant relationship between cam morphology and radiographic measures of hip OA. Further longitudinal studies should explore the relationship between cam morphology and hip OA in younger people.

Effectiveness of a high volume injection as treatment for chronic Achilles tendinopathy: randomised controlled trial.

OBJECTIVE: To study whether a high volume injection without corticosteroids improves clinical outcome in addition to usual care for adults with chronic midportion Achilles tendinopathy. DESIGN: Patient and assessor blinded, placebo controlled randomised clinical trial. SETTING: Sports medicine department of a large district general hospital, the Netherlands. PARTICIPANTS: 80 adults (aged 18-70 years) with clinically diagnosed chronic midportion Achilles tendinopathy and neovascularisation on ultrasonography. 39 were randomised to a high volume injection without corticosteroids and 41 to placebo. INTERVENTIONS: Participants were instructed to perform an exercise programme for 24 weeks (usual care) combined with one 50 mL high volume injection of saline and lidocaine (intervention group) or one 2 mL placebo injection of saline and lidocaine (placebo group) at baseline. MAIN OUTCOME MEASURES: Primary outcome was pain and function assessed using the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire at 24 weeks (analysed using a generalised estimation equations model). Secondary outcomes were patient satisfaction, return to sport, degree of ultrasonographic Doppler flow, visual analogue scale on 10 hop test, power and flexibility of the gastrocnemius and soleus muscles, pain detect questionnaire for neuropathic pain, and pain coping inventory. Participants were evaluated at baseline and at 2, 6, 12, and 24 weeks. RESULTS: Only one participant (1%) was lost to follow-up. The estimated mean VISA-A score improved significantly, from 40.4 (95% confidence interval 32.0 to 48.7) at baseline to 59.1 (50.4 to 67.8) at 24 weeks in the high volume injection group and from 36.9 (27.1 to 46.8) to 58.5 (47.9 to 69.1) in the placebo group. The VISA-A score over time did not differ between the groups (adjusted between group difference at 24 weeks 0.5 points, 95% confidence interval -17.8 to 18.8). No significant between group differences were found for patient satisfaction (21/37 (57%) v 19/39 (49%) patients, P=0.50) and return to desired sport (15/29 (52%) v 19/31 (61%) patients active in sports, P=0.65) at 24 weeks. None of the other secondary outcomes differed between the two groups. CONCLUSIONS: A high volume injection without corticosteroids in addition to usual care is not effective for symptom reduction in patients with chronic midportion Achilles tendinopathy. On the basis of our findings, we cannot recommend the use of a high volume injection in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov NCT02996409.

Classifying Cam Morphology by the Alpha Angle: A Systematic Review on Threshold Values.

BACKGROUND: The alpha angle is the most often used measure to classify cam morphology. There is currently no agreement on which alpha angle threshold value to use. PURPOSE: To systematically investigate the different alpha angle threshold values used for defining cam morphology in studies aiming to identify this threshold and to determine whether data are consistent enough to suggest an alpha angle threshold to classify cam morphology. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: The Embase, Medline (Ovid), Web of Science, Cochrane Central, and Google Scholar databases were searched from database inception to February 28, 2019. Studies aiming at identifying an alpha angle threshold to classify cam morphology were eligible for inclusion. RESULTS: We included 4 case-control studies, 10 cohort studies, and 1 finite-element study from 2437 identified publications. Studies (n = 3) using receiver operating characteristic (ROC) curve analysis to distinguish asymptomatic people from patients with femoroacetabular impingement syndrome consistently observed alpha angle thresholds between 57° and 60°. A 60° threshold was also found to best discriminate between hips with and without cam morphology in a large cohort study based on a bimodal distribution of the alpha angle. Studies (n = 8) using the upper limit of the 95% reference interval as threshold proposed a wide overall threshold range between 58° and 93°. When stratified by sex, thresholds between 63° and 93° in male patients and between 58° and 94° in female patients were reported. CONCLUSION: Based on the available evidence, mostly based on studies using ROC curve analysis, an alpha angle threshold of ≥60° is currently the most appropriate to classify cam morphology. Further research is required to fully validate this threshold.

The relationship between cam morphology and hip and groin symptoms and signs in young male football players.

