Osteoarthritis In Adults Research Articles

Two-year 3D gait outcomes following in-situ pinning or modified Dunn procedure in children with slipped capital femoral epiphysis

BackgroundSlipped Capital Femoral Epiphysis (SCFE) is femoral head slippage off the femoral neck through the physis occurring in children aged 8–16 years. Surgical intervention is required in all paediatric cases and there is no universal agreement on choice of surgical procedure. Research questionWhat are the two-year 3D gait outcomes in children with SCFE who have undergone in-situ pinning (PIN) or modified Dunn procedure (MDP) compared with normative reference values? Methods17 children with SCFE who had undergone PIN (n=7, slip severity mild to moderate) or MDP (n=10, slip severity moderate to severe) surgical procedures prospectively underwent a 3D gait analysis post-surgery (2∙0 ± 0∙5 years). Ten age-matched children were also recruited to provide normative reference values. The conventional gait model was modified to incorporate Hara hip equations and Lerner pelvic tracking methods. Gait Profile Scores, Gait Variable Scores, kinematics, kinetics and spatiotemporal data were calculated for each group. ResultsOverall gait pattern, determined by the Gait Profile Score, indicated that both SCFE groups differed from the normative reference group (PIN 6∙6 ± 2∙5⁰, MDP 6∙2 ± 2∙0⁰ vs. 4∙0 ± 1∙3⁰ norm, p<0∙05). Normalised walking speed was reduced in the MDP group (0∙40 ± 0∙04) compared to the normative reference group (0∙46 ± 0∙06; p=0∙032). SignificanceGait patterns of children with SCFE treated with PIN was more markedly altered than that of children with SCFE treated with MDP, despite having lower SCFE severity. Increased external hip rotation observed in the PIN group may be a pre-cursor for osteoarthritis in adulthood. Therefore the use of the corrective MDP which normalises hip rotation may be beneficial for reducing functional impairments.

Circular RNA Gtdc1 Protects Against Offspring Osteoarthritis Induced by Prenatal Prednisone Exposure by Regulating SRSF1-Fn1 Signaling.

Chondrodysplasia is closely associatedwith low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0-20 and underwent long-distance running during postnatal weeks (PWs) 24-28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28. In vitro experiments are performed to elucidate the mechanism. PPE decreased cartilage proliferation and matrix synthesis, causing offspring chondrodysplasia. Following long-distance running, the PPE group exhibited more typical osteoarthritis-like changes. Molecular analysis revealedthat PPE caused cartilage circRNomics imbalance in which circGtdc1 decreased most significantly and persisted postnatally. Mechanistically, prednisolone reduced circGtdc1 expression and binding with Srsf1 to promote degradation of Srsf1 via K48-linked polyubiquitination. This further inhibited the formation of EDA/B+Fn1 and activation of PI3K/AKT and TGFβ pathways, reducing chondrocyte proliferation and matrix synthesis. Finally, intra-articular injection of offspring with AAV-circGtdc1 ameliorated PPE-induced chondrodysplasia, but this effect is reversed by Srsf1 knockout. Altogether, this study confirms that PPE causes chondrodysplasia and susceptibility to osteoarthritis by altering the circGtdc1-Srsf1-Fn1 axis; in vivo, overexpression of circGtdc1 can represent an effective intervention target for ameliorating PPE-induced chondrodysplasia.

Intra- and interobserver reliability analysis of pediatric lower limb parameters on digital long leg radiographs

BackgroundMalalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention.ObjectiveFirst, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length?MethodsTwo observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated.ResultsThe intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849–0.999; Inter-ICC2,1: 0.864–0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia.ConclusionsIn conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA.Trial registration: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053.Level of evidenceI, Diagnostic Study.

