The aim of this study was to determine the value of scaphoidtrapezium osteoarthritis (ST osteoarthritis) as an early sign of calcium pyrophosphate dihydrate disease (CPDD) in a cohort of patients undergoing surgery for osteoarthritis of the first carpometacarpal joint. We examined whether patients with cartilage calcification of the wrist at the time of operation had ST osteoarthritis, indicating CPDD at an earlier time (retrospective study), and whether patients with ST osteoarthritis but without cartilage calcification at the time of surgery develop radiological or clinical signs of CPDD at a later time (prospective study). From 1 January 1989 to 31 December 1995 a total of 169 patients (from an orthopaedic clinic) with a diagnosis of osteoarthritis of the first carpometacarpal joint were included in the study; 167 underwent surgery and two were treated without. Of the 16 patients showing calcification on surgery and therefore included in the retrospective study, 12 had prior radiographs, of which eight showed ST osteoarthritis. Among these, four had no concomitant cartilage calcification in the prior radiographs. Of the 32 patients in the prospective group having ST osteoarthritis but no calcifications at the time of surgery, 27 could be clinically examined. Of these, two showed cartilage calcifications on the follow-up radiographs of the hands. The presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD, especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist. ST osteoarthritis may then point to the correct diagnosis. PMID:11254235
Peter, A; Simmen, B R; Brühlmann, P; Michel, B A; Stucki, G
Osteoarthritis is a painful and disabling disease that affects millions of patients. Its aetiology is largely unknown, but is most likely multi-factorial. Osteoarthritis poses a dilemma: it often begins attacking different joint tissues long before middle age, but cannot be diagnosed until it becomes symptomatic decades later, at which point structural alterations are already quite advanced. In this review, osteoarthritis
Martin Michaelis; Bernhard J. Kirschbaum; Karl A. Rudolphi; Heike A. Wieland
Osteoarthritis is the most common form of arthritis and is associated with the aging process. Osteoarthritis is a chronic disease causing the deterioration of the cartilage within a joint. For most people, the cause of osteoarthritis is unknown, but metabolic, ...
This study aimed to determine whether osteoarthritis of the scaphoid-trapezium joint (ST osteoarthritis) is associated with calcium pyrophosphate deposition disease (CPDD) in an elderly population with or without concomitant polyarthritis of the finger joints (FIPO). An age- and gender matched case-control study was performed at a university hospital outpatient clinic. Cases and controls were identified from a clinical registry. The case ascertainment process included: (1) chart review for evidence of pyrophosphate crystals from arthrocentesis and/or cartilage calcifications and (2) blinded reading of hand X-rays by three observers for calcification of the triangular fibrocartilage and/or cartilage calcification around the spatium triangulare. Osteoarthritis was graded from 0 to 4 according to the Standard Atlas of Radiographs. The association of ST osteoarthritis with the diagnosis was examined using chi2 tests or the Wilcoxon rank sum test as appropriate. From 65 potential cases, 30 fulfilled the inclusion/exclusion criteria whereas from 185 potential controls, 81 fulfilled the inclusion/exclusion criteria. Thirty controls were matched to cases for gender and age. ST osteoarthritis was much more severe in CPDD (median: 3.0) than in patients with FIPO (median: 0.3) and was strongly associated with the diagnosis (odds ratio 13.8; CI 3.4-59.8). Definite ST osteoarthritis identified CPDD with a sensitivity of 83% and a specificity of 73% with regard to FIPO. It was concluded that the presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD in an elderly, predominantly female population with a high prevalence of FIPO. Especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist, ST osteoarthritis may point to the correct diagnosis. PMID:11206349
Stucki, G; Hardegger, D; Böhni, U; Michel, B A
Osteo-arthritis is the chronic degenerative disease associated with joint pain and loss of joint function. It is caused by 'wear and tear' on a joint. Knee is the most commonly Involved joint. Disease is so crippling that patient is unable to walk independently from bed to bathroom. The major causes of osteo-arthritis are age, gender, obesity, medical condition and hereditary. The signs and symptoms of osteo-arthritis are pain, joint stiffness, joint swelling, and loss of function. No blood tests are helpful in diagnosing osteo-arthritis. Management of osteo-arthritis includes non-pharmacological, pharmacological and surgical. A relatively new procedure is viscosupplementation, in which a preparation of hyaluronic acid is injected into the knee joint. Hyaluronic acid is a naturally occurring substance found in the synovial fluid. It acts as a lubricant to enable bones to move smoothly over each other and a shock absorber for joint loads. The decrease in the elastic and viscous properties of synovial fluid in osteo-arthritis results from both a reduced molecular size and a reduced concentration of hyaluronic acid in the synovial fluid. Viscosupplementation may be a therapeutic option for individuals with osteo-arthritis of the knee. Viscosupplementation has been shown to relieve pain in many patients who cannot get relief from non-medicinal measures or analgesic drugs. This article is to know the mechanism of action, patients' selection criteria, rationale and efficacy of viscosupplimentation in the management of osteo-arthritis of knee. PMID:24765695
Chandra, Rajesh; Mahajan, Sumit
Mechanics means relating to or caused by movement or physical forces. In this paper, I shall contend that OA is almost always caused by increased physical forces causing damage to a joint. While examples of joint injury causing osteoarthritis are numerous, I shall contend that most or almost all osteoarthritis is caused in part by mechanically induced injury to joint tissues. Further, once joint pathology has developed, as is the case for almost all clinical osteoarthritis, pathomechanics overwhelms all other factors in causing disease progression. Treatments which correct the pathomechanics have long lasting favorable effects on pain and joint function compared with treatments that suppress inflammation which have only temporary effects. I shall lastly contend that the mechanically induced joint injury leads to variable inflammatory responses but that the role of this inflammation in worsening structural damage in an already osteoarthritic joint has not yet been proven.
Felson, David T.
Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X/46,XX in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases.
Kinne, Raimund W; Liehr, Thomas; Beensen, Volkmar; Kunisch, Elke; Zimmermann, Thomas; Holland, Heidrun; Pfeiffer, Robert; Stahl, Hans-Detlev; Lungershausen, Wolfgang; Hein, Gert; Roth, Andreas; Emmrich, Frank; Claussen, Uwe; Froster, Ursula G
Osteoarthritis (OA) of the spine involves the facet joints, which are located in the posterior aspect of the vertebral column and, in humans, are the only true synovial joints between adjacent spinal levels. Facet joint osteoarthritis (FJ OA) is widely prevalent in older adults, and is thought to be a common cause of back and neck pain. The prevalence of facet-mediated pain in clinical populations increases with increasing age, suggesting that FJ OA might have a particularly important role in older adults with spinal pain. Nevertheless, to date FJ OA has received far less study than other important OA phenotypes such as knee OA, and other features of spine pathoanatomy such as degenerative disc disease. This Review presents the current state of knowledge of FJ OA, including relevant anatomy, biomechanics, epidemiology, and clinical manifestations. We present the view that the modern concept of FJ OA is consonant with the concept of OA as a failure of the whole joint, and not simply of facet joint cartilage.
Gellhorn, Alfred C.; Katz, Jeffrey N.; Suri, Pradeep
Osteoarthritis (OA) can be a progressive, disabling disease, leading to diminished quality of life, and, for over 500,000 individuals annually in the US, total joint replacement. The etiology of OA will vary among individuals, with potential roles for systemic factors (such as genetics and obesity) as well as for local biomechanical factors (such as muscle weakness, joint laxity and traumatic
Steven B Abramson; Mukundan Attur; Yusuf Yazici
Background Peripheral joint osteoarthritis is a major cause of pain and functional limitation. Few treatments are safe and effective. Objectives To assess the effects of acupuncture for treating peripheral joint osteoarthritis. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE, and EMBASE (both through December 2007), and scanned reference lists of articles. Selection criteria Randomized controlled trials (RCTs) comparing needle acupuncture with a sham, another active treatment, or a waiting list control group in people with osteoarthritis of the knee, hip, or hand. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We calculated standardized mean differences using the differences in improvements between groups. Main results Sixteen trials involving 3498 people were included. Twelve of the RCTs included only people with OA of the knee, 3 only OA of the hip, and 1 a mix of people with OA of the hip and/or knee. In comparison with a sham control, acupuncture showed statistically significant, short-term improvements in osteoarthritis pain (standardized mean difference -0.28, 95% confidence interval -0.45 to -0.11; 0.9 point greater improvement than sham on 20 point scale; absolute percent change 4.59%; relative percent change 10.32%; 9 trials; 1835 participants) and function (-0.28, -0.46 to -0.09; 2.7 point greater improvement on 68 point scale; absolute percent change 3.97%; relative percent change 8.63%); however, these pooled short-term benefits did not meet our predefined thresholds for clinical relevance (i.e. 1.3 points for pain; 3.57 points for function) and there was substantial statistical heterogeneity. Additionally, restriction to sham-controlled trials using shams judged most likely to adequately blind participants to treatment assignment (which were also the same shams judged most likely to have physiological activity), reduced heterogeneity and resulted in pooled short-term benefits of acupuncture that were smaller and non-significant. In comparison with sham acupuncture at the six-month follow-up, acupuncture showed borderline statistically significant, clinically irrelevant improvements in osteoarthritis pain (-0.10, -0.21 to 0.01; 0.4 point greater improvement than sham on 20 point scale; absolute percent change 1.81%; relative percent change 4.06%; 4 trials;1399 participants) and function (-0.11, -0.22 to 0.00; 1.2 point greater improvement than sham on 68 point scale; absolute percent change 1.79%; relative percent change 3.89%). In a secondary analysis versus a waiting list control, acupuncture was associated with statistically significant, clinically relevant short-term improvements in osteoarthritis pain (-0.96, -1.19 to -0.72; 14.5 point greater improvement than sham on 100 point scale; absolute percent change 14.5%; relative percent change 29.14%; 4 trials; 884 participants) and function (-0.89, -1.18 to -0.60; 13.0 point greater improvement than sham on 100 point scale; absolute percent change 13.0%; relative percent change 25.21%). In the head-on comparisons of acupuncture with the ‘supervised osteoarthritis education’ and the ‘physician consultation’ control groups, acupuncture was associated with clinically relevant short- and long-term improvements in pain and function. In the head on comparisons of acupuncture with ‘home exercises/advice leaflet’ and ‘supervised exercise’, acupuncture was associated with similar treatment effects as the controls. Acupuncture as an adjuvant to an exercise based physiotherapy program did not result in any greater improvements than the exercise program alone. Information on safety was reported in only 8 trials and even in these trials there was limited reporting and heterogeneous methods. Authors' conclusions Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our pre-defined
Manheimer, Eric; Cheng, Ke; Linde, Klaus; Lao, Lixing; Yoo, Junghee; Wieland, Susan; van der Windt, Danielle AWM; Berman, Brian M; Bouter, Lex M
Although a large number of studies have been made to identify genetic loci associated with osteoarthritis (OA), there are only a few that have been reported to be associated with OA in many regions and countries. One of the reasons for the lack of success may be small effect sizes. A sufficiently large sample size is required for the genetic epidemiology on OA to elucidate genetic influence regarding the occurrence and progression. PMID:24769680
... Plain Osteoarthritis Reference Summary Introduction Osteoarthritis is a common disease that affects about 20 million Americans and is ... in the spine. Summary Osteoarthritis is a fairly common disease. Recent medical and surgical advances have helped greatly ...
The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population.
Lories, Rik J U; Luyten, Frank P
Osteoarthritis is manifested both by macroscopically visible lesions and by spe- cific histological indicators. Although traditional views of the disease process invoke physical abrasion of joint surfaces, recent studies indicate that tissue- level changes may precede grossly visible lesions of articular cartilage. This study investigates the association between gross and histological indicators of osteoarthritis at the manual interphalangeal joints, and
Brian S. Bentley; Robert V. Hill
Introduction Patellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting. Methods This was a population-based cross-sectional study of 745 adults aged ?50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: 'any OA' and 'moderate to severe OA'. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets. Results Distinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA. Conclusions Early isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.
Pisotriquetral (PT) osteoarthritis (OA) and enthesopathy of the flexor carpi ulnaris (FCU) are pathologies of the hypothenar eminence which both often remain undiagnosed, but can cause ulnar wrist pain. This study determined the prevalence of these pathologies in an older donor population. Twenty wrists were obtained from 10 cadavers with an age ranging from 65 to 94 years. Radiographs were taken of all wrists with the hand in pisotriquetral view and were assessed for osteoarthritic changes of the PT joint and signs of enthesopathy of the FCU. Ten wrists were grossly dissected and the other ten wrists were sagitally sectioned at a thickness of 10 ?m. The wrists were analyzed for type and grade of osteoarthritis and signs of enthesopathy. On radiology, 2 out of 20 wrists showed no signs of osteoarthritis, 5 wrists showed severe changes. One wrist showed signs of enthesopathy. On macroscopy, 9 out of 10 wrists showed osteoartritic changes; 5 of these were severely osteoarthritic. On microscopy, all wrists showed some degree of osteoarthritis of which five showed severe changes. Signs of enthesopathy were seen in seven wrists. Pisotriquetral osteoarthritis has a high prevalence in the older donor population and may therefore be a cause of ulnar sided wrist pain. It should therefore always be considered in the differential diagnosis of ulnar sided wrist pain. By performing clinical examination with these pathologies in mind, diagnosis could be a lot faster. Furthermore, based on our results, radiographs seem to be not accurate in diagnosing osteoarthritis of the PT joint and enthesopathy of the FCU. PMID:24876685
Kofman, K E; Schuurman, A H; Mulder, M C; Verlinde, S A M W; Gierman, L M; van Diest, P J; Bleys, R L A W
Objective: To ascertain the extent to which the "Chingford knee" (that is, contralateral knee of the middle aged, obese, female patient with unilateral knee osteoarthritis (OA)) is a high risk radiographically normal joint as opposed to a knee in which radiographic changes of OA would have been apparent in a more extensive radiographic examination. Methods: Subjects were 180 obese women, aged 45–64 years, with unilateral knee OA, based on the standing anteroposterior (AP) view. Subjects underwent a series of radiographic knee examinations: semiflexed AP, supine lateral, and Hughston (patellofemoral (PF)) views. Bony changes of OA were graded by consensus of two readers. Medial tibiofemoral joint space width was measured by digital image analysis. Knee pain was assessed by the WOMAC OA Index after washout of all OA pain drugs. Results: Despite the absence of evidence of knee OA in the standing AP radiograph, only 32 knees (18%) were radiographically normal in all other views. Ninety four knees (52%) exhibited TF knee OA in the semiflexed AP and/or lateral view. PF OA was seen in 121 knees (67%). Subjects with PF OA reported more severe knee pain than those without PF OA (mean WOMAC scores 9.9 v 8.3, p<0.05). Conclusion: The Chingford knee is not a radiographically normal joint. The high rate of incidence of OA reported previously for this knee (?50% within two years) may also reflect progression of existing OA or changes in radioanatomical positioning at follow up that showed evidence of stable disease that was present at baseline.
Mazzuca, S; Brandt, K; German, N; Buckwalter, K; Lane, K; Katz, B
Abstract Osteoarthritis is the most common joint disorder and a major cause of disability with a major socio-economic impact. In these circumstances is very important to understand its pathogenesis. Although previous research focused primarily on changes in the articular cartilage, more recent studies have highlighted the importance of the subchondral bone, synovium, menisci, ligaments, periarticular muscles and nerves. Now osteoarthritis is viewed as a multifactorial disease affecting the whole joint. Abbreviations: TNF-? – tumor necrosis factor alpha, IL-1 – interleukin -1, IL-6 – interleukin-6, COMP- cartilage oligomeric matrix protein, BSP - bone sialoprotein, MRI - magnetic resonance imaging, NTx - cross-linked N-telopeptide of type I collagen, CTx – C-telopeptide-cross-linked collagen type I, TGF-? – transforming growth factor beta, MMPs- matrix metaloproteinases, VEGF-vascular endothelial growth factor, bFGF - basic fibroblast growth factor.
Man, GS; Mologhianu, G
There is clear evidence that the age period coinciding with the peak age of the menopause is associated with an increased prevalence of osteoarthritis and this fits in with clinical observation of high likelihood of presentation at this age. A number of pieces of biological evidence also support the notion that changes in sex hormone status might influence risk of degenerative disease at peripheral joint sites. There do not appear, however, to be any important epidemiological predictors based on menstrual or obstetric history that might be useful in predicting who these women might be.
Silman, A J; Newman, J
Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis (non-erosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the "itis" suffix. The term "erosion" has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention. PMID:23610748
Rothschild, Bruce M
Osteoarthritis (OA) has long been considered a "wear and tear" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an "inflammatory" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. PMID:23194896
Cartilage link protein of high purity was prepared and used in an enzyme linked immunosorbent assay (ELISA). Antibodies to link protein were sought in the sera of 98 patients with rheumatic disorders; 38 with rheumatoid arthritis (RA), 29 with osteoarthritis (OA), 13 with psoriatic arthritis (PA), nine with ankylosing spondylitis (AS), nine with systemic lupus erythematosus (SLE), and in 83 healthy controls. Antibodies were detected in all groups with the following prevalences: 21/83 normals, 9/38 RA, 7/29 OA, 7/13 PA, 3/9 AS, and 4/9 SLE. No statistically significant differences existed between the groups with regard to either prevalence or mean titre of anti-link antibodies. Serum antibodies to proteoglycan link protein appear to be no more common in patients with rheumatic disorders than in healthy controls. Images
Austin, A K; Hobbs, R N; Anderson, J C; Butler, R C; Ashton, B A
Osteoarthritis (OA) is a debilitating disease in which primarily weight-bearing joints undergo progressive degeneration. Despite the widespread prevalence of OA in the adult population, very little is known about the factors responsible for the generation and maintenance of OA pain. Vasoactive intestinal peptide (VIP) was identified in the synovial fluid of arthritis patients nearly 20 years ago and the aim
Jason J. McDougall; Lisa Watkins; Zongming Li
The role of nuclear medicine in the diagnosis and management of the major arthropathies is critically reviewed, with particular reference to osteoarthritis, rheumatoid and similar forms of arthritis, ankylosing spondylitis, non-specific back pain, gout, the neuropathic joint, avascular necrosis, infection and the consequences of prosthetic joint insertion. Attention is drawn both to practical applications and deficiencies in current techniques and
M. V. Merrick
Three hundred and forty-eight cranial remains from Bronze and Iron Age British, Romano-British, Anglo-Saxon, Eastern Coast Australian aborigines, Medieval Christian Norse, Medieval Scarborough, 17--20th century British and German cultures, were examined for the presence of osteoarthritis in the temporomandibular joints. Cultures exposed to more stringent living conditions and with well-worn teeth had about twice the incidence of osteo-arthritis as the more sophisticated cultures. In general, loss of either molar support or occlusal imbalance were potent aetiological factors in this disease. PMID:380538
Griffin, C J; Powers, R; Kruszynski, R
Osteoarthritis (OA) represents the most prevalent joint disease but neither preventive measures nor disease-modifying OA drugs (DMOADs) are available and a continuing need exists for safe and more effective symptom-modifying therapies. Failures of previous clinical trials on DMOADs in patients with established or advanced disease motivate investigation of mechanisms that maintain joint health. Enhancing such mechanisms may be a novel approach to OA risk reduction. Aging is one of its most important OA risk factors. However, aging of joint cartilage is a process that is distinct from the subsequent cartilage changes that develop as OA is initiated. This review is focused on mechanisms that maintain cell and tissue homeostasis, and how these mechanisms fail during the aging process. Augmentation of homeostasis mechanisms will be discussed as a novel avenue to delay joint aging and reduce OA risk.
Lotz, Martin; Carames, Beatriz
Purpose: The purpose of this study was to investigate the relationship between the presence of joint effusion, joint pain, and protein levels in joint lavage fluid (JL) of patients with internal derangement (ID) and osteoarthritis (OA) of the temporomandibular joint (TMJ).Patients and Methods: Thirty-eight joints in 26 patients with ID and OA of the TMJ were studied. Magnetic resonance imaging
Tetsu Takahashi; Hirokazu Nagai; Hiroshi Seki; Masayuki Fukuda
Osteoarthritis (OA) is the most common joint disease, which is characterized by cartilage loss and concomitant alteration of synovium and subchondral bone metabolism. Pain and stiffness in the affected joints are the main complains. It also causes physical functional impairment. The measurement of joint space width by plain radiography is currently established method for assessing the progression of the disease.
Demet Ofluoglu; Onder Ofluoglu
Background Previous studies in patients with hip and knee osteoarthritis (OA) have advocated the relevance of assessing the number of painful joint sites, other than the primary affected joint, in both research and clinical practice. However, it is unclear whether joint-pain comorbidities can simply be summed up. Methods A total of 401 patients with hip or knee OA completed questionnaires on demographic variables and joint-pain comorbidities. Rasch analysis was performed to evaluate whether a sum score of joint-pain comorbidities can be calculated. Results Self-reported joint-pain comorbidities showed a good fit to the Rasch model and were not biased by gender, age, disease duration, BMI, or patient group. As a group, joint-pain comorbidities covered a reasonable range of severity levels, although the sum score had rather low reliability levels suggesting it cannot discriminate well among patients. Conclusions Joint-pain comorbidities, in other than the primary affected joints, can be summed into a joint pain comorbidity score. Nevertheless, its use is discouraged for individual decision making purposes since its lacks discriminative power in patients with minimal or extreme joint pain.
With the recognition that osteoarthritis is a disease of the whole joint, attention has focused increasingly on features in the joint environment which cause ongoing joint damage and are likely sources of pain. This article reviews current ways of assessing osteoarthritis progression and what factors potentiate it, structural abnormalities that probably produce pain, new understandings of the genetics of osteoarthritis,
David T Felson
The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn?/0Fmod?/?). Given the unavailability of cell lines, we first isolated primary MCCs and found that they were phenotypically unique from hyaline articular chondrocytes isolated from the knee joint. Using Bgn?/0 Fmod?/? MCCs, we discovered the early basis for temporomandibular joint osteoarthritis arises from abnormal and accelerated chondrogenesis. Transforming growth factor (TGF)-?1 is a growth factor that is critical for chondrogenesis and binds to both biglycan and fibromodulin. Our studies revealed the sequestration of TGF-?1 was decreased within the ECM of Bgn?/0 Fmod?/? MCCs, leading to overactive TGF-?1 signal transduction. Using an explant culture system, we found that overactive TGF-?1 signals induced chondrogenesis and ECM turnover in this model. We demonstrated for the first time a comprehensive study revealing the importance of the ECM in maintaining the mandibular condylar cartilage integrity and identified biglycan and fibromodulin as novel key players in regulating chondrogenesis and ECM turnover during temoporomandibular joint osteoarthritis pathology.
Embree, Mildred C.; Kilts, Tina M.; Ono, Mitsuaki; Inkson, Colette A.; Syed-Picard, Fatima; Karsdal, Morten A.; Oldberg, Ake; Bi, Yanming; Young, Marian F.
Through the use of polymerase chain reaction (PCR)-electron spray ionization (ESI)-time of flight (TOF)-mass spectrometry (MS), we identified multiple periodontal pathogens within joint tissues of individuals undergoing replacement arthroplasties of the knee. The most prevalent of the periodontal pathogens were Treponema denticola and Enterococcus faecalis, the latter of which is commonly associated with apical periodontitis. These findings were unique to periprosthetic joint infections (PJI) of the knee and were never observed for PJIs of other lower extremity joints (hip and ankle) or upper extremity joints (shoulder and elbow). These data were confirmed by multiple independent methodologies including fluorescent in situ hybridization (FISH) which showed the bacteria deeply penetrated inside the diseased tissues, and 454-based deep 16S rDNA sequencing. The site-specificity, the tissue investment, and the identical findings by multiple nucleic-acid-based techniques strongly suggests the presence of infecting bacteria within these diseased anatomic sites. Subsequently, as part of a control program using PCR-ESI-TOF-MS, we again detected these same periodontal pathogens in aspirates from patients with osteoarthritis who were undergoing primary arthroplasty of the knee and thus who had no history of orthopedic implants. This latter finding raises the question of whether hematogenic spread of periodontal pathogens to the knee play a primary or secondary- exacerbatory role in osteoarthritis. PMID:24921460
Ehrlich, Garth D; Hu, Fen Z; Sotereanos, Nicholas; Sewicke, Jeffrey; Parvizi, Javad; Nara, Peter L; Arciola, Carla Renata
Osteoarthritis is one of the most common causes of pain originating from the acromioclavicular (AC) joint. An awareness of\\u000a appropriate diagnostic techniques is necessary in order to localize clinical symptoms to the AC joint. Initial treatments\\u000a for AC joint osteoarthritis, which include non-steroidal anti-inflammatory drugs (NSAIDS) and corticosteroids, are recommended\\u000a prior to surgical interventions. Distal clavicle excision, the main surgical
Salvatore Docimo Jr; Dellene Kornitsky; Bennett Futterman; David E. Elkowitz
Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases.
Conde, Javier; Scotece, Morena; Gomez, Rodolfo; Lopez, Veronica; Gomez-Reino, Juan Jesus; Gualillo, Oreste
Background: Osteoarthritis (OA) is a chronic degenerative joint disease that is a clinically and economically important disease. The increased prevalence of OA with aging, coupled to the demographics of aging populations, make OA a high priority health care problem. Viscosupplementation (VS) is a well-established treatment option in knee OA that is included in the professional guidelines for treatment of this joint disease, and could potentially provide a useful alternative in treating such patients with painful OA. Theoretically VS is an approach that should apply to all synovial joints. Objectives: The aim of this review is to assess the efficacy and safety of viscosupplementation with Hylan GF-20 (Synvisc®) in the management of joint pain in osteoarthritis. Methods: The following databases were searched: Medline, Database of Abstract on Reviews and Effectiveness, Cochrane Database of Systematic Reviews. Furthermore, the lists of references of retrieved publications were manually checked for additional references. The search terms Review, Viscosupplementation, Osteoarthritis, Hyaluronic acid, Hyaluronan, Sodium Hyaluronate, Hylan GF-20, Synvisc, intra-articular injection were used to identify all studies relating to the use of Synvisc® viscosupplementation therapy in OA. Results: Hylan GF-20 is a safe and effective treatment for decreasing pain and improving function in patients suffering from knee and hip OA but new evidences are emerging for its use in other joints.
Migliore, A.; Giovannangeli, F.; Granata, M.; Lagana, B.
Proprioception plays an integral role in neuromotor control of the knee joint and deficits in knee joint proprioception are well documented in individuals with knee osteoarthritis (OA). However, the functional relevance of these deficits is not clear. This cross-sectional study evaluated the relationship between knee joint proprioception and pain and disability in a large cohort of individuals with knee OA.
Kim L. Bennell; Rana S. Hinman; Ben R. Metcalf; Kay M. Crossley; Rachelle Buchbinder; Michael Smith; Geoffrey McColl
Osteoarthritis is a heterogeneous disease characterized by variable clinical features, biochemical\\/genetic characteristics,\\u000a and responses to treatments. To optimize palliative effects of current treatments and develop efficacious disease-modifying\\u000a interventions, treatments may need to be tailored to the individual or a subset of osteoarthritic joints. The purpose of this\\u000a review is to explore the current literature on the clinical and physiological variability
Jeffrey B. Driban; Michael R. Sitler; Mary F. Barbe; Easwaran Balasubramanian
Objectives. To investigate the associations of radiographic finger joint osteoarthritis (ROA), hand laterality (right\\/left) and anatomical location within the hand, with finger joint pain. Methods. Radiographs of both hands of 295 female dentists and 248 female teachers were examined for the presence of osteoarthritis in each finger joint, using grades 0 ¼ no OA, 1 ¼ doubtful OA, 2 ¼
Paivi Leino-Arjas; Musculoskeletal Disorders
Objective The objective of this study was to evaluate the usefulness of bone scan procedures for the diagnosis of temporomandibular joint (TMJ) osteoarthritis. Methods From February 2009 to June 2009, 22 patients (4 males and 18 females) from Seoul National University Bundang Hospital, Republic of Korea, were diagnosed with TMJ disorder. They were examined by clinical examination, plain radiograph and bone scan and were categorized into three groups: normal, internal derangement and osteoarthritis. TMJ uptake ratios and asymmetrical indices were calculated. Results There were no significant differences in uptake ratios associated with pain and bone change. However, significant results were obtained when comparing uptake ratios between the osteoarthritis and non-osteoarthritis groups. Conclusion It was concluded from this study that bone scans may help to diagnose osteoarthritis when increased uptake ratios are observed.
Kim, J-H; Kim, Y-K; Kim, S-G; Yun, P-Y; Kim, J-D; Min, J-H
Mesenchymal stem cells have the capacity to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle and adipose tissue. These multipotent cells have been isolated from bone marrow and from other adult tissues including skeletal muscle, fat and synovium. Because of their multipotentiality and capacity for self renewal adult stem cells may represent units of active regeneration of tissues damaged as a result of trauma or disease. In certain degenerative diseases such as osteoarthritis (OA) stem cells are depleted, and have reduced proliferative capacity and reduced ability to differentiate. The delivery of stem cells to these individuals may therefore enhance repair or inhibit the progressive destruction of the joint. We have developed methods for the delivery of mesenchymal stem cell preparations taken from bone marrow to the injured knee joint. This treatment has the potential to stimulate regeneration of cartilage and retard the progressive destruction of the joint that typically occurs following injury. PMID:12708651
Barry, Frank P
Objective: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout). Methods: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n = 283), osteoarthritis (n = 105), and pseudogout (n = 65), and in healthy controls (n = 35). Activity of MMP-1 and MMP-3 in ?2 macroglobulin complexes was measured using specific low molecular weight fluorogenic substrates. ProMMP-1, proMMP-3, and TIMP-1 (tissue inhibitor of metalloproteinase 1) were quantified by immunoassay. Results: Mean levels of proMMP-1, proMMP-3, and TIMP-1 were increased in injury, osteoarthritis, and pseudogout compared with controls. MMP-1 activity was increased in pseudogout and injury groups over control levels, whereas MMP-3 activity was increased only in the pseudogout group. The increase in MMP-1 activity coincided with a decrease in TIMP-1 levels in the injury group. Conclusions: Patients with joint injury have a persistent increase in proMMP-1 and proMMP-3 in synovial fluid and an increase in activated MMPs, which are not inhibited by TIMP. The differences in activation and inhibition patterns between the study groups are consistent with disease specific patterns of MMP activation and/or inhibition in joint pathology.
Tchetverikov, I; Lohmander, L; Verzijl, N; Huizinga, T; TeKoppele, J; Hanemaaijer, R; DeGroot, J
Significant advances have occurred in the symptomatic management of osteoarthritis over the past several decades. However, the development of so called disease-modifying osteoarthritis drugs is in a more formative stage. Although increased knowledge of osteoarthritis pathophysiologic pathways provides more rational opportunity for targeting specific elements of the degenerative process, limitations in our ability to measure disease progression/regression hamper assessment. Development of more sophisticated plain radiographic techniques and the use of additional technologies such as magnetic resonance imaging and gadolinium-enhanced magnetic resonance imaging of cartilage provide potential for more reproducible approaches. Noninvasive biomarkers that reflect structural change are the subject of intense investigation. Studies describing disease-modification effects provide optimism that disease prevention, retardation, and reversal are attainable. PMID:15760576
Moskowitz, Roland W; Hooper, Michele
OBJECTIVES--To test the hypothesis that bone scintigraphy will predict the outcome of osteoarthritis (OA) of the knee joint. METHODS--Ninety four patients (65 women, 29 men; mean age 64.2 years) with established OA of one or both knee joints were examined in 1986, when radiographs and bone scan images (early and late phase) were also obtained. The patients were recalled, re-examined, and had further radiographs taken in 1991. Paired entry and outcome radiographs were read by a single observer, blinded to date order and other data. Scan findings and other entry variables were related to outcome. Progression of OA of the knee was defined as an operation on the knee or a decrease in the tibiofemoral joint space of 2 mm or more. RESULTS--Over the five year study period 10 patients died and nine were lost to follow up. Fifteen had an operation on one or both knees (22 knees). Of the remaining 120 knees (60 patients) analysed radiographically, 14 (12%) had progressed in the manner defined. Of 32 knees with severe scan abnormalities, 28 (88%) showed progression, whereas none of the 55 knees with no scan abnormality at entry progressed. The strong negative predictive power of scintigraphy could not be accounted for by disease severity or any combination of entry variables. Pain severity predicted a subsequent operation, but age, sex, symptom duration, and obesity had no predictive value. CONCLUSIONS--Scintigraphy predicts subsequent loss of joint space in patients with established OA of the knee joint. This is the first description of a powerful predictor of change in this disease. The finding suggests that the activity of the subchondral bone may determine loss of cartilage.
Dieppe, P; Cushnaghan, J; Young, P; Kirwan, J
Osteoarthritis (OA) is the most common arthritis which affects the human body and can affect the temporomandibular joint (TMJ). The diagnosis of TMJ OA is essentially based on clinical examination. However, laboratory tests and radiographic exams are also useful to exclude other diseases. The diagnosis of OA may be difficult because of other TMJ pathologies that can have similar clinical and radiographic aspects. The purpose of this study was to describe an unusual case of bilateral TMJ OA in an advanced stage and discuss its most common clinical, laboratory, and radiographic findings, focusing on their importance in the differential diagnosis with other TMJ diseases. Erosion, sclerosis, osteophytes, flattening, subchondral cysts, and a reduced joint space were some of the radiographic findings in TMJ OA. We concluded that, for the correct differential diagnosis of TMJ OA, it is necessary to unite medical history, physical examination, laboratory tests, and radiographic findings. Computed tomography is the test of choice for evaluating bone involvement and for diagnosing and establishing the degree of the disease.
Ferrazzo, K. L.; Osorio, L. B.; Ferrazzo, V. A.
Osteoarthritis (OA) is a prevalent and disabling condition for which few safe and effective therapeutic options are available. Current approaches are largely palliative and in an effort to mitigate the rising tide of increasing OA prevalence and disease impact, modifying the structural progression of OA has become a focus of drug development. This Review describes disease modification and discusses some
David J. Hunter
\\u000a Osteoarthritis is the most prevalent joint disease in the elderly population. In this chapter, the authors discuss the classification\\u000a criteria and the modifiable and non-modifiable risk factors for osteoarthritis. The relationship between age-associated changes\\u000a in the musculoskeletal system and the development of osteoarthritis is also explained.
Crisostomo Bialog; Anthony M. Reginato
We present for the first time in vivo experimental evidence that quantitative photoacoustic tomography (qPAT) has the potential to detect osteoarthritis (OA) in the finger joints. In this pilot study, 2 OA patients and 4 healthy volunteers were enrolled, and their distal interphalangeal (DIP) joints were examined photoacoustically by a PAT scanner. Tissue absorption coefficient images of all the examined joints, which were unavailable from the conventional PAT, were recovered using our finite element based qPAT approach. The recovered quantitative photoacoustic images revealed significant differences in the tissue absorption coefficient of the joint cavity (cartilage and synovial fluid) between the OA and normal joints. PMID:20639920
Xiao, Jiaying; Yao, Lei; Sun, Yao; Sobel, Eric S; He, Jishan; Jiang, Huabei
Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. The authors compared the prevalence of degenerative joint disease among 17 male runners with 18 male nonrunners. Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. They did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest that long-duration, high-mileage running need to be associated with premature degenerative joint disease in the lower extremities.
Panush, R.S.; Schmidt, C.; Caldwell, J.R.; Edwards, N.L.; Longley, S.; Yonker, R.; Webster, E.; Nauman, J.; Stork, J.; Pettersson, H.
The Knee injury and Osteoarthritis Outcome Score (KOOS) was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short-term and long-term symptoms and function in subjects with knee injury and osteoarthritis. The KOOS holds five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS has been validated for several orthopaedic interventions such as anterior cruciate ligament reconstruction, meniscectomy and total knee replacement. In addition the instrument has been used to evaluate physical therapy, nutritional supplementation and glucosamine supplementation. The effect size is generally largest for the subscale QOL followed by the subscale Pain. The KOOS is a valid, reliable and responsive self-administered instrument that can be used for short-term and long-term follow-up of several types of knee injury including osteoarthritis. The measure is relatively new and further use of the instrument will add knowledge and suggest areas that need to be further explored and improved.
Roos, Ewa M; Lohmander, L Stefan
Osteoarthritis (OA) is a disease of the joints that affects several million individuals worldwide. This disease, which involves mainly the diarthrodial joints, is chronic and develops slowly over decades, making it very difficult to precisely identify the different etiological and risk factors that influence its onset. At present, most therapies for OA are symptomatic. This review will focus on new
Johanne Martel-Pelletier; Lukas M. Wildi; Jean-Pierre Pelletier
Objectives: Previous studies of patients with primary hand and ankle osteoarthritis (OA) have suggested the presence of two major polyarticular OA (POA) phenotypes, designated Type 1 and Type 2. The former, characterised by sentinel distal interphalangeal (IP) (DIP) or proximal IP (PIP) joint OA resembles generalised OA (GOA), whereas the latter characterised by sentinel metacarpophalangeal (MCP)2,3 OA, resembles the arthropathy
Graeme J Carroll; W. H. Breidahl; J. Jazayeri
The management of osteoarthritis of the shoulder in young, active patients is a challenge, and the optimal treatment has yet to be completely established. Many of these patients wish to maintain a high level of activity, and arthroplasty may not be a practical treatment option. It is these patients who may be excellent candidates for joint-preservation procedures in an effort to avoid or delay joint replacement. Several palliative and restorative techniques are currently optional. Joint debridement has shown good results and a combination of arthroscopic debridement with a capsular release, humeral osteoplasty, and transcapsular axillary nerve decompression seems promising when humeral osteophytes are present. Currently, microfracture seems the most studied reparative treatment modality available. Other techniques, such as autologous chondrocyte implantation and osteochondral transfers, have reportedly shown potential but are currently mainly still investigational procedures. This paper gives an overview of the currently available joint preserving surgical techniques for glenohumeral osteoarthritis.
van der Meijden, Olivier A.; Gaskill, Trevor R.; Millett, Peter J.
Although excessive mechanical stress is assumed to be one of the factors contributing to pathogenesis of temporomandibular joint (TMJ) osteoarthritis (OA), no pure mechanical-stress-induced OA model has been developed without surgical manipulation or puncture of the joint cavity. The purpose of this study was to establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive,
T. Fujisawa; T. Kuboki; T. Kasai; W. Sonoyama; S. Kojima; J. Uehara; C. Komori; H. Yatani; T. Hattori; M. Takigawa
In the setting of end-stage osteoarthritis of the knee, total knee arthroplasty is the gold-standard treatment. Recently, a minimally invasive, joint preserving treatment option in the treatment of medial osteoarthritis of the knee has been developed. It is called the KineSpring(®) (Moximed(®) International GmbH, Zurich, Switzerland). The goal of this novel device is to reduce medial compartment loading without significantly affecting the loading of the lateral compartment. In this context, the current authors present a case of device failure using these new implants, which at 7 months post-op necessitated revision surgery with complete removal of the device. PMID:23912420
Citak, Mustafa; Kendoff, Daniel; O Loughlin, Padhraig F; Klatte, Till O; Gebauer, Matthias; Gehrke, Thorsten; Haasper, Carl
Background: Osteoarthritis is the most common joint disorder in the world today and affects over 27 million individuals in the US. The standard treatment of osteoarthritis is the use of NSAIDs, which come with a list of potentially serious side effects, the most common being GI perforation and bleeding. Bromelain, a proteolytic enzyme that is found in the stem of
Scott T Hall
Background Radiographic joint changes are used to diagnose osteoarthritis; however, they alone do not adequately predict who experiences\\u000a symptoms.\\u000a \\u000a \\u000a \\u000a Purpose To examine psychological risk and resilience factors in combination with an objective indicator of disease severity (knee\\u000a X-rays) to determine what factors best account for pain and physical functioning in an early knee osteoarthritis (KOA) population.\\u000a \\u000a \\u000a \\u000a Methods Structural equation modeling was used to
Lisa Johnson Wright; Alex J. Zautra; Scott Going
Summary Objective To estimate the prevalence of erosive disease in first carpometacarpal joints (CMCJs) and investigate its clinical impact compared with radiographic thumb base (TB) osteoarthritis (OA). Patient and methods Standardized assessments with hand radiographs were performed in participants of two population-based cohort studies in North Staffordshire with hand symptoms lasting ?1 day in the past month. Erosive disease was defined as the presence of eroded or remodeled phase in ?1 interphalangeal joint (IPJ) or first CMCJ following the Verbruggen–Veys classification. Hand pain and function were assessed with Australian/Canadian Hand Osteoarthritis Index (AUSCAN). Prevalence was estimated by dividing the number of persons with erosive lesions by population size. Linear and logistic regression analyses were used to contrast clinical determinants between persons with erosions and with radiographic TB OA. Results were presented as mean differences and odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for age, sex and radiographic severity. Results 1,076 participants were studied (60% women, mean age 64.7 years (SD 8.3); 24 persons had erosive disease in the TB. The prevalence of erosive disease in first CMCJs was 2.2% (95% CI 1.4, 3.3). Only 0.5% (95% CI 0.2, 1.2) had erosive disease affecting IPJs and first CMCJs combined. More persons with erosive disease of first CMCJs reported pain in their TB than persons with radiographic TB OA, AUSCAN pain and function scores were similar. Conclusion Erosive disease of first CMCJs was present in 2.2% of subjects with hand pain and was often not accompanied by erosions in IPJs. Erosive disease was associated with TB pain, but not with the level of pain, when compared with radiographic TB OA.