BACKGROUND: Conflicting and limited high-quality prospective data are available on the associations between cam morphology and hip and groin symptoms and range of motion (ROM). OBJECTIVES: This cross-sectional cohort study investigated associations between cam morphology presence, size and duration and symptoms and ROM. METHODS: Academy male football players (n = 49, 17-24 years) were included. Standardized antero-posterior pelvic and frog-leg lateral radiographs were obtained at baseline, 2.5- and 5-year follow-up. The femoral head-neck junction was quantified by: Visual score. Cam morphology (flattening or prominence), large cam (prominence). Alpha angle. Cam morphology (≥60°), large cam (≥78°). Cam morphology duration was defined as long (first present at baseline) or short (only from 2.5- to 5-year follow-up). Current symptoms at 5-year follow-up were assessed using a hip and groin pain question and by the "Hip and Groin Outcome Score" (HAGOS). HAGOS scores were categorized into: most symptoms (≥2 domains in lowest interquartile range [IQR]), least symptoms (≥2 domains in highest IQR). Hip ROM was measured by goniometry at 5-year follow-up. RESULTS: Large cam morphology based on visual score was associated with hip and groin pain (23.8% vs. 7.1%, OR: 3.17, CI: [1.15-8.70], P = .026), but not with HAGOS scores. Cam morphology presence, size, and duration were associated with limited flexion of around 6° and/or 3° to 6° for internal rotation. CONCLUSION: Cam morphology presence, size, and duration were associated with limited hip flexion and/or internal rotation, but differences might not exceed the minimal clinical important difference. Whether cam morphology results in symptoms is uncertain.

Cam morphology in young male football players mostly develops before proximal femoral growth plate closure: a prospective study with 5-yearfollow-up.

OBJECTIVES: Cam morphology is not completely understood. The aim of this study was threefold: (1) to investigate if cam morphology development is associated with growth plate status; (2) to examine whether cam morphology continues to develop after growth plate closure; and (3) to qualitatively describe cam morphology development over 5-year follow-up. METHODS: Academy male football players (n=49) participated in this prospective 5-year follow-up study (baseline 12-19 years old). Anteroposterior and frog-leg lateral views were obtained at baseline (142 hips), 2.5-year (126 hips) and 5-year follow-up (98 hips). Cam morphology on these time points was defined as: (A) visual scores of the anterior head-neck junction, classified as: (1) normal, (2) flattening, and (3) prominence; and (B) alpha angle ≥60°. Proximal femoral growth plates were classified as open or closed. Cam morphology development was defined as every increase in visual score and/or increase in alpha angle from <60° to ≥60°, between two time points. This resulted in 224 measurements for cam morphology development analysis. RESULTS: Cam morphology development was significantly associated with open growth plates based on visual score (OR: 10.03, 95% CI 3.49 to 28.84, p<0.001) and alpha angle (OR: 2.85, 95% CI 1.18 to 6.88, p=0.020). With both definitions combined, cam developed in 104 of 142 hips during follow-up. Of these 104 hips, cam developed in 86 hips (82.7%) with open growth plate and in 18 hips (17.3%) with a closed growth plate. Cam morphology developed from 12 to 13 years of age until growth plate closure around 18 years. CONCLUSION: Cam morphology of the hip is more likely to develop with an open growth plate.

The Prevalence of Cam and Pincer Morphology and Its Association With Development of Hip Osteoarthritis.

Synopsis Our understanding of femoroacetabular impingement syndrome is slowly improving. The number of studies on all aspects (etiology, prevalence, pathophysiology, natural history, treatment, and preventive measures) of femoroacetabular impingement syndrome has grown exponentially over the past few years. This commentary provides the latest updates on the prevalence of cam and pincer hip morphology and its relationship with development of hip osteoarthritis (OA). Cam and pincer morphology is highly prevalent in the general population and in this paper is presented for different subgroups based on age, sex, ethnicity, and athletic activity. Methodological issues in determining prevalence of abnormal hip morphology are also discussed. Cam morphology has been associated with development of hip OA, but the association between pincer morphology and hip OA is much less clear. Results from reviewed studies, as well as remaining gaps in literature on this topic, are critically discussed and put into perspective for the clinician. J Orthop Sports Phys Ther 2018;48(4):230-238. doi:10.2519/jospt.2018.7816.

