Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

A Scoping Review of the Recent Clinical Practice Regarding the Evaluation of Bone Mineral Density in Children and Adolescents with Neuromuscular Diseases.

Introduction: Neuromuscular Diseases (NMD) are associated with decreased bone strength due to altered muscle-bone interaction. However, the evaluation of bone quality remains a certain challenge in these patients. The purpose of this scoping review is to investigate the recent literature regarding the assessment of Bone Mineral Density (BMD) in this population. Methods: An electronic search of the PubMed and Scopus database was performed considering studies published in the English literature after 2007 that evaluated BMD in pediatric and adolescent patients with NMD. We excluded studies that evaluated patients > 20 years, studies not involving humans, and studies investigating bone mineral density in various pediatric conditions, but without specific data on NMD. Results: Overall, 19 studies were included that evaluated BMD in 1983 patients with NMD. Duchenne Muscular Dystrophy was the most widely studied disease (n = 11 studies). Dual energy X-ray absorptiometry (DEXA) was the most common diagnostic modality for BMD evaluation, while the most frequent site for BMD measurement was the lumbar spine (89.4%, n = 17 studies), followed by total body BMD (68.4%, n = 13 studies). Low BMD in children with NMD was demonstrated in all studies, especially after loss of ambulation. Moreover, a positive correlation between lower BMD and older age was shown. Conclusions: BMD evaluation in NMD remains a clinical challenge, as indicated by the high heterogeneity regarding the optimal site and technique for the evaluation of bone quality in these patients. Although DXA is currently the diagnostic modality of choice, a consensus regarding the optimal site for BMD measurement, and the adjustment method for its obtained measurements for parameters such as age and height is needed.

The impact of glenoid parameters and implant overstuffing on functional outcomes of shoulder hemiarthroplasty in patients with glenohumeral joint arthritis.

PURPOSE: The outcomes of shoulder hemiarthroplasty are highly dependent on the baseline glenoid morphology and the rotator cuff integrity. The objective of this study was to assess whether certain glenoid parameters and implant overstuffing are associated with worse clinical outcomes following shoulder hemiarthroplasty. METHODS: We retrospectively reviewed 25 patients who underwent shoulder hemiarthroplasty for shoulder arthritis, with a mean follow-up of 5.3 years. The baseline glenoid morphology, the glenoid wear rate, the proximal humeral head migration and implant overstuffing were evaluated radiologically in all patients. The radiological parameters were correlated with the functional outcomes. RESULTS: The Constant-Murley score, the ASES score, and the OSS score were significantly better for patients with a concentric baseline glenoid compared to those with an eccentric glenoid. The Constant-Murley score and the ASES score were also improved in patients without implant overstuffing compared to patients with implant overstuffing (p < 0.05). However, glenoid wear was not associated with worse functional outcomes (p = 0.23 for Constant-Murley score, p = 0.15 for ASES score and p = 0.27 for OSS score). Last, a worse Constant-Murley score was strongly correlated with proximal humeral head migration (p < 0.001), while worse ASES and OSS scores were moderately correlated with proximal humeral head migration (p < 0.001). CONCLUSION: Our findings indicate that the results of hemiarthroplasty can be improved through careful selection of patients upon the baseline glenoid type morphology and proper implant sizing to avoid implant overstuffing. Moreover, glenoid wear is not associated with worse clinical outcomes, therefore shoulder hemiarthroplasty should be reconsidered as an alternative in younger patients with shoulder arthritis.

Serum biomarkers for the assessment of muscle damage in various surgical approaches in primary total hip arthroplasty: a systematic review of comparative studies.