Risk factors of developmental dysplasia of the hip in a single clinical center

Developmental dysplasia of the hip (DDH) is the main cause of early-onset hip osteoarthritis in adulthood. Early screening of DDH is the key to avoiding these severe complications. This study aimed to assure the risk factors are suitable for screening patients with DDH in our region. We retrospectively analyzed 10,668 patients (21,336 hips) at our hospital. Overall, 204 patients with pathological DDH and 408 patients with normal hips were included in this study. All patients were diagnosed by performing ultrasound examinations according to the Graf technique. The risk factors were assessed based on patients’ clinical data. Pearson’s chi-square or Fisher’s exact tests and multivariate logistic regression analysis were performed for statistical analysis. A total of 204 patients were diagnosed with pathologic DDH and were treated with the Pavlik harness. Among these, 184 patients were female. There were 73 cases of first birth, 13 had oligohydramnios, 13 had foot deformity, 31 had breech delivery, 6 had congenital muscular torticollis. Female sex, vaginal delivery, breech presentation, oligohydramnios and foot deformity were identified as the risk factors for DDH. The risk factors of DDH in our clinical center were confirmed in our clinical center, this can supply the screening advice for the doctors.

Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?

Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?

Clinical and genetic characteristics of Legg-Calve-Perthes disease

Legg-Calve-Perthes disease (LCPD) is a known childhood form of idiopathic femoral head osteonecrosis. It is characterized by a sequence of events involving the capital femoral epiphysis. The disease process is associated with the disruption of the blood supply to the femoral head. In most cases, LCPD appears in a sporadic form. Occurrences of cases in families have also been reported, with some families having more than two affected individuals. The disease etiology is still unknown, however, various factors have been considered for the pathogenesis of LCPD, including very low body weight or short stature at birth, maternal smoking, and secondhand smoke exposure. Interaction of multiple environmental and genetic factors has also been postulated as an underlying player in the development of the disorder. Hypercoagulability may have a major role in LCPD development. Families segregating LCPD largely demonstrate autosomal dominant inheritance. Variants in coagulations genes (Factor 5 and Factor 2) and collagen encoding gene (COL2A1) have been linked to the disease. However, our knowledge of the LCPD pathogenic factors is limited. A better understanding of the association between LCPD and causative factors, for example, the role of hypercoagulability in osteonecrosis development, might lead to the development of improved treatments, to shorten the acute phase of the disease during childhood as well as to possibly reduce the long-term effects of osteoarthritis in adulthood. Detection of large-effect variants underlying LCPD may help in offering extended screening for all first-degree family members. In this review, we would like to discuss the etiological factors underlying LCPD with special emphasis on the role of coagulation factors and mutations in the genes encoding those coagulation factors.

Programming changes in GLUT1 mediated the accumulation of AGEs and matrix degradation in the articular cartilage of female adult rats after prenatal caffeine exposure

Osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal glucose metabolism. Our laboratory previously reported that prenatal caffeine exposure (PCE) can induce intrauterine maternal glucocorticoid (GC) overexposure in IUGR offspring and increase susceptibility to osteoarthritis after birth. In the present study, we demonstrated the essential role of glucose transporter 1 (GLUT1) programming changes in the increased matrix degradation of articular cartilage and susceptibility to osteoarthritis in female PCE adult offspring. In vivo, we found that PCE decreased the matrix content but did not significantly change the expression of matrix degradation-related genes in the articular cartilage of female fetal rats. The decreased expression of IGF1 and GLUT1 and the content of advanced-glycation-end-products (AGEs) were also detected. At different postnatal stages (2, 6, and 12 weeks), the cartilage matrix content decreased while the degradation-related genes expression increased in the PCE group. Meanwhile, the expression of IGF1 and GLUT1 and AGEs content in the local cartilage increased. In vitro, the expression levels of IGF1 and GLUT1 were inhibited by corticosterone but remained unchanged under caffeine treatment. Exogenous IGF1 can reverse the corticosterone-induced decrease in GLUT1 expression and promote AGEs production, while mifepristone (a glucocorticoid receptor inhibitor) reversed the corticosterone-induced low expression of IGF1 and GLUT1. Exogenous AGEs can increase the expression of inflammatory factors (IL-6 and TNF-α) and degradation-related genes, and decrease the matrix synthesis-related genes expression in chondrocyte. In conclusion, the GC-IGF1-GLUT1 axis mediated intrauterine dysplasia of articular cartilage, increased accumulation of AGEs and matrix degradation after birth in PCE female offspring, thereby increasing their susceptibility to osteoarthritis in adulthood.