Kwok, W.Y.; Kloppenburg, M.; Marshall, M.; Nicholls, E.; Rosendaal, F.R.; Peat, G.
Osteoarthritis (OA) is not a simple consequence of “wear and tear” or aging—the presence of cytokines suggests a role for\\u000a inflammation. OA is polyarticular in most patients, with metabolic and differential risk factors for prevalence and severity.\\u000a Odds ratios for the prevalence of OA according to formal education levels are similar to those seen for dysregulatory diseases\\u000a such as hypertension,
Osteoarthritis (OA) is a major cause of morbidity worldwide, representing the most common form of arthritis. The radiographic assessment of OA-severity is mainly relied on qualitative criteria, evaluating structural alterations of the joint. In the present study a computer-based image analysis method was developed for the grading of hip OA-severity from radiographic images. The sample of the study comprised 64
Ioannis Boniatis; Elias Panagiotopoulos; Dimitrios Lymberopoulos; George Panayiotakis
Objective Little is known about the natural progression of the disease process of temporomandibular joint (TMJ) osteoarthritis (OA), which affects approximately 1 % of the US population. The goal of this study was to examine the early microarchitectural and molecular changes in the condylar cartilage and subchondral bone in biglycan/fibromodulin (Bgn/Fmod) double-deficient mice, which develop TMJ-OA at 6 months. Methods TMJs from 3 month old (n=44) and 9 month old (n=52) wild-type (WT n=46) and Bgn/Fmod (n=50) double-deficient mice were evaluated. Micro-CT analysis of the subchondral bone (n=24), transmission electron microscopy for condylar cartilage fibril diameters (n=26), and real time PCR analysis for gene expression for bone and cartilage maturation markers (n=45) was performed. Results A statistically significant increase in collagen fibril diameter of the condylar cartilage and a decrease in expression of Parathyroid related protein in the mandibular condylar head were observed in the 3 month Bgn/Fmod double-deficient mice compared to WT controls. The 9 month Bgn/Fmod double-deficient mouse demonstrated an increase in bone volume and total volume in subchondral bone, and an increase in the expression of Collagen Type X and Aggrecan in the mandibular condylar head compared to the WT controls. Conclusion We found that changes in the microarchitecture of the condylar cartilage preceded changes in the subchondral bone during OA in the TMJ in Bgn/Fmod double-deficient mice.
Chen, J.; Gupta, T.; Barasz, J.A.; Kalajzic, Z.; Yeh, W-C.; Drissi, H.; Hand, A.R.; Wadhwa, S.
Museum skull specimens (n = 1,008) of southern sea otters (Enhydra lutris nereis) were examined macroscopically according to defined criteria for the presence, severity and characteristics of temporomandibular joint osteoarthritis (TMJ-OA). The specimens were from stranded young adult to adult animals. Overall, 4.1% of the specimens had findings consistent with TMJ-OA. Of these, 61.0% were from females and 39.0% were from males. In addition, 85.4% of the affected specimens were from adults and 14.6% were from young adults. However, there was no significant association between age and sex with the presence or severity of TMJ-OA. Lesion severity was mild in 41.5%, moderate in 19.5% and severe in 39.0% of affected specimens. The most prominent changes were the presence of osteophytes and subchondral bone defects and porosity. The mandibular condylar process and fossa were affected equally. The lengths of the right and left mandibular heads were significantly associated with age (P = 0.002 and P = 0.003, respectively) and sex (P = 0.0009 and P = 0.001, respectively), but not with the presence of TMJ-OA. The significance of this disease in sea otters remains elusive, but this condition may play an important role in survival of these animals. PMID:23721871
Arzi, B; Winer, J N; Kass, P H; Verstraete, F J M
Osteoarthritis (OA) is a disease of the joints that affects several million individuals worldwide. This disease, which involves mainly the diarthrodial joints, is chronic and develops slowly over decades, making it very difficult to precisely identify the different etiological and risk factors that influence its onset. At present, most therapies for OA are symptomatic. This review will focus on new OA therapeutics in development that are directed toward pain relief as well as others with the potential to reduce or stop the progression of the disease (DMOADs). This article is part of a Special Issue entitled "Osteoarthritis". PMID:22037003
Martel-Pelletier, Johanne; Wildi, Lukas M; Pelletier, Jean-Pierre
Background: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD’s). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint
Eric Abadie; Dominique Ethgen; Bernard Avouac; Gilles Bouvenot; Jaime Branco; Olivier Bruyere; Gonzalo Calvo; Jean-Pierre Devogelaer; Renee Lilianee Dreiser; Gabriel Herrero-Beaumont; Andre Kahan; Godfried Kreutz; Andrea Laslop; Ernst Martin Lemmel; George Nuki; Leo Van De Putte; Luc Vanhaelst; Jean-Yves Reginster
This issue provides a clinical overview of Osteoarthritis focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, https://mksap.acponline.org/, and other resources referenced in each issue of In the Clinic. PMID:24979462
Gelber, Allan C
Objective Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results Osteochondral fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P=0.0012), while joint circumference (P<0.0001) and effusion scores (P<0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery.
Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.
Osteoarthritis of the hands is very common, particularly in elderly people. Little is known though, is the subset of erosive osteoarthritis (EOA), which predicts a poorer prognosis and causes much more discomfort. Even less known is the fact that this subset can evolve into spontaneous ankylosis. We describe eight women (average age 62.6, range 54-74 years) with EOA and spontaneous ankylosis of the proximal interphalangeal (PIP) and/or distal interphalangeal (DIP) joints. In total, 21 PIP joints (0-7 per patient) were found with EOA and nine PIP joints (0-3 per patient) with ankylosis. In one patient, ankylosis of the PIP was already seen at the first presentation. In the other cases, it took an average of 77.4 months (range 34-119) for EOA to develop into ankylosis of the PIP. For DIP joints, the numbers were 17 joints (1-4 per patient) with EOA and three joints (0-1 per patient) with ankylosis, respectively. In one patient, ankylosis of the DIP was already seen at the first presentation. Ankylosis was found significantly more often on the left hand (n?=?10) compared to the right hand (n?=?2; p?0.0005), while all the patients were right handed. No difference in handedness was found for the occurrence of EOA. Although rare, PIP or DIP joint with EOA can-over the course of several painful years-develop into a spontaneous pain-free ankylosis. Ankylosis was more commonly found in the left hand than in the right hand, probably due right handedness. PMID:24752344
Ter Borg, E-J; Bijlsma, J W J
Traditional imaging, represented by radiographs, provides a very concise description of anatomical pathology of bony structures. Both degenerative and inflammatory joint diseases are characterized by progressive joint destruction, and valid, reproducible measures of disease impact are available. Much effort has been expended to develop scoring systems for joint destruction in both osteoarthritis and rheumatoid arthritis, and the most common internationally accepted semiobjective scores are presented. The anatomical pathology mirrors the past activity of the disease, and advanced imaging gives an impression of the actual disease processes, which subsequently lead to the damage. Such information is required to facilitate the development of efficient therapy against arthritis. Newer technology, exemplified by MRI and ultrasound Doppler, supplements images of structural change with functional data of ongoing disease activity. This chapter focuses on the possibilities for quantification of images in MRI and ultrasound, in which postcontrast enhancement and Doppler information, respectively, are of special interest for the evaluation of the inflammatory changes of arthritis. To save time and eliminate human bias, automation is mandatory. In ultrasound, semiautomatic evaluations are coming that allow for a real-time, reproducible estimate of disease activity. With MRI fully automated algorithms have been developed for processing of data of bony structures, cartilage, and soft tissue, and are currently being implemented into everyday clinical practice. PMID:19250239
Kubassova, Olga; Boesen, Mikael; Peloschek, Philipp; Langs, Georg; Cimmino, Marco A; Bliddal, Henning; Torp-Pedersen, Søren
... beginning to appreciate that structural differences of the knee joint and thigh muscles, differences in the ways male and female athletes move, and other sex differences explain why women are more susceptible to anterior cruciate ligament injuries than men. They are also developing strategies to ...
Osteoarthritis (OA) is a prevalent and disabling condition for which few safe and effective therapeutic options are available. Current approaches are largely palliative and in an effort to mitigate the rising tide of increasing OA prevalence and disease impact, modifying the structural progression of OA has become a focus of drug development. This Review describes disease modification and discusses some of the challenges involved in the discovery and development of disease-modifying OA drugs (DMOADs). A variety of targeted agents are in mature phases of development; specific agents that are beyond preclinical development in phase II and III trials and show promise as potential DMOADs are discussed. A research agenda with respect to disease modification in OA is also provided, and some of the future challenges we face in this field are discussed. PMID:21079644
Hunter, David J
We evaluated the efficacy of intra-articular viscosupplementation with sodium hyaluronate in the management of osteoarthritis of the subtalar joint. A total of 22 patients, aged 22 to 72 years (mean 53), with symptomatic subtalar joint osteoarthritis of 1 to 20 years' duration (mean 4.2) and a severity of Kellgren-Lawrence grade II to IV and Paley and Hall grade 1 to 3, were entered into the present study. Intra-articular injections of 10 mg sodium hyaluronate (Euflexxa) were administered weekly to the subtalar joint for 3 weeks. Clinical evaluations and objective scoring using the American Orthopaedic Foot and Ankle Society Ankle Hindfoot score, visual analog scale, maximum walking distance, pain frequency, and subjective global function were performed at baseline and 4, 12, and 28 weeks after treatment. Significant improvement occurred in the American Orthopaedic Foot and Ankle Society Ankle Hindfoot scores (baseline score 54.5, week 28 score 73.7; p < .01) and visual analog scale assessment (baseline pain, stiffness, and function score 5.4, 5.8, and 6.9; week 28 pain, stiffness, and function score 2.8, 3.1, and 3.8, respectively; p < .01). Global assessment showed improvement in 18 of 20 patients completing the study (p < .01). The tolerated walking distance significantly improved from 770 ± 886 m to 2,075 ± 1,500 m (p < .001). Improvement lasted for more than 6 months. Intra-articular injection of sodium hyaluronate should be considered in the conservative management of subtalar osteoarthritis. PMID:23333279
Mei-Dan, Omer; Carmont, Michael; Laver, Lior; Mann, Gideon; Maffulli, Nicola; Nyska, Meir
Nonhuman primates are a valuable model for osteoarthritis. Osteoarthritis has been extensively studied in nonhuman primates in both naturally occurring and induced disease states. However, little published information describes naturally occurring osteoarthritis of the coxofemoral joints of nonhuman primates. We report a case of naturally occurring coxofemoral joint osteoarthritis in a rhesus macaque. This case radiographically resembled hip dysplasia reported in other species and demonstrated a rapid progression in severity of lameness, with accompanying loss of muscle mass in the affected limb. We excised the femoral head and neck to alleviate the pain that accompanied the osteoarthritis. Physical therapy was initiated, and dual-energy X-ray absorptiometry and video recordings were performed to evaluate the macaque's response to surgical intervention. By 3 mo postoperatively, the macaque had regained full use of the affected limb.
Dufour, Jason P; Phillippi-Falkenstein, Kathrine; Bohm, Rudolf P; Veazey, Ronald S; Carnal, Jean
The current study investigated the compensatory load redistribution due to osteoarthritis of the elbow joint using ground reaction forces of all four legs, simultaneously measured on a treadmill with integrated force plates. Three groups of dogs were used: the first group was clinically sound; the second group suffered from a naturally occurring osteoarthritis of the elbow joint, and a reversible
Barbara A. Bockstahler; A. Vobornik; Marion Müller; Christian Peham
Background: Initial reports have shown the efficacy of fixed distraction for the treatment of ankle osteoarthritis. We hypothesized that allowing ankle motion during distraction would result in significant improvements in outcomes compared with distraction without ankle motion. Methods: We conducted a prospective randomized controlled trial comparing the outcomes for patients with advanced ankle osteoarthritis who were managed with anterior osteophyte removal and either (1) fixed ankle distraction or (2) ankle distraction permitting joint motion. Thirty-six patients were randomized to treatment with either fixed distraction or distraction with motion. The patients were followed for twenty-four months after frame removal. The Ankle Osteoarthritis Scale (AOS) was the main outcome variable. Results: Two years after frame removal, subjects in both groups showed significant improvement compared with the status before treatment (p < 0.02 for both groups). The motion-distraction group had significantly better AOS scores than the fixed-distraction group at twenty-six, fifty-two, and 104 weeks after frame removal (p < 0.01 at each time point). At 104 weeks, the motion-distraction group had an overall mean improvement of 56.6% in the AOS score, whereas the fixed-distraction group had a mean improvement of 22.9% (p < 0.01). Conclusion: Distraction improved the patient-reported outcomes of treatment of ankle osteoarthritis. Adding ankle motion to distraction showed an early and sustained beneficial effect on outcome. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Saltzman, Charles L.; Hillis, Stephen L.; Stolley, Mary P.; Anderson, Donald D.; Amendola, Annunziato
Osteoarthritis (OA) is a slowly, progressive, ultimately degenerative disorder of movable joints, mainly characterized by joint pain and functional limitation and affecting all joint structures not just articular cartilage, but also the subchondral bone, ligaments, capsule, synovial membrane, and menisci. OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced. There are currently no pharmacological interventions available to patients for modifying the underlying disease (DMOADs) in relation to major drug development challenges. The current regulatory draft guidances for clinical development programs for DMOAD agents suggest radiographic joint space narrowing (JSN) as a primary endpoint. However, research efforts must continue to characterize imaging alternatives with greater sensitivity to change to enable development of new DMOADs. Past experience with DMOAD clinical trials indicate that pharmacologic agents must demonstrate pristine safety, and that consideration for special populations is important to avoid failed studies. More research is needed to determine what constitutes clinically meaningfulness for DMOAD activity in particular as it relates to OA progression. Current research pursues a variety of molecular targets including anti-catabolic agents to slow or halt OA progression and anabolic drugs to induce cartilage re-growth. PMID:20199396
Le Graverand-Gastineau, Marie-Pierre Hellio
Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We provide a review of recent data reported on the investigation of DMOADs in clinical trials, including compounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin, inhibitors of inducible nitric oxide synthase (iNOS), doxycycline, glucosamine, and diacereine. We discuss the challenges associated with the drug development process in general and with DMOADs in particular, and we advance the need for a new development paradigm for DMOADs. Two central elements in this paradigm are a stronger focus on the biology of the joint and the application of new and more sensitive biomarkers allowing redesign of clinical trials in osteoarthritis. PMID:18590824
Qvist, Per; Bay-Jensen, Anne-Christine; Christiansen, Claus; Dam, Erik B; Pastoureau, Philippe; Karsdal, Morten A
Objective To compare quantitative estimates of change in joint space width (JSW) with semiquantitative ratings of the progression of joint space narrowing (JSN) with respect to sensitivity to change over time. Methods 431 obese women 45 to 64 years old with unilateral radiographic knee osteoarthritis were randomised to 30 months' treatment with doxycycline 100 mg twice daily or placebo. Quantitative estimates of change in JSW in the medial tibiofemoral compartment from fluoroscopically assisted semiflexed AP radiographs were obtained at baseline and 16 and 30 months after randomisation. Radiographic JSN was rated (0–3 scale) in the same images by two readers using a standard atlas. Changes in overall severity of knee osteoarthritis were derived from gradings of conventional standing AP radiographs at baseline and 30 months, with blinding to treatment group and chronological order of examination. Results Follow up radiographs were obtained from 381 subjects (88%) at 16 months and from 367 (85%) at 30 months. The treatment groups did not differ in the frequency of significant loss of JSW by dichotomous criteria (?0.5 mm, ?1.0 mm, ?20%, or ?50% of baseline JSW). Progressors and non?progressors, as defined by each of the dichotomous outcomes, differed significantly in mean value for quantitative measurement of change in JSW at 30 months (p?0.001). Conclusions Quantitative and semiquantitative indicators of progression of osteoarthritis in fluoroscopically standardised radiographs of osteoarthritic knees are highly related, but the effect of doxycycline on articular cartilage thickness was more easily detected with quantitative measurements of change in JSW than with semiquantitative ratings of JSN.
Mazzuca, S A; Brandt, K D; Katz, B P; Lane, K A; Buckwalter, K A
There is mounting evidence that vascular pathology plays a role in the initiation and\\/or progression of the major disease of joints: osteoarthritis (OA). Potential mechanisms are: episodically reduced blood flow through the small vessels in the subchondral bone at the ends of long bones, and related to this, reduced interstitial fluid flow in subchondral bone. Blood flow may be reduced
D. M. Findlay
Individuals with knee OA often exhibit greater co-contraction of antagonistic muscle groups surrounding the affected joint which may lead to increases in dynamic joint stiffness. These detrimental changes in the symptomatic limb may also exist in the contralateral limb, thus contributing to its risk of developing knee osteoarthritis. The purpose of this study is to investigate the interlimb symmetry of dynamic knee joint stiffness and muscular co-contraction in knee osteoarthritis. Muscular co-contraction and dynamic knee joint stiffness were assessed in 17 subjects with mild to moderate unilateral medial compartment knee osteoarthritis and 17 healthy control subjects while walking at a controlled speed (1.0m/s). Paired and independent t-tests determined whether significant differences exist between groups (p<0.05). There were no significant differences in dynamic joint stiffness or co-contraction between the OA symptomatic and OA contralateral group (p=0.247, p=0.874, respectively) or between the OA contralateral and healthy group (p=0.635, p=0.078, respectively). There was no significant difference in stiffness between the OA symptomatic and healthy group (p=0.600); however, there was a slight trend toward enhanced co-contraction in the symptomatic knees compared to the healthy group (p=0.051). Subjects with mild to moderate knee osteoarthritis maintain symmetric control strategies during gait. PMID:24768278
Collins, A T; Richardson, R T; Higginson, J S
Although older age is the greatest risk factor for OA, OA is not an inevitable consequence of growing old. Radiographic changes of OA, particularly osteophytes, are common in the aged population but symptoms of joint pain may be independent of radiographic severity in many older adults. Aging changes in the musculoskeletal system increase the propensity to OA but the joints affected and the severity of disease are most closely related to other OA risk factors such as joint injury, obesity, genetics, and anatomical factors that affect joint mechanics. The aging changes in joint tissues that contribute to the development of OA include cell senescence that results in development of the senescent secretory phenotype and aging changes in the matrix, including formation of advanced glycation end-products that affect the mechanical properties of joint tissues. An improved mechanistic understanding of joint aging will likely reveal new therapeutic targets to slow or halt disease progression. The ability to slow progression of OA in older adults will have enormous public health implications given the aging of our population and the increase in other OA risk factors such as obesity.
Anderson, A. Shane; Loeser, Richard F.
OBJECTIVE--To test reliability of joint space width (JSW) measurements as a predictor of cartilage thickness in knees of patients with osteoarthritis (OA), using high definition microfocal radiography. METHOD--JSW was measured from weight bearing plain film macroradiographs taken in the tunnel view and compared with the sum of femoral and tibial cartilage thicknesses measured from double contrast macroarthrograms of the same
J C Buckland-Wright; D G Macfarlane; J A Lynch; M K Jasani; C R Bradshaw
OBJECTIVE—To assess the effect of standing position on joint space width (JSW) measurements of the hips with and without osteoarthritis (OA) on pelvic radiographs.?METHODS—Adult patients aged 18 or more had pelvic anteroposterior conventional radiographs standing and supine performed by a single radiologist in the same radiology unit according to standardised guidelines. JSW measurements in mm were made by a single reader blind to patients' identity and type of view, using a 0.1 mm graduated magnifying glass directly laid over the radiograph, at the narrowest point for OA hips or at the vertical joint space for non-OA hips. Agreement of JSW between both views was assessed using the Bland and Altman graphical analysis.?RESULTS—JSW was greater on standing than supine radiographs, for example, 7.1% for OA hips. Mean (SD) differences and limits of agreement (mm) between both views were 0.08 (0.27) and ?0.46 to 0.62 for the 70 non-OA hips, 0.02 (0.31) and ?0.60 to 0.64 for the 46 OA hips. Corresponding 95% confidence intervals of mean differences were 0.02, ?0.14 mm and ?0.07, ?0.11 mm.?CONCLUSIONS—Measurements of JSW of the hip on pelvic standing and supine radiographs are concordant. Changes less than or equal to 0.64 mm between the two views are similar or inferior to radiological progression of OA.?? Keywords: hip; osteoarthritis; joint space width; radiograph
Auleley, G.; Rousselin, B.; Ayral, X.; Edouard-Noel, R.; Dougados, M.; Ravaud, P.
Introduction Osteoarthritis of the talonavicular joint caused by inflammatory, degenerative, and post-traumatic arthritis has been commonly described, and isolated arthrodesis for talonavicular joint has usually been performed for such conditions. However, arthritis accompanied by pseudarthrosis of the navicular bone is an extremely rare case, and to the best of our knowledge, isolated arthrodesis for this situation has not been previously described in any published reports. Case presentation The patient was a 39-year-old Japanese man. He had complained of pain in his left middle foot since a fall from his motorcycle six months previously. Radiographs and computed tomography (CT) scans revealed pseudarthrosis of the navicular bone. MRI indicated mild arthritic change in the talonavicular joint and avascular necrosis of the navicular bone. We performed an isolated arthrodesis of the talonavicular joint with two 6.5 mm cancellous screws. One year after the operation, radiographical bone union had been obtained, and the patient reported no pain and complete satisfaction with the result. Conclusions Isolated talonavicular arthrodesis is one of the effective procedures for the treatment of traumatic talonavicular arthritis with pseudarthrosis of the navicular bone both in providing pain relief and functional improvement.
OBJECTIVE: To assess the usefulness of pyridinoline (Pyr) and deoxypyridinoline (Dpyr), intermolecular crosslinks of collagen, as markers in the evaluation of arthritis, by studying their distribution in tissues from knee joints. METHODS: Joint tissues (cartilage, bone, synovium) were obtained during operation from 10 patients with osteoarthritis (OA) and 10 patients with rheumatoid arthritis (RA). Synovium was also obtained from 10 non-arthritic (NA) subjects. Hydroxyproline was measured in hydrolysed tissue samples and converted to an equivalent collagen content. The amounts of Pyr and Dpyr crosslinks measured in the hydrolysed samples using a fluorescence technique were expressed as mumol/mol of collagen. RESULTS: Pyr and Dpyr were distributed in all three tissues, but in different amounts. The ratio of the contents of Pyr and (Pyr:Dpyr) was 50:1 in cartilage, 3:1 in bone, and 25:1 in synovium. OA cartilage had a greater Dpyr content than the RA cartilage, but there was no other significant difference in the contents of Pyr and Dpyr and the ratio Pyr:Dpyr in the joint tissues from patients with OA or RA. In synovium, there was no significant difference between the contents of Pyr and Dpyr and the Pyr:Dpyr ratio among OA, RA, and NA tissues. CONCLUSION: Both Pyr and Dpyr were located in cartilage, bone, and synovium. A significant amount of Pyr and Dpyr in these joint tissues, especially in synovium, may contribute to the urinary excretion of those crosslinks that is observed in arthritis.
Takahashi, M; Kushida, K; Hoshino, H; Suzuki, M; Sano, M; Miyamoto, S; Inoue, T
Background Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures. Scope Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis. Findings The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement. Conclusion The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process.
Cooper, Cyrus; Adachi, Jonathan D.; Bardin, Thomas; Berenbaum, Francis; Flamion, Bruno; Jonsson, Helgi; Kanis, John A.; Pelousse, Franz; Lems, Willem F.; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Reiter, Susanne; Reginster, Jean-Yves; Rizzoli, Rene; Bruyere, Olivier
Basic calcium phosphate (BCP) crystals include partially carbonate-substituted hydroxyapatite, octacalcium phosphate, and\\u000a tricalcium phosphate. They may form deposits, which are frequently asymptomatic but may give rise to a number of clinical\\u000a syndromes including calcific periarthritis, Milwaukee shoulder syndrome, and osteoarthritis, in and around joints. Recent\\u000a data suggest that magnesium whitlockite, another form of BCP, may play a pathologic role in
Eamonn S. Molloy; Geraldine M. McCarthy
Objective. The purpose of this study was to investigate the correlations between the concentrations of pain-related mediators in synovial fluid and the degree of synovitis and between the concentrations of pain-related mediators and the degree of joint pain in patients with internal derangement and osteoarthritis of the temporomandibular joint. Study Design. The concentrations of substance P, serotonin, bradykinin, leukotriene B4
Masaaki Nishimura; Natsuki Segami; Keiseki Kaneyama; Tohikazu Suzuki; Masahisa Miyamaru
It is important to know the magnitude and patterns of joint loading in people with knee osteoarthritis (OA), since altered loads are implicated in onset and progression of the disease. We used an EMG-driven forward dynamics model to estimate joint loads during walking in a subject with knee OA and a healthy control subject. Kinematic, kinetic, and surface EMG data were used to predict muscle forces using a Hill-type muscle model. The muscle forces were used to balance the frontal plane moment to obtain medial and lateral condylar loads. Loads were normalized to body weight (BWs) and the mean of three trials taken. The OA subject had greater medial and lower lateral loads compared to the control subject. Seventy-five to 80% of the total load was borne on the medial compartment in the control subject, compared to 90-95% in the OA subject. In fact, complete lateral unloading occurred during midstance for the OA subject. Loading for the healthy subject was consistent with the data from instrumented knee studies. In the future, the model can be used to analyze the impact of various interventions to reduce the loads on the medial compartment in people with knee OA. PMID:21901754
Kumar, Deepak; Rudolph, Katherine S; Manal, Kurt T
Osteoarthritis [MIM 165720] is a common late-onset articular joint disease for which no pharmaceutical intervention is available to attenuate the cartilage degeneration. To identify a new osteoarthritis susceptibility locus, a genome-wide linkage scan and combined linkage association analysis were applied to 179 affected siblings and four trios with generalized osteoarthritis (The GARP study). We tested, for confirmation by association, 1478
I. Meulenbelt; J. L. Min; S. D. Bos; N. Riyazi; J. J. Houwing-Duistermaat; wijk van der H. J; H. M. Kroon; M. Nakajima; S. Ikegawa; A. G. Uitterlinden; J. B. J. van Meurs; Deure van der W. M; T. J. Visser; A. B. Seymour; N. Lakenberg; R. van der Breggen; D. Kremer; P. Tikka-Kleemola; M. Kloppenburg; J. Loughlin; P. E. Slagboom
Objective The objective of this study was to assess, with knee radiography, joint space narrowing (JSN) and its relationship to meniscal\\u000a tears, anterior cruciate ligament (ACL) ruptures, articular cartilage erosion, and duration of pain in patients with knee\\u000a osteoarthritis.\\u000a \\u000a \\u000a \\u000a Materials and methods A total of 140 patients who had knee osteoarthritis and underwent primary total knee replacement (TKR) surgery, with unicompartmental\\u000a medial
Wing P. Chan; Guo-Shu Huang; Shu-Mei Hsu; Yue-Cune Chang; Wei-Pin Ho
Introduction Arthritis in the trapeziometacarpal joint of the thumb can cause swelling and loss of motion. Treatment options include arthrodesis, replacement arthroplasty and interposition arthroplasty. Our objective in this clinical study was to determine outcomes after trapezial arthroplasty with a silicone rubber implant and the relationship between self-reported and measured outcomes. Methods At the Hand and Upper Limb Centre, St. Joseph's Hospital, London, Ont., a tertiary care centre, we reviewed a series of 26 patients with advanced osteoarthritis who underwent silicone rubber trapezial arthroplasty. The follow-up averaged 6.5 years. We assessed the outcomes subjectively, and by clinical, functional and radiographic examination. Results Although 88% of patients reported some improvement in pain and satisfaction, when quantified the improvement was less impressive: only 5.7 (on a visual analogue scale of 1–10, poor–excellent) for pain and 5.6 for satisfaction. Superior subjective results were reported by patients older than 60 years. Osteoarthritic changes had caused pronounced functional impairment in the hands of patients who underwent surgery and those who did not, so that any long-term benefit of surgery was not measurable. Patients had difficulty manipulating both small and large objects on the Jebsen's hand function test. Peri-implant and carpal radiographic lytic changes were observed in 90% of patients. Six patients (20%) required revision surgery (3 early, 3 late), including 1 with a pathologic scaphoid fracture. Conclusions Although clinical, functional and radiographic results were poor, they did not predict either satisfaction or pain improvement reported by patients, illustrating the need for a comprehensive standardized outcome evaluation to make informed decisions on the value of surgical intervention for osteoarthritis of the trapeziometacarpal joint.
MacDermid, Joy C.; Roth, James H.; Rampersaud, Y. Raj; Bain, Gregory I.
The incidence of age-related musculoskeletal impairment is steadily rising throughout the world. Musculoskeletal conditions are closely linked with aging and inflammation. They are leading causes of morbidity and disability in man and beast. Aging is a major contributor to musculoskeletal degeneration and the development of osteoarthritis (OA). OA is a degenerative disease that involves structural changes to joint tissues including synovial inflammation, catabolic destruction of articular cartilage and alterations in subchondral bone. Cartilage degradation and structural changes in subchondral bone result in the production of fragments of extracellular matrix molecules. Some of these biochemical markers or “biomarkers” can be detected in blood, serum, synovial fluid, and urine and may be useful markers of disease progression. The ability to detect biomarkers of cartilage degradation in body fluids may enable clinicians to diagnose sub-clinical OA as well as determining the course of disease progression. New biomarkers that indicate early responses of the joint cartilage to degeneration will be useful in detecting early, pre-radiographic changes. Systems biology is increasingly applied in basic cartilage biology and OA research. Proteomic techniques have the potential to improve our understanding of OA physiopathology and its underlying mechanisms. Proteomics can also facilitate the discovery of disease-specific biomarkers and help identify new therapeutic targets. Proteomic studies of cartilage and other joint tissues may be particularly relevant in diagnostic orthopedics and therapeutic research. This perspective article discusses the relevance and potential of proteomics for studying age-related musculoskeletal diseases such as OA and reviews the contributions of key investigators in the field.
Background In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee. Methods In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years) with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15) on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed. Results Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65) within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively), the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52). Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed. Conclusions According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.
Objectives. Joint pain comorbidity (JPC) is common in individuals with knee OA. This study investigates the longitudinal association between JPC and health-related quality of life (HRQoL) and physical activity levels in individuals with knee OA. Methods. Data from the progression cohort of the Osteoarthritis Initiative (n = 1233; age 61 years and 58% females) were analysed. JPC was considered present if individuals reported pain in three or more joint groups, including the knee joints. HRQoL was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life subscale, and self-reported physical activity was determined using the Physical Activity Scale for the Elderly (PASE). Generalized estimating equation (GEE) analyses were performed, adjusted for age, sex, duration of complaints, medical comorbidity, and physical and mental functioning. Results. Over the 4-year period, 32% of participants never reported JPC, whereas 12% always reported JPC. GEE modelling demonstrated that having JPC was negatively associated with HRQoL [regression coefficient ? (95% CI) ?3.57 (?4.69, ?2.44)] and not associated with physical activity [?1.32 (?6.61, 3.98)]. Conclusion. Considering the impact of JPC on the HRQoL of individuals with knee OA, the assessment of JPC in individuals with knee OA might be a daily routine.
Hoogeboom, Thomas J.; den Broeder, Alfons A.; de Bie, Rob A.
Little effort has gone into the development of more effective analgesics for osteoarthritic pain. Efforts to improve symptomatic therapy for osteoarthritis have been deflected or diluted by a decision to pursue the development of disease-modifying OA drugs (DMOADs). These agents' main mechanism of action is directed not at the relief of joint pain but at slowing the progression of structural damage. This article describes the results of a recent randomized placebo-controlled designed to examine the DMOAD effect in humans of the tetracycline antibiotic doxycycline, and reviews the experience gained from other recent DMOAD trials in humans. PMID:16504832
Brandt, Kenneth D; Mazzuca, Steven A
Osteoarthritis (OA) is an age-related condition and the leading cause of pain, disability and shortening of adult working life in the UK. The incidence of OA increases with age, with 25% of the over 50s population having OA of the knee. Despite promising preclinical data covering various molecule classes, there is regrettably at present no approved disease-modifying OA drugs (DMOADs). With the advent of next generation sequencing technologies, other therapeutic areas, in particular oncology, have experienced a paradigm shift towards defining disease by its molecular composition. This paradigm shift has enabled high resolution patient stratification and supported the emergence of personalised or precision medicines. In this review we evaluate the potential for the development of OA therapeutics to undergo a similar paradigm shift given that OA is increasingly being recognised as a heterogeneous disease affecting multiple joint tissues. We highlight the evidence for the role of these tissues in OA pathology as different "hallmarks" of OA biology and review the opportunities to identify and develop targeted disease-modifying pharmacological therapeutics. Finally, we consider whether it is feasible to expect the emergence of personalised disease-modifying medicines for patients with OA and how this might be achieved. PMID:24632293
Tonge, D P; Pearson, M J; Jones, S W
Purpose Previous positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis\\u000a (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation.\\u000a \\u000a \\u000a \\u000a Procedures FDG-PET scans of hands and wrists were performed in patients with RA and
E. H. Elzinga; C. J. van der Laken; E. F. I. Comans; A. A. Lammertsma; B. A. C. Dijkmans; A. E. Voskuyl
Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB2 receptors may have therapeutic potential for treating OA pain. PMID:24282543
Burston, James J; Sagar, Devi Rani; Shao, Pin; Bai, Mingfeng; King, Emma; Brailsford, Louis; Turner, Jenna M; Hathway, Gareth J; Bennett, Andrew J; Walsh, David A; Kendall, David A; Lichtman, Aron; Chapman, Victoria
Background People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M?=?4.1, SD?=?2.4 versus M?=?3.1, SD?=?2.4; p?0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B?=?0.37, p?=?0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.
Classical surgical options for osteoarthritis of the thumb carpometacarpal joint irreversibly des-troy the normal anatomy of the wrist. Although overall satisfaction rates with these procedures are high, time to achieve normal hand function and ability to work may take 12-16 weeks. Therefore a non-ablative less invasive surgical option would be interesting. We injected adipose tissue into the thumb carpometacarpal joint in a pilot study. Average preoperative pain according to a VAS was 7.4 in action and 3.8 during rest. It was reduced considerably to 2.2 in action and 0 during rest after 1 month and to 2.4 and 0.8, respectively, 3 months after surgery. The reduction of pain in action was statistically significant 1 month after injection (p=0.042). Average grip strength was 78% and pinch grip strength was 74% in comparison to the healthy side preop-eratively, 89% and 80% one month postoperatively and 93% and 89%, respectively, 3 months postoperatively. An average DASH score of 58 preoperative was reduced to 36 after 1 month and 33 after 3 months. The amelioration of hand function was statistically significant (p=0.042 and p=0.043). There were no side effects and all patients were satisfied. These preliminary results are promising. Adipose tissue injection seems to be an alternative to consider, especially as it does not exclude classical surgical options in cases of failure. PMID:24777461
Herold, C; Fleischer, O; Allert, S
OBJECTIVE--To test the hypothesis that farmers are at high risk of hip osteoarthritis and to investigate possible causes for such a hazard. DESIGN--Cross sectional survey. SETTING--Five rural general practices. SUBJECTS--167 male farmers aged 60-76 and 83 controls from mainly sedentary jobs. All those without previous hip replacement underwent radiography of the hip. MAIN OUTCOME MEASURES--Hip replacement for osteoarthritis or radiological
P. Croft; D. Coggon; M. Cruddas; C. Cooper
A computer-based system was designed for the grading and quantification of hip osteoarthritis (OA) severity. Employing an active-contours segmentation model, 64 hip joint space (HJS) images (18 normal, 46 osteoarthritic) were obtained from the digitized radiographs of 32 unilateral and bilateral OA-patients. Shape features, generated from the HJS-images, and a hierarchical decision tree structure was used for the grading of
Ioannis Boniatis; Dionisis Cavouras; Lena Costaridou; Ioannis Kalatzis; Elias Panagiotopoulos; George Panayiotakis
Hand osteoarthritis (OA) is one of the most common localization of OA affecting predominantly women. The etiology seems to be multifactorial and the disease heterogeneous, comprising several clinical and radiological subsets. Hand OA includes thumb base (trapeziometarcarpal joint), metacarpophalangeal joints, distal and proximal interphalangeal joints OA. We reviewed below the prevalence, diagnosis, imaging, epidemiology, risk factors, but mostly the last discoveries in the biology and pathophysiology with particular attention to the potential role of adipokines and genetic factors. Finally, we also reviewed the different treatments currently available as well as potential future therapies. PMID:22871418
Gabay, Odile; Gabay, Cem
Osteoarthritis (OA) is a slowly evolving articular disease that affects cartilage, underlying bone and surrounding soft tissues. OA is also named degenerative joint disease. OA is thought to by triggered by a non-inflammatory degeneration of articular cartilage, leading to reactive bone formation, and hypertrophy of the joint capsule. OA is the most common joint disorder in people over 65 years
Denis J. Marcellin-Little
Background There is limited evidence for the clinical and cost effectiveness of occupational therapy (OT) approaches in the management\\u000a of hand osteoarthritis (OA). Joint protection and hand exercises have been proposed by European guidelines, however the clinical\\u000a and cost effectiveness of each intervention is unknown.\\u000a \\u000a \\u000a This multicentre two-by-two factorial randomised controlled trial aims to address the following questions:\\u000a \\u000a \\u000a • Is joint
Krysia S Dziedzic; Susan Hill; Elaine Nicholls; Alison Hammond; Helen Myers; Tracy Whitehurst; Jo Bailey; Charlotte Clements; David GT Whitehurst; Sue Jowett; June Handy; Rhian W Hughes; Elaine Thomas; Elaine M Hay
Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.
Fernandes, Amilton M.; Herlofsen, Sarah R.; Karlsen, Tommy A.; Kuchler, Axel M.; Fl?isand, Yngvar; Brinchmann, Jan E.
Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage. PMID:23671648
Fernandes, Amilton M; Herlofsen, Sarah R; Karlsen, Tommy A; Küchler, Axel M; Fløisand, Yngvar; Brinchmann, Jan E
Osteoarthritis (OA) is often a progressive and disabling disease resulting from a combination of risk factors, including age, genetics, trauma, and knee alignment, as well as an imbalance of physiologic processes resulting in inflammatory cascades on a molecular level. The synovium, bone, and cartilage are each involved in the pathophysiological mechanisms that lead to progressive joint degeneration, and, thus, also serve as targets for therapies. Efforts to identify disease-modifying osteoarthritis drugs (DMOADs) have been hampered by several factors, but the focus has now shifted toward the validation of chemical and imaging biomarkers that should aid in DMOAD development. In this review, we summarize current pathological mechanisms occurring in the individual but interconnected compartments of OA joints, as well as discuss related therapeutic interventions that are currently available or on the horizon. PMID:17922674
Krasnokutsky, Svetlana; Samuels, Jonathan; Abramson, Steven B
ObjectiveTo identify predictive factors for total knee replacement (TKR) using data from MRI of knee osteoarthritis patients in a phase III multicentre disease-modifying osteoarthritis drug (DMOAD) study.MethodsKnee osteoarthritis patients from a 2-year clinical trial evaluating licofelone versus naproxen were investigated for the incidence of TKR of the study knee. Patients (n=161) who completed the study according to protocol were selected.