Degradation, Intra-Articular Biocompatibility, Drug Release, and Bioactivity of Tacrolimus-Loaded Poly(d-l-lactide-PEG)-b-poly(l-lactide) Multiblock Copolymer-Based Monospheres.

The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)-b-poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic-hydrophilic block ratio. The monospheres were 30 µm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation. Rat knees were injected with three different doses of tacrolimus (10 wt %) loaded monospheres (2.5, 5.0, and 10 mg), contralateral control knees with saline. Micro-CT and histology showed no negative changes on cartilage, indicating good biocompatibility. Minor osteophyte formation was seen in a dose dependent fashion, suggesting local drug release and therapeutic action thereof. To investigate in vivo drug release, tacrolimus monospheres were injected into horse joints, after which multiple blood and synovial fluid samples were taken. Sustained intra-articular release was seen during the entire four-week follow-up, with negligible systemic drug concentrations (<1 ng/mL), confirming the feasibility of local intra-articular drug delivery without provoking systemic effects. Intra-articular injection of unloaded monospheres led to a transient inflammatory reaction, measured by total synovial leucocyte count (72 h). This reaction was significantly lower in joints injected with tacrolimus loaded monospheres, showing not only the successful local tacrolimus delivery but also local anti-inflammatory action. This local anti-inflammatory potential without systemic side-effects can be beneficial in the treatment of inflammatory joint diseases, among which is osteoarthritis.

Osteoporotic Vertebral Fracture Prevalence Varies Widely Between Qualitative and Quantitative Radiological Assessment Methods: The Rotterdam Study.

Accurate diagnosis of vertebral osteoporotic fractures is crucial for the identification of individuals at high risk of future fractures. Different methods for radiological assessment of vertebral fractures exist, but a gold standard is lacking. The aim of our study was to estimate statistical measures of agreement and prevalence of osteoporotic vertebral fractures in the population-based Rotterdam Study, across two assessment methods. The quantitative morphometry assisted by SpineAnalyzer® (QM SA) method evaluates vertebral height loss that affects vertebral shape whereas the algorithm-based qualitative (ABQ) method judges endplate integrity and includes guidelines for the differentiation of vertebral fracture and nonfracture deformities. Cross-sectional radiographs were assessed for 7582 participants aged 45 to 95 years. With QM SA, the prevalence was 14.2% (95% CI, 13.4% to 15.0%), compared to 4.0% (95% CI, 3.6% to 4.5%) with ABQ. Inter-method agreement according to kappa (κ) was 0.24. The highest agreement between methods was among females (κ = 0.31), participants age >80 years (κ = 0.40), and at the L1 level (κ = 0.40). With ABQ, most fractures were found at the thoracolumbar junction (T12 -L1 ) followed by the T7 -T8 level, whereas with QM SA, most deformities were in the mid thoracic (T7 -T8 ) and lower thoracic spine (T11 -T12 ), with similar number of fractures in both peaks. Excluding mild QM SA deformities (grade 1 with QM) from the analysis increased, the agreement between the methods from κ = 0.24 to 0.40, whereas reexamining mild deformities based on endplate depression increased agreement from κ = 0.24 to 0.50 (p <0.001). Vertebral fracture prevalence differs significantly between QM SA and ABQ; reexamining QM mild deformities based on endplate depression would increase the agreement between methods. More widespread and consistent application of an optimal method may improve clinical care. © 2017 American Society for Bone and Mineral Research.

Functional and evolutionary consequences of cranial fenestration in birds.

Ostrich-like birds (Palaeognathae) show very little taxonomic diversity while their sister taxon (Neognathae) contains roughly 10,000 species. The main anatomical differences between the two taxa are in the crania. Palaeognaths lack an element in the bill called the lateral bar that is present in both ancestral theropods and modern neognaths, and have thin zones in the bones of the bill, and robust bony elements on the ventral surface of their crania. Here we use a combination of modeling and developmental experiments to investigate the processes that might have led to these differences. Engineering-based finite element analyses indicate that removing the lateral bars from a neognath increases mechanical stress in the upper bill and the ventral elements of the skull, regions that are either more robust or more flexible in palaeognaths. Surgically removing the lateral bar from neognath hatchlings led to similar changes. These results indicate that the lateral bar is load-bearing and suggest that this function was transferred to other bony elements when it was lost in palaeognaths. It is possible that the loss of the load-bearing lateral bar might have constrained diversification of skull morphology in palaeognaths and thus limited taxonomic diversity within the group.