Challenges and outcome of total hip arthroplasty in patients with developmental dysplasia of the hip: a clinical series with a spectrum of disease manifestation and technical notes

&lt;p class="abstract"&gt;&lt;span lang="EN-IN"&gt;Patients with developmental dysplasia of hip eventually lead on to secondary osteoarthritis in adulthood and may end up with total hip arthroplasty at a younger age. Because of the altered anatomy of dysplastic hips, total hip arthroplasty in these patients is a technically demanding procedure. Altered anatomy of the acetabulum and proximal femur together with leg length discrepancy pose challenges during total hip arthroplasty. Since the majority of the patients are in the younger age group, soft tissue balance is of great importance to maximise postoperative functional result and longevity of prosthesis. In this paper, we present a series of our patients with a spectrum of disease manifestation from mild to severe form and also discuss the associated challenges and the technical solutions and their outcome.&lt;/span&gt;&lt;/p&gt;

Adolescent knee pain and patellar dislocations are associated with patellofemoral osteoarthritis in adulthood: A case control study

BackgroundThere is a lack of information about the association between patellofemoral osteoarthritis (PFOA) and both adolescent anterior knee pain (AKP) and previous patellar dislocations. MethodsThis case-control study involved 222 participants from our knee arthroplasty database answering a questionnaire. One hundred and eleven patients suffering from PFOA were 1:1 matched by gender with a unicompartmental tibiofemoral arthritis control group. Multivariate correlation and binary logistic regression analysis were performed, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. ResultsAn individual is 7.5 times more likely to develop PFOA if they have suffered from adolescent AKP (OR 7.5, 95% CIs 1.51 to 36.94). Additionally, experiencing a patellar dislocation increases the likelihood of development of PFOA, with an adjusted odds ratio of 3.2 (95% CIs 1.25 to 8.18). A 44-year difference in median age of first dislocation was also observed between the groups. ConclusionThis should bring into question the traditional belief that adolescent anterior knee pain is a benign pathology. Patellar dislocation is also a significant risk factor. These patients merit investigation, we encourage clinical acknowledgement of the potential consequences when encountering patients suffering from anterior knee pain or patellar dislocation.

O44 Adolescent Knee Pain is Associated with Patellofemoral Osteoarthritis in Adulthood: A Case–Control Study

O44 Adolescent Knee Pain is Associated with Patellofemoral Osteoarthritis in Adulthood: A Case–Control Study

Genetic skeletal dysplasias: a guide to diagnosis and management.

The skeletal dysplasias are a large, heterogeneous group of genetic disorders characterised by abnormal growth, development and remodelling of the bones and cartilage that comprise the human skeleton. They typically present with disproportionate short stature in childhood, or premature osteoarthritis in adulthood. The latest classification lists 456 disorders under 40 group headings differentiated by specific clinical, radiographic and molecular criteria. Establishing an accurate diagnosis is important to predict final height, expected complications and treatment, and for specific genetic and psychological counselling. In addition to the skeletal disorder, individuals frequently demonstrate abnormalities of hearing, vision, neurological, pulmonary, renal or cardiac function that require multidisciplinary assessment. This review provides a guide to diagnosis and discusses management principles for the common limb and spinal abnormalities that affect quality of life for the majority.

The Efficacy and Complications of 2-Hole 3.5 mm Reconstruction Plates and 4 mm Noncanulated Cancellous Screws for Temporary Hemiepiphysiodesis Around the Knee