Jean-Pierre Raynauld; Johanne Martel-Pelletier; Boulos Haraoui; Denis Choquette; Marc Dorais; Lukas M Wildi; François Abram; Jean-Pierre Pelletier
Hyperextension of the thumb metacarpophalangeal (MCP) joint is frequently seen with trapeziometacarpal osteoarthritis, but there is no consensus on the indication for, or type of, treatment. We re-examined 12 thumbs at a mean of 9 (range 6-13) years following MCP capsulodesis using a suture anchor performed with trapeziectomy. Mean MCP hyperextension improved from 45° pre-operatively to 19° at 1 year post-operatively. At 9 years follow-up, it had increased to 30° but was still significantly better than pre-operatively (p = 0.007). Mean MCP flexion was 37° and near normal opposition was retained. The median pain score had improved from 5.5 to 1 (p = 0.002). Thumb key and tip pinch and hand grip strength showed no significant change from pre-operative values. No thumb MCP had symptomatic radiological degeneration. Our results suggest that MCP capsulodesis preserves a useful range of MCP flexion but stretches out over time. However, this did not result in increased pain or thumb weakness. PMID:23783806
Miller, N J K; Davis, T R C
This article reports the orthodontic treatment of a patient with skeletal mandibular retrusion and an anterior open bite due to temporomandibular joint osteoarthritis (TMJ-OA) using miniscrew anchorage. A 46-year-old woman had a Class II malocclusion with a retropositioned mandible. Her overjet and overbite were 7.0 mm and -1.6 mm, respectively. She had limited mouth opening, TMJ sounds, and pain. Condylar resorption was observed in both TMJs. Her TMJ pain was reduced by splint therapy, and then orthodontic treatment was initiated. Titanium miniscrews were placed at the posterior maxilla to intrude the molars. After 2 years and 7 months of orthodontic treatment, an acceptable occlusion was achieved without any recurrence of TMJ symptoms. The retropositioned mandible was considerably improved, and the lips showed less tension upon lip closure. The maxillary molars were intruded by 1.5 mm, and the mandible was subsequently rotated counterclockwise. Magnetic resonance imaging of both condyles after treatment showed avascular necrosis-like structures. During a 2-year retention period, an acceptable occlusion was maintained without recurrence of the open bite. In conclusion, correction of open bite and clockwise-rotated mandible through molar intrusion using titanium miniscrews is effective for the management of TMJ-OA with jaw deformity.
Yamano, Eizo; Inubushi, Toshihiro; Kuroda, Shingo
The joint capsule is vital to the function of synovial joints. It seals the joint space, provides passive stability by limiting movements, provides active stability via its proprioceptive nerve endings and may form articular surfaces for the joint. It is a dense fibrous connective tissue that is attached to the bones via specialised attachment zones and forms a sleeve around the joint. It varies in thickness according to the stresses to which it is subject, is locally thickened to form capsular ligaments, and may also incorporate tendons. The capsule is often injured, leading to laxity, constriction and/or adhesion to surrounding structures. It is also important in rheumatic disease, including rheumatoid arthritis and osteoarthritis, crystal deposition disorders, bony spur formation and ankylosing spondylitis. This article concentrates on the specialised structures of the capsule--where capsular tissues attach to bone or form part of the articulation of the joint. It focuses on 2 joints: the rat knee and the proximal interphalangeal (PIP) joint of the human finger. The attachments to bone contain fibrocartilage, derived from the cartilage of the embryonic bone rudiment and rich in type II collagen and glycosaminoglycans. The attachment changes with age, when type II collagen spreads into the capsular ligament or tendon, or pathology--type II collagen is lost from PIP capsular attachments in rheumatoid arthritis. Parts of the capsule that are compressed during movement adapt by becoming fibrocartilaginous. Such regions accumulate cartilage-like glycosaminoglycans and may contain type II collagen, especially in aged material.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928639
Ralphs, J R; Benjamin, M
Background The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas. Methods In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits. Results Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (rs = 0.68 and rs = 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (rs = 0.64, p < 0.001). Conclusion Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.
Osteoarthritis (OA) is the most common form of arthritis and has multiple risk factors including joint injury. The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint "organ" and analyzed using microarrays. Histologic changes seen in OA, including articular cartilage lesions and osteophytes, were present in the medial tibial plateaus of the DMM knees beginning at the earliest (2 week) time point and became progressively more severe by 16 weeks. 427 probe sets (371 genes) from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin. Immunostaining revealed the presence of these three proteins in cartilage and soft tissues including ligaments as well as in the fibrocartilage covering osteophytes. The results support a phasic development of OA with early matrix remodeling and transcriptional activity followed by a more quiescent period that is not maintained. This implies that the response to an OA intervention will depend on the timing of the intervention. The quiescent period at 8 weeks may be due to the maturation of the osteophytes which are thought to temporarily stabilize the joint. PMID:23382930
Loeser, Richard F; Olex, Amy L; McNulty, Margaret A; Carlson, Cathy S; Callahan, Michael; Ferguson, Cristin; Fetrow, Jacquelyn S
Osteoarthritis (OA) is the most common form of arthritis and has multiple risk factors including joint injury. The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint “organ” and analyzed using microarrays. Histologic changes seen in OA, including articular cartilage lesions and osteophytes, were present in the medial tibial plateaus of the DMM knees beginning at the earliest (2 week) time point and became progressively more severe by 16 weeks. 427 probe sets (371 genes) from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin. Immunostaining revealed the presence of these three proteins in cartilage and soft tissues including ligaments as well as in the fibrocartilage covering osteophytes. The results support a phasic development of OA with early matrix remodeling and transcriptional activity followed by a more quiescent period that is not maintained. This implies that the response to an OA intervention will depend on the timing of the intervention. The quiescent period at 8 weeks may be due to the maturation of the osteophytes which are thought to temporarily stabilize the joint.
Loeser, Richard F.; Olex, Amy L.; McNulty, Margaret A.; Carlson, Cathy S.; Callahan, Michael; Ferguson, Cristin; Fetrow, Jacquelyn S.
An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was
S P Robins; P Stewart; C Astbury; H A Bird
Advances in computational mechanics, constitutive modeling, and techniques for subject-specific modeling have opened the door to patient-specific simulation of the relationships between joint mechanics and osteoarthritis (OA), as well as patient-specific preoperative planning. This article reviews the application of computational biomechanics to the simulation of joint contact mechanics as relevant to the study of OA. This review begins with background regarding OA and the mechanical causes of OA in the context of simulations of joint mechanics. The broad range of technical considerations in creating validated subject-specific whole joint models is discussed. The types of computational models available for the study of joint mechanics are reviewed. The types of constitutive models that are available for articular cartilage are reviewed, with special attention to choosing an appropriate constitutive model for the application at hand. Issues related to model generation are discussed, including acquisition of model geometry from volumetric image data and specific considerations for acquisition of computed tomography and magnetic resonance imaging data. Approaches to model validation are reviewed. The areas of parametric analysis, factorial design, and probabilistic analysis are reviewed in the context of simulations of joint contact mechanics. Following the review of technical considerations, the article details insights that have been obtained from computational models of joint mechanics for normal joints; patient populations; the study of specific aspects of joint mechanics relevant to OA, such as congruency and instability; and preoperative planning. Finally, future directions for research and application are summarized. PMID:23445048
Henak, Corinne R; Anderson, Andrew E; Weiss, Jeffrey A
Osteoarthritis (OA) can be a progressive disabling disease, which results from the pathological imbalance of degradative and reparative processes, with concomitant inflammatory changes. The synovium, bone, and cartilage are each well established sites involved in the pathophysiological mechanisms that lead to progressive joint degeneration. The search for disease-modifying osteoarthritis drugs, DMOADs, has been hampered by several factors, including the variable progression of disease, the lack of specificity and sensitivity of standard radiography, and the fact that the slowing of radiographic progression may not result in corresponding improvement in pain and function. As a result, there is general agreement that development of DMOADs will be facilitated by advances in imaging and the validation of chemical biomarkers. Such biomarkers should be useful tools that will identify patients at risk for disease progression and predict responses to candidate structure-modifying drugs. PMID:17121495
Abramson, Steven; Krasnokutsky, Svetlana
We have retrospectively reviewed 17 thumbs in 16 patients with osteoarthritis of the thumb carpometacarpal joints, for which arthroplasty was performed using Kaarela's method. Postoperatively, three thumbs in two patients had poor outcomes; both patients had a sharp slope of the base of the first metacarpal. Serial radiographic measurements suggested that this sharp slope affected the adducted position of the first metacarpal, and led to the appearance of a metacarpophalangeal joint hyperextension deformity of the thumb. This radiological finding could be a prognostic predictor after surgery for osteoarthritis of the thumb carpometacarpal joint. PMID:23413854
Tonogai, Ichiro; Hamada, Yoshitaka; Hibino, Naohito
Nociceptive tolerance is improved by bradykinin receptor B1 antagonism and joint morphology is protected by both endothelin type A and bradykinin receptor B1 antagonism in a surgical model of osteoarthritis
Introduction Endothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator bradykinin (BK), which acts via bradykinin receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner. Methods Osteoarthritis was surgically induced in male rats by transection of the right anterior cruciate ligament. Animals were subsequently treated with weekly intra-articular injections of specific peptide antagonists of ETA and/or BKB1. Hind limb nociception was measured by static weight bearing biweekly for two months post-operatively. Post-mortem, right knee joints were analyzed radiologically by X-ray and magnetic resonance, and histologically by the OARSI histopathology assessment system. Results Single local BKB1 antagonist treatment diminished overall hind limb nociception, and accelerated post-operative recovery after disease induction. Both ETA and/or BKB1 antagonist treatments protected joint radiomorphology and histomorphology. Dual ETA/BKB1 antagonism was slightly more protective, as measured by radiology and histology. Conclusions BKB1 antagonism improves nociceptive tolerance, and both ETA and/or BKB1 antagonism prevents joint cartilage degradation in a surgical model of osteoarthritis. Therefore, they represent a novel therapeutic strategy: specific receptor antagonism may prove beneficial in disease management.
Osteoarthritis (OA) is the most common form of joint disease. Although OA was previously thought to be a progressive, degenerative disorder, it is now known that spontaneous arrest or reversal of the disease can occur. Conventional medications are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be at least as effective as nonsteroidal anti-inflammatory drugs at relieving the symptoms of OA, and preliminary evidence suggests some of these compounds may exert a favorable influence on the course of the disease. PMID:10559548
Gaby, A R
Background Two of the commonest chronic diseases experienced by older people in the general population are cardiovascular diseases and osteoarthritis. These conditions also commonly co-occur, which is only partly explained by age. Yet, there have been few studies investigating specific a priori hypotheses in testing the comorbid interaction between two chronic diseases and related health and healthcare outcomes. It is also unknown whether the stage or severity of the chronic disease influences the comorbidity impact. The overall plan is to investigate the interaction between cardiovascular severity groups (hypertension, ischaemic heart disease and heart failure) and osteoarthritis comorbidity, and their longitudinal impact on health and healthcare outcomes relative to either condition alone. Methods From ten general practices participating in a research network, adults aged 40?years and over were sampled to construct eight exclusive cohort groups (n?=?9,676). Baseline groups were defined on the basis of computer clinical diagnostic data in a 3-year time-period (between 2006 and 2009) as: (i) without cardiovascular disease or osteoarthritis (reference group), (ii) index cardiovascular disease groups (hypertension, ischaemic heart disease and heart failure) without osteoarthritis, (iii) index osteoarthritis group without cardiovascular disease, and (vi) index cardiovascular disease groups comorbid with osteoarthritis. There were three main phases to longitudinal follow-up. The first (survey population) was to invite cohorts to complete a baseline postal health questionnaire, with 10 monthly brief interval health questionnaires, and a final 12-month follow-up questionnaire. The second phase (linkage population) was to link the collected survey data to patient clinical records with consent for the 3-year time-period before baseline, during the 12-month survey period and the 12?months after final questionnaire (total 5?years). The third phase (denominator population) was to construct an anonymised clinical data archive for the study five year period for the total baseline cohorts, linking clinical information such as diagnosis, prescriptions and referrals. Discussion The outcomes of the study will result in the determination of the specific interaction between cardiovascular severity and osteoarthritis comorbidity on the change and progression of physical health status in individuals and on the linked and associated clinical-decision making process in primary care.
Osteoarthritis has grown to become a widely prevalent disease that has major implications in both individual and public health. Although originally considered to be a degenerative disease driven by "wear and tear" of the articular cartilage, recent evidence has led to a consensus that osteoarthritis pathophysiology should be perceived in the context of the entire joint and multiple tissues. MRI is becoming an increasingly more important modality for imaging osteoarthritis, due to its excellent soft tissue contrast and ability to acquire morphological and biochemical data. This review will describe the pathophysiology of osteoarthritis as it is associated with various tissue types, highlight several promising MR imaging techniques for osteoarthritis and illustrate the expected appearance of osteoarthritis with each technique. J. Magn. Reson. Imaging 2014;39:1346-1356. © 2014 Wiley Periodicals, Inc. PMID:24677706
Shapiro, Lauren M; McWalter, Emily J; Son, Min-Sun; Levenston, Marc; Hargreaves, Brian A; Gold, Garry E
An adult male white Bengal tiger (Panthera tigris tigris) with pronounced atrophy of the pelvic musculature was diagnosed with degenerative osteoarthritis of the coxofemoral joints. Initial management with the nonsteroidal anti-inflammatory drug meloxicam and a semisynthetic sodium pentosan polysulfate resulted in clinical improvement and radiographic stabilization of the arthritic condition over several months. However, because pain was still evident, bilateral denervation of the coxofemoral joints was performed, successfully ameliorating the signs of osteoarthritic pain in the tiger. Meloxicam has shown good clinical efficacy for the treatment of osteoarthritis and other painful conditions in large felids. Coxofemoral joint denervation offers many advantages for the treatment of osteoarthritis in exotic carnivore species, and should be considered a viable treatment modality. PMID:17319147
Whiteside, Douglas P; Remedios, Audrey M; Black, Sandra R; Finn-Bodner, Susan T
Introduction Osteoarthritis (OA), the most prevalent form of joint disease, affecting as much as 13% of the world’s population. In the United States, it is the leading cause of disability in people over age 65 and is characterized by progressive cartilage loss, bone remodeling, osteophyte formation and synovial inflammation with resultant joint pain and disability. There are no treatments marketed for structural disease modification; current treatments mainly target symptoms, with >75% of patients reporting need for additional symptomatic treatment. Areas covered Drugs in later development (Phase II-III) for osteoarthritis pain and joint structural degeneration are reviewed. Not covered are procedural (e.g. arthrocentesis, physical therapy), behavioral (e.g. weight loss, pain coping techniques) or device (e.g. knee braces, surgical implants) based treatments. Expert opinion More in depth understanding of the pathophysiology of the disease, as well as elucidation of the link between clinical symptomatology and structural changes in the joint will likely lead to development of novel target classes with promising efficacy in the future. Efficacy notwithstanding, there remain significant hurdles to overcome in clinical development of these therapeutics, inherent in the progression pattern of the disease as well as challenges with readouts for both pain and structure modification trials.
SUMMARY Objective Clinically, radiographic joint space narrowing (JSN) is regarded a surrogate of cartilage loss in osteoarthritis (OA). Using magnetic resonance imaging (MRI), we explored the magnitude and regional distribution of differences in cartilage thickness and subchondral bone area associated with specific Osteoarthritis Research Society International (OARSI) JSN grades. Method Seventy-three participants with unilateral medial JSN were selected from the first half (2678 cases) of the OA Initiative cohort (45, 21, and 7 with OARSI JSN grades 1, 2, and 3, respectively, no medial JSN in the contra-lateral knee). Bilateral sagittal baseline DESSwe MRIs were segmented by experienced operators. Intra-person between-knee differences in cartilage thickness and subchondral bone areas were determined in medial femorotibial subregions. Results Knees with medial OARSI JSN grades 1, 2, and 3 displayed a 190 ?m (5.2%), 630 ?m (18%), and 1560 ?m (44%) smaller cartilage thickness in weight-bearing medial femorotibial compartments compared to knees without JSN, respectively. The weight-bearing femoral condyle displayed relatively greater differences than the posterior femoral condyle or the medial tibia (MT). The central subregion within the weight-bearing medial femur (cMF) of the femoral condyle (30–75°), and the external and central subregions within the tibia displayed relatively greater JSN-associated differences compared to other medial femorotibial subregions. Knees with higher JSN grades also displayed larger than contralateral femorotibial subchondral bone areas. Conclusions This study provides quantitative estimates of JSN-related cartilage loss, with the central part of the weight-bearing femoral condyle being most strongly affected. Knees with higher JSN grades displayed larger subchondral bone areas, suggesting that an increase in subchondral bone area occurs in advanced OA.
Eckstein, F.; Wirth, W.; Hunter, D.J.; Guermazi, A.; Kwoh, C.K.; Nelson, D.R.; Benichou, O.
... Post-Injury Response Could be Key Step in Osteoarthritis Development Scientists long considered osteoarthritis (OA) a disease of wear and tear. Use ... for treatment, and perhaps prevention, of this common joint disease. The study, conducted in the laboratory of William ...
Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies.
The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multi-faceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis.
Hui, Alexander Y.; McCarty, William J.; Masuda, Koichi; Firestein, Gary S.; Sah, Robert L.
BACKGROUND: Arthritis is a leading cause of disability in the United States. Total knee arthroplasty (TKA) has become the gold standard to manage the pain and disability associated with knee osteoarthritis (OA). Although more than 400 000 primary TKA surgeries are performed each year in the United States, not all individuals with knee OA elect to undergo the procedure. No
Joseph A Zeni Jr; Michael J Axe; Lynn Snyder-Mackler
The origin of pain in osteoarthritis is poorly understood, but it is generally thought to arise from inflammation within the innervated structures of the joint, such as the synovium, capsule and bone. We investigated the role of nerve growth factor (NGF) in pain development in murine OA, and the analgesic efficacy of the soluble NGF receptor, TrkAD5. OA was induced
Kay E. McNamee; Annika Burleigh; Luke L. Gompels; Marc Feldmann; Shelley J. Allen; Richard O. Williams; David Dawbarn; Tonia L. Vincent; Julia J. Inglis
ObjectivesTo explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA.Methods161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500
J.-P. Pelletier; J.-P. Raynauld; J. Caron; F. Mineau; F. Abram; M. Dorais; B. Haraoui; D. Choquette; J. Martel-Pelletier
Osteoarthritis (OA) is a chronic degenerative disease of the joints caused by wide variety of factors. factors. This paper\\u000a provides a review of the clinical and experimental research on integrated Chinese and Western medicine in the treatment of\\u000a osteoarthritis. Western medicine in the treatment of osteoarthritis. (1) Clinical research: integrated Chinese and Western\\u000a medicine therapies were used including physiotherapy, medications,
He-ming Wang; Jun-ning Liu; Yi Zhao
Osteoarthritis is a disorder of cartilage that affects almost 85% of the population by age 75. A lack of rigorous clinical and radiographic criteria for defining the disorder makes precise determination of its prevalence impossible. The process of wear and tear explains many manifestations of osteoarthritis, but it does not account for some of the clinical findings or the biochemical changes in osteoarthritic cartilage. Thus, other factors such as heredity, hormones, and diet may play a role. Treatment consists of teaching patients about their disease, alleviating pain, and preserving joint function. Nonsteroidal anti-inflammatory drugs may be no more effective than simple analgesics in relieving the pain of this disorder. Moreover, some nonsteroidal anti-inflammatory drugs can adversely affect cartilage metabolism, and most are possibly dangerous in elderly patients. Drugs that inhibit the production or activity of chondrolytic enzymes can slow the degeneration of cartilage in some animals, but their effects on humans with osteoarthritis are unproved. The surgical repair of severely damaged joints can have gratifying results. Images Figure 2.
Sack, K E
Objective: Idiopathic osteoarthritis is the most common form of osteoarthritis (OA) world-wide and remains the leading cause of disability and the associated socio-economic burden in an increasing aging population. Traditionally, OA has been viewed as a degenerative joint disease characterized by progressive destruction of the articular cartilage and changes in the subchondral bone culminating in joint failure. However, the etiology
Kei Imagawa; MC de Andrés; Ko Hashimoto; Dominic Pitt; Eiji Itoi; Mary B. Goldring; Helmtrud I. Roach; Richard O. C. Oreffo
The aim of this study was to evaluate the use of splint treatment for therapy of osteoarthritis of temporomandibular joint, and to compare the level of anxiety (State-Trait Anxiety Inventory, STAI) and clinical characteristics between 16 patients and 20 asymptomatic dental school students. Magnetic resonance imaging (MRI) was used for all subjects. Dental students showed a statistically significant higher capacity of mouth opening (p < 0.05), and lower level of anxiety (p < 0.05 for STAI 1, and p < 0.001 for STAI 2) than patients. Patients who had suffered chronic pain before splint treatment had a higher value of anxiety by STAI 1 test (p < 0.05). PMID:21263397
Badel, Tomislav; Lovko, Sandra Kocijan; Podoreski, Dijana; Pavcin, Ivana Savi?; Kern, Josipa
OBJECTIVE We examined the effects of a tailored activity-pacing intervention on self-perceived joint stiffness in adults with osteoarthritis (OA). METHOD Thirty-two adults with hip or knee OA were randomized to a tailored or general activity-pacing intervention. Participants’ symptoms and physical activity over 5 days were used to tailor activity pacing. The outcome was self-perceived joint stiffness measured at baseline, 4 wk, and 10 wk. A linear mixed regression model was used. RESULTS The tailored group significantly improved in stiffness compared with the general group over time. We found a significantly different linear trend between groups (Time × Group, p = .046) in which the tailored group had decreasing stiffness over the three time points, denoting continued improvement. The general group’s stiffness improved from baseline to 4 wk but returned to baseline levels at 10 wk. CONCLUSION Tailoring activity pacing may be effective in sustaining improvements in self-perceived joint stiffness in adults with OA.
Schepens, Stacey L.; Braun, Marcia E.; Murphy, Susan L.
Symptomatic medial compartment knee osteoarthritis (OA) is the leading cause of musculoskeletal pain and disability in adults. Therapies intended to unload the medial knee compartment have yielded unsatisfactory results due to low patient compliance with conservative treatments and high complication rates with surgical options. There is no widely available joint-unloading treatment for medial knee OA that offers clinically important symptom alleviation, low complication risk, and high patient acceptance. The KineSpring(®) Knee Implant System (Moximed, Inc, Hayward, CA, USA) is a first-of-its-kind, implantable, extra-articular, extra-capsular prosthesis intended to alleviate knee OA-related symptoms by reducing medial knee compartment loading while overcoming the limitations of traditional joint-unloading therapies. Preclinical and clinical studies have demonstrated excellent prosthesis durability, substantial reductions in medial compartment and total joint loads, and clinically important improvements in OA-related pain and function. The purpose of this report is to describe the KineSpring System, including implant characteristics, principles of operation, indications for use, patient selection criteria, surgical technique, postoperative care, preclinical testing, and clinical experience. The KineSpring System has potential to bridge the gap between ineffective conservative treatments and irreversible surgical interventions for medial compartment knee OA. PMID:23717052
Clifford, Anton G; Gabriel, Stefan M; O'Connell, Mary; Lowe, David; Miller, Larry E; Block, Jon E
Symptomatic medial compartment knee osteoarthritis (OA) is the leading cause of musculoskeletal pain and disability in adults. Therapies intended to unload the medial knee compartment have yielded unsatisfactory results due to low patient compliance with conservative treatments and high complication rates with surgical options. There is no widely available joint-unloading treatment for medial knee OA that offers clinically important symptom alleviation, low complication risk, and high patient acceptance. The KineSpring® Knee Implant System (Moximed, Inc, Hayward, CA, USA) is a first-of-its-kind, implantable, extra-articular, extra-capsular prosthesis intended to alleviate knee OA-related symptoms by reducing medial knee compartment loading while overcoming the limitations of traditional joint-unloading therapies. Preclinical and clinical studies have demonstrated excellent prosthesis durability, substantial reductions in medial compartment and total joint loads, and clinically important improvements in OA-related pain and function. The purpose of this report is to describe the KineSpring System, including implant characteristics, principles of operation, indications for use, patient selection criteria, surgical technique, postoperative care, preclinical testing, and clinical experience. The KineSpring System has potential to bridge the gap between ineffective conservative treatments and irreversible surgical interventions for medial compartment knee OA.
Clifford, Anton G; Gabriel, Stefan M; O'Connell, Mary; Lowe, David; Miller, Larry E; Block, Jon E
Background There is limited evidence for the clinical and cost effectiveness of occupational therapy (OT) approaches in the management of hand osteoarthritis (OA). Joint protection and hand exercises have been proposed by European guidelines, however the clinical and cost effectiveness of each intervention is unknown. This multicentre two-by-two factorial randomised controlled trial aims to address the following questions: • Is joint protection delivered by an OT more effective in reducing hand pain and disability than no joint protection in people with hand OA in primary care? • Are hand exercises delivered by an OT more effective in reducing hand pain and disability than no hand exercises in people with hand OA in primary care? • Which of the four management approaches explored within the study (leaflet and advice, joint protection, hand exercise, or joint protection and hand exercise combined) provides the most cost-effective use of health care resources Methods/Design Participants aged 50 years and over registered at three general practices in North Staffordshire and Cheshire will be mailed a health survey questionnaire (estimated mailing sample n = 9,500). Those fulfilling the eligibility criteria on the health survey questionnaire will be invited to attend a clinical assessment to assess for the presence of hand or thumb base OA using the ACR criteria. Eligible participants will be randomised to one of four groups: leaflet and advice; joint protection (looking after your joints); hand exercises; or joint protection and hand exercises combined (estimated n = 252). The primary outcome measure will be the OARSI/OMERACT responder criteria combining hand pain and disability (measured using the AUSCAN) and global improvement, 6 months post-randomisation. Secondary outcomes will also be collected for example pain, functional limitation and quality of life. Outcomes will be collected at baseline and 3, 6 and 12 months post-randomisation. The main analysis will be on an intention to treat basis and will assess the clinical and cost effectiveness of joint protection and hand exercises for managing hand OA. Discussion The findings will improve the cost-effective evidence based management of hand OA. Trial registration identifier: ISRCTN33870549
Athletes, and an increasing number of middle aged and older people who want to participate in athletics, may question whether regular vigorous physical activ ity increases their risk of developing osteoarthritis. To answer this, the clinical syndrome of osteoarthritis must be distinguished from periarticular soft tissue pain associated with activity and from the development of osteophytes. Sports that subject joints
Joseph A. Buckwalter
The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA.
King, Lauren K.; March, Lyn; Anandacoomarasamy, Ananthila
Purpose: This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF).Materials and Methods: Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints),
Takanori Shibata; Ken-Ichiro Murakami; Eiro Kubota; Hiroshi Maeda
Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects ? 1% of the population worldwide, and unlike OA, generally involves many joints because of
Salahuddin Ahmed; Jeremy Anuntiyo; Charles J. Malemud; Tariq M. Haqqi
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Objective: Ibuprofen – a non-steroidal anti-inflammatory drug (NSAID)- and glucosamine sulfate – a natural compound and a food supplement- are two therapeutic agents which have been widely used for treatment of patients with temporomandibular joint (TMJ) disorders. This study was aimed to compare the effectiveness and safety of these two medications in the treatment of patients suffering from TMJ disorders. Methods: After obtaining informed consent, 60 patients were randomly allocated to two groups. Patients with painful TMJ, TMJ crepitation or limitation of mouth opening entered the study. Exclusion criteria were history of depressive disorders, cardiovascular disease, musculoskeletal disorders, asthma, gastrointestinal problems, kidney or liver dysfunction or diabetes mellitus, dental diseases needing ongoing treatment; taking aspirin or warfarin, or concomitant treatment of TMJ disorder with other agents or methods. Thirty patients were treated with ibuprofen 400 mg twice a day, (mean age 27.12 ± 10.83 years) and 30 patients (mean age 26.60 ± 10) were treated with glucosamine sulfate 1500 mg daily. Patients were visited 30, 60 and 90 days after starting the treatment, pain and mandibular opening were checked and compared within and between two groups. Findings: Comparing with baseline measures, both groups had significantly improved post-treatment pain (P < 0.0001 for both groups) and mandibular opening (P value: 0.001 for glucosamine sulfate and 0.03 for ibuprofen). Post treatment pain and mandibular opening showed significantly more improvement in the glucosamine treated patients (P < 0.0001 and 0.01 respectively). Rate of adverse events was significantly lower in the P value glucosamine sulfate group (P < 0.0001). Conclusion: This investigation demonstrated that comparing with a commonly prescribed NSAID – ibuprofen-, glucosamine sulfate is a more effective and safer therapeutic agent for treatment of patients with TMJ degenerative join disorder.
Haghighat, Abbas; Behnia, Ali; Kaviani, Naser; Khorami, Behnam
The purpose of the given research is the comparison of efficiency of conventional treatment of myofascial pain syndromes of patients with osteoarthritis (OA) of hip and knee joints and therapy with additional application of low level laser therapy (LLLT) under dynamic control of clinical picture, rheovasographic, electromyographic examinations, and parameters of peroxide lipid oxidation. The investigation was made on 143 patients with OA of hip and knee joints. Patients were randomized in 2 groups: basic group included 91 patients, receiving conventional therapy with a course of LLLT, control group included 52 patients, receiving conventional treatment only. Transcutaneous ((lambda) equals 890 nm, output peak power 5 W, frequency 80 - 3000 Hz) and intravenous ((lambda) equals 633 nm, output 2 mW in the vein) laser irradiation were used for LLLT. Studied showed, that clinical efficiency of LLLT in the complex with conventional treatment of myofascial pain syndromes at the patients with OA is connected with attenuation of pain syndrome, normalization of parameters of myofascial syndrome, normalization of the vascular tension and parameters of rheographic curves, as well as with activation of antioxidant protection system.
Gasparyan, Levon V.
Purpose: The aim of this study was to investigate the potential use of multimodality functional imaging techniques to identify the quantitative optical findings that can be used to distinguish between osteoarthritic and normal finger joints. Methods: Between 2006 and 2009, the distal interphalangeal finger joints from 40 female subjects including 22 patients and 18 healthy controls were examined clinically and scanned by a hybrid imaging system. This system integrated x-ray tomosynthetic setup with a diffuse optical imaging system. Optical absorption and scattering images were recovered based on a regularization-based hybrid reconstruction algorithm. A receiver operating characteristic curve was used to calculate the statistical significance of specific optical features obtained from osteoarthritic and healthy joints groups. Results: The three-dimensional optical and x-ray images captured made it possible to quantify optical properties and joint space width of finger joints. Based on the recovered optical absorption and scattering parameters, the authors observed statistically significant differences between healthy and osteoarthritis finger joints. Conclusions: The statistical results revealed that sensitivity and specificity values up to 92% and 100%, respectively, can be achieved when optical properties of joint tissues were used as classifiers. This suggests that these optical imaging parameters are possible indicators for diagnosing osteoarthritis and monitoring its progression.
Yuan Zhen; Zhang Qizhi; Sobel, Eric S.; Jiang Huabei [Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611 (United States); Division of Rheumatology, College of Medicine, University of Florida, Gainesville, Florida 32611 (United States); Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611 (United States)
Background Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism. Objective To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions. Methods Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay. Results The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction. Conclusions Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.
Wang, Xue-Dong; Kou, Xiao-Xing; He, Dan-Qing; Zeng, Min-Min; Meng, Zhen; Bi, Rui-Yun; Liu, Yan; Zhang, Jie-Ni; Gan, Ye-Hua; Zhou, Yan-Heng
The technique of vibration arthrography (VAG) permits the non-invasive evaluation of internal derangements of the knee. In this method, the delicate sounds emitted from a joint are recorded by a sensitive detector which is placed on a joint, and the resultant signals are depicted by an oscilloscope. The primary objective in this study was to examine the vibration signal patterns
The most prevalent musculoskeletal condition that results in joint pain is osteoarthritis (OA), with nearly 70% of the population >65 years of age demonstrating radiographic evidence of this disease. The knee is the joint commonly affected. Therapy for OA of the knee is directed at decreasing joint pain and increasing function and includes both pharmacologic and nonpharmacologic interventions. Pharmacologic therapy
Jennifer M. Thompson
Osteoarthritis (OA) is a common joint disorder that afflicts more than 20 million Americans, with greater than 80% of individuals older than 75 years of age demonstrating radiographic evidence of disease. Initial treatment involves behavioral modification with emphasis placed on weight loss, exercise, and patient education. Simple oral analgesics such as acetaminophen and nonsteroidal anti-inflammatory medications may be employed in
Kamal I. Bohsali
OBJECTIVE: To determine the effects of low intensity weight-bearing exercise on osteoarthritis (OA) of the knee. METHODS: Synovial fluid keratan sulfate (KS) and hydroxyproline were measured as markers of cartilage degradation. The Arthritis Impact Measurement Scales (AIMS) were used to measure health status, and a visual analog scale for pain assessment was used before and after intervention. An exercise (EX) group (n = 15) received a thrice-weekly 12-week low intensity exercise program and a weekly educational program, and a minimal treatment (Min RX) group (n = 15) received only the education program. RESULTS: Pain levels declined in the EX group, and the Min RX group showed improvement on the AIMS. Synovial fluid was obtained in 11 subjects before and after the intervention. Levels of KS and hydroxyproline did not change. CONCLUSION: Further study of exercise effects should include both clinical and biologic parameters to examine the outcome of exercise as a therapeutic intervention in OA of the knee.
Bautch, J. C.; Malone, D. G.; Vailas, A. C.
Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability.
Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K
We compared histologic, immunohistochemical, and vascular findings in synovial biopsies from individuals with Gulf War Veterans\\u000a Illness and joint pain (GWVI) to findings in normal and osteoarthritis (OA) synovium. The following parameters were assessed\\u000a in synovial biopsies from ten individuals with GWVI: lining thickness, histologic synovitis score, and vascular density in\\u000a hematoxylin & eosin-stained sections; and CD68+ lining surface cells
F. Pessler; L. X. Chen; L. Dai; C. Gomez-Vaquero; C. Diaz-Torne; M. E. Paessler; C. Scanzello; N. Çakir; E. Einhorn; H. R. Schumacher
Individuals with first carpo-metacarpal (CMC) osteoarthritis (OA) often experience pain and difficulty with functional activities. Thus, designing orthotics to improve function and decrease pain is common practice. These therapists designed an orthosis using a combination of neoprene and thermoplastic materials to create a soft orthosis that provides support to the first CMC joint - Victoria Priganc, PhD, OTR, CHT, CLT. PMID:23523512
Bani, Monireh Ahmadi; Arazpour, Mokhtar; Curran, Sarah
Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases and causes of lameness in the dogs. The osteoarthritic disease process involves the entire synovial joint, encompassing the synovium, cartilage and underlying bone. Joint failure results from an abnormal mechanical strain causing damage to normal tissue or failure of pathologically impaired articular cartilage and bone under the influence of
Yves Henrotin; Christelle Sanchez; Marc Balligand
Health disparities in total joint replacement have been documented based on gender and ethnicity in multiple countries. Absent are studies exploring the meaning of the procedures among diverse women, which is necessary to fully understand the impact of the disparity. Drawing on ethnographic data from a life course exploration of disablement among Mexican American women with mobility impairments, one woman’s reasons for forgoing a joint replacement are considered. It is suggested that inequalities in disablement cannot be understood without considering the mulitple cultural conflicts and loyalties that push and pull women in multiple directions.
Health disparities in total joint replacement have been documented based on gender and ethnicity in multiple countries. Absent are studies exploring the meaning of the procedures among diverse women, which is necessary to fully understand the impact of the disparity. Drawing on ethnographic data from a life course exploration of disablement among Mexican American women with mobility impairments, one woman's reasons for forgoing a joint replacement are considered. It is suggested that inequalities in disablement cannot be understood without considering the multiple cultural conflicts and loyalties that push and pull women in multiple directions. PMID:21767094
Objective Magnetic resonance imaging (MRI) was used to assess whether knees with advanced radiographic disease (medial joint space narrowing = mJSN) encounter greater longitudinal cartilage loss than contra-lateral knees with earlier disease (no or less mJSN). Methods Participants were selected from 2678 cases in the Osteoarthritis Initiative, based on exhibition of bilateral pain, BMI>25, mJSN in one knee, no or less mJSN in the contra-lateral knee, and no lateral JSN in both knees. 80 participants (age 60.6±9.1 yrs) fulfilled these criteria. Medial tibial and femoral cartilage morphology was analyzed from baseline and 1-year follow-up sagittal DESSwe 3 Tesla MRI of both knees, by experienced readers blinded to the timepoint and mJSN status. Results Knees with more radiographic mJSN displayed greater medial cartilage loss (-80 ?m), assessed by MRI, than contra-lateral knees with less mJSN (-57?m). The difference reached statistical significance in participants with mJSN grade 2 or 3 (p=0.005 to p=0.08), but not in participants with mJSN grade 1 (p=0.28 to 0.98). In knees with more mJSN, cartilage loss increased with higher grades of mJSN (p=0.003 in the medial femur). Knees with mJSN grade 2 or 3 displayed greater cartilage loss in the weight-bearing medial femur than in the posterior femur or in the medial tibia (p=0.048). Conclusion Knees with advanced mJSN displayed greater cartilage loss than contra-lateral knees with less mJSN. These data suggest that radiography can be used to stratify fast structural progressors, and that MRI cartilage thickness loss is more pronounced at advanced radiographic disease stage.
Eckstein, Felix; Benichou, Olivier; Wirth, Wolfgang; Nelson, David R; Maschek, Susanne; Hudelmaier, Martin; Kwoh, C. Kent; Guermazi, Ali; Hunter, David
Discoidin domain receptor 1 (DDR-1)-deficient mice exhibited a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) as early as 9 weeks of age. They showed typical histological signs of OA, including surface fissures, loss of proteoglycans, chondrocyte cluster formation, collagen type I upregulation, and atypical collagen fibril arrangements. Chondrocytes isolated from the TMJs of DDR-1-deficient mice maintained their osteoarthritic characteristics when placed in culture. They expressed high levels of runx-2 and collagen type I, as well as low levels of sox-9 and aggrecan. The expression of DDR-2, a key factor in OA, was increased. DDR-1-deficient chondrocytes from the TMJ were positively influenced towards chondrogenesis by a three-dimensional matrix combined with a runx-2 knockdown or stimulation with extracellular matrix components, such as nidogen-2. Therefore, the DDR-1 knock-out mouse can serve as a novel model for temporomandibular disorders, such as OA of the TMJ, and will help to develop new treatment options, particularly those involving tissue regeneration. PMID:23912900
Schminke, Boris; Muhammad, Hayat; Bode, Christa; Sadowski, Boguslawa; Gerter, Regina; Gersdorff, Nikolaus; Bürgers, Ralf; Monsonego-Ornan, Efrat; Rosen, Vicki; Miosge, Nicolai
Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation. PMID:24046512
Hauser, Ross A; Orlofsky, Amos
Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation.
Hauser, Ross A.; Orlofsky, Amos
OBJECTIVE—To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined.?METHODS—Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively.?RESULTS—All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1 (PAI-1) were also increased.?CONCLUSION—Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulting in increased uPA catalytic activity that may play a part in tissue destruction in RA.??
Busso, N.; Peclat, V.; So, A.; Sappino, A.