PURPOSE: Using serum biomarkers, this systematic review assessed soft tissue injury following different total hip arthroplasty surgical approaches. The purposes were to determine if there is any advantage between the standard and minimal invasive approaches, and to compare tissue damage of the respective surgical approaches using biomarkers such as creatine kinase, myoglobin, c-reactive protein, erythrocyte sedimentation rate, skeletal troponin and interleukins. METHOD: A search in Pubmed/MEDLINE, Scopus and Web of Science databases was conducted in October 2021 with the use of PRISMA guidelines. Search items were ("biomarkers" OR "markers" OR "tissue damage" OR "muscle damage") AND "approach" AND ("total hip arthroplasty" OR "total hip replacement"). Inclusion criteria were prospective, randomized, controlled trials or prospective, comparative studies, comparing serum markers for muscle damage in two or more surgical approaches for primary total hip arthroplasty. Exclusion criteria were study protocols, case reports, systematic reviews, meta-analyses, studies in non-English language or without available full text, and studies not recording biomarkers of muscle damage. RESULTS: Initial search revealed 508 studies; after subtraction of duplicates, and exclusion criteria, 31 studies remained for analysis. No advantage between different approaches was found when evaluating biomarkers, and no specific biomarkers had a distinct role in tissue damage in total hip arthroplasty. Anterior and minimally invasive approaches were associated with lower values of soft tissue (creatine kinase) and inflammation (c-reactive protein) biomarkers compared to the standard approaches. CONCLUSION: Measurement of serum biomarkers after primary total hip arthroplasty for the estimation of tissue damage has unclear or little clinical value. TRIAL REGISTRATION: PROSPERO Registration: CRD42022303959.

Association of vitamin D, BMD and knee osteoarthritis in postmenopausal women.

OBJECTIVES: The aim of this study was to analyze the association of knee OA with bone mineral density (BMD) and vitamin D serum levels in postmenopausal women. METHODS: A cross-sectional study including 240 postmenopausal women with knee OA was conducted. Demographic data were recorded along with balance and functionality scores. Knee OA severity was assessed by the radiological Kellgren & Lawrence scale. BMD and T-scores were calculated in hips and lumbar spine. Serum levels of vitamin D were also measured. RESULTS: High BMI (p<0.005), high number of children (p=0.022) and family history of hip fracture (p=0.011) are significantly associated with knee OA severity. Lumbar spine OP is negatively associated with knee OA (p<0.005). A significant difference was detected between vitamin D deficiency and severe knee OA, adjusted for BMD [OR (95%CI); 3.1 (1.6-6.1), p=0.001]. BMD does not affect the relationship of vitamin D levels in relation to OA and vitamin D levels do not affect the relationship of BMD with OA. CONCLUSIONS: Low BMD has a protective role against knee OA while vitamin D deficiency contributes significantly to knee OA severity. However, the association between OA and OP is not affected by vitamin D deficiency and the association of OA and vitamin D serum levels is not affected by BMD.

Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women. METHODS: This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant. RESULTS: All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling. CONCLUSION: No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.

Three-dimensional printing in anatomy teaching: current evidence.

PURPOSE: The critical literature review investigates the extent to which the current evidence supports that three-dimensional printing (3DP) could play an important role in human anatomy education. METHODS: PubMed, ERIC, and Cochrane databases were searched for papers dealing with the outcomes of 3DP implementation in human undergraduate anatomy education. The following data were extracted from each paper: authors, year of publication, type of study (comparative or not), number of participants, level of outcome according to Kirkpatrick hierarchy, influence of 3DP on acquisition of anatomical knowledge and skills, as well as perceptions about the 3DP use in anatomy teaching. RESULTS: Eight papers were eligible for analysis. All of them comprised comparison of 3DP with other anatomy teaching tools. Two papers evaluated only students' perceptions about 3DP, while six papers explored its impact on students' knowledge. The 3DP was statistically significantly superior to two-dimensional images in terms of the investigated parameters. However, comparison between 3DP and cadavers' dissection by students did not take place in any study. CONCLUSION: The 3DP implementation in anatomy education showed promising outcomes. However, the lack of studies which compared the educational effectiveness of 3DP with that of cadavers' dissection is highlighted. It seems that 3DP could certainly be used as an adjunct to cadavers' dissection. Further research could clarify if 3DP could obtain a more prominent role in anatomy pedagogy compared to other anatomy teaching modalities.