Persistent angular deformities around the knee can lead to growth-plate damage in childhood and osteoarthritis in adulthood. The treatment options include osteotomy and hemiepiphysiodesis. Tension-band plate hemiepiphysiodesis with 8-plate is an effective way to correct these deformities. However, its high cost makes it less available in many countries. In the present series, we have used 3.5 mm reconstruction plates for tension-band temporary hemiepiphysiodesis. Twenty-one patients with bilateral angular deformities of the knee (42 extremities) underwent temporary hemiepiphysiodesis with 3.5 mm reconstruction plates. The diagnosis, BMI, weight, amount of correction of the deformity age, and device failure were analyzed. The mean follow-up period after plate removal was 17 months (ranging from 8 to 24 mo). The mean age of the patients was 10 years and 3 months (± 2 y and 10 mo). Complete correction of the deformities was achieved in 86% of patients. Of the 58 plate and screw constructs, 10% had screw breakage. Patients with genu valgum had 2 screw failures (6.25%), but in the genu varum group there were 4 screw failures (40%). Of the 3 patients who did not have complete correction of the deformities, 2 had mucopolysaccharidosis and 1 was nearing skeletal maturity (16 y old). The age of the patient, body weight, BMI, and degrees of angulation did not have any statistically significant correlation with the screw failure. Screw failures in female patients were more common than in male patients. All implant failures occurred in idiopathic patients. The efficacy of 3.5 mm reconstruction plates for temporary hemiepiphysiodesis around the knee is similar to that of 8-plates. However, the reconstruction plates have a lower cost and are easily available. Noncanulated 3.5 or 4.5 mm cortical screws seem to be superior to 4 mm noncanulated cancellous screws. Level 3.

Management of developmental dysplasia of the hip in young adults

The term developmental dysplasia of the hip (DDH) describes a spectrum of disorders that results in abnormal development of the hip joint. If not treated successfully in childhood, these patients may go on to develop hip symptoms and/or secondary osteoarthritis in adulthood. In this review we describe the altered anatomy encountered in adults with DDH along with the management options, and the challenges associated with hip arthroscopy, osteotomies and arthroplasty for the treatment of DDH in young adults.Cite this article: Bone Joint J 2013;95-B:732–7.

The robust association between childhood physical abuse and osteoarthritis in adulthood: Findings from a representative community sample

Research suggests a role of early-life trauma in the development of arthritis. This study investigated the relationship between childhood physical abuse and osteoarthritis (OA) while controlling for age, sex, race, and socioeconomic status (SES), in addition to the following types of risk factors for OA: 1) concurrent childhood stressors, 2) adult health behaviors, and 3) depression. Data from the provinces of Manitoba and Saskatchewan were selected from the 2005 Canadian Community Health Survey (n = 13,093). Respondents with missing arthritis data or with arthritis types other than OA were excluded (n = 1,985). Of the 11,108 remaining respondents, 6.9% (n = 854) reported childhood physical abuse by someone close to them, and 10.1% (n = 1,452) reported that they had been diagnosed with OA by a health professional. The regional-level response rate was 84%. When adjusting for all 3 types of risk factors, a significant association between childhood physical abuse and OA was found (odds ratio [OR] 1.56, 95% confidence interval [95% CI] 1.21-2.00). In contrast, when adjusting for age, sex, race, and SES only, the OR was 1.99 (95% CI 1.57-2.52). The association between childhood physical abuse and OA remained significant, even after controlling for many risk factors that may mediate the relationship. Further research is needed to investigate potential pathways through which arthritis develops as a consequence of childhood physical abuse.

Slipped capital femoral epiphysis update

Slipped capital femoral epiphysis (SCFE) is the most common adolescent hip condition. Its importance lies in its high morbidity if not diagnosed and treated in its early stages, not only in childhood but also as a cause of osteoarthritis in adulthood. This article highlights key diagnostic tools and optimal treatment plans for SCFE. SCFE involves displacement between the proximal femoral neck and the femoral head at the level of the open physis, with biomechanical and biochemical factors implicated. Acute major trauma is rarely involved; a gradual onset of symptoms and deformity is more common. Patients with unstable SCFE are in severe pain and unable to bear weight. SCFE occasionally is associated with endocrine or metabolic abnormality (hypothyroidism, panhypopituitarism and renal rickets). On physical examination, limited internal rotation of the affected hip is usual; obligatory external rotation of hip in flexion is classic. Diagnosis is confirmed on anteroposterior and frog-leg lateral radiographs of both hips. Treatment is surgical, with stabilization across the physis by in-situ pinning being the gold standard. Prompt diagnosis and timely surgical treatment usually lead to excellent long-term results with minimal morbidity. It is crucial to recognize that groin pulls are very rare in adolescents. Children with suggestive groin symptoms should have hip anteroposterior and frog-leg lateral radiographs to rule out the much more common SCFE.