Objective People with knee osteoarthritis (OA) are thought to walk with high loads at the knee which are yet to be quantfied using modeling techniques that account for subject specific EMG patterns, kinematics and kinetics. The objective was to estimate medial and lateral loading for people with knee OA and controls using an approach that is sensitive to subject specific muscle activation patterns. Methods 16 OA and 12 control (C) subjects walked while kinematic, kinetic and EMG data were collected. Muscle forces were calculated using an EMG-Driven model and loading was calculated by balancing the external moments with internal muscle and contact forces Results OA subjects walked slower and had greater laxity, static and dynamic varus alignment, less flexion and greater knee adduction moment (KAM). Loading (normalized to body weight) was no different between the groups but OA subjects had greater absolute medial load than controls and maintained a greater %total load on the medial compartment. These patterns were associated with body mass, sagittal and frontal plane moments, static alignment and close to signficance for dynamic alignment. Lateral compartment unloading during mid-late stance was observed in 50% of OA subjects. Conclusions Loading for control subjects was similar to data from instrumented prostheses. Knee OA subjects had high medial contact loads in early stance and half of the OA cohort demonstared lateral compartment lift-off. Results suggest that interventions aimed at reducing body weight and dynamic malalignment might be effective in reducing medial compartment loading and establishing normal medio-lateral load sharing patterns.
Kumar, Deepak; Manal, Kurt T.; Rudolph, Katherine S.
Objective In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers’ experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the MRI Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. Methods The MOAKS instrument refines the scoring of BMLs (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). Results With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near perfect agreement (0.81–1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement < 75%. Conclusion MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness.
Hunter, David J; Guermazi, Ali; Lo, Grace H; Grainger, Andrew J; Conaghan, Philip G; Boudreau, Robert M; Roemer, Frank W.
Objective To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline. Methods Cases were selected from a pool of 2,678 subjects enrolled in the Osteoarthritis Initiative cohort. Inclusion criteria for the present study were unilateral medial JSN, bilateral frequent knee pain, and body mass index (BMI) ?25 kg/m2. Baseline and 1-year fixed flexion radiographs of both knees were read (blinded to time point) using an automated algorithm for minimum JSW and JSW at 4 fixed locations in the medial compartment. Results Sixty-seven participants met the inclusion criteria: 43 women and 24 men, with mean ± SD age 60 ± 9 years and mean ± SD BMI 31 ± 4 kg/m2. Thirty-seven subjects (55%) had ?1 definite tibiofemoral osteophyte. The average progression in no-JSN knees was comparable with that in JSN knees (approximately ?0.2 mm/year). However, JSW change was more variable in no-JSN knees, resulting in standardized response means (SRMs; the mean/SD) of approximately ?0.24 in no-JSN knees versus approximately ?0.41 in JSN knees on average at the 4 fixed locations, and SRMs of ?0.24 and ?0.35, respectively, for minimum JSW. Young age and high BMI were associated with increased progression, especially in JSN knees. Conclusion JSN and no-JSN knees progressed at a comparable rate, but a wider distribution of JSW change in no-JSN knees resulted in a poorer sensitivity to change in these knees.
BENICHOU, O. D.; HUNTER, D. J.; NELSON, D. R.; GUERMAZI, A.; ECKSTEIN, F.; KWOH, K.; MYERS, S. L.; WIRTH, W.; DURYEA, J.
Many elders suffer from chronic pain resulting from osteoarthritis (OA) of the knee or hip. This review identifies useful pain measures for assessing OA. Several disease-specific pain measures are discussed: Arthritis Impact Measurement Scales pain subscale, Western Ontario and McMaster University OA Index pain subscale, pain subscales of the Index of Severity for OA of the Hip or of the Knee, and Knee Pain Scale. Generic pain measures, the verbal descriptor scale, and the 21-point box scale, also are discussed. Because knee/hip OA is characterized by pain that is activated during or aggravated by certain activities, disease-specific pain scales that measure pain associated with these various activities are more effective than a generic pain scale. PMID:12714963
Tsai, Pao-Feng; Tak, Sunghee
Shoulder pain may occur as a secondary symptom to a wide range of conditions, including rotator cuff disorders, glenohumeral osteoarthritis, or adhesive capsulitis. One common factor linking these diseases is inflammation. Understanding the role of inflammation in shoulder disorders can help physicians to manage and treat these common problems. Here, I document a perspective on these pathologies of shoulder. PMID:19224130
The objective of this report was to conduct a search of the published literature on the use of S-adenosyl-L-methionine (SAMe) for the treatment of osteoarthritis, depression, and liver disease, and on the basis of that search, to evaluate the evidence for...
Osteoarthritis of the shoulder is a gradual wearing of the articular cartilage that leads to pain and stiffness. As the joint surface degenerates, the subchondral bone remodels, losing its sphericity and congruity. The joint capsule also becomes thickened, leading to further loss of shoulder rotation. This painful condition is a growing problem in the aging population. In most cases, diagnosis of degenerative joint disease of the shoulder can be made with careful history, physical examination, and radiography. The symptoms and degree of shoulder arthritis visible on radiography determine the best treatment option. Mild degenerative joint disease can be treated with physical therapy and over-the-counter anti-inflammatory medications such as acetaminophen or nonsteroidal anti-inflammatory drugs. More advanced cases of osteoarthritis that are refractory to nonoperative management can be managed with corticosteroid injections. In severe cases, surgery is indicated. Surgical options include arthroscopic debridement, arthroscopic capsular release, and, in the most severe instances, hemiarthroplasty or total shoulder arthroplasty. PMID:18788237
Millett, Peter J; Gobezie, Reuben; Boykin, Robert E
Joint pain may result from traumas or repeated microtraumas, as in sports injuries. Pain in osteoarthritis starts before any\\u000a objective finding. It has been demonstrated that in the first stages of this disease, pain is due to intraosseous venous engorgement\\u000a for the earlier thickening of the cortical bone under the articular cartilage. The mechanisms of inflammatory pain are more\\u000a complex
Massimo Zoppi; Elisabetta Beneforti
Nociceptive impulse activity was recorded extracellularly from single A delta and C primary afferents of the guinea pig's medial articular nerve after induction of an experimental osteoarthritis in the knee joint by partial medial menisectomy and transection of the anterior cruciate ligament (PMM+TACL). Also, the analgesic effects of intra-articular hyaluronan solutions were evaluated. Healthy, PMM+TACL operated, sham-operated (opening of the joint capsule without PMM and TACL surgery) and acutely inflamed (intra-articular kaolin-carrageenan, K-C) animals were used. The stimulus protocol consisted of torque meter-controlled, standardized innocuous and noxious inward and outward rotations of the joint. This stimulus protocol of 50 s duration was repeated every 5 min for 70 min. One day, one week and three weeks after PMM+TACL, the movement-evoked discharges of A delta articular afferents were increased significantly over values found in sham-operated animals. The discharges of C fibers were significantly augmented only one week after PMM+TACL surgery. Filling of the joint cavity with a high viscosity hyaluronan solution (hylan G-F 20, Synvisc) immediately and three days after surgery reduced significantly the enhanced nerve activity observed in joint afferent fibers one day and one week after surgery. Augmentation of movement-evoked discharges in K-C acutely inflamed knee joints was similar to that observed one week after PMM+TACL. Our results indicate that in the PMM+TACL model of osteoarthritis in guinea pigs, enhancement of nociceptive responses to joint movement was primarily associated to post-surgical inflammation. Intra-articular injection of an elastoviscous hyaluronan solution reduced the augmented nerve activity. PMID:17197090
Gomis, Ana; Miralles, Ana; Schmidt, Robert F; Belmonte, Carlos
The therapeutic management of patients with osteoarthritis aims to decrease pain and inflammation, improve physical function, and to apply safe and effective treatments. A patient-centered approach implies the active participation of the patient in the design of the treatment plan and in timely and informed decision-making at all stages of the disease. The nucleus of treatment is patient education, physical activity and therapeutic exercise, together with weight control in overweight or obese patients. Self-care by the individual and by the family is fundamental in day-to-day patient management. The use of physical therapies, technical aids (walking sticks, etc.) and simple analgesics, opium alkaloids, and antiinflammatory drugs have demonstrated effectiveness in controlling pain, improving physical function and quality of life and their use is clearly indicated in the treatment of osteoarthritis. Conservative surgery and joint replacement is indicated when treatment goals are not achieved in specific patients. PMID:24467960
Vargas Negrín, Francisco; Medina Abellán, María D; Hermosa Hernán, Juan Carlos; de Felipe Medina, Ricardo
Background Osteoarthritis affecting the first metatarsophalangeal joint of the foot is a common condition which results in pain, stiffness and impaired ambulation. Footwear modifications and foot orthoses are widely used in clinical practice to treat this condition, but their effectiveness has not been rigorously evaluated. This article describes the design of a randomised trial comparing the effectiveness of rocker-sole footwear and individualised prefabricated foot orthoses in reducing pain associated with first metatarsophalangeal joint osteoarthritis. Methods Eighty people with first metatarsophalangeal joint osteoarthritis will be randomly allocated to receive either a pair of rocker-sole shoes (MBT® Matwa, Masai Barefoot Technology, Switzerland) or a pair of individualised, prefabricated foot orthoses (Vasyli Customs, Vasyli Medical™, Queensland, Australia). At baseline, the biomechanical effects of the interventions will be examined using a wireless wearable sensor motion analysis system (LEGSys™, BioSensics, Boston, MA, USA) and an in-shoe plantar pressure system (Pedar®, Novel GmbH, Munich, Germany). The primary outcome measure will be the pain subscale of the Foot Health Status Questionnaire (FHSQ), measured at baseline and 4, 8 and 12 weeks. Secondary outcome measures will include the function, footwear and general foot health subscales of the FHSQ, severity of pain and stiffness at the first metatarsophalangeal joint (measured using 100 mm visual analog scales), global change in symptoms (using a 15-point Likert scale), health status (using the Short-Form-12® Version 2.0 questionnaire), use of rescue medication and co-interventions to relieve pain, the frequency and type of self-reported adverse events and physical activity levels (using the Incidental and Planned Activity Questionnaire). Data will be analysed using the intention to treat principle. Discussion This study is the first randomised trial to compare the effectiveness of rocker-sole footwear and individualised prefabricated foot orthoses in reducing pain associated with osteoarthritis of the first metatarsophalangeal joint, and only the third randomised trial ever conducted for this condition. The study has been pragmatically designed to ensure that the findings can be implemented into clinical practice if the interventions are found to be effective, and the baseline biomechanical analysis will provide useful insights into their mechanism of action. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12613001245785
Background This study investigated 18F-fluorodeoxyglucose (18F-FDG) uptake at knee joints for determination of metabolic alteration in association with the advance of age and joint degeneration such as osteoarthritis (OA). Methods A total of 166 knees from 83 healthy persons who presented for routine health examination and positron emission tomography-computed tomography (PET/CT) were enrolled in this study. History of knee OA and joint symptoms and signs were reviewed. The maximum standardized uptake values (SUVmax) of cartilage and mean SUV (SUVmean) between the epiphyseal plates of femur and tibia were evaluated at knee joints. Assessment of radiological bony changes was performed using the Kallgren-Lawrence (K/L) grading system with reconstructed CT images of the knee. The joint symptoms and signs were counted and used for diagnosis of clinical and radiological OA of the knee. Results The SUVmean of the knee joints showed a remarkable increase with aging in females (r?=?0.503, p?0.01). Remarkable changes of SUVmean were observed with history of OA (p?0.01). The SUVmean of joint and the intra-articular SUVmax showed higher values in clinical and radiological OA than in normal joints (p?0.01). Joint-SUVmean showed significant correlation with OA severity graded according to K/L score (p?0.05). The intra-articular SUVmax showed a significant increase in symptomatic joints, indicating OA in correlation with the joint-SUVmean (p?=?0.01). Conclusions The increasing 18F-FDG uptakes of knee joints showed agreement with aging in females and clinical and radiological knee OA, indicating that the metabolic alterations were consistent with diagnosis and demographic aspect of OA as a surrogate marker for degeneration of the knee in association with aging.
Osteoarthritis (OA) is the most frequent cause of disability in the USA, affecting up to 32.8% of patients over the age of sixty. Treatment of shoulder OA is often controversial and includes both nonoperative and surgical modalities. Nonoperative modalities should be utilized before operative treatment is considered, particularly for patients with mild-to-moderate OA or when pain and functional limitations are modest despite more advanced radiographic changes. If conservative options fail, surgical treatment should be considered. Although different surgical procedures are available, as in other joints affected by severe OA, the most effective treatment is joint arthroplasty. The aim of this work is to give an overview of the currently available treatments of shoulder OA.
Purpose To evaluate the long-term clinical and radiographic outcomes of trapeziectomy with abductor pollicis longus tendon interposition arthroplasty for moderate to severe osteoarthritis of the thumb carpometacarpal joint (Eaton stages III-IV). Methods We evaluated 13 patients (15 thumbs) who underwent trapeziectomy and abductor pollicis longus tendon interposition arthroplasty for end-stage osteoarthritis of the thumb carpometacarpal joint, at an average follow-up of 15 years. Subjective clinical outcomes evaluated included visual analogue scale scores and disability of arm shoulder and hand score questionnaires. Objective clinical evaluation included lateral pinch and grip tests, and a range of active and passive thumb movements. All patients underwent a radiological assessment by two independent senior radiologists. Wherever possible, results obtained from the operated thumbs were compared to the non-operated side. Results At a mean of 15 years post operation (range 15–17 years), there was no statistical difference between the operated and non-operated hands with regards to grip and pinch strength. In all cases CMC and MCPJ range of motion in the operative hand was either equal to or greater than non-operative counterparts. Mean visual analogue scale score was 2.13 and mean DASH score was 16.85. Mean carpal height was 0.52 and mean trapezial space ratio was 0.163. There were no early or late complications recorded and no revision surgery was required. Conclusion It is the opinion of these authors that abductor pollicis longus tendon interposition arthroplasty is able to provide high-quality long-term results for patients who suffer from moderate to severe osteoarthritis of the thumb carpometacarpal joint. Level of evidence Therapeutic Level IV.
Avisar, Erez; Elvey, Michael; Wasrbrout, Ziv; Aghasi, Maurice
Metalloproteinases such as the matrix metalloproteinases (MMPs) and disintegrin-metalloproteinases with thrombospondin motifs (ADAMTSs) have been implicated in the pathological destruction of joint tissues in rheumatoid arthritis and osteoarthritis. These enzymes degrade extracellular matrix macromolecules and modulate factors governing cell behavior. They may also be involved in tissue repair, but become a part of the destructive disease process due to overexpression.
Gillian Murphy; Hideaki Nagase
Different thresholds for detecting osteophytes and joint space narrowing exist between the site investigators and the centralized reader in a multicenter knee osteoarthritis study--data from the Osteoarthritis Initiative
Objective To evaluate how the reading of knee radiographs by site investigators differs from that by an expert musculoskeletal radiologist who trained and validated them in a multicenter knee osteoarthritis (OA) study. Materials and methods A subset of participants from the Osteoarthritis Initiative progression cohort was studied. Osteophytes and joint space narrowing (JSN) were evaluated using Kellgren-Lawrence (KL) and Osteoarthritis Research Society International (OARSI) grading. Radiographs were read by site investigators, who received training and validation of their competence by an expert musculoskeletal radiologist. Radiographs were re-read by this radiologist, who acted as a central reader. For KL and OARSI grading of osteophytes, discrepancies between two readings were adjudicated by another expert reader. Results Radiographs from 96 subjects (49 women) and 192 knees (138 KL grade?2) were included. The site reading showed moderate agreement for KL grading overall (kappa=0.52) and for KL?2 (i.e., radiographic diagnosis of “definite OA”; kappa=0.41). For OARSI grading, the site reading showed substantial agreement for lateral and medial JSN (kappa=0.65 and 0.71), but only fair agreement for osteophytes (kappa=0.37). For KL grading, the adjudicator’s reading showed substantial agreement with the centralized reading (kappa=0.62), but only slight agreement with the site reading (kappa=0.10). Conclusion Site investigators over-graded osteophytes compared to the central reader and the adjudicator. Different thresholds for scoring of JSN exist even between experts. Our results suggest that research studies using radiographic grading of OA should use a centralized reader for all grading.
Guermazi, Ali; Hunter, David J.; Li, Ling; Benichou, Olivier; Eckstein, Felix; Kwoh, C. Kent; Nevitt, Michael
Osteoarthritis (OA) is considered a multifactorial disease whose development and progression may include several structural\\u000a abnormalities aside from cartilage destruction. Bone marrow lesions (BMLs) have been reported to be associated with OA pathology,\\u000a and several studies have advocated its close connection to the severity of joint structural alterations and pain, the main\\u000a OA clinical manifestation. Hence, BMLs may not only
Massoud Daheshia; Jian Q. Yao
Digital osteoarthritis relates to primarily the distal interphalangeal (DIP) and first carpometacarpal (CMC-I) joints. Heberden's nodes often accompany osteoarthritis of the DIP joints. Osteoarthritis of the PIP joints can be more painful and more inflammatory. It can be at the origin of Bouchard's nodes. The DIP and the PIP joints can be the seat of erosive lesions. Osteoarthritis of the MCP joints is rare. Osteoarthritis of the CMC-I joint is sometimes at the origin of a deformity of the thumb impairing its function and an atrophy of the thenar muscles. Treatment includes non-pharmacological and pharmacological modalities. Surgery is proposed after failure of the conservative approach. PMID:20408461
Van Linthoudt, Daniel
Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from the iliac crest, depending on age and overall physical fitness. Here, we analyzed whether the availability and chondrogenic differentiation capacity
Alwin Scharstuhl; Bernhard Schewe; Karin Benz; Christoph Gaissmaier; H. J. Buhring; Reinout Stoop
Osteoarthritis (OA) encompassed a large and heterogeneous number of disorders affecting joints and bones, which culminate in a joint failure. In general, OA can be defined as a degenerative disease characterized by biomechanical and architectural deteriorations of the articular cartilage. After the age of 60 years, more than 80% of the people have radiological signs of OA in the knee,
PEI-HSI CHOU; SHEN-KAI CHEN; YOU-LI CHOIA; SIU-WAI LEE; FONG-CHING SU; TING-SHENG LIN
Objective Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. Design We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20–100%), pain relief (10–100%), major toxicity (0.1–2%), and cost ($1,000–$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. Results Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and $230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15%. Cost-effectiveness was most sensitive to likelihoods of suspended progression and pain relief. DMOADs costing $3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20% and 70%. At a cost of $5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. Conclusions Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria.
Losina, Elena; Daigle, Meghan E.; Reichmann, William M.; Suter, Lisa G.; Hunter, David J.; Solomon, Daniel H.; Walensky, Rochelle P.; Jordan, Joanne M.; Burbine, Sara A.; Paltiel, A. David; Katz, Jeffrey N.
Osteoarthritis (degenerative joint disease) is the most common joint disorder. It mostly affects cartilage. The top layer of cartilage breaks down and wears away. Osteoarthritis is of two types, primary (idiopathic) and secondary. In idiopathic osteoarthritis, the most common form of the disease, no predisposing factor is apparent. Secondary OA is pathologically indistinguishable from idiopathic OA but is attributable to an underlying cause. In Ayurveda the disease Sandhivata resembles with osteoarthritis which is described under Vatavyadhi. The NSAIDs are the main drugs of choice in modern medicine which have lots of side effects and therefore are not safe for long-term therapy. Raktamokshan, i.e., blood letting is one of the ancient and important parasurgical procedures described in Ayurveda for treatment of various diseases. Of them, Jalaukavacharana or leech therapy has gained greater attention globally, because of its medicinal values. The saliva of leech contains numerous biologically active substances, which have antiinflammatory as well as anesthetic properties. Keeping this view in mind we have started leech therapy in the patients of osteoarthritis and found encouraging results.
Rai, P. K.; Singh, A. K.; Singh, O. P.; Rai, N. P.; Dwivedi, A. K.
Objective It is widely believed that there are multiple sources of pain at a tissue level in osteoarthritis (OA). MRIs provide a wealth of anatomic information and may allow identification of specific features associated with pain. We hypothesized that in knees with OA, bone marrow lesions (BMLs), synovitis, and effusion would be associated with weight-bearing and (less so with) non-weight-bearing pain independently. Methods In a cross-sectional study of persons with symptomatic knee OA using univariate and multivariate logistic regressions with maximal BML, effusion, and synovitis defined by Boston Leeds Osteoarthritis Knee Score as predictors, and knee pain using weight-bearing and non-weight-bearing Western Ontario and McMaster University OA Index pain questions as the outcome, we tested the association between MRI findings and knee symptoms Results 160 participants, mean age 61 (±9.9), mean BMI 30.3 (±4.7) and 50% female, stronger associations were seen with weight-bearing compared with non-weight-bearing knee pain with adjusted risk ratios (RRs) of weight-bearing knee pain, for increasing maximal BML scores of 1.0 (referent) (maximal BML = 0), 1.2, 1.9, and 2.0 (p for trend = 0.006). For effusion scores, adjusted ORs of knee pain were 1.0, 1.7, 2.0, and 2.6 (p for trend = 0.0004); and for synovitis scores, adjusted ORs were 1.0, 1.4, 1.5, and 1.9 (p for trend = 0.22). Conclusion Cross-sectionally, maximal BML and effusion scores are independently associated with weight-bearing and less so with non-weight-bearing knee pain, supporting the idea that pain in OA is multifactorial. These MRI features should be considered as possible new treatment targets in knee OA.
Lo, GH; McAlindon, TE; Niu, J; Zhang, Y; Beals, C; Dabrowski, C; Hellio Le Graverand, MP; Hunter, DJ
Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging population. Obesity is an important risk factor for initiation and progression of OA. It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints. However, emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people. Adipocyte-derived molecules ‘‘adipokines’’ have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis. Therefore, the aim of this review is to summarize the current knowledge on the role of adipokines including leptin, adiponectin, visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis, classifying disease severity, monitoring disease progression, and testing pharmacological interventions for OA. In OA patients, leptin, visfatin and resistin showed increased production whereas adiponectin showed decreased production. Leptin and adiponectin are far more studied than visfatin and resistin. Importantly, altered adipokine levels also contribute to a wide range of diseases. Further experiments are still crucial for understanding the relationship between adipokines and OA.
Poonpet, Thitiya; Honsawek, Sittisak
Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging population. Obesity is an important risk factor for initiation and progression of OA. It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints. However, emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people. Adipocyte-derived molecules ''adipokines'' have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis. Therefore, the aim of this review is to summarize the current knowledge on the role of adipokines including leptin, adiponectin, visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis, classifying disease severity, monitoring disease progression, and testing pharmacological interventions for OA. In OA patients, leptin, visfatin and resistin showed increased production whereas adiponectin showed decreased production. Leptin and adiponectin are far more studied than visfatin and resistin. Importantly, altered adipokine levels also contribute to a wide range of diseases. Further experiments are still crucial for understanding the relationship between adipokines and OA. PMID:25035835
Poonpet, Thitiya; Honsawek, Sittisak
Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2–7.2), BS2: 4.8%, 95% CI: 3.8–5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ? 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA.
Zamli, Zaitunnatakhin; Adams, Michael A.; Tarlton, John F.; Sharif, Mohammed
Osteoarthritis and falls are common conditions affecting older individuals which are associated with disability and escalating health expenditure. It has been widely assumed that osteoarthritis is an established risk factor for falls in older people. The relationship between osteoarthritis and falls has, quite surprisingly, not been adequately elucidated, and published reports have been conflicting. Our review of the existing literature has found limited evidence supporting the current assumption that the presence of osteoarthritis is associated with increased risk of falls with suggestions that osteoarthritis may actually be protective against falls related fractures. In addition, joint arthroplasty appears to increase the risk of falls in individuals with osteoarthritis. PMID:23864423
Ng, Chin Teck; Tan, Maw Pin
The osteoarthritis disease process affects not only the cartilage but also the entire joint structure, including the synovium, bone and periarticular muscles. Characteristically, abnormal biomechanical forces result in an imbalance between chondrocyte anabolic and catabolic pathways, which ultimately leads to progressive joint destruction. Within cartilage and synovium, pro-inflammatory cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own production and induce
Steven B. Abramson; Yusuf Yazici
The radiological and tomographic aspects of the sternoclavicular joint were examined in 10 patients with psoriatic arthritis to evaluate better how this joint was affected using different radiological techniques. Imaging of the sternoclavicular joint showed that computed tomography provides a better visualisation of erosions, subchondral cysts, and sclerosis than standard radiography and conventional linear tomography. Images
Taccari, E; Spadaro, A; Riccieri, V; Guerrisi, R; Guerrisi, V; Zoppini, A
Pain in the peripheral joints is an increasingly common problem, resulting in significant patient disability and health-care expenditure. Osteoarthritis (OA), a syndrome of joint pain with associated structural changes, is the most prevalent joint disease, yet the etiology of pain in OA is not entirely clear. Traditional assessment of the structure–pain relationship in knee OA has relied on conventional radiography,
Claire YJ Wenham; Philip G Conaghan
The association of hydroxyapatite deposition with osteoarthritis pathogenesis and progression remains controversial, even\\u000a after decades of study. Hydroxyapatite crystals are found in osteoarthritis in advanced disease only. Even then, hydroxyapatite\\u000a crystals are found in such small amounts that special analytical techniques are required to detect the crystals. Further,\\u000a the osteoarthritic joint fluid appears noninflammatory, suggesting that such hydroxyapatite crystals have
Kenneth P. H. Pritzker
Shoulder pain may occur as a secondary symptom to a wide range of conditions, including rotator cuff disorders, glenohumeral\\u000a osteoarthritis, or adhesive capsulitis. One common factor linking these diseases is inflammation. Understanding the role of\\u000a inflammation in shoulder disorders can help physicians to manage and treat these common problems. Here, I document a perspective\\u000a on these pathologies of shoulder.
Articular cartilage extracellular matrix and cell function change with age and are considered to be the most important factors in the development and progression of osteoarthritis. The multifaceted nature of joint disease indicates that the contribution of cell death can be an important factor at early and late stages of osteoarthritis. Therefore, the pharmacologic inhibition of cell death is likely to be clinically valuable at any stage of the disease. In this article, we will discuss the close association between diverse changes in cartilage aging, how altered conditions influence chondrocyte death, and the implications of preventing cell loss to retard osteoarthritis progression and preserve tissue homeostasis.
Grogan, Shawn P; D'Lima, Darryl D
Osteoarthritis is a degenerative articular disease with complex pathogeny because diverse factors interact causing a process of deterioration of the cartilage. Despite the multifactorial nature of this pathology, from the 50’s it´s known that certain forms of osteoarthritis are related to a strong genetic component. The genetic bases of this disease do not follow the typical patterns of mendelian inheritance and probably they are related to alterations in multiple genes. The identification of a high number of candidate genes to confer susceptibility to the development of the osteoarthritis shows the complex nature of this disease. At the moment, the genetic mechanisms of this disease are not known, however, which seems clear is that expression levels of several genes are altered, and that the inheritance will become a substantial factor in future considerations of diagnosis and treatment of the osteoarthritis.
Fernandez-Moreno, Mercedes; Rego, Ignacio; Carreira-Garcia, Vanessa; Blanco, Francisco J
Osteoarthritis is a progressive joint disease characterized by cartilage degradation and bone remodeling. Transglutaminases\\u000a catalyze a calcium-dependent transamidation reaction that produces covalent cross-linking of available substrate glutamine\\u000a residues and modifies the extracellular matrix. Increased transglutaminases-mediated activity is reported in osteoarthritis,\\u000a but the relative contribution of transglutaminases-2 (TG2) is uncertain. We describe TG2 expression in human femoral osteoarthritis\\u000a and in wild-type
A. Orlandi; F. Oliva; G. Taurisano; E. Candi; A. Di Lascio; G. Melino; L. G. Spagnoli; U. Tarantino
Osteoarthritis is a common joint disease that currently lacks disease-modifying treatments. Development of therapeutic agents for osteoarthritis requires better understanding of the disease and cost-effective in vivo models that mimic the human disease. Here, we analyzed the joints of STR/ort mice, a model for spontaneous osteoarthritis, for levels of inflammatory and oxidative stress markers and measured serum cytokines to characterize the local and systemic inflammatory status of these mice. Markers of low-grade inflammatory and oxidative stress—RAGE, AGE, S100A4, and HMGB1—were evaluated through immunohistochemistry. Of these, AGE and HMGB1 levels were elevated strongly in hyperplastic synovium, cartilage, meniscus, and ligaments in the joints of STR/ort mice compared with CBA mice, an osteoarthritis-resistant mouse strain. These increases (particularly in the synovium, meniscus, and ligaments) correlated with increased histopathologic changes in the cartilage. Serum analysis showed higher concentrations of several cytokines including IL1?, IL12p70, MIP1?, and IL5 in STR/ort mice, and these changes correlated with worsened joint morphology. These results indicate that STR/ort mice exhibited local and systemic proinflammatory conditions, both of which are present in human osteoarthritis. Therefore, the STR/ort mouse model appears to be a clinically relevant and cost-effective small animal model for testing osteoarthritis therapeutics.
Nambiar, Bindu; Hutto, Elizabeth; Ewing, Patty J; Piraino, Susan; Berthelette, Patricia; Sookdeo, Cathleen; Matthews, Gloria; Armentano, Donna
Osteoarthritis is a common joint disease that currently lacks disease-modifying treatments. Development of therapeutic agents for osteoarthritis requires better understanding of the disease and cost-effective in vivo models that mimic the human disease. Here, we analyzed the joints of STR/ort mice, a model for spontaneous osteoarthritis, for levels of inflammatory and oxidative stress markers and measured serum cytokines to characterize the local and systemic inflammatory status of these mice. Markers of low-grade inflammatory and oxidative stress-RAGE, AGE, S100A4, and HMGB1-were evaluated through immunohistochemistry. Of these, AGE and HMGB1 levels were elevated strongly in hyperplastic synovium, cartilage, meniscus, and ligaments in the joints of STR/ort mice compared with CBA mice, an osteoarthritis-resistant mouse strain. These increases (particularly in the synovium, meniscus, and ligaments) correlated with increased histopathologic changes in the cartilage. Serum analysis showed higher concentrations of several cytokines including IL1?, IL12p70, MIP1?, and IL5 in STR/ort mice, and these changes correlated with worsened joint morphology. These results indicate that STR/ort mice exhibited local and systemic proinflammatory conditions, both of which are present in human osteoarthritis. Therefore, the STR/ort mouse model appears to be a clinically relevant and cost-effective small animal model for testing osteoarthritis therapeutics. PMID:22330250
Kyostio-Moore, Sirkka; Nambiar, Bindu; Hutto, Elizabeth; Ewing, Patty J; Piraino, Susan; Berthelette, Patricia; Sookdeo, Cathleen; Matthews, Gloria; Armentano, Donna
INTRODUCTION: The pharmacological management of osteoarthritis normally begins with the administration of acetaminophen or a nonselective nonsteroidal anti-inflammatory drug. However, acetaminophen may not be efficacious in all patients, and nonsteroidal anti-inflammatory drugs may be associated with gastrointestinal and cardiovascular adverse effects. CASE PRESENTATION: A 79-year-old Caucasian man with bilateral hip pain was diagnosed with osteoarthritis of the hip. His past
Jennifer Yanow; Marco Pappagallo
The relationship between long-term ballet dancing and eventual arthrosis of the hip, ankle, subtalar, and first metatarsophalangeal joint was examined in 19 former professional female dancers, aged 50 to 70 years. The dancers were compared with pair-matched controls. All 38 women underwent medical history taking, clinical ex amination, and roentgenography of the joints studied. The roentgenographs were independently judged by
C. Niek van Dijk; Liesbeth S. L. Lim; Alina Poortman; Ernst H. Strübbe; Rene K. Marti
Osteoarthritis (OA) is a disease of the entire joint. Different treatment strategies for OA have been proposed and tested\\u000a clinically without the desired efficacy. One reason for the scarcity of current chondroprotective agents may be the insufficient\\u000a understanding of the patho-physiology of the joint and whether the joint damage is reversible or irreversible. In this review,\\u000a we compile emerging data
Anne-Christine Bay-JensenSuzi; Suzi Hoegh-Madsen; Erik Dam; Kim Henriksen; Bodil Cecillie Sondergaard; Philippe Pastoureau; Per Qvist; Morten A. Karsdal
Diacerein and its active metabolite rhein are promising disease modifying agents for osteoarthritis (OA). Boswellic acid is an active ingredient of Gugglu; a herbal medicine commonly administered in osteoarthritis. Both of them possess excellent anti-inflammatory and anti-arthritic activities. It was thought interesting to conjugate rhein and boswellic acid into a mutual prodrug (DSRB) and evaluate its efficacy on collagenase-induced osteoarthritis in rats wherein the conjugate, rhein, boswellic acid and their physical mixture, were tested based on various parameters. Oral administration of 3.85 mg of rhein, 12.36 mg of boswellic acid and 15.73 mg of DSRB which would release equimolar amounts of rhein and boswellic acid, exhibited significant restoration in rat body weight as compared to the untreated arthritic control group. Increase in knee diameter (mm), due to edema was observed in group injected with collagenase, which reduced significantly with the treatment of conjugate. The hematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (CRP, SALP, SGOT and SGPT) in the osteoarthritic rats were significantly brought back to normal values on treatment with conjugate. It also showed better anti-ulcer activity than rhein. Further the histopathological studies revealed significant anti-arthritic activity of conjugate when compared with the arthritic control group. In conclusion, the conjugate at the specified dose level of 15.73 mg/kg, p. o. (BID) showed reduction in knee diameter and it could significantly normalize the hematological and biochemical abnormalities in collagenase-induced osteoarthritis in rats. Further the histopathological studies confirmed the additive anti-arthritic effect of DSRB as compared to plain rhein. PMID:23701173
Dhaneshwar, Suneela; Dipmala, Patil; Abhay, Harsulkar; Prashant, Bhondave
Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes
The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.
Raynauld, Jean-Pierre; Martel-Pelletier, Johanne; Berthiaume, Marie-Josee; Beaudoin, Gilles; Choquette, Denis; Haraoui, Boulos; Tannenbaum, Hyman; Meyer, Joan M; Beary, John F; Cline, Gary A; Pelletier, Jean-Pierre
Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes.
The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 +/- 3.0% for global cartilage and -5.5 +/- 4.3% for the medial compartment at 12 months, and -5.7 +/- 4.4% and -8.3 +/- 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression. PMID:16507119
Raynauld, Jean-Pierre; Martel-Pelletier, Johanne; Berthiaume, Marie-Josée; Beaudoin, Gilles; Choquette, Denis; Haraoui, Boulos; Tannenbaum, Hyman; Meyer, Joan M; Beary, John F; Cline, Gary A; Pelletier, Jean-Pierre
Objective. DIP joint OA is common but has few cost-effective, evidence-based interventions. Pain and deformity [radial or ulnar deviation of the joint or loss of full extension (extension lag)] frequently lead to functional and cosmetic issues. We investigated whether splinting the DIP joint would improve pain, function and deformity. Methods. A prospective, radiologist-blinded, non-randomized, internally controlled trial of custom splinting of the DIP joint was carried out. Twenty-six subjects with painful, deforming DIP joint hand OA gave written, informed consent. One intervention joint and one control joint were nominated. A custom gutter splint was worn nightly for 3 months on the intervention joint, with clinical and radiological assessment at baseline, 3 and 6 months. Differences in the change were compared by the Wilcoxon signed rank test. Results. The median average pain at baseline was similar in the intervention (6/10) and control joints (5/10). Average pain (primary outcome measure) and worst pain in the intervention joint were significantly lower at 3 months compared with baseline (P = 0.002, P = 0.02). Differences between intervention and control joint average pain reached significance at 6 months (P = 0.049). Extension lag deformity was significantly improved in intervention joints at 3 months and in splinted joints compared with matched contralateral joints (P = 0.016). Conclusion. Short-term night-time DIP joint splinting is a safe, simple treatment modality that reduces DIP joint pain and improves extension of the digit, and does not appear to give rise to non-compliance, increased stiffness or joint restriction. Trial registration: clinical trials.gov, http://clinicaltrials.gov, NCT01249391.
Kennedy, Donna L.; Carlisle, Katharine E.; Freidin, Andrew J.; Szydlo, Richard M.; Honeyfield, Lesley; Satchithananda, Keshthra; Vincent, Tonia L.
Three new software systems, Ingenuity pathway analysis(IPA, TranscriptomeBrowser and MetaCore, were compared by analyzing chondrocyte microarray data of Kashin-Beck disease (KBD) and primary knee osteoarthritis(OA) to understand the pathway or network analysis software which has a superior function to identify target genes with easy operation and effective for differential diagnosis and treatment of KBD and OA. RNA was isolated from cartilage samples taken from KBD patients and OA ones. Agilent 44K human whole genome oligonucleotide microarrays were used to detect differentially expressed genes. From IPA, we identified one significant canonical pathway and two significant networks. From GeneHub analysis, we got three networks. One significant canonical pathway and one significant network were obtained from TranscriptomeBrowser analysis. POSTN and LEF1 which were got from IPA, RAC2 which was identified by both of the IPA and TranscriptomeBrowser may be most closely related to the etiopathogenesis of KBD. According to our data analysis, IPA and TranscriptomeBrowser are suitable for pathway analysis, while, TranscriptomeBrowser is suitable for network analysis. The significant genes obtained from IPA and TranscriptomeBrowser analysis may thus provide a better understanding of the molecular details in the pathogenesis of KBD and also provide useful pathways and network maps for future research in osteochondrosis. PMID:23069848
Wang, Sen; Duan, Chen; Zhang, Feng; Ma, Weijuan; Guo, Xiong
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
Lotz, M; Martel-Pelletier, J; Christiansen, C; Brandi, M-L; Bruyere, O; Chapurlat, R; Collette, J; Cooper, C; Giacovelli, G; Kanis, J A; Karsdal, M A; Kraus, V; Lems, W F; Meulenbelt, I; Pelletier, J-P; Raynauld, J-P; Reiter-Niesert, S; Rizzoli, R; Sandell, L J; Van Spil, W E; Reginster, J-Y
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
Lotz, M; Martel-Pelletier, J; Christiansen, C; Brandi, M-L; Bruyere, O; Chapurlat, R; Collette, J; Cooper, C; Giacovelli, G; Kanis, J A; Karsdal, M A; Kraus, V; Lems, W F; Meulenbelt, I; Pelletier, J-P; Raynauld, J-P; Reiter-Niesert, S; Rizzoli, R; Sandell, L J; Van Spil, W E; Reginster, J-Y
Taping can be used to reduce pain in knee osteoarthritis. There are different methods of taping, but the common effect is to exert a medially directed force on the patella to increase the patellofemoral contact area, thereby decreasing joint stress and reducing pain. Taping can be performed by a physiotherapist, but self taping can be taught, which enhances self management. Taping for knee osteoarthritis has National Health and Medical Research Council (NHMRC) Level I evidence of efficacy for pain relief and is associated with negligible adverse effects that generally include minor skin irritation. PMID:24130976
This update develops the actual therapeutic options in the management of the joint involvement of calcium pyrophosphate deposition disease (CPPD), basic calcium phosphate (BCP) deposition disease, hemochromatosis (HH), ochronosis, oxalosis, and Wilson's disease. Conventional pharmaceutical treatment provides benefits for most diseases. Anti-interleukine-1 (IL-1) treatment could provide similar results in CPPD than in gout flares. There is only limited evidence about the efficacy of preventive long-term colchicine intake, methotrexate, and hydroxychloroquine in chronic CPPD. Needle aspiration and lavage have satisfactory short and midterm results in BCP. Extracorporeal shockwave therapy has also proved its efficacy for high-doses regimes. Phlebotomy does not seem to have shown real efficacy on joint involvement in HH so far. Iron chelators' effects have not been assessed on joint involvement either, while IL-1 blockade may prove useful. NSAIDs have limited efficacy on joint involvement of oxalosis, while colchicine and steroids have not been assessed either. The use of nitisinone for ochronotic arthropathy is still much debated, but it could provide beneficial effects on joint involvement. The effects of copper chelators have not been assessed either in the joint involvement of Wilson's disease. NSAIDs should be avoided because of the liver affection they may worsen.