Cam Deformity and Acetabular Dysplasia as Risk Factors for Hip Osteoarthritis.

OBJECTIVE: Cam deformity and acetabular dysplasia have been recognized as relevant risk factors for hip osteoarthritis (OA) in a few prospective studies with limited sample sizes. To date, however, no evidence is available from prospective studies regarding whether the magnitude of these associations differs according to sex, body mass index (BMI), and age. METHODS: Participants in the Rotterdam Study cohort including men and women ages 55 years or older without OA at baseline (n = 4,438) and a mean follow-up of 9.2 years were included in the study. Incident radiographic OA was defined as a Kellgren/Lawrence grade of ≥2 or a total hip replacement at follow-up. Alpha and center-edge angles were measured to determine the presence of cam deformity and acetabular dysplasia/pincer deformity, respectively. Odds ratios (ORs) were calculated to assess the associations between both deformities and the development of OA. RESULTS: Subjects with cam deformity (OR 2.11, 95% confidence interval [95% CI] 1.55-2.87) and those with acetabular dysplasia (OR 2.19, 95% CI 1.50-3.21) had a 2-fold increased risk of developing OA compared with subjects without deformity, while pincer deformity did not increase the risk of OA. Stratification analyses showed that the associations of cam deformity and acetabular dysplasia with OA were driven by younger individuals, whereas BMI did not influence the associations. Female sex appears to modify the risk of hip OA related to acetabular dysplasia. CONCLUSION: Individuals with cam deformity and those with acetabular dysplasia are predisposed to OA; these associations were independent of other well-known risk factors. Interestingly, both deformities predisposed to OA only in relatively young individuals. Therefore, early identification of these conditions is important.

Ethnic Differences in Bony Hip Morphology in a Cohort of 445 Professional Male Soccer Players.

BACKGROUND: Participation in high-impact athletic activities has recently been associated with a higher prevalence of cam deformity. Bony hip morphology has also emerged as an important factor in the development of hip osteoarthritis. However, it is unknown whether bony morphology differs between ethnicities in athletes participating in high-impact sports. PURPOSE: To investigate whether the prevalence of specific bony hip morphological abnormalities differed between professional male soccer players of diverse ethnic backgrounds. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Professional male soccer players from an entire league attending preparticipation screening were invited to participate in this study. Ethnicity was registered, and standardized radiographs of anteroposterior pelvic and Dunn views were obtained. Cam and pincer deformity, and acetabular dysplasia were quantified using the alpha angle, triangular index, and lateral center-edge angle (LCEA). Regression analyses with generalized estimating equations were used to determine prevalence differences in bony hip morphology. RESULTS: A total of 445 male soccer players (890 hips; mean age ± SD, 25 ± 4.9 years) participated in the study, representing the following ethnic groups: Arabic (59%), black (24%), Persian (7%), white (6%), East Asian (2%), and other (2%). The prevalence of cam deformity (alpha angle >60°) ranged from 57.5% to 71.7% across 4 of the groups, but East Asians had a significantly lower prevalence (18.8%; P ≤ .032). A large cam deformity (alpha angle >78°) was more prevalent in white (33.3%) compared with black soccer players (17.8%; P = .041) and was absent in East Asian players. Pincer deformity (LCEA >40°) was uncommon (3%) in all ethnicities. The prevalence of acetabular dysplasia (LCEA <20°) ranged from 8.0% to 16.7%, apart from the white group, in which prevalence was only 1.9% (P = .03). CONCLUSION: The prevalence of a cam deformity and acetabular dysplasia differed between ethnicities in this cohort of professional male soccer players. These findings suggest that there may be ethnic differences in both acetabular morphology and femoral bony response to athletic load.