Developmental Dysplasia of the Hip

Hippocrates (400 BC) first described atraumatic hip dislocations in children in his books “Instruments of Reduction” and “On Articulations,” and provided guidelines for diagnosis and treatment. Throughout most of recent history the entity was called, “congenital dislocation of the hip,” although within the past decade “developmental dysplasia of the hip” (or DDH) has become the preferred term. Early diagnosis and treatment of DDH is a major issue of health care providers, including pediatricians and orthopaedic surgeons. Late diagnosis results in more complex treatments with higher rates of failures and complications. Late diagnosis also may lead to disabling osteoarthritis in adulthood. It is therefore well accepted that all newborn infants should be carefully screened for DDH, not only those with risk factors. Physical examination using the Ortolani [5] and Barlow [2] maneuvers is most widely used to diagnose newborn DDH. However, late-diagnosed or late-onset hip dislocations needing treatment are not rare and screening guidelines need to be adjusted to diagnose these patients. Static and dynamic ultrasound screening popularized by Graff [3] and Harcke et al. [4] are well-accepted diagnostic tools that add valuable information to the physical examination and are considered the “gold standard” for diagnosis in some countries. However, ultrasound evaluation of the hips has not been universally adapted even in the industrialized world and in developing countries is not widely available. Therefore, there is still a place for simple, effective, and inexpensive methods to allow early diagnosis. In this symposium a series of articles systematically addresses various aspects of diagnosis and current treatment strategies. Orthopaedic surgeons should rely on Pavlik harness [1] treatment in early diagnosed patients. If unsuccessful, closed and/or open reduction and casting should be carried out by experienced pediatric orthopaedic surgeons. Several open reduction techniques are described as well as some of the differing types of pelvic osteotomies. Unsuccessful surgical attempts will most likely lead to substantial morbidity in the future life of the patient. Debate on techniques used to obtain concentric reduction and facilitate optimal hip development, or to prevent late osteoarthritis, will continue in the foreseeable future. Therefore future studies will need to demonstrate which techniques offer substantial and which offer only marginal benefits and which will be universally applicable in all countries. Only longer-term followup studies of these treatments will allow an accurate assessment of a reduction in the risk of secondary adult osteoarthritis. The guest editors are indebted to the contributing authors and to Dr. Richard Brand, who guided the processing of this symposium.

Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3.

Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia that can present in childhood with a variable phenotype of short stature and pain and stiffness in the large joints, and often progresses to early-onset osteoarthritis in adulthood. Mutations in the matrilin-3 gene (MATN3) have recently been shown to underlie some forms of autosomal dominant MED. To date all MED mutations in matrilin-3 cluster in the single A-domain, suggesting that they may disrupt the structure and/or function of this important domain. To determine the effects of MATN3 mutations on the structure and function of matrilin-3 we expressed both normal and mutant matrilin-3 in mammalian cells. Wild-type (wt) matrilin-3 was efficiently secreted into conditioned medium, whereas mutant matrilin-3 was retained and accumulated within the cell. Furthermore, when the mutant A-domains were examined individually, they existed primarily in an unfolded conformation. Co-immunoprecipitation experiments demonstrated that the mutant A-domains were specifically associated with ERp72, a chaperone protein known to be involved in mediating disulfide bond formation. Light microscopy of cartilage from an MED patient with a MATN3 mutation showed the presence of intracellular material within the chondrocytes, whilst the overall matrix appeared normal. On electron micrographs, the inclusions noted at the light microscopy level appeared to be dilated cisternae of rough endoplasmic reticulum and immunohistochemical analysis confirmed that the retained protein was matrilin-3. In summary, the data presented in this paper suggest that MED caused by MATN3 mutations is the result of an intracellular retention of the mutant protein.