Richette, Pascal; Flipo, Rene-Marc
This update develops the actual therapeutic options in the management of the joint involvement of calcium pyrophosphate deposition disease (CPPD), basic calcium phosphate (BCP) deposition disease, hemochromatosis (HH), ochronosis, oxalosis, and Wilson's disease. Conventional pharmaceutical treatment provides benefits for most diseases. Anti-interleukine-1 (IL-1) treatment could provide similar results in CPPD than in gout flares. There is only limited evidence about the efficacy of preventive long-term colchicine intake, methotrexate, and hydroxychloroquine in chronic CPPD. Needle aspiration and lavage have satisfactory short and midterm results in BCP. Extracorporeal shockwave therapy has also proved its efficacy for high-doses regimes. Phlebotomy does not seem to have shown real efficacy on joint involvement in HH so far. Iron chelators' effects have not been assessed on joint involvement either, while IL-1 blockade may prove useful. NSAIDs have limited efficacy on joint involvement of oxalosis, while colchicine and steroids have not been assessed either. The use of nitisinone for ochronotic arthropathy is still much debated, but it could provide beneficial effects on joint involvement. The effects of copper chelators have not been assessed either in the joint involvement of Wilson's disease. NSAIDs should be avoided because of the liver affection they may worsen. PMID:24895535
Pascart, Tristan; Richette, Pascal; Flipo, René-Marc
Most commonly affected joints of the hand in osteoarthritis include the carpometacarpal joint of the thumb (CMC 1) and the distal (DIP) and proximal (PIP) interphalangeal joints. Ageing, female gender, genotype, heavy work causing pressure on the hands, and injuries predispose to osteoarthritis in the hand. The pain is likely to be due to secondary synovitis caused by molecules released from the joint cartilage. Initial treatment of osteoarthritis is always conservative: analgesic medication, splint and physiotherapy. Surgery is considered for severe symptoms. The most common procedures include arthrodeses and arthroplasties with autogenous grafts or implants. PMID:22448556
Waris, Eero; Waris, Ville; Konttinen, Yrjö T
Osteoarthritis (OA) is a common disease in aging dogs and cats but frequently goes undiagnosed and untreated. Although OA cannot be cured, long-term management of the disease can be very rewarding for the veterinary medical team as well as pet owners. Managing pain with pain medications is an essential first step. There are a wealth of pain medications available, including nonsteroidal antiinflammatory drugs, gabapentin, amantadine, and tramadol. There are also physical modalities available for pain reduction. Weight management and nutritional joint support are also important in aspects of managing OA in dogs and cats. Finally, physical rehabilitation is a great way to improve mobility and keep pets active as they age. PMID:20188335
Rychel, Jessica K
Summary Objective To examine racial differences in tibiofemoral joint (TFJ) and patellofemoral joint (PFJ) radiographic osteoarthritis in African-American (AA) and Caucasian men and women. Method Multiple logistic regression was used to evaluate cross-sectional associations between race and tibiofemoral osteoarthritis (TF-OA) and the presence, severity and location of individual radiographic features of tibiofemoral joint osteoarthritis [TFJ-OA] (osteophytes, joint space narrowing [JSN], sclerosis and cysts) and patellofemoral joint osteoarthritis (PFJ-OA) (osteophytes, JSN and sclerosis), using data from the Johnston County Osteoarthritis Project. Proportional odds ratios (POR) assessed severity of TF-OA, TFJ and PFJ osteophytes, and JSN, adjusting for confounders. Generalized estimating equations accounted for auto-correlation of knees. Results Among 3187 participants (32.5% AAs; 62% women; mean age 62 years), 6300 TFJ and 1957 PFJ were included. Compared to Caucasians, AA men were more likely to have TF-OA (adjusted odds ratio [aOR] = 1.36; 95% CI, 1.00–1.86); tri-compartmental TFJ and PFJ osteophytes (aOR = 3.06; 95%CI = 1.96–4.78), and TFJ and PFJ sclerosis. AA women were more likely than Caucasian to have medial TFJ and tri-compartmental osteophytes (aOR = 2.13; 1.55–2.94), and lateral TFJ sclerosis. AAs had more severe TF-OA than Caucasians (adjusted cumulative odds ratio [aPOR] = 2.08; 95% CI, 1.19–3.64 for men; aPOR = 1.56; 95% CI, 1.06–2.29 for women) and were more likely to have lateral TFJ JSN. Conclusions Compared to Caucasians, AAs were more likely to have more severe TF-OA; tri-compartmental disease; and lateral JSN. Further research to clarify the discrepancy between radiographic features in OA among races appears warranted.
Braga, L.; Renner, J. B.; Schwartz, T. A.; Woodard, J.; Helmick, C. G.; Hochberg, M. C.; Jordan, J. M.
Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and white matter damages. However, the interrelationship of volumetric changes between grey and white matter remains poorly understood in AD. Using joint independent component analysis, this study identified joint grey and white matter volume reductions based on structural magnetic resonance imaging data to construct the covariant networks in twelve AD patients and fourteen normal controls (NC). We found that three networks showed significant volume reductions in joint grey–white matter sources in AD patients, including (1) frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2) temporal/parietal/occipital-frontal/occipital, and (3) temporal-precentral/postcentral. The corresponding expression scores distinguished AD patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2 and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2 and 3, respectively. Furthermore, the combined source of three significant joint sources best predicted the AD/NC group membership with 92.9% sensitivity and 83.3% specificity. Our findings revealed joint grey and white matter loss in AD patients, and these results can help elucidate the mechanism of grey and white matter reductions in the development of AD.
Guo, Xiaojuan; Han, Yuan; Chen, Kewei; Wang, Yan; Yao, Li
A summary of the evidence linking exercise and osteoarthritis is given in the table. In summary, normal joints appear to tolerate prolonged vigorous low impact exercise without accelerated development of osteoarthritis. The risk of developing osteoarthritis appears to be increased in sporting activities that continually expose normal joints to high levels of impact or torsional loading and in individuals who continue sporting activities after they have injured supporting structures in the joint (like ligaments, tendons, and menisci). The hypothesis that high impact loads to joints over time will accelerate the development of osteoarthritis in exposed joints must now be examined in a longitudinal study.
Lane, N E
Abstract The extracts of Scutellaria baicalensis and Acacia catechu have been shown in previous studies to alleviate joint discomfort, reduce stiffness, and improve mobility by reducing the production of proinflammatory molecules over long periods of supplementation. The acute effects of intake of these extracts have not yet been investigated. Thus, we carried out a 1 week clinical trial to examine the extent to which UP446—a natural proprietary blend of S. baicalensis and A. catechu (UP446)—decreases knee joint pain, mobility, and biomarkers of inflammation in comparison to naproxen. Seventy-nine men and women (40–90 years old) diagnosed as having mild to moderate osteoarthritis (OA) consumed either 500?mg/day of the UP446 supplement or 440?mg/day of naproxen for 1 week in a double-blind randomized control trial. Pain, knee range of motion (ROM), and overall physical activity were evaluated at the start and at the end of treatment. Fasting blood was collected to determine serum interleukins 1? and 6, tumor necrosis factor-?, C-reactive protein, and hyaluronic acid. The UP446 group experienced a significant decrease in perceived pain (P=.009) time dependently. Stiffness was significantly reduced by both treatments (P=.002 UP446, P=.008 naproxen). Significant increases in mean ROM over time (P=.04) were found in the UP446 group. These findings suggest that UP446 is effective in reducing the physical symptoms associated with knee OA.
Ormsbee, Lauren T.; Elam, Marcus L.; Campbell, Sara C.; Rahnama, Nader; Payton, Mark E.; Brummel-Smith, Ken; Daggy, Bruce P.
Abstract The extracts of Scutellaria baicalensis and Acacia catechu have been shown in previous studies to alleviate joint discomfort, reduce stiffness, and improve mobility by reducing the production of proinflammatory molecules over long periods of supplementation. The acute effects of intake of these extracts have not yet been investigated. Thus, we carried out a 1 week clinical trial to examine the extent to which UP446-a natural proprietary blend of S. baicalensis and A. catechu (UP446)-decreases knee joint pain, mobility, and biomarkers of inflammation in comparison to naproxen. Seventy-nine men and women (40-90 years old) diagnosed as having mild to moderate osteoarthritis (OA) consumed either 500?mg/day of the UP446 supplement or 440?mg/day of naproxen for 1 week in a double-blind randomized control trial. Pain, knee range of motion (ROM), and overall physical activity were evaluated at the start and at the end of treatment. Fasting blood was collected to determine serum interleukins 1? and 6, tumor necrosis factor-?, C-reactive protein, and hyaluronic acid. The UP446 group experienced a significant decrease in perceived pain (P=.009) time dependently. Stiffness was significantly reduced by both treatments (P=.002 UP446, P=.008 naproxen). Significant increases in mean ROM over time (P=.04) were found in the UP446 group. These findings suggest that UP446 is effective in reducing the physical symptoms associated with knee OA. PMID:24611484
Arjmandi, Bahram H; Ormsbee, Lauren T; Elam, Marcus L; Campbell, Sara C; Rahnama, Nader; Payton, Mark E; Brummel-Smith, Ken; Daggy, Bruce P
Arthroscopy of the hip joint has developed into a useful tool for the hip surgeon. Hip joint anatomy, however, makes special demands of the arthroscopist. He needs to be familiar with the arthroscopic anatomy of the hip and its variations. Moreover, he should have practical training in the technique of hip arthroscopy prior to his first intraoperative experience in order to avoid complications. A complete arthroscopic inspection of the hip can be achieved by using a combined procedure: whereas the central hip compartment can be scoped only by distraction of the joint, the periphery can be better seen without traction. Whether to place the patient supine or lateral is dependent on personal experience. No matter which position is used, the positioning technique has to be exact. The literature has shown that most complications are related to traction. Before the first portal is placed, the joint vacuum force should be broken by distension of air or fluid. This leads to maximum distraction of the joint and reduces the risks of damage to labrum and cartilage during first access to the joint. For a diagnostic round through the central compartment, at least two portals have to be placed. The use of a 3-portal technique increases the range of inspection. Due to the relatively thin soft tissue mantle and greater distance to neurovascular structures, the anterolateral or lateral portal should be used as the first portals to the central compartment. In addition, the anterolateral portal is the standard portal to the periphery of the hip. The posterolateral or anterior portal should be used as a supplementary portal. The following indications have been described for an arthroscopic procedure of the hip: loose bodies, labral lesions, synovial diseases such as chondromatosis and pigmented villonodular synovitis, associated lesions in underlying osteoarthritis, ruptures of the teres ligament, malorientation of the acetabulum and proximal femur and, last but not least, "idiopathic" hip pain. The use of hip arthroscopy in infectious arthritis, avascular necrosis of the femoral head, Perthes' disease, osteochondrosis dissecans and complications after total hip replacement is less frequent. Here, in addition to its diagnostic value, operative arthroscopy of the hip offers removal of loose bodies, resection of the labrum and ligaments, synovial biopsy, partial synovectomy, microfracturing, lavage and placement of intraarticular drainage. The first results of arthroscopic procedures in the hip are promising. In addition to its diagnostic value and contribution to the understanding of intraarticular anatomy and pathology, recent studies have demonstrated the advantages of the arthroscopic treatment of the hip. PMID:11381758
Dienst, M; Kohn, D
Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency
Jorge A Roman-Blas; Santos Castañeda; Raquel Largo; Gabriel Herrero-Beaumont
Introduction Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and “stemness” characteristics, which resemble those of ESCs. We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. Methods A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-beige mice were injected with iPSCs and sacrificed to test for teratoma formation. Results After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. Conclusion FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy.
Partial trapeziectomy with suspension ligamentoplasty is a commonly performed treatment of thumb osteoarthritis. Nevertheless, the post-operative recovery remains long and critical reason for which different modifications of the surgical technique have been proposed. To compare two suspension ligamentoplasty techniques, one with a mitek anchor and another without, a retrospective study of 55 consecutive operated patients was performed. A detailed clinical analysis of pain, function and a radiologic assessment of the trapeziometacarpal space were performed. Mitek anchor fixation was associated with a shorter convalescence period. However, in spite of an improved radiological maintenance of the scaphometacarpal space, mitek anchor fixation was associated with an impaired postoperative function and residual pain when compared with the conventional suspension ligamentoplasty procedure. Patient's satisfaction was comparable in both groups. In our series stabilization of the suspension ligamentoplasty procedure by the insertion of a mitek anchor did not bring the hoped benefits to the patients with a trapeziometacarpal arthritis. PMID:22415426
Nordback, S; Erba, P; Wehrli, L; Raffoul, W; Egloff, D V
To assess the diagnostic value of intra-articular anesthetic hip injection in patients with hip pain atypical for osteoarthritis (OA), literature was searched. Included were studies assessing the diagnostic value of anesthetic hip injections in differentiating between pain caused by OA or another source. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CI) were calculated. Of the 1387 potentially eligible articles, nine case series with high risk of bias could be included. The pooled sensitivity was 0.97 (95% CI 0.87, 0.99). Specificity was 0.91 (95% CI 0.83, 0.95). For clinical practice, no recommendation can be made regarding the use of hip injections for diagnosing hip OA. High quality, accurately reported studies are needed to provide better evidence on the diagnostic role of hip injection. PMID:24524775
Dorleijn, Desiree M J; Luijsterburg, Pim A J; Bierma-Zeinstra, Sita M A; Bos, Pieter K
Preclinical osteoarthritis (OA) models are often employed in studies investigating disease-modifying OA drugs (DMOADs). In this study we present a comprehensive, longitudinal evaluation of OA pathogenesis in a rat model of OA, including histologic and biochemical analyses of articular cartilage degradation and assessment of subchondral bone sclerosis. Male Sprague-Dawley rats underwent joint destabilization surgery by anterior cruciate ligament transection and
C Thomas G. Appleton; David D. McErlain; Vasek Pitelka; Neil Schwartz; Suzanne M. Bernier; James L. Henry; David W. Holdsworth; Frank Beier
According to the United States Centers for Disease Control and Prevention, osteoarthritis (OA) affects nearly 27 million Americans aged 25 and older. While there is evidence that obesity, joint injury and some sports are risk factors for incident knee OA, the factors associated with its progression remain unclear. PMID:24779814
Osteoarthritis is a chronic joint disease characterized by pain and immobility due to a gradual loss of cartilage. Current treatments are palliative; there is no cure. With a growing interest in alternative therapies, due in part to safety issues regarding pharmacological treatments like Celebrex, safe dietary compounds that help the body regenerate cartilage tissue are of great clinical importance. The
Heather Joy Hosea Blewett
Apart from being the most common joint disorder worldwide, osteoarthritis (OA) has a significant functional effect on those affected. The disease disproportionally affects women more than men. Current guidelines supported by professional organizations composed of multidisciplinary experts offer important practical insights into managing OA. This paper reflects recommendations from the National Institute for Health and Clinical Excellence, the American Geriatrics
Pamela Stitzlein Davies
Osteoarthritis (OA) is a degenerative joint disease with a high prevalence among older people. To date, the pathogenesis of the disease and the link between muscle function and OA is not entirely understood. As there is no known cure for OA, current research focuses on prevention and symptomatic treatment of the disorder. Recent research has indicated that muscle weakness precedes the onset of OA symptoms. Furthermore, several studies show a beneficial effect of land-based aerobic and strengthening exercises on pain relief and joint function. Therefore, current research focuses on the possibility to employ exercise and sports in the prevention and treatment of OA.
Valderrabano, Victor; Steiger, Christina
Similarly to humans, healthy, wild-type mice develop osteoarthritis, including of the temporomandibular joint (TMJ), as a result of aging. Pro-inflammatory cytokines, such as IL-1?, IL-6, and TNF?, are known to contribute to the development of osteoarthritis, whereas TGF? has been associated with articular regeneration. We hypothesized that a balance between IL-1? and TGF? underlies the development of TMJ osteoarthritis, whereby IL-1? signaling down-regulates TGF? expression as part of disease pathology. Our studies in wild-type mice, as well as the Col1-IL1?XAT mouse model of osteoarthritis, demonstrated an inverse correlation between IL-1? and TGF? expression in the TMJ. IL-1? etiologically correlated with joint pathology, whereas TGF? expression associated with IL-1? down-regulation and improvement of articular pathology. Better understanding of the underlying inflammatory processes during disease will potentially enable us to harness inflammation for orofacial tissue regeneration.
Lim, W.H.; Toothman, J.; Miller, J.H.; Tallents, R.H.; Brouxhon, S.M.; Olschowka, M.E.; Kyrkanides, S.
The initiation, progression, and severity of knee osteoarthritis (OA) has been associated with decreased muscular strength and alterations in joint biomechanics. Chronic OA pain may lead to anxiety, depression, fear of movement, and poor psychological outlook. The fear of movement may prevent participation in exercise and social events which could lead to further physical and social isolation. Resistance exercise (RX) has been shown to be an effective intervention both for decreasing pain and for improving physical function and self-efficacy. RX may restore muscle strength and joint mechanics while improving physical function. RX may also normalize muscle firing patterns and joint biomechanics leading to reductions in joint pain and cartilage degradation. These physical adaptations could lead to improved self-efficacy and decreased anxiety and depression. RX can be prescribed and performed by patients across the OA severity spectrum. When designing and implementing an RX program for a patient with knee OA, it is important to consider both the degree of OA severity as well as the level of pain. RX, either in the home or at a fitness facility, is an important component of a comprehensive regimen designed to offset the physical and psychological limitations associated with knee OA. Unique considerations for this population include: 1) monitoring pain during and after exercise, 2) providing days of rest when disease flares occur, and 3) infusing variety into the exercise regimen to encourage adherence.
Vincent, Kevin R.; Vincent, Heather K.
Aim: This study was designed to evaluate the efficacy of addition of integrated yoga therapy to therapeutic exercises in osteoarthritis (OA) of knee joints. Materials and Methods: This was a prospective randomized active control trial. A total of t participants with OA of knee joints between 35 and 80 years (yoga, 59.56 ± 9.54 and control, 59.42 ± 10.66) from the outpatient department of Dr. John's Orthopedic Center, Bengaluru, were randomly assigned to receive yoga or physiotherapy exercises after transcutaneous electrical stimulation and ultrasound treatment of the affected knee joints. Both groups practiced supervised intervention (40 min per day) for 2 weeks (6 days per week) with followup for 3 months. The module of integrated yoga consisted of shithilikaranavyayama (loosening and strengthening), asanas, relaxation techniques, pranayama, meditation and didactic lectures on yama, niyama, jnana yoga, bhakti yoga, and karma yoga for a healthy lifestyle change. The control group also had supervised physiotherapy exercises. A total of 118 (yoga) and 117 (control) were available for final analysis. Results: Significant differences were observed within (P < 0.001, Wilcoxon's) and between groups (P < 0.001, Mann–Whitney U-test) on all domains of the Short Form-36 (P < 0.004), with better results in the yoga group than in the control group, both at 15th day and 90th day. Conclusion: An integrated approach of yoga therapy is better than therapeutic exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in improving knee disability and quality of life in patients with OA knees.
Ebnezar, John; Nagarathna, Raghuram; Bali, Yogitha; Nagendra, Hongasandra Ramarao
The knee is often a site of injury that can often lead to a chronic disease known as osteoarthritis (OA). The disease may be initiated, in part, by acute injuries to joint cartilage and its cells. In a recent study by this laboratory, using Flemish Giant rabbits, an impact compressive load on the tibial femoral joint was shown to cause
Daniel I. Isaac; Eric G. Meyer; Kaitlyn S. Kopke; Roger C. Haut
Pisotriquetral osteoarthritis is important to consider in the differential diagnosis of chronic ulnar-sided wrist pain. It can develop following traumatic injury to the pisiform or in rheumatic diseases, such as rheumatoid arthritis or psoriatic arthritis. It has been shown that pisiformectomy can relieve symptoms in cases that have not responded to nonoperative treatment, and the excision does not compromise the function or strength of the wrist. Most studies focus on posttraumatic causes of pisotriquetral osteoarthritis. In the current study, rheumatic causes are also considered and the outcomes are compared. This retrospective study included 35 patients who underwent pisiformectomy for pisotriquetral osteoarthritis. All patients underwent a thorough diagnostic evaluation to exclude other etiologies for ulnar-sided wrist pain. Radiological examinations including posteroanterior and lateral views of the wrist and a tangential view of the pisotriquetral joint were analyzed. All patients had excellent or very good results after pisiformectomy, with a significant reduction in pain. No significant difference was found in the outcomes for patients with rheumatic vs posttraumatic osteoarthritis. Patients with rheumatic causes of pisotriquetral osteoarthritis can be successfully treated with pisiformectomy. With respect to idiopathic causes, these patients need a longer postoperative period to gain full pain relief. It is important to consider the possibility of pisotriquetral osteoarthritis after excluding other diagnoses in patients with rheumatic osteoarthritis. PMID:24093697
Lautenbach, Martin; Eisenschenk, Andreas; Langner, Inga; Arntz, Ulrike; Millrose, Michael
Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes
The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA
Jean-Pierre Raynauld; Johanne Martel-Pelletier; Marie-Josée Berthiaume; Gilles Beaudoin; Denis Choquette; Boulos Haraoui; Hyman Tannenbaum; Joan M Meyer; John F Beary; Gary A Cline; Jean-Pierre Pelletier
Osteoarthritic disease is the result of mechanical and biological events that destabilize the normal processes of degradation and synthesis of articular cartilage chondrocytes, extracellular matrix, and subchondral bone. Osteoarthritis of the knee can cause symptoms ranging from mild to disabling. Initial management of most patients should be nonoperative, but because of the progressive nature of the disease, many patients with osteoarthritis of the knee eventually benefit from operative treatment. Various procedures have been described for treatment of the osteoarthritic knee, ranging from arthroscopic lavage and debridement to total knee arthroplasty. The aim of this study was to evaluate the clinical results of distraction arthroplasty combined with arthroscopic lavage and drilling of cartilage defects for treatment of osteoarthritis of the knee. Nineteen patients (15 women and 4 men; age range, 39-65 years) were operated on. Pre- and postoperative findings were compared. A control group comprising 42 patients treated with only arthroscopic procedures was evaluated for comparison. Follow-up ranged from 3 to 5 years. Results were evaluated both clinically and radiologically postoperatively and throughout the follow-up period. Clinically, pain and walking capacity improved in most patients. Radiologically, joint space widening and improvement of the tibiofemoral angle was noted in nearly all patients. PMID:21815573
Aly, Tarek A; Hafez, Kamal; Amin, Osama
Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.
Young, Allan A; McLennan, Susan; Smith, Margaret M; Smith, Susan M; Cake, Martin A; Read, Richard A; Melrose, James; Sonnabend, David H; Flannery, Carl R; Little, Christopher B
Objective To evaluate the risk factors for early radiographic changes of knee osteoarthritis. Methods Subjects (n?=?114) with unilateral or bilateral grade 0–1 knee osteoarthritis underwent x ray examination of the knees (semiflexed anteroposterior view) and assessment with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at baseline and 30?months later. Severity of joint space narrowing (JSN) and osteophytosis were graded in randomly ordered serial radiographs by two readers, blinded to the sequence of the films, using standard pictorial atlases. Results The odds of an initial appearance of radiographic features of knee osteoarthritis at month 30 were more than threefold greater in African Americans than in whites (osteophytosis: odds ratio (OR) 3.30, 95% confidence interval (CI) 1.04 to 10.54; JSN: OR 3.49, 95% CI 1.16 to 10.68). In addition, the appearance of osteophytosis was positively related to baseline stiffness (OR 1.91/2.1 points on the 2–10 WOMAC scale, 95% CI 1.29 to 2.82). Conclusions The distinction between incident and established, but early, radiographic knee osteoarthritis is difficult because of the limits to which all possible evidence of the disease can be ruled out in a conventional baseline knee radiograph. Nonetheless, our finding that African Americans were at greater risk of early osteophytosis and JSN than other subjects differs from the results of our previous analysis of risk factors for progressive knee osteoarthritis in the same subjects. The development of osteophytes also was associated with joint stiffness. Future investigations should focus on the systemic and local influences that these ostensible risk factors represent.
Mazzuca, Steven A; Brandt, Kenneth D; Katz, Barry P; Ding, Yan; Lane, Kathleen A; Buckwalter, Kenneth A
Objectives: To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis. Methods: Review of past and current literature relative to collagen hydrolysate metabolism, and assessment of clinical investigations of therapeutic trials in osteoarthritis and osteoporosis. Results: Hydrolyzed gelatin products have long been used in pharmaceuticals and foods; these products are generally recognized as safe food
Roland W. Moskowitz
Osteoarthritis of the trapeziometacarpal joint is a common pathology. When the trapezium is not large enough to allow using a total joint arthroplasty or in case of peritrapezial osteoarthrosis, the authors used a trapeziectomy with interposition of an absorbable L-polylactic acid anchovy (Arex(®)615R). This technique is simple and fast. From 2006 to 2010, out of 68 implants, nine displayed a prolonged inflammatory reaction, both clinically and radiologically abnormal, leading the patients to undergo revision surgery for removal of the implant before the end of the third postoperative year. Histological analysis highlighted in all the cases a resorptive gigantocellular immune foreign body reaction. PMID:23665309
Semere, A; Forli, A; Corcella, D; Mesquida, V; Loret, M G; Moutet, F
Temporomandibular disorder (TMD) is an inclusive term in which those conditions disturbing the masticatory function are embraced. It has been estimated that 33% of the population have signs of TMD, but less than 5% of the population will require treatment. The objective of this study was to measure the frequency of TMD in rheumatoid arthritis (RA), osteoarthrosis (OA), ankylosing spondylitis (AS) and systemic lupus erythematosus, and to define the limitations in everyday's life that patients perceive when present. A six-month survey of consecutive outpatients in a rheumatology clinic in a teaching hospital in Mexico was carried out. We defined TMD as: 1) the presence of pain; 2) difficulty on mouth opening, chewing or speaking; 3) the presence of non-harmonic movements of the temporomaxilar joints. All three characteristics had to be present. Z test was used to define differences between proportions. We present the results of 171 patients. Overall, 50 patients had TMD according to our operational definition (29.24%). Up to 76% of the sample had symptoms associated with the condition. TMD is more frequent in OA and in AS (29.24% vs 38% OA, P=0.009; 39% AS; P=0.005). We found no association between the severity of TMD and the request for specific attention for the discomfort produced by the condition. Only 8 of 50 (16%) patients with TMD had requested medical help for their symptoms, and they were not the most severe cases. TMD is more frequent in RA and OA. Although it may produce severe impairment, patients seem to adapt easily. PMID:23884028
Aceves-Avila, F J; Chávez-López, M; Chavira-González, J R; Ramos-Remus, C
We analyze a bioeconomic model of a multiple-host disease problem involving wildlife and livestock. The social planner’s choices\\u000a include targeted (i.e., infectious versus healthy) livestock harvests, non-targeted wildlife harvests, environmental habitat\\u000a variables, and on-farm biosecurity to prevent cross-species contacts. The model is applied to bovine tuberculosis among Michigan\\u000a white-tailed deer and cattle. We find optimal controls may target the livestock
Richard D. Horan; Christopher A. Wolf; Eli P. Fenichel; Kenneth H. Mathews Jr
BACKGROUND: Osteoarthritis is the most frequent chronic joint disease which causes pain and disability of especially hip and knee. According to international guidelines and the Dutch general practitioners guidelines for non-traumatic knee symptoms, acetaminophen should be the pain medication of first choice for osteoarthritis. However, of all prescribed pain medication in general practice, 90% consists of non-steroidal anti-inflammatory drugs compared
Saskia PJ Verkleij; Pim AJ Luijsterburg; Bart W Koes; Arthur M Bohnen; Sita MA Bierma-Zeinstra
Objective To evaluate if two different measures of synovial activation, baseline Hoffa-synovitis and effusion-synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis (OA) of the knee. Methods Non-contrast enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a STIR sequence in the coronal plane. Hoffa-synovitis, effusion-synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic OA nor MRI-detected tibio-femoral cartilage damage at the baseline visit. Presence of Hoffa-synovitis was defined as any grade ?2 (range from 0–3) and effusion-synovitis as any grade ?2 (range from 0–3). We performed logistic regression to examine the relation of presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders of cartilage loss. Results Of 514 knees included in the analysis, prevalence of Hoffa-synovitis and effusion-synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion-synovitis was associated with an increased risk for cartilage loss (odds ratio (OR) = 2.7, 95% confidence intervals 1.4–5.1, p=0.002); however, no such an association was observed for baseline Hoffa-synovitis (OR =1.0, 95% confidence intervals 0.5–2.0). Conclusions Baseline effusion-synovitis, but not Hoffa-synovitis, predicted cartilage loss. Our findings suggest that effusion-synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in future development of cartilage lesions in knees without OA.
Roemer, Frank W.; Guermazi, Ali; Felson, David T.; Niu, Jingbo; Nevitt, Michael C.; Crema, Michel D.; Lynch, John A.; Lewis, Cora E.; Torner, James; Zhang, Yuqing
Alleviation of pain and inhibition of inflammation are the primary goals of pharmacotherapy of osteoarthritis (OA). These therapeutic goals can almost always be accomplished by the use of analgesics and nonsteroidal anti-inflammatory drugs (NSAID). One of the main problems of NSAIDs is their gastrointestinal toxicity, for which a prophylactic medication should be considered particularly amongst risk groups. Recent studies have shown that COX-2-selective and maybe also non-selective NSAIDs increase the cardiovascular risk so that their application is getting now drastically restricted. Pharmacological results published until now suggest that a clinically relevant minor analgesic and/or anti-inflammatory effect can be attained with the use of some of the SYmptomatic Slow Acting Drugs in OA (SYSADOAs). However, no clinical studies exist, which can positively confirm prevention, slowing down or reversal of any advanced joint cartilage destruction by any individual medication. Disease modifying therapy is still in its infancy; discovery and development of novel therapeutic targets and agents are an extremely difficult task, currently challenging many pharmaceutical companies and academic institutions. PMID:16616797
Steinmeyer, Jürgen; Konttinen, Yrjö T
There is growing evidence of the role that nutrition can play in the management of veterinary patients with osteoarthritis. Current evidence supports nutritional management of body weight and dietary fortification with the long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Additional studies suggest that supplements and diet additives such as glucosamine, chondroitin sulfate, antioxidants, and green-lipped mussel may also have some benefit in managing osteoarthritis. Additional research evaluating pets with naturally occurring disease, using validated owner questionnaires and objective measurements, is needed. PMID:22581724
The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1
Jobke, B.; Bolbos, R.; Saadat, E.; Cheng, J.; Li, X.; Majumdar, S.
Background and purpose The optimal treatment for isolated patellofemoral osteoarthritis is unclear at present. We systematically reviewed the highest level of available evidence on the nonoperative and operative treatment of isolated patellofemoral osteoarthritis to develop an evidenced-based discussion of treatment options. Methods A systematic computerized database search (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), and EMBASE) was performed in March 2009. The quality of the studies was assessed independently by two authors using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We extracted data from 44 articles. The best available evidence for treatment of isolated patellofemoral osteoarthritis is sparse and of generally low methodological quality. Nonoperative treatment using physiotherapy (GRADE: high quality, weak recommendation for use), taping (GRADE: moderate quality, weak recommendation for use), or injection therapy (GRADE: very low quality, weak recommendation for use) may result in short-term relief. Joint-preserving surgical treatment may result in insufficient, unpredictable, or only short-term improvement (GRADE: low quality, weak recommendation against use). Total knee replacement with patellar resurfacing results in predictable and good, durable results (GRADE: low quality, weak recommendation for use). Outcome after patellofemoral arthroplasty in selected patients is good to excellent (GRADE: low quality, weak recommendation for use). Interpretation Methodologically good quality comparative studies, preferably using a patient-relevant outcome instrument, are needed to establish the optimal treatment strategy for patients with isolated patellofemoral osteoarthritis.
Poolman, Rudolf W; van Kampen, Albert
... NSAIDs) (Beyond the Basics) Acromioclavicular joint injuries Biceps tendinopathy and tendon rupture Brachial plexus syndromes Evaluation of ... and diagnosis of rotator cuff tears Rotator cuff tendinopathy Shoulder impingement syndrome Related Searches Osteoarthritis Patient information ...
To describe a technique termed Suture Anchor Arthroplasty' (SAA), for thumb carpometacarpal joint osteoarthritis and to report the clinical results. SAA is a surgical technique similar to Ligament Reconstruction Tendon Interposition' (LRTI) Arthroplasty, ...
N. L. Taylor R. Strauch
Osteoarthritis, usually considered a wear and tear, or age-associated disease, is generally regarded as inexorably progressive once it has become clinically symptomatic. Enormous advances in the understanding of the normal cell biology of hyaline cartilage, synovium, and bone have led some to suspect that the process can be arrested, or even reversed. Some of the lines of evidence, both experimental and clinical, supporting this proposition, are presented in this paper. I first noted an apparent partial reversal of severe osteoarthritis of the hips in an 85-year-old man, as assessed by reappearance of hip joint spaces, when examined radiologically. The favorable change persisted until his death at age 92. Since then a number of similar cases have been observed, other types of evidence of reversibility examined, and an extensive study of the literature made. Five main areas are described: Modern and ancient concepts of osteoarthritis; myths and misconceptions; theories of etiology and pathogenesis; advances in basic knowledge of tissue involved and lines of evidence of arrest or reversibility derived from these advances; and an outline of practical, clinical management based on the cell biology of hyaline cartilage, synovium, and bone, especially subchondral bone. Aspirin is emphasized as the drug of choice and a method of administration is described. PMID:6344622
Bland, J H
Background Osteoarthritis is a common progressive joint disease, involving not only the joint lining but also cartilage, ligaments, and bone. For the last ten years, majority of published review articles were not specific to osteoarthritis of the knee, and strength of evidence and clinical guidelines were not appropriately summarized. Objectives To appraise the literature by summarizing the findings of current evidence and clinical guidelines on the diagnosis and treatment of knee osteoarthritis pain. Methodology English journal articles that focused on knee osteoarthritis related pain were searched via PubMed (1 January 2002 – 26 August 2012) and Physiotherapy Evidence Database (PEDro) databases, using the terms ‘knee’, ‘osteoarthritis’ and ‘pain’. In addition, reference lists from identified articles and related book chapters were included as comprehensive overviews. Results For knee osteoarthritis, the highest diagnostic accuracy can be achieved by presence of pain and five or more clinical or laboratory criteria plus osteophytes. Some inconsistencies in the recommendations and findings were found between the clinical guidelines and systematic reviews. Generally, paracetamol, oral and topical non-steroidal anti-inflammatory drugs, opioids, corticosteroid injections and physical therapy techniques, such as therapeutic exercises, joint manual therapy and transcutaneous electrical nerve stimulation, can help reduce pain and improve function. Patient education programs and weight reduction for overweight patients are important to be considered. Conclusions Some inconsistencies in the recommendations and findings were found between the clinical guidelines and systematic reviews. However, it is likely that a combination of pharmacological and non-pharmacological treatments is most effective in treating patients with knee osteoarthritis.
Alshami, Ali M.
Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR. SFs from patients with a loose joint prosthesis and patients with OA, but not SFs from healthy subjects, significantly enhanced 45Ca release, effects associated with increased mRNA expression of calcitonin receptor and tartrate-resistant acid phosphatase. The mRNA expression of receptor activator of nuclear factor-kappa-B ligand (rankl) and osteoprotegerin (opg) was enhanced by SFs from both patient categories. The mRNA expressions of nfat2 (nuclear factor of activated T cells 2) and oscar (osteoclast-associated receptor) were enhanced only by SFs from patients with OA, whereas the mRNA expressions of dap12 (DNAX-activating protein 12) and fcrgamma (Fc receptor common gamma subunit) were not affected by either of the two SF types. Bone resorption induced by SFs was inhibited by addition of OPG. Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity. The mRNA expression of alkaline phosphatase and osteocalcin was increased by SFs from patients with OA, whereas only osteocalcin mRNA was increased by SFs from patients with a loose prosthesis. Our findings demonstrate the presence of a factor (or factors) stimulating both osteoclast and osteoblast activities in SFs from patients with a loose joint prosthesis and periprosthetic osteolysis as well as in SFs from patients with OA. SF-induced bone resorption was dependent on activation of the RANKL/RANK/OPG pathway. The bone-resorbing activity could not be attributed solely to any of the known pro-inflammatory cytokines, well known to stimulate bone resorption, or to RANKL or prostaglandin E2 in SFs. The data indicate that SFs from patients with a loose prosthesis or with OA stimulate bone resorption and that SFs from patients with OA are more prone to enhance bone formation. PMID:17316439
Andersson, Martin K; Lundberg, Pernilla; Ohlin, Acke; Perry, Mark J; Lie, Anita; Stark, André; Lerner, Ulf H
There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the United States alone by 2030. Because disease pathogenesis is associated with inappropriate articular chondrocyte maturation resembling that seen during normal endochondral ossification, pathways that govern the maturation of articular chondrocytes are candidate therapeutic targets. It is well established that parathyroid hormone (PTH) acting via the type 1 PTH receptor induces matrix synthesis and suppresses maturation of chondrocytes. We report that the PTH receptor is up-regulated in articular chondrocytes after meniscal injury and in osteoarthritis in humans and in a mouse model of injury-induced knee osteoarthritis. To test whether recombinant human PTH(1-34) (teriparatide) would inhibit aberrant chondrocyte maturation and associated articular cartilage degeneration, we administered systemic teriparatide (Forteo), a Food and Drug Administration-approved treatment for osteoporosis, either immediately after or 8 weeks after meniscal/ligamentous injury in mice. Knee joints were harvested at 4, 8, or 12 weeks after injury to examine the effects of teriparatide on cartilage degeneration and articular chondrocyte maturation. Microcomputed tomography revealed increased bone volume within joints from teriparatide-treated mice compared to saline-treated control animals. Immediate systemic administration of teriparatide increased proteoglycan content and inhibited articular cartilage degeneration, whereas delayed treatment beginning 8 weeks after injury induced a regenerative effect. The chondroprotective and chondroregenerative effects of teriparatide correlated with decreased expression of type X collagen, RUNX2 (runt-related transcription factor 2), matrix metalloproteinase 13, and the carboxyl-terminal aggrecan cleavage product NITEGE. These preclinical findings provide proof of concept that Forteo may be useful for decelerating cartilage degeneration and inducing matrix regeneration in patients with osteoarthritis. PMID:21937758
Sampson, Erik R; Hilton, Matthew J; Tian, Ye; Chen, Di; Schwarz, Edward M; Mooney, Robert A; Bukata, Susan V; O'Keefe, Regis J; Awad, Hani; Puzas, J Edward; Rosier, Randy N; Zuscik, Michael J
Osteoarthritis is a common joint disease for which there are currently no disease-modifying drugs available. Degradation of the cartilage extracellular matrix is a central feature of the disease and is widely though to be mediated by proteinases that degrade structural components of the matrix, primarily aggrecan and collagen. Studies on transgenic mice have confirmed the central role of Adamalysin with Thrombospondin Motifs 5 (ADAMTS-5) in aggrecan degradation, and the collagenolytic matrix metalloproteinase MMP-13 in collagen degradation. This review discusses recent advances in current understanding of the mechanisms regulating expression of these key enzymes, as well as reviewing the roles of other proteinases in cartilage destruction.
Troeberg, Linda; Nagase, Hideaki
Introduction Patients with rheumatoid arthritis (RA) have increased risk of cardiovascular (CV) events. We sought to test the hypothesis that due to increased inflammation, CV disease and risk factors are associated with increased risk of future RA development. Methods The population-based Nord-Trøndelag health surveys (HUNT) were conducted among the entire adult population of Nord-Trøndelag, Norway. All inhabitants 20 years or older were invited, and information was collected through comprehensive questionnaires, a clinical examination, and blood samples. In a cohort design, data from HUNT2 (1995–1997, baseline) and HUNT3 (2006–2008, follow-up) were obtained to study participants with RA (n?=?786) or osteoarthritis (n?=?3,586) at HUNT3 alone, in comparison with individuals without RA or osteoarthritis at both times (n?=?33,567). Results Female gender, age, smoking, body mass index, and history of previous CV disease were associated with self-reported incident RA (previous CV disease: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CV disease were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.23-2.36)) or restricting the analysis to cases with a hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.13-2.74)). History of previous CV disease was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). Conclusion A history of previous CV disease was associated with increased risk of incident RA but not osteoarthritis.