Outcomes of the use of plastination in anatomy education: current evidence.

PURPOSE: We aimed to evaluate the quantity and quality of current evidence concerning the outcomes of use of plastinated specimens in anatomy education. METHODS: We performed a narrative literature review, searching for papers dealing with the use of plastination in anatomy education. PubMed, Scopus, ERIC, Cochrane, Web of Science and CINAHL complete electronic databases were searched. The following data were extracted: author(s), year of publication, type of study (comparative or not), number of participants, evaluation of statistical significance, educational outcomes and their level according to Kirkpatrick hierarchy. RESULTS: Six studies were eligible for analysis. Five of them evaluated only students' reactions about plastination and one study also assessed their examinations results. There were four non-comparative and two comparative studies. Only a study evaluated statistical significance (p < 0.05) with higher score of perception in 2nd year undergraduate medical students, who were more familiar with plastination in comparison to 1st year students. Although the use of plastination was accompanied by positive outcomes in the majority of studies (five out of six), this method was not proved superior to traditional cadavers dissection. CONCLUSIONS: The existing evidence about the outcomes of the use of plastination in anatomy education is relatively limited and lacks comparative studies with statistical significant results. Positive students' reactions were generally noted, but further research is needed to clarify if plastination could be of benefit to students' attitude and anatomy knowledge.

Accuracy and Interobserver and Intraobserver Reliability of Ultrasound in the Early Diagnosis of Occult Scaphoid Fractures: Diagnostic Criteria and a Way of Interpretation.

The purpose of this study was to illustrate the usefulness of ultrasound in the early diagnosis of occult scaphoid fractures. Forty-eight patients with clinical symptoms of scaphoid fracture and negative initial X-rays were examined. All patients underwent ultrasonography in the emergency room (ER). After 14 days, a computed tomography (CT) scan was performed, which confirmed or not the initial suspicion of fracture. Twenty-two patients were found with subperiosteal hematoma, while six also had cortical discontinuity. The sensitivity of ultrasound in the diagnosis of occult scaphoid fractures was 90% and the specificity was 85.7%. The positive prognostic value was 81.8%. The authors support the use of the scaphoid ultrasound only under strict circumstances. If subperiosteal hematoma or cortical discontinuity is present, there is a high likelihood of scaphoid fracture. On the contrary, if the ultrasound is negative and symptoms persist, the patient will require a CT scan or magnetic resonance imaging for definitive diagnosis. (Journal of Surgical Orthopaedic Advances 28(1):1-9, 2019).

Central band reconstruction for the treatment of Essex-Lopresti injury : A novel technique using the brachioradialis tendon.

Longitudinal stability of the forearm is mainly provided by three structures: the radiocapitellar contact, which acts as the primary stabilizer, the central band of the interosseous ligamentous complex (IOLC) and the intact triangular fibrocartilage complex (TFCC). In an Essex-Lopresti lesion the forearm becomes fully destabilized, since all of these three components are injured. Fixation or replacement of the radial head with a metallic prosthesis along with repair of the TFCC and stabilization of the distal radioulnar joint (DRUJ) are well-established treatment goals. However the reconstruction of the central band of the IOLC remains to some extent controversial. The authors believe that the reconstruction of the central band, particularly in active patients, is crucial in order to restore normal load distribution through the forearm, thus ensuring both transverse and longitudinal stability. In this article, we present a case with an Essex-Lopresti lesion, which was effectively treated acutely with restoration of all three components of the injury (radial head prosthesis, DRUJ repair and reconstruction of the central band of the IOLC). A novel technique by rerouting the brachioradialis tendon is described in detail.

Platelet-rich plasma injections for carpal tunnel syndrome: a systematic and comprehensive review.