A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between FE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning. PMID:24786914
Mootanah, R; Imhauser, C W; Reisse, F; Carpanen, D; Walker, R W; Koff, M F; Lenhoff, M W; Rozbruch, S R; Fragomen, A T; Dewan, Z; Kirane, Y M; Cheah, K; Dowell, J K; Hillstrom, H J
A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between EE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning.
Mootanah, R.; Imhauser, C.W.; Reisse, F.; Carpanen, D.; Walker, R.W.; Koff, M.F.; Lenhoff, M.W.; Rozbruch, S.R.; Fragomen, A.T.; Dewan, Z.; Kirane, Y.M.; Cheah, Pamela A.; Dowell, J.K.; Hillstrom, H.J.
We compared histologic, immunohistochemical, and vascular findings in synovial biopsies from individuals with Gulf War Veterans Illness and joint pain (GWVI) to findings in normal and osteoarthritis (OA) synovium. The following parameters were assessed in synovial biopsies from ten individuals with GWVI: lining thickness, histologic synovitis score, and vascular density in hematoxylin & eosin-stained sections; and CD68+ lining surface cells and CD15+, CD3+, CD8+, CD20+, CD38+, CD68+, and Ki-67+ subintimal cells and von Willebrand Factor+ vessels immunohistochemically. Comparisons were made to synovial specimens from healthy volunteers (n = 10) and patients with OA or RA (n = 25 each). Histologic appearance and quantitative assessments were nearly identical in the GWVI and normal specimens. Vascular density was between 25% (H & E stains; p = 0.003) and 31% (vWF immunostains; p = 0.02) lower in GWVI and normal specimens than in OA. CD68+ macrophages were the most common inflammatory cells in GWVI (45.3 +/- 10.1 SEM cells/mm(2)) and normal synovium (45.6 +/- 7.4) followed by CD3+ T cells (GWVI, 15.1 +/- 6.3; normal, 27.1 +/- 9.2), whereas there were practically no CD20+, CD38+, and CD15+ cells. All parameters except lining thickness and CD15 and CD20 expression were significantly higher in OA. Five (20%) OA specimens contained significant fractions of humoral immune cells in mononuclear infiltrates, although the overall differences in the relative composition of the OA mononuclear infiltrates did not reach statistical significance compared to GWVI and normal synovium. In summary, the GWVI and normal synovia were indistinguishable from each other and contained similar low-grade inflammatory cell populations consisting almost entirely of macrophages and T cells. PMID:18414968
Pessler, F; Chen, L X; Dai, L; Gomez-Vaquero, C; Diaz-Torne, C; Paessler, M E; Scanzello, C; Cakir, N; Einhorn, E; Schumacher, H R
There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1?) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.
Rhouma, Mohamed; de Oliveira El Warrak, Alexander; Troncy, Eric; Beaudry, Francis; Chorfi, Younes
Discrepancies exist between radiographic osteoarthritis of the knee (OAK) and report of knee joint pain. Little is known about how these two definitions of osteoarthritis (OA) and their correlates differ between African American (AA) and Caucasian (CA) women.Objective We compared the prevalence of radiographic OAK and knee joint pain in AA and CA women, and the congruency of these outcomes
L. Lachance; M. Sowers; D. Jamadar; M. Jannausch; M. Hochberg; M. Crutchfield
Osteoarthritis (OA) is one of the most common forms of degenerative joint disease and a major cause of pain and disability affecting the aging population. It is estimated that more than 20 million Americans and 35 to 40 million Europeans suffer from OA. Analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are the only therapeutic treatment options for OA. Effective pharmacotherapy for OA, capable of restoring the original structure and function of damaged cartilage and other synovial tissue, is urgently needed, and research into such disease-modifying osteoarthritis drugs (DMOADs) is in progress. This is the first of three reviews focusing on OA therapeutics. This paper provides an overview of current research into potential structure-modifying drugs and more appropriately targeted pharmacological therapy. The challenges and opportunities in this area of research and development are reviewed, covering the most up-to-date initiatives, trends, and topics. PMID:24061701
Objectives. The 5-yr longitudinal study tested the hypothesis that serum and urinary markers of type II collagen metabolism would be associated with radiological progression of disease in patients with mild-to-moderate knee osteoarthritis (OA). Methods. Synthesis of type IIA collagen and degradation of total type II collagen were assessed in 135 patients with mild-to-moderate knee OA over 5 yrs using serum
M. Sharif; J. Kirwan; N. Charni; L. J. Sandell; C. Whittles; P. Garnero
Objective: To describe an in vivo model in the rat in which change in weight distribution is used as a measure of disease progression and efficacy of acetaminophen and two nonsteroidal anti-inflammatory drugs (NSAIDs) in a model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA).Methods: Intra-articular injections of MIA and saline were administered to male Wistar rats (175–200g) into the right and
S. E Bove; S. L Calcaterra; R. M Brooker; C. M Huber; R. E Guzman; P. L Juneau; D. J Schrier; K. S Kilgore
Digital imaging combined with picture archiving and communication system (PACS) access allows detailed image retrieval and magnification. Calcium pyrophosphate dihydrate (CPPD) crystals preferentially deposit in fibrocartilages, the cartilage of the acromioclavicular (AC) joint being one such structure. We sought to determine if examination of the AC joints on magnified PACS imaging of chest films would be useful in identifying chondrocalcinosis (CC). Retrospective radiographic readings and chart reviews involving 1,920 patients aged 50 or more who had routine outpatient chest radiographs over a 4-month period were performed. Knee radiographs were available for comparison in 489 patients. Medical records were reviewed to abstract demographics, chest film reports, and diagnoses. AC joint CC was identified in 1.1 % (21/1,920) of consecutive chest films. Patients with AC joint CC were 75 years of age versus 65.4 in those without CC (p?0.0002). Four hundred eighty-nine patients had knee films. Six of these patients had AC joint CC, and of these, five also had knee CC (83 %). Of the 483 without AC joint CC, 62 (12 %) had knee CC (p?=?0.002). Patients with AC joint CC were more likely to have a recorded history of CPPD crystal deposition disease than those without AC joint CC (14 versus 1 %, p?=?0.0017). The prevalence of AC joint CC increases with age and is associated with knee CC. A finding of AC joint CC should heighten suspicion of pseudogout or secondary osteoarthritis in appropriate clinical settings and, in a young patient, should alert the clinician to the possibility of an associated metabolic condition. PMID:23609408
Parperis, Konstantinos; Carrera, Guillermo; Baynes, Keith; Mautz, Alan; Dubois, Melissa; Cerniglia, Ross; Ryan, Lawrence M
Background and purpose The presence of bone marrow edema in patients with osteoarthritis is associated with pain and disease progression. Management of bone edema with the synthetic prostacyclin iloprost may be complicated by side effects. Calcium dobesilate, a treatment for chronic venous disease, shares some pharmacological actions with iloprost but appears to be better tolerated. Anecdotal reports have suggested that calcium dobesilate may be useful for medical management of osteoarthritis, possibly by reducing bone marrow edema, and this study was performed to investigate possible benefits of treatment. Methods The effects of a 6-week period of oral calcium dobesilate administration on tibial intramedullary pressure dynamics and physical joint characteristics were evaluated in 20 rabbits with unilaterally induced knee osteoarthritis that were randomly allocated to either a treatment group or a placebo control group. Treatment or placebo started 8 weeks after induction of osteoarthritis, and was followed by a 4-week washout period. Results Calcium dobesilate did not affect joint thickness or range of motion, nor individual pressure measurements, compared to placebo. Pressure ranges in the operated limb were greater than in the intact limb after 8 weeks, and approached those of the intact limb after 6 weeks of treatment with calcium dobesilate but not with placebo. Inter-limb differences were lower (p = 0.02) in the dobesilate group following the washout period. Interpretation Calcium dobesilate had a detectable effect on pressure dynamics in the subchondral bone of osteoarthritic joints in this model. The significance of these effects for pain and function should be established.
Symptomatic sacroiliac (SI) joint disease is poorly understood. The literature provides no clear aetiology for SI joint pathology, making evaluation and diagnosis challenging. We hypothesised that patients with documented sacroiliac pain might provide insight into the aetiology of these symptoms. Specifically, we questioned whether SI joint symptoms might be associated with abnormal hip radiographs. We reviewed the pelvic and hip radiographs of a prospectively collected cohort of 30 consecutive patients with SI joint pathology. This database included 33 hips from 30 patients. Radiographic analysis included measurements of the lateral centre edge angle, Tönnis angle, and the triangular index, of the ipsilateral hip. Evidence for retrotorsion of the hemipelvis was recorded. Hips were graded on the Tönnis grading system for hip arthrosis. In this cohort 14/33 (42%) of hips had evidence of significant osteoarthrosis indicated by Tönnis grade 2 or greater and 15/33 (45%) displayed subchondral cyst formation around the hip or head neck junction. In assessing acetabular anatomy, 21% (7/33) had retroversion, 12% (4/33) had a lateral centre edge angle >40° with 3% (1/33) >45°. Tönnis angle was <0° in 27% (9/33). Coxa profunda and acetabuli protrusio were present in 47% (17/33) and 3% (1/33), respectively. When femoral head morphology was assessed, 33% (11/33) showed evidence of cam impingement. Overall, 76% (25/33) had at least one abnormality on their hip radiograph. A significant number of patients meeting strict diagnostic criteria for SI joint pain had radiographic evidence of femoroacetabular impingement (FAI) and hip arthrosis. The clinician should maintain FAI in the differential diagnosis when investigating patients with buttock pain. PMID:23417531
Morgan, Patrick M; Anderson, Anthony W; Swiontkowski, Marc F
Osteoarthritis presents in primary and secondary forms. The primary, or idiopathic, form occurs in previously intact joints without any inciting agent, whereas the secondary form is caused by underlying predisposing factors (eg, trauma). The diagnosis of osteoarthritis is primarily based on thorough history and physical examination findings, with or without radiographic evidence. Although some patients may be asymptomatic initially, the most common symptom is pain. Treatment options are generally classified as pharmacologic, nonpharmacologic, surgical, and complementary and/or alternative, typically used in combination to achieve optimal results. The goals of treatment are alleviation of symptoms and improvement in functional status. PMID:24209720
Taruc-Uy, Rafaelani L; Lynch, Scott A
Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain.
Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.
There are a variety of oral and topical pharmaceutical agents for the treatment of osteoarthritis. To date there is no pharmacologic agent proved to prevent disease progression. This article focuses primarily on the medications used for symptomatic relief and palliation of pain. The article reviews the medications' mechanisms of action and the available efficacy literature, as well as indications, contraindications, and common adverse effects. PMID:22632707
Cheng, David S; Visco, Christopher J
The aim of this thesis is to gain more insight in the characteristics of end-stage osteoarthritic patients who are about to undergo total knee replacement surgery. Their use of medication, potential markers of actual characteristics of joint damage and inflammation, and effects of potential disease modification by drugs were studied. \\u000a\\u000aFor this purpose, a clinical trial was performed with patients
T. N. de Boer
Erosive osteoarthritis (OA) is a subcategory of OA in which destructive changes occur in the joints, probably as a result\\u000a of a combination of inflammatory inciters and phenomena. The major changes occur in the distal and proximal interphalangeal\\u000a joints, root joints of the thumb, and less commonly other hand and centripetal joints. A familial tendency suggests hereditary\\u000a predisposition, and women
George E. Ehrlich
Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the United States, especially among older adults. Treatment options have primarily focused on alleviating the pain often associated with this condition. Acetaminophen and nonsteroidal anti inflammatory drugs (NSAIDs) are often employed for relief of mild-to moderate pain associated with OA. NSAIDs are typically more effective than acetaminophen; however, because of adverse effects associated with long-term use of NSAIDS, acetaminophen is considered first-line therapy. Safety concerns of traditional pharmacotherapeutic agents used in the management of OA, such as NSAIDs and opioids, have led healthcare professionals to seek other options. Trials of disease modulating agents that focus on preventing further damage to the joints have the potential to change how this disease state is managed. This article reviews nonpharmacologic and pharmacologic approaches to management of OA of the knee and hip. PMID:20726384
Seed, Sheila M; Dunican, Kaelen C; Lynch, Ann M
Osteoarthritis (OA) is a chronic degenerative disease of the joints caused by wide variety of factors. factors. This paper provides a review of the clinical and experimental research on integrated Chinese and Western medicine in the treatment of osteoarthritis. Western medicine in the treatment of osteoarthritis. (1) Clinical research: integrated Chinese and Western medicine therapies were used including physiotherapy, medications, acupuncture, functional training, intra-articular injection of sodium hyaluronate therapy, and arthroscopic debridement with Chinese medicine articular iontophoresis therapy. articular iontophoresis therapy. (2) Experimental research: modern methods were used in studying the mechanism of Chinese medicine in slowing down cartilage degeneration, promoting articular cartilage repair, inhibiting synovial inflammation, and blocking cartilage destruction. inflammation, and blocking cartilage destruction. In addition, this article also reviews the advantages, prospects, and problems of the therapies. and problems of the therapies. PMID:20697952
Wang, He-ming; Liu, Jun-ning; Zhao, Yi
Objectives Our objective was to determine the relationship between osteoarthritis (OA) and heart diseases (myocardial infarction (MI), angina, congestive heart failure (CHF)) and stroke using population-based survey data. Design Cross-sectional study. Setting Canadian Community Health Survey (CCHS). Participants Adult participants in the CCHS cycles 1.1, 2.1 and 3.1 were included. CCHS provides nationally representative data on health determinants, health status and health system utilisation. We have identified 40?817 self-reported OA subjects and selected 1:1 matched non-OA respondents by age, sex and CCHS cycles. Main outcome measures Self-reported heart disease was the primary outcome and MI, angina, CHF and stroke were considered as secondary outcomes. Multivariable logistic regression models were used to estimate the ORs after adjusting for sociodemographic status, obesity, physical activity, smoking status, fruit and vegetable consumption, medication use, diabetes, hypertension and chronic obstructive pulmonary disease. Results The mean age of OA cases was 66?years and 71.6% were women. OA exhibited increased odds of prevalent heart disease, and adjusted overall OR (95% CI) was 1.45 (1.36 to 1.54), 1.35 (1.21 to 1.50) among men and 1.51 (1.39 to 1.64) among women with OA. OA showed increased ORs for angina and CHF in both men and women, and for MI in women. ORs (95% CI) for men and women, respectively, were 1.08 (0.91 to 1.28) and 1.49 (1.28 to 1.75) for MI, 1.76 (1.43 to 2.17) and 1.84 (1.59 to 2.14) for angina, 1.50 (1.13 to 1.97) and 1.81 (1.49 to 2.21) for CHF, and 1.08 (0.83 to 1.40) and 1.13 (0.93 to 1.37) for stroke. Conclusions Prevalent OA was associated with self-reported heart disease, particularly angina, and CHF in both men and women, after controlling for established risk factors for these conditions. This study provides a rationale for further investigation of the association between OA and heart disease in longitudinal studies for investigating possible biological and behavioural mechanisms.
Rahman, M Mushfiqur; Kopec, Jacek A; Cibere, Jolanda; Goldsmith, Charlie H; Anis, Aslam H
The purpose of this study was to establish if osteoarthritis in older adults was associated with ability to accurately and continuously track leg movement in a model of therapy to improve age-related impairments of proprioception, kinesthesia, and coordination of muscles at the knee joint. 24 older adults without osteoarthritis and 24 older adults with osteoarthritis participated. Software generated a moving, on-screen sine wave and a vertically traveling disc. Participants attempted to keep the disc on the sine wave by bending and straightening the leg. Older adults without osteoarthritis performed better than older adults with osteoarthritis in one of two conditions. There was a relationship between osteoarthritis and reduced accuracy of leg movement. Further research will be required to specifically define this relationship and to establish if such interventions to improve accuracy of knee movement will positively affect functional capabilities of individuals with osteoarthritis. PMID:24724520
Williamson, Elizabeth Mae; Marshall, Philip H
Osteoarthritis is a common degenerative disorder of the articular cartilage associated with hypertrophic bone changes. Risk factors include genetics, female sex, past trauma, advancing age, and obesity. The diagnosis is based on a history of joint pain worsened by movement, which can lead to disability in activities of daily living. Plain radiography may help in the diagnosis, but laboratory testing usually does not. Pharmacologic treatment should begin with acetaminophen and step up to nonsteroidal anti-inflammatory drugs. Exercise is a useful adjunct to treatment and has been shown to reduce pain and disability. The supplements glucosamine and chondroitin can be used for moderate to severe osteoarthritis when taken in combination. Corticosteroid injections provide inexpensive, short-term (four to eight weeks) relief of osteoarthritic flare-ups of the knee, whereas hyaluronic acid injections are more expensive but can maintain symptom improvement for longer periods. Total joint replacement of the hip, knee, or shoulder is recommended for patients with chronic pain and disability despite maximal medical therapy. PMID:22230308
The osteoarthritis disease process affects not only the cartilage but also the entire joint structure, including the synovium, bone and periarticular muscles. Characteristically, abnormal biomechanical forces result in an imbalance between chondrocyte anabolic and catabolic pathways, which ultimately leads to progressive joint destruction. Within cartilage and synovium, pro-inflammatory cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own production and induce chondrocytes to produce additional catabolic mediators, including proteases, chemokines, nitric oxide, and prostaglandins. The success of targeted biological therapy in rheumatoid arthritis has taught that the blockade of a single dominant cytokine can lead to remarkable clinical benefit, even in complex disease. The effectiveness of biologicals in inflammatory arthritides as disease modifying agents has increased the likelihood that similar strategies can be developed to target specific molecular mechanisms in osteoarthritis (OA). However, since the clinical development program for disease-modifying OA drugs (DMOADs) is complicated by the slow progression of disease in many patients, the introduction of DMOADs will be greatly enhanced by advances in imaging and biomarkers that serve as validated surrogate endpoints for meaningful clinical outcomes. PMID:16567019
Abramson, Steven B; Yazici, Yusuf
Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further. PMID:20034712
Amir, G; Goldfarb, A W; Nyska, M; Redlich, M; Nyska, A; Nitzan, D W
Evaluation of glycosaminoglycan (GAG) concentration in articular cartilage is of particular interest to the study of degenerative joint diseases such as osteoarthritis (OA). Noninvasive imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) have demonstrated the potential to assess biochemical markers of cartilage integrity such as GAG content; however, many imaging techniques are available and the optimization
Carmen Taylor; Julio Carballido-Gamio; Sharmila Majumdar; Xiaojuan Li
Osteoarthritis is a primary cause of disability and functional incapacity. Pharmacological treatment is currently limited to symptomatic management, and in advanced stages, surgery remains the only solution. The therapeutic armamentarium for osteoarthritis remains poor in treatments with an effect on joint structure, that is, disease-modifying osteoarthritis drugs (DMOADs). Glucosamine sulfate and chondroitin sulfate are the only medications for which some conclusive evidence for a disease-modifying effect is available. Strontium ranelate is currently indicated for the prevention of fracture in severe osteoporosis. Its efficacy and safety as a DMOAD in knee osteoarthritis has recently been explored in the SEKOIA trial, a 3-year randomized, double-blind, placebo-controlled trial. Outpatients with knee osteoarthritis, Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) of 2.5-5 mm received strontium ranelate 1 g/day (n = 558) or 2 g/day (n = 566), or placebo (n = 559). This sizable population was aged 62.9 years and had a JSW of 3.50 ± 0.84 mm. Treatment with strontium ranelate led to significantly less progression of knee osteoarthritis: estimates for annual difference in joint space narrowing versus placebo were 0.14 mm [95% confidence interval (CI) 0.05-0.23 mm; p < 0.001] for 1 g/day and 0.10 mm (95% CI 0.02-0.19 mm; p = 0.018) for 2 g/day, with no difference between strontium ranelate groups. Radiological progression was less frequent with strontium ranelate (22% with 1 g/day and 26% with 2 g/day versus 33% with placebo, both p < 0.05), as was radioclinical progression (8% and 7% versus 12%, both p < 0.05). Symptoms also improved with strontium ranelate 2 g/day only in terms of total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score (p = 0.045), and its components for pain (p = 0.028) and physical function (p = 0.099). Responder analyses using a range of criteria for symptoms indicated that the effect of strontium ranelate 2 g/day on pain and physical function was clinically meaningful. Strontium ranelate was well tolerated. The observation of both structure and symptom modification with strontium ranelate 2 g/day makes SEKOIA a milestone in osteoarthritis research and treatment. PMID:24101948
Reginster, Jean-Yves; Beaudart, Charlotte; Neuprez, Audrey; Bruyère, Olivier
Calcium pyrophosphate dihydrate deposition disease (CPDD, tophaceous pseudogout) is a rare crystal arthropathy characterized by calcium pyrophosphate crystal deposition in joint spaces, episodes of synovitis, and radiological features of chondrocalcinosis. We present a case of 61-year-old woman who presented with left temporomandibular joint (TMJ) pain, difficulty chewing, left facial numbness, left-sided hearing loss, and left TMJ swelling. Imaging of the temporal fossa revealed a large mass emanating from the temporal bone at the TMJ, extending into the greater wing of the sphenoid and involving the mastoid bone and air cells posteriorly. Fine needle aspiration demonstrated polarizable crystals with giant cells. Intraoperatively, the TMJ was completely eroded by the mass. Final pathology was consistent with tophaceous pseudogout. CPDD has rarely been reported involving the skull base. None of the cases originally described by McCarty had TMJ pseudogout. Symptoms are generally pain, swelling, and hearing loss. Management is nearly always surgical with many patients achieving symptomatic relief with resection. CPDD is associated with many medical problems (including renal failure, gout, and hyperparathyroidism), but our patient had none of these risk factors. This case demonstrates that CPDD can involve the skull base and is best treated with skull base surgical techniques. PMID:23946918
Srinivasan, Vasisht; Wensel, Andrew; Dutcher, Paul; Newlands, Shawn; Johnson, Mahlon; Vates, George Edward
Calcium pyrophosphate dihydrate deposition disease (CPDD, tophaceous pseudogout) is a rare crystal arthropathy characterized by calcium pyrophosphate crystal deposition in joint spaces, episodes of synovitis, and radiological features of chondrocalcinosis. We present a case of 61-year-old woman who presented with left temporomandibular joint (TMJ) pain, difficulty chewing, left facial numbness, left-sided hearing loss, and left TMJ swelling. Imaging of the temporal fossa revealed a large mass emanating from the temporal bone at the TMJ, extending into the greater wing of the sphenoid and involving the mastoid bone and air cells posteriorly. Fine needle aspiration demonstrated polarizable crystals with giant cells. Intraoperatively, the TMJ was completely eroded by the mass. Final pathology was consistent with tophaceous pseudogout. CPDD has rarely been reported involving the skull base. None of the cases originally described by McCarty had TMJ pseudogout. Symptoms are generally pain, swelling, and hearing loss. Management is nearly always surgical with many patients achieving symptomatic relief with resection. CPDD is associated with many medical problems (including renal failure, gout, and hyperparathyroidism), but our patient had none of these risk factors. This case demonstrates that CPDD can involve the skull base and is best treated with skull base surgical techniques.
Srinivasan, Vasisht; Wensel, Andrew; Dutcher, Paul; Newlands, Shawn; Johnson, Mahlon; Vates, George Edward
Background: For persons with unicompartment knee osteoarthritis (OA), off-unloader braces are a mechanical intervention designed to reduce pain, improve physical function, and possibly slow disease progression. Pain relief is thought to be mediated by distracting the involved compartment via external varus or valgus forces applied to the knee. In so doing, tibiofemoral alignment is improved, and load is shifted off the degenerative compartment, where exposure to potentially damaging and provocative mechanical stresses are reduced. Objectives: To provide a synopsis of the evidence documented in the scientific literature concerning the efficacy of off-loader knee braces for improving symptomatology associated with painful disabling medial compartment knee OA. Search Strategy: Relevant peer-reviewed publications were retrieved from a MEDLINE search using the terms with the reference terms osteoarthritis, knee, and braces (per Medical Subject Headings), plus a manual search of bibliographies from original and review articles and appropriate Internet resources. Results: For persons with combined unicompartment knee OA and mild to moderate instability, the strength of recommendation reported by the Osteoarthritis Research Society International in the ability of off-loader knee braces to reduce pain, improve stability, and diminish the risk of falling was 76% (95% confidence interval, 69%-83%). The more evidence the treatment is effective, the higher the percentage. Conclusions: Given the encouraging evidence that off-loader braces are effective in mediating pain relief in conjunction with knee OA and malalignment, bracing should be fully used before joint realignment or replacement surgery is considered. With the number of patients with varus deformities and knee pain predicted to increase as the population ages, a reduction of patient morbidity for this widespread chronic condition in combination with this treatment modality could have a positive impact on health care costs and the economic productivity and quality of life of the affected individuals.
Ramsey, Dan K.; Russell, Mary E.
Efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus): study protocol for a randomised placebo controlled trial
Background Osteoarthritis of the first metatarsophalangeal joint (MPJ) of the foot, termed hallux limitus, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc®) to reduce pain and improve function in people with hallux limitus. Methods One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria) will be recruited. Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc®) or sterile saline (placebo) into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc® or sterile saline according to the treatment group they are in) either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest), stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global satisfaction with the treatment, health-related quality of life (assessed using the Short-Form-36 version two questionnaire), magnitude of symptom change, use of pain-relieving medication and changes in dynamic plantar pressure distribution (maximum force and peak pressure) during walking. Data will be collected at baseline, then 1, 3 and 6 months post-treatment. Data will be analysed using the intention to treat principle. Discussion This study is the first randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis of the first MPJ (hallux limitus). The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if this form of treatment is found to be an effective treatment strategy. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12607000654459
Munteanu, Shannon E; Menz, Hylton B; Zammit, Gerard V; Landorf, Karl B; Handley, Christopher J; ElZarka, Ayman; DeLuca, Jason
The term "acetabular dysplasia" suggests a smaller than normal acetabulum or one that is abnormally vertical. Acetabular dysplasia has been linked to the development of hip osteoarthritis over the last 90 years in 3 ways. First, it has been linked through the concept that biomechanical forces can cause osteoarthritis. A smaller than normal acetabulum will result in a smaller than normal contact surface between the femoral head and the acetabulum. This will generate increased pressure per unit of area, which will precipitate articular cartilage failure when the pressure reaches a critical point. Osteoarthritis will ensue in response to this cartilage failure. A more vertical than normal acetabulum will be associated with increased shear. When that shear reaches a critical level, articular cartilage will fail, leading that to osteoarthritis. This critical level, for a small or a steep acetabulum, may differ between individuals, based on their biology and their life styles. Second, it has been linked by multiple empirical studies. One of these is Wiberg's 1939 thesis entitled "Studies on Dysplastic Acetabula and Congenital Subluxation of the Hip Joint with Special reference to the Complication of Osteoarthritis." It is among the most quoted and most powerful works in the Orthopaedic literature connecting a disease entity with an antecedent. Third, the linkage is reenforced by an absence of glaring exceptions to the hypothesis that acetabular dysplasia causes osteoarthritis. Orthopaedic surgeons just do not report on dysplastic hips in the arthritis-free elderly. The inability of the Orthopaedic community to identify even 1 elderly, arthritis-free individual with significant hip dysplasia should not carry weight in establishing the concept that acetabular dysplasia causes osteoarthritis. However, the longer this case report goes unpublished, the more certain orthopaedic surgeons will be that the 2 are linked. PMID:23764788
Osteoarthritis (OA) is the most common musculoskeletal disorder world-wide and has enormous social and economic consequences.\\u000a OA is a multifactorial disorder in which ageing, genetic, hormonal and mechanical factors are all major contributors to its\\u000a onset and progression. The primary lesion in OA would appear to occur in the articular cartilage (AC) which covers the weight-bearing\\u000a surfaces of diarthrodial joints.
Peter Ghosh; Margaret Smith
We studied the impact of the diagnostic label of osteoarthritis and educational information on family members' attributions, perceptions, and willingness to help older parents with pain. Undergraduate students (N = 636) were randomly assigned to one of three conditions where they read vignettes about an older mother with chronic pain, which varied…
Thomas, Kali S.; McIlvane, Jessica M.; Haley, William E.
Osteoarthritis is a major public health burden. The incidence of osteoarthritis increases with advancing age. Symptomatic treatments aimed at alleviating the pain and thereby restoring joint function form the basis of the treatment. The chronic course requires long-term treatment with special attention to minimizing the side effects of drugs. Acetaminophen has a good risk\\/benefit ratio that has prompted international consensus
Philippe Bertin; Karim Keddad; Isabelle Jolivet-Landreau
Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a better understanding of how estrogen acts on joints and other tissues in OA will aid the development of specific and safe estrogen ligands as novel therapeutic agents targeting the OA joint as a whole organ.
Two cases of Charcot-like joints in patients with pseudogout who were otherwise neurologically intact are presented. The arthropathy of pseudogout should include Charcot-like joints and it is emphasized that an apparent Charcot joint should raise the question of pseudogout.
Helms, C.A.; Chapman, G.S.; Wild, J.H.
The earliest stages of osteoarthritis are characterized by peripheral pathology; however, during disease progression chronic pain emerges-a major symptom of osteoarthritis linked to neuroplasticity. Recent clinical imaging studies involving chronic pain patients, including osteoarthritis patients, have demonstrated that functional properties of the brain are altered, and these functional changes are correlated with subjective behavioral pain measures. Currently, preclinical osteoarthritis studies have not assessed if functional properties of supraspinal pain circuitry are altered, and if these functional properties can be modulated by pharmacological therapy either by direct or indirect action on brain systems. In the current study, functional connectivity was first assessed in order to characterize the functional neuroplasticity occurring in the rodent medial meniscus tear (MMT) model of osteoarthritis-a surgical model of osteoarthritis possessing peripheral joint trauma and a hypersensitive pain state. In addition to knee joint trauma at week 3 post-MMT surgery, we observed that supraspinal networks have increased functional connectivity relative to sham animals. Importantly, we observed that early and sustained treatment with a novel, peripherally acting broad-spectrum matrix metalloproteinase (MMP) inhibitor (MMPi) significantly attenuates knee joint trauma (cartilage degradation) as well as supraspinal functional connectivity increases in MMT animals. At week 5 post-MMT surgery, the acute pharmacodynamic effects of celecoxib (selective cyclooxygenase-2 inhibitor) on brain function were evaluated using pharmacological magnetic resonance imaging (phMRI) and functional connectivity analysis. Celecoxib was chosen as a comparator, given its clinical efficacy for alleviating pain in osteoarthritis patients and its peripheral and central pharmacological action. Relative to the vehicle condition, acute celecoxib treatment in MMT animals yielded decreased phMRI infusion responses and decreased functional connectivity, the latter observation being similar to what was detected following chronic MMPi treatment. These findings demonstrate that an assessment of brain function may provide an objective means by which to further evaluate the pathology of an osteoarthritis state as well as measure the pharmacodynamic effects of therapies with peripheral or peripheral and central pharmacological action. PMID:22982372
Upadhyay, Jaymin; Baker, Scott J; Rajagovindan, Rajasimhan; Hart, Michelle; Chandran, Prasant; Hooker, Bradley A; Cassar, Steven; Mikusa, Joseph P; Tovcimak, Ann; Wald, Michael J; Joshi, Shailen K; Bannon, Anthony; Medema, Jeroen K; Beaver, John; Honore, Prisca; Kamath, Rajesh V; Fox, Gerard B; Day, Mark
The first joint replacement surgery was performed in 1919. Since then, joint replacement surgery has undergone tremendous development in terms of surgical technique and anesthetic management. In this era of nuclear family and independent survival, physical mobility is of paramount importance. In recent years, with an increase in life expectancy, advances in geriatric medicine and better insurance coverage, the scenario of joint replacement surgery has changed significantly. Increasing number of young patients are undergoing joint replacement for pathologies like rheumatoid arthritis and ankylosing spondylitis. The diverse pathologies and wide range of patient population brings unique challenges for the anesthesiologist. This article deals with anesthetic issues in joint replacement surgery in patients with comorbidities.
Kakar, P N; Roy, Preety Mittal; Pant, Vijaya; Das, Jyotirmoy
Knee osteoarthritis is a common disabling condition that affects more than one-third of persons older than 65 years. Exercise, weight loss, physical therapy, intra-articular corticosteroid injections, and the use of nonsteroidal anti-inflammatory drugs and braces or heel wedges decrease pain and improve function. Acetaminophen, glucosamine, ginger, S-adenosylmethionine (SAM-e), capsaicin cream, topical nonsteroidal anti-inflammatory drugs, acupuncture, and tai chi may offer some benefit. Tramadol has a poor trade-off between risks and benefits and is not routinely recommended. Opioids are being used more often in patients with moderate to severe pain or diminished quality of life, but patients receiving these drugs must be carefully selected and monitored because of the inherent adverse effects. Intra-articular corticosteroid injections are effective, but evidence for injection of hyaluronic acid is mixed. Arthroscopic surgery has been shown to have no benefit in knee osteoarthritis. Total joint arthroplasty of the knee should be considered when conservative symptomatic management is ineffective. PMID:21661710
Ringdahl, Erika; Pandit, Sandesh
Background Osteoarthritis (OA) has a significant impact on individuals' ability to work. Our goal was to investigate the effects of the site of OA (knee, hip, hand, foot, lower back or neck) on employment reduction due to OA (EROA). Methods and Findings This study involved a random sample of 6,000 patients with OA selected from the Medical Service Plan database in British Columbia, Canada. A total of 5,491 were alive and had valid addresses, and of these, 2,259 responded (response rate?=?41%), from which 2,134 provided usable data. Eligible participants were 19 or older with physician diagnosed OA based on administrative data between 1992 and 2006. Data of 688 residents were used (mean age 62.1 years (27 to 86); 60% women). EROA had three levels: no reduction; reduced hours; and total cessation due to OA. The (log) odds of EROA was regressed on OA sites, adjusting for age, sex, education and comorbidity. Odds ratios (ORs) represented the effect predicting total cessation and reduced hours/total cessation. The strongest effect was found in lower back OA, with OR?=?2.08 (95% CI: 1.47, 2.94), followed by neck (OR?=?1.59; 95% CI: 1.11, 2.27) and knee (OR?=?1.43; 95% CI: 1.02, 2.01). We found an interaction between sex and foot OA (men: OR?=?1.94; 95% CI: 1.05, 3.59; women: OR?=?0.89; 95% CI?=?0.57, 1.39). No significant effect was found for hip OA (OR?=?1.33) or hand OA (OR?=?1.11). Limitations of this study included a modest response rate, the lack of an OA negative group, the use of administrative databases to identify eligible participants, and the use of patient self-reported data. Conclusions After adjusting for socio-demographic variables, comorbidity, and other OA disease sites, we find that OA of the lower back, neck and knee are significant predictors for EROA. Foot OA is only significantly associated with EROA in males. For multi-site combinations, ORs are multiplicative. These findings may be used to guide resource allocation for future development/improvement of vocational rehabilitation programs for site-specific OA.
Sayre, Eric C.; Li, Linda C.; Kopec, Jacek A.; Esdaile, John M.; Bar, Sherry; Cibere, Jolanda
Recently, we developed a new tensor for total knee arthroplasty (TKA) procedures enabling soft tissue balance assessment throughout\\u000a the range of motion while reproducing post-operative joint alignment with the patello-femoral (PF) joint reduced and the tibiofemoral\\u000a joint aligned. Using the tensor with a computer-assisted navigation system, we investigated the relationship between various\\u000a intra-operative joint gap values and their post-operative flexion
Tomoyuki Matsumoto; Kiyonori Mizuno; Hirotsugu Muratsu; Nobuhiro Tsumura; Naomasa Fukase; Seiji Kubo; Shinichi Yoshiya; Masahiro Kurosaka; Ryosuke Kuroda
... bursa or tendon sheath to treat bursitis and tendonitis, respectively. What benefit is derived from a joint ... conditions, such as rheumatoid arthritis, psoriatic arthritis, gout, tendonitis, bursitis and, occasionally, osteoarthritis. What usually is injected ...
Biochemical investigations into the pathogenesis of osteoarthritis have, for the last two decades, concentrated on the mechanisms involved in the destruction of the articular cartilage. Although bone changes are known to occur, the biochemistry of the collagenous matrix within osteoarthritic bone has received scant attention. We report that bone collagen metabolism is increased within osteoarthritic femoral heads, with the greatest changes occurring within the subchondral zone. Collagen synthesis and its potential to mineralize were determined by the carboxy-terminal propeptide content and alkaline phosphatase activity, respectively. These data supported elevated new matrix formation. Our finding of a three- to fourfold increase in TGF-beta in osteoarthritic bone indicates that this might represent a stimulus for the increased collagen synthesis observed. Of additional significance is the hypomineralization of deposited collagen in the subchondral zone of osteoarthritic femoral heads, supporting a greater proportion of osteoid in the diseased tissue. The cross-linking of collagen was similar to that observed for controls. In addition, the degradative potential of osteoarthritic bone was considerably higher as demonstrated by increased matrix metalloproteinase 2 activity, and again the greater activity was associated with the subchondral bone tissue. The polarization exhibited in the metabolism of bone collagen from osteoarthritic hips might exacerbate the processes involved in joint deterioration by altering joint morphology. This in turn may alter the distribution of mechanical forces to the various tissues, to which bone is a sensitive responder. Bone collagen metabolism is clearly an important factor in the pathogenesis of osteoarthritis and certainly warrants further biochemical study.
Mansell, J P; Bailey, A J
Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.
Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo
Objective: To test whether knee stabilization therapy, prior to strength/functional training, may have added value in reducing activity limitations only in patients with knee osteoarthritis who have knee instability and (i) low upper leg muscle strength, (ii) impaired knee proprioception, (iii) high knee laxity, or (iv) frequent episodes of knee instability. Design: Subgroup analyses in a randomized controlled trial comparing 2 exercise programmes (with/without knee stabilization therapy) (STABILITY; NTR1475). Patients: Participants from the STABILITY-trial with clinical knee osteoarthritis and knee instability (n?=?159). Methods: Effect modification by upper leg muscle strength, knee proprioception, knee laxity, and patient-reported knee instability were determined using the interaction terms "treatment group*subgroup factor", with the outcome measures WOMAC physical function (primary), numeric rating scale pain and the Get up and Go test (secondary). Results: Effect modification by muscle strength was found for the primary outcome (p?=?0.01), indicating that patients with greater muscle strength tend to benefit more from the experimental programme with additional knee stabilization training, while patients with lower muscle strength benefit more from the control programme. Conclusion: Knee stabilization therapy may have added value in patients with instability and strong muscles. Thus it may be beneficial if exercises target muscle strength prior to knee stabilization. PMID:24910399
Knoop, Jesper; van der Leeden, Marike; Roorda, Leo D; Thorstensson, Carina A; van der Esch, Martin; Peter, Wilfred F; de Rooij, Mariëtte; Lems, Willem F; Dekker, Joost; Steultjens, Martijn P M
Release of the patellar retinaculum and tibial tubercle elevation have both been advocated for the treatment of patellofemoral degeneration. Questions remain, however, regarding the magnitude and predictability of such effects in diseased joints. Using cadaver knee joints exhibiting a range of patellofemoral cartilage degeneration, we investigated the effects on joint contact pressures on release of the patellar retinaculum, followed by tibial tubercle elevations of 1.25 and 2.5 cm. Retinacular release failed to alter the joint-loading parameters significantly. Tibial tubercle elevation reduced the patello-femoral joint contact area and contact force, but failed to cause a consistent change in contact pressure. Tibial tubercle elevation also caused a migration of the joint contact area superolaterally on the retropatellar surface. This migration occurred in conjunction with ventral tilting of the inferior pole of the patella as the tubercle was elevated, suggesting that significant changes in joint kinematics may result from this procedure. PMID:2213343
Lewallen, D G; Riegger, C L; Myers, E R; Hayes, W C
This study was conducted to characterize movement-induced pain in a rat model of knee joint osteoarthritis and validate this behavioral assessment by evaluating the effects of clinically used analgesic compounds. Unilateral intra-articular administration of a chondrocyte glycolytic inhibitor monoiodoacetate, was used to induce knee joint osteoarthritis in Sprague–Dawley rats. In this osteoarthritis model, histologically erosive disintegration of the articular surfaces
Prasant Chandran; Madhavi Pai; Eric A. Blomme; Gin C. Hsieh; Michael W. Decker; Prisca Honore
Osteoarthritis (OA) is a prevalent joint disease that affects more than 40 million Americans and is characterized by degeneration of the articular cartilage and thickening of the underlying subchondral bone. Although subchondral bone thickening has been implicated in articular cartilage degeneration, very little is known about the composition of subchondral bone in OA. In the present study, infrared microspectroscopy (IRMS)
Lisa M Miller; Jaclyn Tetenbaum Novatt; David Hamerman; Cathy S Carlson
This report describes a very rare case of synovial chondromatosis with deposition of calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout) in the temporomandibular joint (TMJ) of a 46-year-old male patient. Synovial chondromatosis is a non-neoplastic disease characterized by metaplasia of the connective tissue leading to chondrogenesis in the synovial membrane. Pseudogout is an inflammatory disease of the joints caused by the deposition of CPPD, producing similar symptoms to those observed in gout but not hyperuricaemia. Both diseases commonly affect the knee, hip and elbow joints, but rarely affect the TMJ. PMID:23166363
Matsumura, Y; Nomura, J; Nakanishi, K; Yanase, S; Kato, H; Tagawa, T
This report describes a very rare case of synovial chondromatosis with deposition of calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout) in the temporomandibular joint (TMJ) of a 46-year-old male patient. Synovial chondromatosis is a non-neoplastic disease characterized by metaplasia of the connective tissue leading to chondrogenesis in the synovial membrane. Pseudogout is an inflammatory disease of the joints caused by the deposition of CPPD, producing similar symptoms to those observed in gout but not hyperuricaemia. Both diseases commonly affect the knee, hip and elbow joints, but rarely affect the TMJ.
Matsumura, Y; Nomura, J; Nakanishi, K; Yanase, S; Kato, H; Tagawa, T
Purpose of review We discuss herein the recent published epidemiologic data regarding risk factors for incident and progressive knee osteoarthritis (OA), and related knee pain to identify targets for primary and secondary prevention. We also discuss the recently identified methodologic challenges to the study of knee OA, particularly for identifying risk factors for OA progression. Recent findings Recent epidemiologic studies of knee OA have confirmed that being overweight and obese, as well as biomechanical factors such as knee injuries, leg-length inequalities, and likely malalignment increase the risk for incident knee OA. Obesity also appears to play a role in accelerating OA worsening. However, with the exception of malalignment, no risk factors for knee OA progression have been identified. Novel approaches to the study of knee pain have demonstrated a strong association between structural abnormalities and presence of knee pain, contrary to the “so-called” structure-symptom discordance, as well as between fluctuations of knee pain with changes in specific structural lesions. A number of methodologic issues have been identified which may explain, in part, the difficulty in identifying risk factors for knee OA, particularly OA progression. Summary Few new risk factors for knee OA have been identified. Without such knowledge, prevention of OA remains challenging.
Neogi, Tuhina; Zhang, Yuqing
Thirty-eight osteoarthrotic knees were examined to assess the widths of the femorotibial joint spaces. Radiographs were exposed with the patient lying, in a standing position, and with an adduction and abduction force. Forced compression of the osteoarthrotic joint compartment caused, on average, 18% greater narrowing than when loading it in the standing position. Compared to the joint space at rest, the non-weight-bearing compartment widened by 16% in the standing position and narrowed by 20% when stress was applied. Furthermore, the results showed an increase in laxity proportional to the degree of arthrosis. Stress radiographs significantly display the real cartilage width of both joint compartments. Knowledge of the condition of the articular cartilage in the non-weight-bearing compartment is important when considering a transfer of loading stresses by means of osteotomy. PMID:3423831
Tallroth, K; Lindholm, T S
Background Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. Results We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ?3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. Conclusions We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article.
Osteoarthritis (OA) is a multifactorial process affecting cartilage and subchondral bone. Conventional radiographs are inexpensive\\u000a and readily available. The increased knowledge with regard to interpreting weightbearing radiographs of the tibiofemoral joint\\u000a and axial radiographs of the patellofemoral joint will enable these examinations to remain competitive techniques compared\\u000a with more expensive and sophisticated methods, such as MR imaging, when investigating knee
Torsten Boegård; Kjell Jonsson
A genetic deficit mediated by SNP rs143383 that leads to reduced expression of GDF5 is strongly associated with large-joint osteoarthritis. We speculated that this deficit could be attenuated by the application of exogenous GDF5 protein and as a first step we have assessed what effect such application has on primary osteoarthritis chondrocyte gene expression. Chondrocytes harvested from cartilage of osteoarthritic patients who had undergone joint replacement were cultured with wildtype recombinant mouse and human GDF5 protein. We also studied variants of GDF5, one that has a higher affinity for the receptor BMPR-IA and one that is insensitive to the GDF5 antagonist noggin. As a positive control, chondrocytes were treated with TGF-?1. Chondrocytes were cultured in monolayer and micromass and the expression of genes coding for catabolic and anabolic proteins of cartilage were measured by quantitative PCR. The expression of the GDF5 receptor genes and the presence of their protein products was confirmed and the ability of GDF5 signal to translocate to the nucleus was demonstrated by the activation of a luciferase reporter construct. The capacity of GDF5 to elicit an intracellular signal in chondrocytes was demonstrated by the phosphorylation of intracellular Smads. Chondrocytes cultured with TGF-?1 demonstrated a consistent down regulation of MMP1, MMP13 and a consistent upregulation of TIMP1 and COL2A1 with both culture techniques. In contrast, chondrocytes cultured with wildtype GDF5, or its variants, did not show any consistent response, irrespective of the culture technique used. Our results show that osteoarthritis chondrocytes do not respond in a predictable manner to culture with exogenous GDF5. This may be a cause or a consequence of the osteoarthritis disease process and will need to be surmounted if treatment with exogenous GDF5 is to be advanced as a potential means to overcome the genetic deficit conferring osteoarthritis susceptibility at this gene.
Ratnayake, Madhushika; Ploger, Frank; Santibanez-Koref, Mauro; Loughlin, John
Even though osteoarthritis (OA) is mainly considered as a degradative condition of the articular cartilage, there is increasing body of data demonstrating the involvement of all branches of the immune system. Genetic, metabolic or mechanical factors cause an initial injury to the cartilage resulting in release of several cartilage specific auto-antigens, which trigger the activation of immune response. Immune cells including T cells, B cells and macrophages infiltrate the joint tissues, cytokines and chemokines are released from different kind of cells present in the joint, complement system is activated, cartilage degrading factors such as matrix metalloproteins (MMPs) and prostaglanding E2 (PGE2) are released, resulting in further damage to the articular cartilage. There is considerable success in the treatment of rheumatoid arthritis using anti-cytokine therapies. In OA, however, these therapies did not show much effect, highlighting more complex nature of pathogenesis of OA. This needs the development of more novel approaches to treat OA, which may include therapies that act on multiple targets. Plant natural products have this kind of properties and may be considered for future drug development efforts. Here we reviewed the studies implicating different components of the immune system in the pathogenesis of OA.
Haseeb, Abdul; Haqqi, Tariq M.
Osteoarthritis (OA) is the most common type of arthritis worldwide and rapidly increasing with ageing populations. It is a major source of pain and disability for individuals and economic burden for health economies. Modern imaging, in particular magnetic resonance imaging (MRI), has helped us to understand that OA is a dynamic remodelling process involving all the structures within the joint. Inflammation is common in OA, with a high prevalence of synovitis seen on imaging, and this has been associated with joint pain. MRI detected changes within the subchondral bone are also common and associated with pain and structural progression. Targeting individual pathologies may offer potential new therapeutic options for OA; this is particularly important given the current treatments are often limited by side effects or lack of efficacy. New approaches to understanding the pathology and pain pathways in OA offer hope of novel analgesic options, for example, monoclonal antibodies against nerve growth factor and centrally acting drugs such as duloxetine, tapentadol and bradykinin receptor antagonists have all recently undergone trials in OA. While treatment for OA has until now relied on symptom management, for the first time, recent trials suggest that structure modification may be possible by treating the subchondral bone. PMID:23568255
Wenham, Claire Y J; Conaghan, Philip G
Background The association between progression of knee osteoarthritis and progression of osteoarthritis at sites distant from the knee is unclear because of a lack of multisite longitudinal progression data. Objective To examine the association between radiological progression of knee osteoarthritis and osteoarthritis of the hands, hips, and lumbar spine in a population based cohort. Methods 914 women had knee x?rays taken 10 years apart, which were read for the presence of osteophytes and joint space narrowing (JSN). Progression status was available for hand, hip, and lumbar spine x?rays over the same 8 to 10 year period. The association between progression of knee osteoarthritis and osteoarthritis at other sites was analysed using odds ratios (OR) and 95% confidence intervals (CI) in logistic regression models. Results 89 of 133 women had progression of knee osteoarthritis based on osteophytes, and 51 of 148 based on JSN definition. Progression of JSN in the knee was predicted by progression in lumbar spine disc space narrowing (OR?=?2.9 (95% CI 1.2 to 7.5)) and hip JSN (OR?=?2.0 (1.0 to 4.2)). No consistent effects were seen for hand osteoarthritis. The associations remained after adjustment for age and body mass index. Conclusions Progression of knee osteoarthritis is associated with progression of lumbar spine and hip osteoarthritis. This may have implications for trial methodology, the selection of patients for osteoarthritis research, and advice for patients on prognosis of osteoarthritis.
Hassett, G; Hart, D J; Doyle, D V; March, L; Spector, T D
Objective To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW)\\u000a in hand radiographs. Repeatability, accuracy and sensitivity to changes in JSW were determined. The influence of joint location\\u000a and joint shape on the measurements was tested.\\u000a \\u000a \\u000a \\u000a \\u000a Methods A mechanical micrometer set-up was developed to define and adjust the true JSW in an acrylic phantom
Kasper Huétink; Ronald van ’t Klooster; Bart L. Kaptein; Iain Watt; Margreet Kloppenburg; Rob G. H. H. Nelissen; Johan H. C. Reiber; Berend C. Stoel
The role of inflammation in the development, progression, and clinical features of osteoarthritis has become an area of intense research in recent years. This led to the recognition of synovitis as an important source of inflammation in the joint and indicated that synovitis is intimately associated with pain and osteoarthritis progression. In this review, we discuss another emerging source of inflammation that could play a role in disease development/progression: the infrapatellar fat pad (IFP). The aim of this review is to offer a comprehensive view of the pathology of IFP as obtained from magnetic resonance studies, along with its characterization at both the cellular and the molecular level. Furthermore, we discuss the possible function of this organ in the pathological processes in the knee by summarizing the knowledge regarding the interactions between IFP and other joint tissues and discussing the pro- versus anti-inflammatory functions this tissue could have. We hope that this review will offer an overview of all published data regarding the IFP and will indicate novel directions for future research.
Hip osteoarthritis is a common cause of musculoskeletal pain in older adults and may result in decreased mobility and quality\\u000a of life. Although the presentation of hip osteoarthritis varies, surgical management is required when the disease is severe,\\u000a longstanding, and unresponsive to nonoperative treatments. For stakeholders to plan for the expected increased demand for\\u000a surgical procedures related to hip osteoarthritis,
Simon Dagenais DC; Shawn Garbedian; Eugene K. Wai
Arthroscopy of the hip joint was performed in 19 children with Legg-Calvé-Perthes' disease. Proliferation of the synovium was pronounced both in the acetabular fossa and over the inner wall of the capsule. Hypervascularity was seen on the acetabular labrum in every stage of the disease. Microscopically, hyperplasia of the synovial lining cells was observed, but inflammatory changes in the synovial tissue were inconspicuous in the early stage of the disease. Although hypertrophy of the endothelial cells of the vessels was seen in the late stage of the disease, it was not distinct in the initial or fragmentation stages. Joint pain improved after irrigation during arthroscopy. PMID:7839839
Suzuki, S; Kasahara, Y; Seto, Y; Futami, T; Furukawa, K; Nishino, Y
Osteoarthritis as well as rheumatoid arthritis lead to chronical progressive destruction of diseased joints. As aggressive new treatments need to be evaluated, plenty of (semi-) quantitative methods for the radiological joint evaluation had been developed. They lack sufficient reproducibility due to their low objectivity. Modern approaches of computer-assisted radiological quantification should increase the reproducibility and efficiency of radiological scoring. Automatically calculated, computer-assisted measurements of joint space, cartilage- and synovial volume, periarticular assessment of bone mineral density and quantitative analysis of the subchondral plate will have major impact on the radiological routine of the future. PMID:11197934
Peloschek, P L; Sailer, J; Kainberger, F; Boegl, K; Imhof, H
The effect of articular joint shape and congruence on kinematics, contact stress, and the natural progression of joint disease continue to be a topic of interest in the orthopedic biomechanics literature. Currently, the most widely used metrics of assessing skeletal joint shape and congruence are based on average principal curvatures across the articular surfaces. Here we propose a method for comparing articular joint shape and quantifying joint congruence based on three-dimensional (3D) histograms of curvature-shape descriptors that preserve spatial information. Illustrated by experimental results from the trapeziometacarpal joint, this method could help unveil the interrelations between joint shape and function and provide much needed insight for the high incidence of osteoarthritis (OA)-a mechanically mediated disease whose onset has been hypothesized to be precipitated by joint incongruity. PMID:24976300
Halilaj, Eni; Laidlaw, David H; Moore, Douglas C; Crisco, Joseph J
\\u000a Joint tissues, including cartilage, bone, meniscus, tendon, ligament and synovial membrane, are exposed to high mechanical\\u000a stimulation. The response of these tissues to mechanical strains is a key factor of the OA onset and progression. Any little\\u000a failure in this mechanical function may lead to cell phenotype alteration and tissue damages. While mechanical responses of\\u000a cartilage are well known, very
Christelle Sanchez; Marianne Mathy-Hartert; Yves Henrotin
Osteoarthritis is a degenerative joint disease mostly occurring in the knee and commonly seen in middle-aged and elderly adults. Intra-articular injection of hyaluronic acid has been widely used for treatment of knee osteoarthritis. The aim of this study was to evaluate the efficacy of intra-articular injection of a novel highly cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, on knee articular cartilage in a rabbit model of collagenase-induced knee osteoarthritis. After induction of experimental osteoarthritis by intra-articular injection of collagenase, adult New Zealand white rabbits (n = 12) were divided into 3 groups. Group 1 (control group) received 0.3 ml phosphate buffered saline into the right knee joint. Group 2 received 0.3 ml cross-linked hyaluronic acid (33 mg/ml) into the right knee joint. Group 3 received a mixture of 0.15 ml cross-linked hyaluronic acid (33 mg/ml), 0.05 ml ropivacaine hydrochloride 1 % and 0.1 ml triamcinolone acetonide (10 mg/ml) into the right knee joint. Intra-articular injections were given 4 weeks after first collagenase injection and were administered once a week for 3 weeks. Gross pathology and histological evaluation of rabbits' knee joints were performed after 16 weeks following initial collagenase injection. Histological analysis of sections of right knee joints at lesion sites showed a significant decrease in Mankin's score in groups treated with hyaluronic acid alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide versus control group (p < 0.05 and p < 0.01 respectively). This evidence was consistent with strong articular degenerative changes in control right knee joints (grade III osteoarthritis), while the treated groups revealed less severe articular degenerative changes (grade II osteoarthritis). The present results show that cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, produces a significant improvement in knee articular cartilage degeneration in a rabbit model of collagenase-induced osteoarthritis. PMID:23389746
Iannitti, Tommaso; Elhensheri, Mohamed; Bingöl, Ali O; Palmieri, Beniamino
Background: The purpose of this research was to study the effects of 8 weeks of Hata yoga exercises on women with knee osteoarthritis. Studies about effects of Yoga on different chronic diseases show that these exercises have positive effects on chronic diseases. As knee osteoarthritis is very common among middle age women we decided to measure effectiveness of these exercises on knee osteoarthritis. Methods: Sample included 30 women with knee osteoarthritis who voluntarily participated in this semi-experimental study and were divided into a control group (15) and a yoga group (15). The yoga group received 60 minutes sessions of Hata yoga, 3 times a week and for 8 weeks. Pain, symptoms, daily activities, sports and spare-time activities, and quality of life were respectively measured by Visual Analog Scale (VAS) and Knee injury and Osteoarthritis Outcome Scale (KOOS) questionnaire. The Analysis of Variance (ANOVA) method for repetitive data was used to analyze the results (P = 0.05). Results: Findings showed that pain and symptoms were significantly decreased and scores of daily activities, sports, spare-time activities, and quality of life were significantly increased in the yoga group. Conclusions: It seems that yoga can be used as a conservative treatment besides usual treatments and medications to improve the condition of people with osteoarthritis.
Ghasemi, Gholam A; Golkar, Ainaz; Marandi, Sayyd M
Much information is available on the role of nitric oxide (NO) in osteoarthritis (OA). However, its role has not been studied in the monosodium iodoacetate (MIA)-induced model of osteoarthritic pain. The present study was undertaken in rats to investigate the effect of iNOS inhibitor S-methylisothiourea (SMT) in MIA-induced osteoathritic pain and disease progression in rats. Osteoarthritis was produced by single intra-articular injection of the MIA in the right knee joint on day 0. Treatment groups were orally gavazed with different doses of SMT (10, 30 and 100mg/kg) and etoricoxib (10mg/kg) daily for 21 days. On days 0, 3, 7, 14 and 21, pain was measured and histopathology of right knee joint was done on day 21. SMT produced analgesia in a dose-dependent manner as shown by mechanical, heat hyperalgesia, knee vocalization, knee squeeze test, and spontaneous motor activity test. SMT reduced NO production in synovial fluid. Histopathological findings indicated that SMT reduced disease progression as evident from complete cartilage formation in rats treated with SMT at 30 mg/kg. In conclusion, the results indicate that SMT attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid. It is suggested that SMT has potential as a therapeutic modality in the treatment of osteoarthritis. PMID:23287799
More, Amar S; Kumari, Rashmi R; Gupta, Gaurav; Lingaraju, Madhu C; Balaganur, Venkanna; Pathak, Nitya N; Kumar, Dhirendra; Kumar, Dinesh; Sharma, Anil K; Tandan, Surendra K
This review discusses the pharmacology, analgesic efficacy, safety and tolerability of topical NSAIDs, salicylates and capsaicin for the management of osteoarthritis (OA) pain. Topical therapies present a valuable therapeutic option for OA pain management, with substantial evidence supporting the efficacy and safety of topical NSAIDs, but less robust support for capsaicin and salicylates. We define topical therapies as those intended to act locally, in contrast to transdermal therapies intended to act systemically. Oral therapies for patients with mild to moderate OA pain include paracetamol (acetaminophen) and NSAIDs. Paracetamol has only weak efficacy at therapeutic doses and is hepatotoxic at doses >3.25 g/day. NSAIDs have demonstrated efficacy in patients with OA, but are associated with dose-, duration- and age-dependent risks of gastrointestinal, cardiovascular, renal, haematological and hepatic adverse events (AEs), as well as clinically meaningful drug interactions. To minimize AE risks, treatment guidelines for OA suggest minimizing NSAID exposure by prescribing the lowest effective dose for the shortest duration of time. Systemic NSAID exposure may also be limited by prescribing topical NSAIDs, particularly in patients with OA pain limited to a few superficial joints. Topical NSAIDs have been available in Europe for decades and were introduced to provide localized analgesia with minimal systemic NSAID exposure. Guidelines of the American Academy of Orthopaedic Surgeons, European League Against Rheumatism (EULAR), Osteoarthritis Research Society International, and National Institute for Health and Clinical Excellence (NICE) state that topical NSAIDs may be considered for patients with mild to moderate OA of the knee or hand, particularly in patients with few affected joints and/or a history of sensitivity to oral NSAIDs. In fact, the EULAR and NICE guidelines state that topical NSAIDs should be considered before oral therapies. Clinical trials of topical NSAIDs, most notably formulations of diclofenac and ketoprofen, have shown efficacy significantly superior to placebo and similar to oral NSAIDs. Most topical NSAIDs (piroxicam being the exception) have shown improved safety and tolerability compared with oral NSAIDs. Topical salicylates and capsaicin are available in the US without a prescription, but neither has shown substantial efficacy in clinical trials, and both have potential to cause serious AEs. Accidental poisonings have been reported with salicylates, and concerns exist that capsaicin-induced nerve desensitization is not fully reversible and that its autonomic nerve effects may increase the risk of skin ulcers in diabetic patients. PMID:21770475
Altman, Roy D; Barthel, H Richard
BackgroundCanine Hip Dysplasia (CHD) is a common inherited disease that affects dog wellbeing and causes a heavy financial and emotional burden to dog owners and breeders due to secondary hip osteoarthritis. The Orthopedic Foundation for Animals (OFA) initiated a program in the 1960's to radiograph hip and elbow joints and release the OFA scores to the public for breeding dogs
Yali Hou; Yachun Wang; George Lust; Lan Zhu; Zhiwu Zhang; Rory J. Todhunter; Amanda Ewart Toland
Therapy for osteoarthritis (OA) is aimed at relieving symptoms and at maximizing function. Therapies can be considered as either symptom modifying OA drugs (SMOADs) or as disease modifying OA drugs (DMOADs). Currently available agents fall into the category of SMOADs. Analgesic medications, particularly paracetamol and capsaicin, have proven efficacy in OA and are recommended first line therapies. Non-steroidal anti-inflammatory drugs (NSAIDs) do appear to provide extra symptomatic benefit for some patients but have greater toxicity. Newer generation NSAIDs may have safety advantages which remain to be confirmed in practice. Further therapies are being developed which aim to prevent cartilage damage and/or aid cartilage restoration, but these DMOADs remain in the experimental stage. PMID:9429735
Brady, S J; Brooks, P; Conaghan, P; Kenyon, L M
Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. PMID:23723266
Palmer, A J R; Brown, C P; McNally, E G; Price, A J; Tracey, I; Jezzard, P; Carr, A J; Glyn-Jones, S
Paracetamol is the first choice mediation for osteoarthritis. The analgetic potential of NSAIDs is slightly higher and they also have some antiphlogistic effect, but their use has to be strictly limited to a short period of time. They should mainly be used in the therapy of the acute and painful phase of osteoarthritis. Among the NSAIDs, Diclofenac is the medication of first choice. In patients with an increased risk of gastrointestinal complications, a protonpumpinhibitor should be added. Patients with cardiovascular risk factors should receive NSAIDs only in case of no appropriate alternative treatments. Opioids have their place in osteoarthritis treatment and should be part of an individualized pain regime, which should also contain a pain diary and proactive monitoring. It is important to emphasize the positive effects of physical activity on the function of the joints as well as the negative effect of overweight and immobility. PMID:20607666
Rosemann, T; Huber, C A; Rosemann, A
Is there an association between the individual anatomy of the scapula and the development of rotator cuff tears or osteoarthritis of the glenohumeral joint?: A radiological study of the critical shoulder angle.
We hypothesised that a large acromial cover with an upwardly tilted glenoid fossa would be associated with degenerative rotator cuff tears (RCTs), and conversely, that a short acromion with an inferiorly inclined glenoid would be associated with glenohumeral osteoarthritis (OA). This hypothesis was tested using a new radiological parameter, the critical shoulder angle (CSA), which combines the measurements of inclination of the glenoid and the lateral extension of the acromion (the acromion index). The CSA was measured on standardised radiographs of three groups: 1) a control group of 94 asymptomatic shoulders with normal rotator cuffs and no OA; 2) a group of 102 shoulders with MRI-documented full-thickness RCTs without OA; and 3) a group of 102 shoulders with primary OA and no RCTs noted during total shoulder replacement. The mean CSA was 33.1° (26.8° to 38.6°) in the control group, 38.0° (29.5° to 43.5°) in the RCT group and 28.1° (18.6° to 35.8°) in the OA group. Of patients with a CSA > 35°, 84% were in the RCT group and of those with a CSA < 30°, 93% were in the OA group. We therefore concluded that primary glenohumeral OA is associated with significantly smaller degenerative RCTs with significantly larger CSAs than asymptomatic shoulders without these pathologies. These findings suggest that individual quantitative anatomy may imply biomechanics that are likely to induce specific types of degenerative joint disorders. PMID:23814246
Moor, B K; Bouaicha, S; Rothenfluh, D A; Sukthankar, A; Gerber, C
The etiology of pain in osteoarthritis is multifactoral, and includes mechanical and inflammatory processes. Intra-articular injections of hyaluronans (HAs) are indicated when non-pharmacological and simple analgesics have failed to relieve symptoms. The HAs appear to reduce pain by restoring both mechanical and biomechanical homeostasis in the joint. There are five FDA-approved injectable preparations of HAs: Hyalgan®, Synvisc®, Supartz®, Orthovisc® and Euflexxa®. They all appear to relieve pain from 4 to 14 weeks after injection and may have disease-modification properties. Although several randomized controlled trials have established the efficacy of this treatment modality, additional high quality randomized control studies with appropriate comparison are still required to clearly define the role of intra-articular HA injections in the treatment of osteoarthritis.
Goldberg, Victor M; Goldberg, Laura
Osteoarthritis (OA) is progressive joint disease characterized by joint inflammation and a reparative bone response and is one of the top five most disabling conditions that affects more than one-third of persons > 65 years of age, with an average estimation of about 30 million Americans currently affected by this disease. Global estimates reveal more than 100 million people are affected by OA. The financial expenditures for the care of persons with OA are estimated at a total annual national cost estimate of $15.5-$28.6 billion per year. As the number of people >65 years increases, so does the prevalence of OA and the need for cost-effective treatment and care. Developing a treatment strategy which encompasses the underlying physiology of degenerative joint disease is crucial, but it should be considerate to the different age ranges and different population needs. This paper focuses on different exercise and treatment protocols (pharmacological and non-pharmacological), the outcomes of a rehabilitation center, clinician-directed program versus an at home directed individual program to view what parameters are best at reducing pain, increasing functional independence, and reducing cost for persons diagnosed with knee OA.
Bhatia, Dinesh; Bejarano, Tatiana; Novo, Mario
Nine patients with facial pain were evaluated with limited bone scans. The scintigrams correlated with microscopy in all patients, although radiographs correlated with microscopy in only five patients. The degenerative disease process in the temporomandibular joint was more extensive in the patients with radiographic and scintigraphic abnormalities than in those with scintigraphic abnormalities alone. The limited bone scan appears useful in detecting early degenerative changes in the temporomandibular joint.
Goldstein, H.A.; Bloom, C.Y.
Osteoarthritis (OA), the most common form of arthritis, is now understood to involve all joint tissues, with active anabolic and catabolic processes. Knee OA in particular is considered to be a largely mechanically-driven disease. As bone adapts to loads by remodeling to meet its mechanical demands, bone alterations likely play an important role in OA development. Subchondral bone changes in bone turnover, mineralization, and volume result in altered apparent and material density of bone that may adversely affect the joint’s biomechanical environment. Subchondral bone alterations such as bone marrow lesions (BMLs) and subchondral bone attrition (SBA) both tend to occur more frequently in the more loaded knee compartments, and are associated with cartilage loss in the same region. Recently, MRI-based 3D bone shape has been shown to track concurrently with and predict OA onset. The contributions of structural abnormalities to the clinical manifestations of knee OA are becoming better understood as well. While a structure-symptom discordance in knee OA is thought to exist, such observations do not take into account all potential factors that can contribute to between-person differences in the pain experience. Using novel methodology, pain fluctuation has been associated with changes in BMLs, synovitis and effusion. SBA has also been associated with knee pain, but the relationship of osteophytes to pain has been conflicting. Understanding the pathophysiologic sequences and consequences of OA pathology will guide rational therapeutic targeting. Importantly, rational treatment targets require understanding what structures contribute to pain as pain is the reason patients seek medical care.
Abstract The Hedgehog (Hh) family of proteins consists of Indian hedgehog (Ihh), sonic hedgehog (Shh), and desert hedgehog (Dhh). These proteins serve as essential regulators in a variety of developmental events. Ihh is mainly produced and secreted by prehypertrophic chondrocytes and regulates chondrocyte hypertrophy and endochondral bone formation during growth plate development. Tissue-specific deletion of the Ihh gene (targeted by Col2a1-Cre) causes early lethality in mice. Transgenic mice with induced Ihh expression exhibit increased chondrocyte hypertrophy and cartilage damage resembling human osteoarthritis (OA). During OA development, chondrocytes recapitulate the differentiation process that happens during the fetal status and which does not occur to an appreciable degree in adult articular cartilage. Ihh expression is up-regulated in human OA cartilage, and this upregulation correlates with OA progression and changes in chondrocyte morphology. A genetic study in mice further showed that conditional deletion of Ihh in chondrocytes attenuates OA progression, suggesting the possibility that blocking Ihh signaling can be used as a therapeutic approach to prevent or delay cartilage degeneration. However, Ihh gene deletion is currently not a therapeutic option as it is lethal in animals. RNA interference (RNAi) provides a means to knockdown Ihh without the severe side effects caused by chemical inhibitors. The currently available delivery methods for RNAi are nanoparticles and liposomes. Both have problems that need to be addressed. In the future, it will be necessary to develop a safe and effective RNAi delivery system to target Ihh signaling for preventing and treating OA. PMID:24844414
Zhou, Jingming; Wei, Xiaochun; Wei, Lei
Aim: To study the effect of integrated yoga on pain, morning stiffness and anxiety in osteoarthritis of knees. Materials and Methods: Two hundred and fifty participants with OA knees (35–80 years) were randomly assigned to yoga or control group. Both groups had transcutaneous electrical stimulation and ultrasound treatment followed by intervention (40 min) for two weeks with follow up for three months. The integrated yoga consisted of yogic loosening and strengthening practices, asanas, relaxation, pranayama and meditation. The control group had physiotherapy exercises. Assessments were done on 15th (post 1) and 90th day (post 2). Results: Resting pain (numerical rating scale) reduced better (P<0.001, Mann–Whitney U test) in yoga group (post 1=33.6% and post 2=71.8%) than control group (post 1=13.4% and post 2=37.5%). Morning stiffness decreased more (P<0.001) in yoga (post 1=68.6% and post 2=98.1%) than control group (post 1=38.6% and post 2=71.6%). State anxiety (STAI-1) reduced (P<0.001) by 35.5% (post 1) and 58.4% (post 2) in the yoga group and 15.6% (post 1) and 38.8% (post 2) in the control group; trait anxiety (STAI 2) reduced (P<0.001) better (post 1=34.6% and post 2=57.10%) in yoga than control group (post 1=14.12% and post 2=34.73%). Systolic blood pressure reduced (P<0.001) better in yoga group (post 1=?7.93% and post 2=?15.7%) than the control group (post 1=?1.8% and post 2=?3.8%). Diastolic blood pressure reduced (P<0.001) better in yoga group (post 1=?7.6% and post 2=?16.4%) than the control group (post 1=?2.1% and post 2=?5.0%). Pulse rate reduced (P<0.001) better in yoga group (post 1=?8.41% and post 2=?12.4%) than the control group (post 1=?5.1% and post 2=?7.1%). Conclusion: Integrated approach of yoga therapy is better than physiotherapy exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in reducing pain, morning stiffness, state and trait anxiety, blood pressure and pulse rate in patients with OA knees.
Ebnezar, John; Nagarathna, Raghuram; Yogitha, Bali; Nagendra, Hongasandra Ramarao
Introduction The meniscus has an important role in force transmission across the knee, but a detailed three-dimensional (3D) morphometric shape analysis of the lateral meniscus to elucidate subject-specific function has not been conducted. The aim of this study was to perform 3D morphometric analyses of the lateral meniscus in order to correlate shape variables with anthropometric parameters, thereby gaining a better understanding of the relationship between lateral meniscus shape and its load-bearing function. Methods The lateral meniscus (LM) was manually segmented from magnetic resonance images randomly selected from the Osteoarthritis Initiative (OAI) non-exposed control subcohort. A 3D statistical shape model (SSM) was constructed to extract the principal morphological variations (PMV) of the lateral meniscus for 50 subjects (25 male and 25 female). Correlations between the principal morphological variations and anthropometric parameters were tested. Anthropometric parameters that were selected included height, weight, body mass index (BMI), femoral condyle width and axial rotation. Results The first principal morphological variation (PMV) was found to correlate with height (r?=?0.569), weight (r?=?0.647), BMI (r?=?0.376), and femoral condyle width (r?=?0.622). The third PMV was found to correlate with height (r?=?0.406), weight (r?=?0.312), and femoral condyle width (r?=?0.331). The percentage of the tibial plateau covered by the lateral meniscus decreases as anthropometric parameters relating to size of the subject increase. Furthermore, when the size of the subject increases, the posterior and anterior horns become proportionally longer and wider. Conclusion The correlations discovered suggest that variations in meniscal shape can be at least partially explained by the levels of loads transmitted across the knee on a regular basis. Additionally, as the size of the subject increases and body weight rises, the coverage percentage of the meniscus is reduced, suggesting that there would be an increase in the load-bearing by the cartilage. However, this reduced coverage percentage is compensated by the proportionally wider and longer meniscal horn.
Background Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA). Methods 1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection. Results On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage. Conclusions These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage.
CD4+CD25+/highCD127low/- regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints--analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood
Introduction CD4+CD25+/highCD127low/- regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients. Methods Treg frequency in a total of 40 patients (18 RA and 22 OA) matched for age and sex was assessed by flow cytometry. Functional status was assessed by analysis of cell surface markers representative of activation, memory and regulation. Results CD4+ T cells infiltrate the SM to higher frequencies in RA joints than in OA joints (P?=?0.0336). In both groups, Tregs accumulate more within the SF and SM than concurrently in PB (P?0.0001). Relative Treg frequencies were comparable in all compartments of RA and OA, but Treg concentration was significantly higher in the SM of RA patients (P?=?0.025). Both PB and SM Tregs displayed a memory phenotype (CD45RO+RA-), but significantly differed in activation status (CD69 and CD62L) and markers associated with Treg function (CD152, CD154, CD274, CD279 and GITR) with only minor differences between RA and OA. Conclusions Treg enrichment into the joint compartment is not specific to inflammatory arthritis, as we found that it was similarly enriched in OA. RA pathophysiology might not be due to a Treg deficiency, because Treg concentration in SM was significantly higher in RA. Synovial Tregs represent a distinct phenotype and are activated effector memory cells (CD62L-CD69+), whereas peripheral Tregs are resting central memory cells (CD62L+CD69-).
Purpose of review Regenerative medicine offers the exciting potential of developing alternatives to total joint replacement for treating osteoarthritis (OA). In this article, we highlight recent work that addresses key challenges of stem cell-based therapies for OA and provide examples of innovative ways in which stem cells can aid in the treatment of OA. Recent findings Significant progress has been made in understanding the challenges to successful stem cell therapy, such as the effects of age or disease on stem cell properties, altered stem cell function due to an inflammatory joint environment, and phenotypic instability in vivo. Novel scaffold designs have been shown to enhance the mechanical properties of tissue-engineered cartilage and have also improved the integration of newly formed tissue within the joint. Emerging strategies such as injecting stem cells directly into the joint, manipulating endogenous stem cells to enhance regenerative capacity, and utilizing stem cells for drug discovery have expanded the potential uses of stem cells in treating OA. Summary A number of recent studies have greatly advanced the development and pre-clinical evaluation of potential stem cell-based treatments for OA through novel approaches focused on cell therapy, tissue engineering, and drug discovery.
Diekman, Brian O.; Guilak, Farshid
The available evidence suggests that genetic factors have a major role in osteoarthritis. It has been believed for over 50 years that a strong genetic component to certain forms of osteoarthritis is present. This genetic influence has now been estimated to be up to 65% in a recent twin study. The nature of the genetic influence in osteoarthritis is speculative and may involve either a structural defect (that is, collagen), alterations in cartilage or bone metabolism, or alternatively a genetic influence on a known risk factor for osteoarthritis such as obesity. Exciting work has showed that mutations in the collagen type 2 are important in some rare, familial forms of osteoarthritis. Further work is needed on isolating the gene or genes involved in the pathogenesis of this common, disabling condition.
Cicuttini, F M; Spector, T D
BACKGROUND—Despite the increasing interest in using knee cartilage volume as an outcome measure in studies of osteoarthritis (OA), it is unclear what components of knee cartilage will be most useful as markers of structure in the tibiofemoral (TF) joint.?OBJECTIVE—To compare the changes that occur in femoral and tibial cartilage volume in normal and osteoarthritic knees and how they relate to radiological grade.?METHODS—82 subjects (44 female, 38 male, age range 35-69 years) with a spectrum of radiological knee OA were examined. Each subject had femoral and tibial cartilage volume in the medial and lateral TF joint determined from T1 weighted fat saturated magnetic resonance images of the knee. Radiological grade of OA was determined from standing knee radiographs.?RESULTS—There was strong correlation between femoral and tibial cartilage volume measured in both the medial (R=0.75, p<0.001) and lateral TF joint (R=0.77, p<0.001). Similar correlations persisted when those with normal and those with OA joints were examined separately at both the medial and lateral TF joint. For each increase in radiological grade of joint space narrowing (0-3), there was a mean (SD) reduction in tibial cartilage volume of 1.00 (0.32) ml in the medial compartment and 0.53 (0.25) ml in the lateral compartment, after adjusting for differences in bone size. Similar changes were seen in the femoral cartilage.?CONCLUSIONS—The amounts of tibial and femoral cartilage are strongly related. It may be that for TF joint disease, measuring tibial cartilage alone may be adequate, given that measurements of the total femoral cartilage are less reproducible and the difficulties inherent in identifying the most appropriate component of femoral cartilage to measure.??
Cicuttini, F; Wluka, A; Stuckey, S
Objective The Hartley guinea pig develops articular cartilage degeneration similar to that seen in idiopathic human osteoarthritis. We investigated whether the application of pulsed low-intensity ultrasound (PLIUS) to the Hartley guinea pig joint would prevent or attenuate the progression of this degenerative process. Methods Treatment of male Hartley guinea pigs was initiated at the onset of degeneration (8 weeks of age) to assess the ability of PLIUS to prevent osteoarthritis, or at a later age (12 months) to assess the degree to which PLIUS acted to attenuate the progression of established disease. PLIUS (30 mW/cm2) was applied to stifle joints for 20 minutes per day over periods ranging from three to ten months, with contralateral limbs serving as controls. Joint cartilage histology was graded according to a modified Mankin scale to evaluate treatment effect. Immunohistochemical staining for IL-1 receptor antagonist (IL-1ra), MMP-3, MMP-13, and TGF-?1 was performed on the cartilage to evaluate patterns of expression of these proteins. Results PLIUS did not fully prevent cartilage degeneration in the prevention groups, but diminished the severity of the disease, with the treated joints showing markedly decreased surface irregularities and a much smaller degree of loss of matrix staining as compared to controls. PLIUS also attenuated disease progression in the groups with established disease, although to a somewhat lesser extent as compared to the prevention groups. Immunohistochemical staining demonstrated a markedly decreased degree of TGF-?1 production in the PLIUS-treated joints. This indicates less active endogenous repair, consistent with the marked reduction in cartilage degradation. Conclusions PLIUS exhibits the ability to attenuate the progression of cartilage degeneration in an animal model of idiopathic human OA. The effect was greater in the treatment of early, rather than established, degeneration.
Gurkan, Ilksen; Ranganathan, Archana; Yang, Xu; Horton, Walter E.; Todman, Martin; Huckle, James; Pleshko, Nancy; Spencer, Richard G.