A series of clinical trials focused on the use of ultrasound-guided platelet-rich plasma (PRP) infusions for the treatment of patients with carpal tunnel syndrome (CTS) were published over the last few years. However, the role of PRP for CTS remains unclear. We performed a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Two reviewers independently conducted the search using multiple databases: MEDLINE/PubMed, SCOPUS, Cochrane Database, and Web of Science. These databases were searched using terms "platelet" AND "rich" AND "plasma" AND "carpal" AND "tunnel". To maximize the search, backward chaining of references from retrieved papers was also undertaken. From the initial 19 studies, only five met our eligibility criteria. These articles included one randomized controlled double-blind study, one randomized controlled single-blind study, one randomized controlled non-blind study, one case-control study, and one case report. The vast majority of the included studies supported that PRP infusion improved the clinical condition of the patients and that PRP infusion was beneficial for patients with mild-to-moderate CTS. Therefore, PRP seems to be an interesting alternative for the treatment of mild-to-moderate CTS which, still, has not been thoroughly investigated. However, despite the promising results of the present studies, PRP has to be further tested before we reach to a definite conclusion regarding its therapeutic value.

No Differences Identified in Transverse Plane Biomechanics Between Medial Pivot and Rotating Platform Total Knee Implant Designs.

BACKGROUND: Total knee arthroplasties (TKAs) using well-designed, fixed bearing prostheses, such as medial pivot (MP), have produced good long-term results. Rotating-platform, posterior-stabilized (RP-PS) mobile bearing implants were designed to decrease polyethylene wear. Sagittal and coronal plane TKA biomechanics are well examined and correlated to polyethylene wear. However, limited research findings describe this relationship in transverse plane. We assumed that although axial plane biomechanics might not be the most destructive parameters on polyethylene wear, it is important to clarify their role because both joint kinematics and kinetics in all 3 planes are important input parameters for TKA wear testing (International Organization for Standardization 14243-1 and 14343-3). Our hypothesis was that transverse plane overall range of motion (ROM) and/or peak moment show differences that reflect on wear advantages when compared RP-PS implants to MP designs. METHODS: Two groups (MPs = 24 and RP-PSs = 22 subjects) were examined by using 3D gait analysis. The variables were total internal-external rotation (IER) ROM and peak IER moments. RESULTS: No statistically significant difference was demonstrated between the 2 groups in kinetics (P = .389) or kinematics (P = .275). CONCLUSION: In the present study, no wear advantages were found between 2 TKAs. Both designs showed identical kinetics at the transverse plane in level-ground walking. Kinematic analysis could not illustrate any statistically significant difference in terms of overall IER ROM. Nevertheless, kinematic gait pattern differences observed possibly reflect different patterns of joint surface motion or abnormal gait patterns. Thus, wear testing with various input waveforms combined with functional data analysis will be necessary to identify the actual effects of gait variability on polyethylene wear.

Two-Stage Revision Protocol in Multidrug Resistant Periprosthetic Infection Following Total Hip Arthroplasty Using a Long Interval Between Stages.

We retrospectively reviewed the medical records of 31 patients with periprosthetic hip infections attempting to evaluate the outcome of a two-stage revision protocol characterized by prolonged interim period (mean=9.2 months, range 8-12 months) prior to the final re-implantation. In 3 cases (9.6%) the 1st stage was repeated after a mean period of 12.3 weeks due to relapse of infection. Five spacer dislocations occurred, not affecting the final clinical outcome after reimplantation, as evaluated by the Harris Hip Score. No protrusions or additional acetabular bone loss was noticed. Our proposed protocol is a simple, safe, efficient and reproducible treatment approach that may be successfully utilized predominantly when dealing with multidrug resistant pathogens.

Risk factors for and complications of distraction osteogenesis.

PURPOSE: Distraction osteogenesis is commonly used for limb deformities and reconstruction of bone defects with satisfactory outcome for the patients. However, it is associated with a risk of complications. The present study aims to assess the incidence of complications and to identify the risk factors that may predict distraction osteogenesis-related complications. MATERIALS AND METHODS: We retrospectively studied 63 patients (mean age 13.5 years; range 3-57 years) who had 74 distraction osteogenesis procedures from 2004 to 2009. A circular external fixator was used in 58 procedures, and a monolateral in 16 procedures. Fixator's time, days of treatment, lengthening percentage, bone healing index, distraction regenerate length and index, risk factors and complications were evaluated. The mean follow-up was 5 years (range 2-7 years). RESULTS: Complications occurred in 57 of the 74 procedures (77%); 70% were major complications and 30% were minor. Complications were more common in adults. Bone healing index, days of treatment and fixator's time were univariate predictors of complications. Bone healing index and adult age were the only multivariate predictors of complications. CONCLUSION: Adult age and bone healing index are the most important multivariate predictors of distraction osteogenesis-related complications. Routine follow-up after implant removal, selection of younger patients with minor risk factors and shorter fixator's time are necessary to reduce the rate of distraction osteogenesis-related complications.

Augmentation of Rotator Cuff Repair Using Umbilical Cord Graft: A Preliminary Observational Study.

Due to the high rate of rotator cuff re-tear there is an extensive research on augmentation of rotator cuff repairs. The purpose of this single center, prospective study was to evaluate the results of augmentation of the rotator cuff repair with an umbilical cord allograft. The graft group in which the rotator cuff repair was augmented with the graft as an on-lay patch was consisted of 14 patients, while the control group was consisted of 10 patients. The primary outcome of the study was incidence of rotator cuff retears, while secondary outcomes included functional and pain scores. At 6 mo there was a significantly higher incidence of retears in the control group (30%) compared to the graft group (0%; P = 0.028), while at 12 mo the retear rates were statistically similar for the two groups (P = 0.46). The Constant-Murley scores, the ASES scores and the VAS score were similar (P > 0.05) for the two groups at all study times. The results of the study indicated that augmentation of the cuff repair with human umbilical cord graft can result in similar patient reported outcomes compared to a cuff repair without augmentation, but with a lower re-tear rate at 6 mo.

Results of total hip arthroplasty differ in subtypes of high dislocation.

BACKGROUND: In a previous study, we described two subtypes of high dislocation of the hip depending on the presence (C1) or absence (C2) of a false acetabulum, yet we have already presented the concise followup of total hip arthroplasty (THA) in these patients as a group at a minimum of 15 years. QUESTIONS/PURPOSES: In this retrospective study, we investigated differences in the results of THA in the C1 and C2 subtypes of high dislocation such as (1) survivorship of the reconstructions; (2) Merle d'Aubigné-Postel clinical scores; (3) leg lengthening and femoral shortening; and (4) site of reattachment and union rate of the greater trochanter. METHODS: We included 49 hips of the C1 subtype and 30 hips of the C2 subtype operated on from 1976 to 1994. We evaluated survivorship (using reoperation for any reason as the end point) and performed chart and radiographic reviews. RESULTS: The 15-year survival was 84% (± 10% [95% CI]) for the C1 subtype and 60% (± 17% [95% CI]) for the C2 subtype (p = 0.001). Cox regression analysis, after adjustment for confounding factors, showed also statistically significantly worse survivorship in the C2 subtype (p = 0.021) and, after adjustment for possible predictive factors, found a statistically significant relationship of high dislocation subtype (p = 0.018) and trochanteric union (p = 0.005) with survival of THAs. Pain, function, and mobility scores improved from preoperative to last followup in C1 and C2 groups but they did not differ between C1 and C2 hips. C2 hips were lengthened more (p < 0.001) despite greater amounts of femoral shortening (p = 0.006). Site of reattachment and the risk of greater trochanter nonunion were not different between the groups. CONCLUSIONS: We found important differences in fundamental parameters after THA in the high-dislocation subtypes, including the risk of revision, which was higher in patients whose hips did not have a false acetabulum. These findings indicate that while reporting THA results in patients with high dislocation, mixing results of the two subtypes may lead to statistical bias.