A midstance reversal of sagittal plane hip motion during walking, or motion discontinuity (MD), has previously been observed in subjects with endstage hip osteoarthritis (OA) and in patients with femoroacetabular impingement. The goal of the present study was to evaluate whether this gait pattern is a marker of OA presence or radiographic severity by analyzing a large IRB approved motion analysis data repository. We also hypothesized that subjects with the MD would show more substantial gait impairments than those with normal hip motion. We identified 150 subjects with symptomatic unilateral hip OA and Kellgren-Lawrence OA severity data on file, and a control group of 159 asymptomatic subjects whose ages fell within 2 standard deviations of the mean OA group age. From the gait data, the MD was defined as a reversal in the slope of the hip flexion angle curve during midstance. Logistic regressions and general linear models were used to test the association between the MD and OA presence, OA severity and, other gait variables. 53% of OA subjects compared to 7.5% of controls had the MD (p<0.001); occurrence of the MD was associated with OA severity (p=0.009). Within the OA subject group, subjects with the MD had reduced dynamic range of motion, peak, extension, and internal rotation moments compared to those who did not (MANCOVA p ? 0.042) after controlling for walking speed. We concluded that sagittal plane motion reversals are indeed associated with OA presence and severity, and with more severe gait abnormalities in subjects with hip OA. PMID:22498313
Foucher, Kharma C; Schlink, Bryan R; Shakoor, Najia; Wimmer, Markus A
High rates of Staphylococcus aureus are reported in prosthetic joint infection (PJI) in rheumatoid arthritis (RA). RA patients are considered to have a high risk of infection with bacteria of potentially oral or dental origin. One thousand four hundred forty-three revisions for infection were reported to the Norwegian Arthroplasty Register (NAR) from 1987 to 2007. For this study 269 infection episodes in 255 OA patients served as control group. In the NAR we identified 49 infection episodes in 37 RA patients from 1987 to 2009. The RA patients were, on average, 10 years younger than the OA patients and there were more females (70% versus 54%). We found no differences in the bacterial findings in RA and OA. A tendency towards a higher frequency of Staphylococcus aureus (18% versus 11%) causing PJI was found in the RA patients compared to OA. There were no bacteria of potential odontogenic origin found in the RA patients, while we found 4% in OA. The bacteria identified in revisions for infection in THRs in patients with RA did not significantly differ from those in OA. Bacteria of oral or dental origin were not found in infected hip joint replacements in RA.
Schrama, J. C.; Lutro, O.; Langvatn, H.; Hallan, G.; Espehaug, B.; Sjursen, H.; Engesaeter, L. B.; Fevang, B.-T.
This paper is a preliminary paper which presents the early findings of an ongoing prospective trial on the use of the TMJ Concepts and Biomet Lorenz total joint replacement systems for the reconstruction of the temporomandibular joint (TMJ). Total alloplastic replacement of the TMJ has become a viable option for many people who suffer from TMJ disease where surgical reconstruction is indicated. Degenerative joint diseases such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, TMJ ankylosis, malunited condylar fractures and tumours can be successfully treated using this technique. There are a number of TMJ prostheses available. Two of the joint replacement products, which have been found to be most reliable and have FDA approval in the United States, are the TMJ Concepts system and the Biomet Lorenz system, and for this reason they are being investigated in this study. This study presents the findings of seven patients with a total of 12 joint replacements using either the TMJ Concepts system or the Biomet Lorenz joint system. Two patients (3 joints) had the TMJ Concepts system and five patients (9 joints) had the Biomet Lorenz system. Although still early, the results were generally pleasing, with the longest replacement having been in position for three years and the most recent six months. The average postoperative mouth opening was 29.7 mm (range 25-35 mm) with an average pain score of 1.7 (range 0-3, minimum score of 0 and maximum 10). Complications were minimal and related to sensory disturbance to the lip in one patient and joint dislocation in two patients. PMID:21332746
Jones, R H B
Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity ?30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness ?4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth ?4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade ?3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare", such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare".
D'Agostino, M; Conaghan, P; Le Bars, M; Baron, G; Grassi, W; Martin-Mola, E; Wakefield, R; Brasseur, J; So, A; Backhaus, M; Malaise, M; Burmester, G; Schmidely, N; Ravaud, P; Dougados, M; Emery, P
Osteoarthritis (OA) is a slow, chronic joint disease characterized by focal degeneration of articular cartilage and alterations of the chemical and mechanical articular function and also major cause of pain and physical disability. There is clinical evidence that increasing dietary n-3 relative to n-6 may be beneficial in terms of symptom management in humans but not all studies conclude that dietary n-3 PUFA supplementation is of benefit, in the treatment of OA. Our recent studies highlight the effect of a biomarine compound (LD-1227) on MMPs, collagen metabolism and on chondrocyte inflammatory markers. Thus, the aim of the present work was to test such bioactive compound versus a common nutraceutical intervention (glucosamine/chrondroitin sulfate) in knee osteoarthritis patients. The patients population consisted of 60 subjects with a recent diagnosis of knee osteoarthririts of mild-moderate severity. Patients were randomized in a double-blind study comparing LD-1227 (group A) versus a mixture of glucosamine (500 mg), chondroitin sulfate (400 mg) (group B). Patients were allowed their established painkillers on demand. At 4, 9 and 18 weeks patients were evaluated as for: VAS score assessing pain at rest, and during physical exercise, Lequesne index, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale and KOOS scale. Moreover, serum concentrations of IL-6, IL-?, CRP, TNF-sR1 and TNF-sR2 were assessed. As compared to GC treatment, LD-1227 yielded a quicker and higher degree of improvement of the whole clinical indexes and a lower NSAIDs use at the end of the study. LD-1227 brought about also a more significant downregulation of the tested cytokines cascade. Taken overall, these data suggest that LD-1227 has the potential to be included in the nutraceutical armamentarium in the management of OA. PMID:24189760
Catanzaro, Roberto; Lorenzetti, Aldo; Solimene, Umberto; Zerbinati, Nicola; Milazzo, Michele; Celep, Gulcip; Sapienza, Chiara; Italia, Angelo; Polimeni, Ascanio; Marotta, Francesco
A comparative study of the distribution of immunoglobulins G, M, and A and C3 in the synovium and inside synovial fluid leucocytes and of the relative levels of IgG, IgM, AND C3 in paired samples of serum and synovial fluid from both seropositive and seronegative patients with rheumatoid arthritis and other types of non-infective synovitis shows that although there is no distinctive immunopathological feature of rheumatoid arthritis, the incidence of immune complexes containing IgG and IgM with and without detectable C3 in the affected synovium or inside synovial fluid granulocytes is higher in rheumatoid arthritis and especially so in seropositive cases. The mean level of C3 in synovial fluid from patients with rheumatoid arthritis is lower than that from the group without rheumatoid arthritis. In contrast to previous reports, extracellular clumps of IgA could be detected in the affected synovium of a number of affected patients. Aggretated human IgG could be bound by some of the synovial biopsies and synovial fluid leucocytes from both seropositive and seronegative rheumatoid arthritis patients. Antinuclear factor and rheumatoid factor could be detected in the synovial fluid but not in the serum of several patients suggesting either selective sequestration or local synthesis of antinuclear and rheumatoid factors in the affected joints. Images
Ghose, T; Woodbury, J F; Ahmad, S; Stevenson, B
Osteoarthritis (OA) is the most common joint disease, mainly affecting middle-aged and elderly persons. People with OA of the knee or hip experience pain and deconditioning that may lead to disability. Treatment goals include pain control, maximizing functional independence, and improving quality of life within the constraints imposed by both OA and comorbidities. Exercise is a core recommendation in all nonpharmacological guidelines for the management of patients with knee or hip OA; it is supposed to ameliorate pain and maybe function as well. Therapeutic ultrasound, neuromuscular as well as transcutaneous electrostimulation, pulsed magnetic field therapy, low-level laser therapy, thermal agents, acupuncture, and assistive devices such as insoles, canes, and braces can be used additionally in a multimodal therapeutic program. They may positively influence pain and function, mobility, and quality of life in patients suffering from OA of the lower limbs. PMID:23519486
Stemberger, Regina; Kerschan-Schindl, Katharina
Hand therapists need to understand the basic science behind the therapy they carry out and the current evidence to make the best treatment decisions. The purpose of this article was to review current conservative therapeutic management of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) of the hand. Treatment interventions such as orthotics, exercise, joint protection, modalities, and adaptive equipment are discussed from a basic science and evidence-based practice perspective. PMID:22326361
Objective Examine the hazard of incident and progressive radiographic OA (rOA) and chronic joint symptoms at the hip and knee by limb length inequality (LLI) in a large, community-based sample. Methods A longitudinal cohort completed baseline (1991–1997) clinical evaluation and identical follow-up assessment (1999–2003) (median follow-up time = 5.9 years, range=3.0–13.1 years). LLI was defined at baseline as a measured difference between limbs of ? 2 cm. The study groups with LLI data comprised 1,583 participants with paired (baseline and follow-up) knee radiographs and 1,453 participants with paired hip radiographs. Multivariable Cox regression models were used to examine the hazard of incident and progressive knee and hip rOA and chronic joint symptoms, while adjusting for demographic and clinical factors. Results The hazard of developing incident knee or hip rOA was 20–30% higher and of developing progressive knee or hip rOA was 35–83% higher among participants with LLI, but results were only statistically significant for progressive knee rOA (adjusted hazard ratio = 1.83, 95% confidence interval = 1.10–3.05). The hazards of progressive chronic knee symptoms and incident and progressive chronic hip symptoms were 13–59% higher among participants with LLI, but were not statistically significant. Conclusion LLI was associated with progressive knee rOA and was non-significantly associated with incident knee or hip rOA and progressive hip rOA, progressive chronic knee symptoms, and incident and progressive chronic hip symptoms. Longer studies may strengthen these associations and help determine whether LLI is a risk factor or marker of these outcomes.
Golightly, Yvonne M.; Allen, Kelli D.; Helmick, Charles G.; Schwartz, Todd A.; Renner, Jordan B.; Jordan, Joanne M.
Executive Summary Objective The purpose of this review was to determine the effectiveness and adverse effects of arthroscopic lavage and debridement, with or without lavage, in the treatment of symptoms of osteoarthritis (OA) of the knee, and to conduct an economic analysis if evidence for effectiveness can be established. Questions Asked Does arthroscopic lavage improve motor function and pain associated with OA of the knee? Does arthroscopic debridement improve motor function and pain associated with OA of the knee? If evidence for effectiveness can be established, what is the duration of effect? What are the adverse effects of these procedures? What are the economic considerations if evidence for effectiveness can be established? Clinical Need Osteoarthritis, the most common rheumatologic musculoskeletal disorder, affects about 10% of the Canadian adult population. Although the natural history of OA is not known, it is a degenerative condition that affects the bone cartilage in the joint. It can be diagnosed at earlier ages, particularly within the sports injuries population, though the prevalence of non-injury-related OA increases with increasing age and varies with gender, with women being twice as likely as men to be diagnosed with this condition. Thus, with an aging population, the impact of OA on the health care system is expected to be considerable. Treatments for OA of the knee include conservative or nonpharmacological therapy, like physiotherapy, weight management and exercise; and more generally, intra-articular injections, arthroscopic surgery and knee replacement surgery. Whereas knee replacement surgery is considered an end-of-line intervention, the less invasive surgical procedures of lavage or debridement may be recommended for earlier and more severe disease. Both arthroscopic lavage and debridement are generally indicated in patients with knee joint pain, with or without mechanical problems, that are refractory to medical therapy. The clinical utility of these procedures is unclear, hence, the assessment of their effectiveness in this review. Lavage and Debridement Arthroscopic lavage involves the visually guided introduction of saline solution into the knee joint and removal of fluid, with the intent of extracting any excess fluids and loose bodies that may be in the knee joint. Debridement, in comparison, may include the introduction of saline into the joint, in addition to the smoothening of bone surface without any further intervention (less invasive forms of debridement), or the addition of more invasive procedures such as abrasion, partial or full meniscectomy, synovectomy, or osteotomy (referred to as debridement in combination with meniscectomy or other procedures). The focus of this health technology assessment is on the effectiveness of lavage, and debridement (with or without meniscal tear resection). Review Strategy The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment. The keywords searched were: arthroscopy, debridement, lavage, wound irrigation, or curettage; arthritis, rheumatoid, osteoarthritis; osteoarthritis, knee; knee or knee joint. Time frame: Only 2 previous health technology assessments were identified, one of which was an update of the other, and included 3 of 4 randomized controlled trials (RCTs) from the first report. Therefore, the search period for inclusion of studies in this assessment was January 1, 1995 to April 24, 2005. Excluded were: case reports, comments, editorials, and letters. Identified were 335 references, including previously published health technology assessments, and 5 articles located through a manual search of references from published articles and health technology assessments. These were examined against the criteria, as described below, which resulted in the in
A total of 329 children with hip pain were examined by ultrasound, which indicated transient synovitis (n = 161), rheumatoid arthritis (n = 16), tuberculoid arthritis (n = 3), septic arthritis (n = 16), Legg-Calvé-Perthes disease (n = 102), and slipped capital femoral epiphysis (n = 31). Using the standard planes described by DEGUM and DGOOC, it is possible to analyze the joint capsule, the surface of the femoral head, and the periarticular structures. In cases of synovitis or joint effusion, a capsular distension can be diagnosed by ultrasound. This distension is typical in transient synovitis, septic and tuberculoid arthritis, juvenile rheumatoid arthritis, and the onset phase of Perthes disease. Because capsular distension exhibits no significant differences in the various diseases, differentiation is not possible with ultrasound in the absence of osseous abnormalities. In cases with both capsular distension and osseous abnormalities, ultrasound usually allows a differentiation between slipped capital femoral epiphysis and Perthes disease as well as septic and unspecific arthritis. PMID:12017857
Konermann, W; Gruber, G
We report a case of a Calcium pyrophosphate dihydrate deposition disease (CPPD) presenting as a mass in the parotid and temporomandibular joint (TMJ) that simulated a parotid tumor. A 35 year-old man presented with pain in the left ear area. A CT Scan of the area showed a large, calcified mass surrounding the left condylar head, and extending into the
Asghar H Naqvi; Jerrold L Abraham; Robert M Kellman; Kamal K Khurana
Behcet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. Erosive arthropathy is extremely rare. We report a 52-year-old female patient with BD demonstrating bone erosion of the sternocostal joint. PMID:19564715
Nanke, Yuki; Kobashigawa, Tsuyoshi; Yago, Toru; Ichikawa, Naomi; Yamanaka, Hisashi; Kotake, Shigeru
Twenty-two patients with primary osteoarthritis (OA) of the knee were studied to determine the effects of OA on laxity of the knee joint. Laxity was measured with a Genucom Knee Analysis System. Ten knees had mild OA (> 50% preservation of joint space). Fifteen knees had moderate OA (some preservation of joint space, but < 50%). Eighteen knees had severe OA (no joint space). A group of 18 knees from 9 healthy (asymptomatic) subjects of ages similar to those of the OA patients were used as controls. Compared to control knees, severe OA knees had less total anteroposterior (AP) translation (12.2 versus 6.6 mm, p < 0.025) and less total tibial rotation (79 versus 59 degrees, p < 0.01). Compared to early OA knees, knees with severe OA had 57% less average total AP translation (15.2 versus 6.6 mm, p < 0.01), 31% less total varus/valgus rotation (15 degrees versus 10.4 degrees, p < 0.016), and 26% less total internal/external tibial rotation (80.1 degrees versus 59 degrees, p < 0.007). These data indicate that osteoarthritic knees tend to have less laxity than normal knees, probably because of a combination of contracture of the ligaments and pressure of osteophytes against ligaments and other capsular structures. PMID:8020213
Brage, M E; Draganich, L F; Pottenger, L A; Curran, J J
To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ?8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p?0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches. PMID:22778059
Albilia, Jonathan B; Tenenbaum, Howard C; Clokie, Cameron M L; Walt, David R; Baker, Gerald I; Psutka, David J; Backstein, David; Peel, Sean A F
Context: Intra-articular injections into the glenohumeral joint are commonly performed by musculoskeletal providers, including orthopaedic surgeons, family medicine physicians, rheumatologists, and physician assistants. Despite their frequent use, there is little guidance for injectable treatments to the glenohumeral joint for conditions such as osteoarthritis, adhesive capsulitis, and rheumatoid arthritis. Evidence Acquisition: We performed a comprehensive review of the available literature on glenohumeral injections to help clarify the current evidence-based practice and identify deficits in our understanding. We searched MEDLINE (1948 to December 2011 [week 1]) and EMBASE (1980 to 2011 [week 49]) using various permutations of intra-articular injections AND (corticosteroid OR hyaluronic acid) and (adhesive capsulitis OR arthritis). Results: We identified 1 and 7 studies that investigated intra-articular corticosteroid injections for the treatment of osteoarthritis and adhesive capsulitis, respectively. Two and 3 studies investigated the use of hyaluronic acid in osteoarthritis and adhesive capsulitis, respectively. One study compared corticosteroids and hyaluronic acid injections in the treatment of osteoarthritis, and another discussed adhesive capsulitis. Conclusion: Based on existing studies and their level of evidence, there is only expert opinion to guide corticosteroid injection for osteoarthritis as well as hyaluronic acid injection for osteoarthritis and adhesive capsulitis.
Gross, Christopher; Dhawan, Aman; Harwood, Daniel; Gochanour, Eric; Romeo, Anthony
Validation of radiographic and arthroscopic scoring of joint pathology requires their comparison with histological measures of disease from the same joint. Fragmentation of the medial coronoid process (FMCP) is a naturally occurring disease of the canine elbow joint that results in osteoarthritis, and the objectives of this study were to compare the severity of histopathological changes in the medial coronoid process (MCP) and medial articular synovial membrane with gross radiographic scoring of elbow joint osteophytosis and the arthroscopic assessment of the MCP articular cartilage surface. Radiographic scoring of osteophytosis and the arthroscopic scoring of visual cartilage pathology of the MCP correlated moderately well with the histopathological evaluation of cartilage damage on the MCP and synovial inflammation in the medial part of the joint, but not with bone pathology in the MCP. Marked cartilage pathology on the MCP was identified in joints with either no radiographic evidence of osteophytosis or with mild cartilage damage that was evident arthroscopically. PMID:19716324
Goldhammer, Marc A; Smith, Sionagh H; Fitzpatrick, Noel; Clements, Dylan N
Osteoarthritis (OA) was once viewed originally as a mechanical disease of “wear and tear,” but advances made during the past two decades suggest that abnormal biomechanics contribute to active dysregulation of chondrocyte biology, leading to catabolism of the cartilage matrix. A number of signaling and transcriptional mechanisms have been studied in relation to the regulation of this catabolic program, but how they specifically regulate the initiation or progression of the disease is poorly understood. Here, we demonstrate that cartilage-specific ablation of Nuclear factor of activated T cells c1 (Nfatc1) in Nfatc2?/? mice leads to early onset, aggressive OA affecting multiple joints. This model recapitulates features of human OA, including loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and eventual progression to cartilage effacement and joint instability. Consistent with the notion that NFATC1 is an OA-suppressor gene, NFATC1 expression was significantly down-regulated in paired lesional vs. macroscopically normal cartilage samples from OA patients. The highly penetrant, early onset, and severe nature of this model make it an attractive platform for the preclinical development of treatments to alter the course of OA. Furthermore, these findings indicate that NFATs are key suppressors of OA, and regulating NFATs or their transcriptional targets in chondrocytes may lead to novel disease-modifying OA therapies.
Greenblatt, Matthew B.; Ritter, Susan Y.; Wright, John; Tsang, Kelly; Hu, Dorothy; Glimcher, Laurie H.; Aliprantis, Antonios O.
Introduction Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair. Methods In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Results Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks. Conclusions Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7.
Singh, A.; Goel, S. C.; Gupta, K. K.; Kumar, M.; Arun, G. R.; Patil, H.; Kumaraswamy, V.; Jha, S.
Knee osteoarthritis (OA) is one of the most prevalent forms of this disease, with the medial compartment most commonly affected. The direction of external forces and limb orientation during walking results in an adduction moment that acts around the knee, and this parameter is regarded as a surrogate measure of medial knee compression. The knee adduction moment is intimately linked
Frank L. Bowling; Neil D. Reeves
In a variety of tissues, cumulative oxidative stress, disrupted mitochondrial respiration, and mitochondrial damage promote aging, cell death, and ultimately, functional failure and degeneration. Because articular cartilage chondroyctes are highly glycolytic, mitochondrially mediated pathogenesis has not been previously applied in models for pathogenesis of osteoarthritis (OA), a cartilage degenerative disease that increases markedly in aging. However, chondrocyte mitochondria respire in
Robert Terkeltaub; Kristen Johnson; Anne Murphy; Soumitra Ghosh
SUMMARY A study of the distribution of osteoarthritis of the hands was carried out in a series of 168 skeletons (77 males, 87 females, four unknown sex) from archaeological sites in England. There were substantial differences in the distribution of the disease between the sexes, but the only significant differences between the hands were shown for the second and third
H. A. WALDRON
... the Arthritis Foundation recommends physical activity and self-management education to help people with osteoarthritis manage their condition, ... Arthritis Foundation suggest several physical activity and self-management education programs that are both proven to be effective ...
... the 7 August 2012 issue of Annals of Internal Medicine (volume 157, pages 180-191). The authors are ... use of viscosupplementation for knee osteoarthritis. Annals of Internal Medicine Summaries for Patients I-36© 2012 American College ...
Osteoarthritis (OA) has traditionally been classified as a noninflammatory arthritis; however, the dichotomy between inflammatory and degenerative arthritis is becoming less clear with the recognition of a plethora of ongoing immune processes within the OA joint and synovium. Synovitis is defined as inflammation of the synovial membrane and is characteristic of classical inflammatory arthritidies. Increasingly recognized is the presence of synovitis in a significant proportion of patients with primary OA, and based on this observation, further studies have gone on to implicate joint inflammation and synovitis in the pathogenesis of OA. However, clinical OA is not one disease but a final common pathway secondary to many predisposing factors, most notably age, joint trauma, altered biomechanics, and obesity. How such biochemical and mechanical processes contribute to the progressive joint failure characteristic of OA is tightly linked to the interplay of joint damage, the immune response to perceived damage, and the subsequent state of chronic inflammation resulting in propagation and progression toward the phenotype recognized as clinical OA. This review will discuss a wide range of evolving data leading to our current hypotheses regarding the role of immune activation and inflammation in OA onset and progression. Although OA can affect any joint, most commonly the knee, hip, spine, and hands, this review will focus primarily on OA of the knee as this is the joint most well characterized by epidemiologic, imaging, and translational studies investigating the association of inflammation with OA.
Lepus, Christin M.
The medical literature was reviewed from 1968-2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular therapies used in the treatment of osteoarthritis. Corticosteroids and hyaluronic acid are the most frequently used intra-articular therapies in osteoarthritis. Other intra-articular substances such as orgotein, radiation synovectomy, dextrose prolotherapy, silicone, saline lavage, saline injection without lavage, analgesic agents, non-steroidal anti-inflammatory drugs, glucosamine, somatostatin, sodium pentosan polysulfate, chloroquine, mucopolysaccharide polysulfuric acid ester, lactic acid solution, and thiotepa cytostatica have been investigated as potentially therapeutic in the treatment of arthritic joints. Despite the lack of strong, convincing, and reproducible evidence that any of the intra-articular therapies significantly alters the progression of osteoarthritis, corticosteroids and hyaluronic acid are widely used in patients who have failed other therapeutic modalities for lack of efficacy or toxicity. As a practical approach for a knee with effusion, steroid injections should be considered while the presence of symptomatic "dry" knees may favour the hyaluronic acid approach. The virtual absence of serious side effects, coupled with the perceived benefits, make these approaches attractive. PMID:12954956
Uthman, I; Raynauld, J-P; Haraoui, B
A consensus, prepared by SECOT, is presented on the management of medial knee compartment osteoarthritis, in order to establish clinical criteria and recommendations directed at unifying the criteria in its management, dealing with the factors involved in the pathogenesis of medial femorotibial knee osteoarthritis, the usefulness of diagnostic imaging techniques, and the usefulness of arthroscopy. Conservative and surgical treatments are also analysed. The experts consulted showed a consensus (agreed or disagreed) in 65.8% of the items considered, leaving 14items where no consensus was found, which included the aetiopathogenesis of the osteoarthritis, the value of NMR in degenerative disease, the usefulness of COX-2 and the chondroprotective drugs, as well as on the ideal valgus tibial osteotomy technique. PMID:24169227
Moreno, A; Silvestre, A; Carpintero, P
Background Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint replacement as the treatment for bone metastasis or hematological diseases of the extremities. Patients and methods 130 patients (mean age 64 (30–85) years, 76 females) received 140 joint replacements due to skeletal metastases (n = 114) or hematological disease (n = 16) during the period 2003–2008. 21 replaced joints were located in the upper extremities and 119 in the lower extremities. Clinical and survival data were extracted from patient files and various registers. Results The probability of patient survival was 51% (95% CI: 42–59) after 6 months, 39% (CI: 31–48) after 12 months, and 29% (CI: 21–37) after 24 months. The following surgical complications were seen (8 of which led to additional surgery): 2–5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery related to the implanted prosthesis was 94% (CI: 89–99) after 1 year and 92% (CI: 85–98) after 2 years. Conclusion Joint replacement operations because of metastatic bone disease do not appear to have given a poorer rate of patient survival than other types of surgical treatment, and the reoperation rate was low.
Sandhigata vata is described under Vatavyadhi in all Ayurvedic texts. Charaka was the first to describe separately “Sandhigata anila”, but it was not included under 80 types of nanatmaja vatavyadhi. Osteoarthritis is the most common degenerative joint disease that begins asymptomatically in middle age with progressive symptoms in advancing age. Majority of people by the age 40 years may develop osteoarthritis, especially in weight bearing joints. Females are prone with 25% prevalence, whereas males have a prevalence of 16%. In the present study, 56 patients fulfilling the diagnostic criteria of Sandhigata vata, divided into two groups. Patients of first group were administered with 500 mg capsule of Shallaki, 6 g per day (in three divided doses) with lukewarm water (n=29) and the second group) capsule Shallaki as above along with local application of Shallaki ointment on the affected joints (n=23). After a course of therapy for 2 months, symptomatic improvement was observed in both the groups at various levels with promising results in the patients of first group.
Gupta, P. K.; Samarakoon, S. M. S.; Chandola, H. M.; Ravishankar, B.
Background Thoughtful use of assessment tools to monitor disease requires an understanding of clinimetric properties. These properties are often under-reported and, thus, potentially overlooked in the clinic. This study aimed to determine the minimal detectable change (MDC) and coefficient of variation per cent (CV%) for tools commonly used to assess the symptomatic and functional severity of knee and hip osteoarthritis. Methods We performed a test-retest study on 136 people awaiting knee or hip arthroplasty at one of two hospitals. The MDC95 (the range over which the difference [change] for 95% of patients is expected to lie) and the coefficient of variation per cent (CV%) for the visual analogue scale (VAS) for joint pain, the six-minute walk test (6MWT), the timed up-and-go (TUG) test, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS) subscales were calculated. Results Knee cohort (n?=?75) - The MDC95 and CV% values were as follows: VAS 2.8 cm, 15%; 6MWT 79 m, 8%; TUG +/-36.7%, 13%; KOOS pain 20.2, 19%; KOOS symptoms 24.1, 22%; KOOS activities of daily living 20.8, 17%; KOOS quality of life 26.6, 44. Hip cohort (n?=?61) - The MDC95 and CV% values were as follows: VAS 3.3 cm, 17%; 6MWT 81.5 m, 9%; TUG +/-44.6%, 16%; HOOS pain 21.6, 22%; HOOS symptoms 22.7, 19%; HOOS activities of daily living 17.7, 17%; HOOS quality of life 24.4, 43%. Conclusions Distinguishing real change from error is difficult in people with severe osteoarthritis. The 6MWT demonstrates the smallest measurement error amongst a range of tools commonly used to assess disease severity, thus, has the capacity to detect the smallest real change above measurement error in everyday clinical practice.
Background Existent biomechanical studies on hip osteoarthritic gait have primarily focused on the end stage of disease. Consequently, there is no clear consensus on which specific gait parameters are of most relevance for hip osteoarthritis patients with mild to moderate symptoms. The purpose of this study was to explore sagittal plane gait characteristics during the stance phase of gait in hip osteoarthritis patients not eligible for hip replacement surgery. First, compared to healthy controls, and second, when categorized into two subgroups of radiographic severity defined from a minimal joint space of ?/>2 mm. Methods Sagittal plane kinematics and kinetics of the hip, knee and ankle joint were calculated for total joint excursion throughout the stance phase, as well as from the specific events initial contact, midstance, peak hip extension and toe-off following 3D gait analysis. In addition, the Western Ontario and McMaster Universities Osteoarthritis Index, passive hip range of motion, and isokinetic muscle strength of hip and knee flexion and extension were included as secondary outcomes. Data were checked for normality and differences evaluated with the independent Student’s t-test, Welch’s t-test and the independent Mann–Whitney U-test. A binary logistic regression model was used in order to control for velocity in key variables. Results Fourty-eight hip osteoarthritis patients and 22 controls were included in the final material. The patients walked significantly slower than the controls (p=0.002), revealed significantly reduced joint excursions of the hip (p<0.001) and knee (p=0.011), and a reduced hip flexion moment at midstance and peak hip extension (p<0.001). Differences were primarily manifested during the latter 50% of stance, and were persistent when controlling for velocity. Subgroup analyses of patients with minimal joint space ?/>2 mm suggested that the observed deviations were more pronounced in patients with greater radiographic severity. The biomechanical differences were, however, not reflected in self-reported symptoms or function. Conclusions Reduced gait velocity, reduced sagittal plane joint excursion, and a reduced hip flexion moment in the late stance phase of gait were found to be evident already in hip osteoarthritis patients with mild to moderate symptoms, not eligible for total hip replacement. Consequently, these variables should be considered as key features in studies regarding hip osteoarthritic gait at all stages of disease. Subgroup analyses of patients with different levels of radiographic OA further generated the hypothesis that the observed characteristics were more pronounced in patients with a minimal joint space ?2 mm.
[Purpose] Osteoarthritis (OA) of the knee is the most common form of joint disease. It is one of the major causes of impaired function that reduces quality of life (QOL) worldwide. The purpose of this study was to compare exercise treatments for hamstring and quadriceps strength in the management of knee osteoarthritis. [Subjects and Methods] Forty patients with OA knee, aged 50–65 years were divided into 2 groups. The first group (57.65±4.78 years) received hot packs and performed strengthening exercises for the quadriceps and hamstring, and stretching exercises for the hamstring. The second group (58.15±5.11 years) received hot packs and performed strengthening exercises for only the quadriceps, and stretching exercise for the hamstring. Outcome measures were the WOMAC (Western Ontario and McMaster Universities OA index questionnaire), Visual Analogue Scale (VAS) assessment of pain, the Fifty-Foot Walk Test (FWS), and Handheld dynamometry. [Results] There was a significant difference between the groups. The first group showed a more significant result than the second group. [Conclusion] Strengthening of the hamstrings in addition to strengthening of the quadriceps was shown to be beneficial for improving subjective knee pain, range of motion and decreasing the limitation of functional performance of patients with knee osteoarthritis.
Al-Johani, Ahmed H; Kachanathu, Shaji John; Ramadan Hafez, Ashraf; Al-Ahaideb, Abdulaziz; Algarni, Abdulrahman D; Meshari Alroumi, Abdulmohsen; Alanezi, Aqeel M.
Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics.
Girolami, Federica; Persiani, Stefano
summary Objective The Osteoarthritis Research Society International initiated a number of working groups to address a call from the US Food and Drug Administration (FDA) on updating draft guidance on conduct of osteoarthritis (OA) clinical trials. The development of disease-modifying osteoarthritis drugs (DMOADs) remains challenging. The Assessment of Structural Change (ASC) Working Group aimed to provide a state-of-the-art critical update on imaging tools for OA clinical trials. Methods The Group focussed on the performance metrics of conventional radiographs (CR) and magnetic resonance imaging (MRI), performing systematic literature reviews for these modalities. After acquiring these reviews, summary and research recommendations were developed through a consensus process. Results For CR, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness of metric measurement of joint space width (JSW). Trials off at least 1 and probably 2 years duration will be required. Although there is much less evidence for hip JSW, it may provide greater responsiveness than knee JSW. For MRI cartilage morphometry in knee OA, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness. The responsiveness of semi-quantitative MRI assessment of cartilage morphology, bone marrow lesions and synovitis was also good in knee OA. Conclusions Radiographic JSW is still a recommended option for trials of structure modification, with the understanding that the construct represents a number of pathologies and trial duration may be long. MRI is now recommended for clinical trials in terms of cartilage morphology assessment. It is important to study all the joint tissues of the OA joint and the literature is growing on MRI quantification (and its responsiveness) of non-cartilage features. The research recommendations provided will focus researchers on important issues such as determining how structural change within the relatively short duration of a trial reflects long-term change in patient-centred outcomes.
Conaghan, P.G.; Hunter, D.J.; Maillefert, J.F.; Reichmann, W.M.; Losina, E.
The objective of this study was to evaluate prospectively the outcome of 21 clinical patients treated with triple pelvic osteotomies during the year following surgery. Specific aims included documenting the time of and extent of improved limb function as measured by force plate analysis, evaluating the progression of degenerative joint disease (DJD) in the treated and untreated coxofemoral joints, and determining whether or not triple pelvic osteotomy resulted in degenerative joint changes in the ipsilateral stifle and hock. Twelve dogs were treated unilaterally and nine dogs were treated bilaterally with triple pelvic osteotomies. There were no differences in mean anteversion angles, angles of inclination, or preoperative DJD between treated hips and untreated hips. Degenerative joint disease progressed significantly in all hips regardless of treatment. Two cases developed hyperextension of their hocks after the triple pelvic osteotomies. However, no radiographic evidence of DJD was observed for any of the stifles or hocks at any observation time. A significant increase in vertical peak force (VPF) scores was noted for treated legs by two-to-three months after surgery, which continued over time. Untreated legs did not show a significant change in VPF scores over time. No differences were found in progression to higher scores when unilaterally treated legs, first-side treated legs, and second-side treated legs were compared. PMID:9590455
Johnson, A L; Smith, C W; Pijanowski, G J; Hungerford, L L
A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety of approaches, they are tightly coupled due to their common biological basis. We hypothesize that the two tasks can potentially benefit each other by a joint analysis, because (i) the association study discovers correlated biomarkers from different data sources, which may help improve diagnosis accuracy, and (ii) the disease status may help identify disease-sensitive associations between genetic variations and MRI features. Based on this hypothesis, we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels based on Gaussian process ordinal regression; in return, the disease status is used to guide the discovery of relationships between the data sources. The sparse projection matrices not only reveal the associations but also select groups of biomarkers related to AD. To learn the model from data, we develop an efficient variational expectation maximization algorithm. Simulation results demonstrate that our approach achieves higher accuracy in both predicting ordinal labels and discovering associations between data sources than alternative methods. We apply our approach to an imaging genetics dataset of AD. Our joint analysis approach not only identifies meaningful and interesting associations between genetic variations, brain structures, and AD status, but also achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods. PMID:24297556
Zhe, Shandian; Xu, Zenglin; Qi, Yuan; Yu, Peng
Intra-articular hyaluronans are used to treat pain associated with osteoarthritis of the knee. Many controlled clinical studies have demonstrated their efficacy for this indication. The rationale for the use of hyaluronans therapeutically is based on observations that hyaluronic acid is an important component of the synovial fluid acting as a cushion and lubricant for the joint and also serving as a major component of the extracellular matrix of the cartilage, helping to enhance the ability of cartilage to resist shear and maintain a resiliency to compression. While intra-articular hyaluronans are indicated at this time only for the treatment of pain in osteoarthritis of the knee, there are data to suggest that they may also be useful in treating degenerative disease of other articular joints, as well as have an impact on disease progression. The mechanisms by which hyaluronans mediate their clinical benefit seem to be multifactorial and biologically related, in contrast to the notion that they provide only viscous fluid replacement. The safety profile of intra-articular hyaluronans is very favorable and, because they are used as a local therapy, there are no known drug interactions-an advantage for patients receiving treatment for comorbid conditions. Some adverse effects, such as pseudosepsis, have been associated with cross-linked hyaluronan agents and do not appear to be class related. PMID:15005296
Kelly, Michael A; Kurzweil, Peter R; Moskowitz, Roland W
Forty-one long-distance runners aged 50 to 72 years were compared with 41 matched community controls to examine associations of repetitive, long-term physical impact (running) with osteoarthritis and osteoporosis. Roentgenograms of hands, lateral lumbar spine, and knees were assessed without knowledge of running status. A computed tomographic scan of the first lumbar vertebra was performed to quantitate bone mineral content. Runners, both male and female, have approximately 40% more bone mineral than matched controls. Female runners, but not male runners, appear to have somewhat more sclerosis and spur formation in spine and weight-bearing knee x-ray films, but not in hand x-ray films. There were no differences between groups in joint space narrowing, crepitation, joint stability, or symptomatic osteoarthritis. Running is associated with increased bone mineral but not, in this cross-sectional study, with clinical osteoarthritis.
Lane, N.E.; Bloch, D.A.; Jones, H.H.; Marshall, W.H. Jr.; Wood, P.D.; Fries, J.F.
Reported here is the case of a 29-year-old male with cervical lymphadenopathy, fever and weight loss, followed by acute painful osteomyelitis of the left hip joint due to cat-scratch disease. The diagnosis was established by detection of IgG antibodies to Bartonella henselae in serum and histologic examination of a lymph node including a positive polymerase chain reaction test. Treatment consisted of clarithromycin and cefotiam for 2 weeks. Four weeks after discharge, all of the patient's symptoms had completely resolved. Magnetic resonance imaging of the left hip joint showed marked regression of bone inflammation 4 months later and normalization after 8 months. Cat-scratch disease should be considered in the differential diagnosis of osteomyelitis in an adult, especially when lymphadenitis is present. PMID:11117643
Krause, R; Wenisch, C; Fladerer, P; Daxböck, F; Krejs, G J; Reisinger, E C
Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4?Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD.
Zhang, Yu; Schuff, Norbert; Ching, Christopher; Tosun, Duygu; Zhan, Wang; Nezamzadeh, Marzieh; Rosen, Howard J.; Kramer, Joel H.; Gorno-Tempini, Maria Luisa; Miller, Bruce L.; Weiner, Michael W.
Summary Objective The TGF-? pathway plays a central role in joint development with polymorphism in TGF-? pathway genes implicated in osteoarthritis susceptibility. One association is to rs12901499, within intron 1 of SMAD3. Since rs12901499 is not in linkage disequilibrium with a non-synonymous polymorphism, it is likely the association is operating by influencing expression of SMAD3. Design Using tissues from the joints of primary osteoarthritis patients who had undergone joint replacement we measured the overall expression of SMAD3 by quantitative real-time PCR. We also measured allelic expression of SMAD3 using these tissues and vascular smooth muscle cells from patients with aneurysms and osteoarthritis syndrome, a rare condition featuring early-onset osteoarthritis. We tested the functional effect of SNPs in vitro using luciferase assays and assessed association with osteoarthritis using a large osteoarthritis case–control dataset. Results We observed that genotype at rs12901499 did not correlate with overall SMAD3 expression or allelic expression. However, genotype at a 3?UTR SNP, rs8031440, did correlate with SMAD3 expression in cartilage (P = 0.005) which was supported by allelic expression data showing that the G allele correlated with decreased SMAD3 expression in joint tissues and vascular smooth muscle cells. This G allele was underrepresented in osteoarthritis cases vs controls (P = 0.027, odds ratio = 0.921). rs8031440 is in perfect linkage disequilibrium with five other SMAD3 3?UTR SNPs and our luciferase analysis identified rs3743342 and rs12595334 as being functional. Conclusion SMAD3 is subject to cis-acting regulatory polymorphism in the tissues of relevance to both primary osteoarthritis and the aneurysms-osteoarthritis syndrome.
Raine, E.V.A.; Reynard, L.N.; van de Laar, I.M.B.H.; Bertoli-Avella, A.M.; Loughlin, J.
We assessed the impact of various forms of spinal degenerative joint disease (DJD) on bone mineral density (BMD) measured by quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in a group of postmenopausal women. Lateral (T4-L4) and AP (L1-L4) spinal radiographs were reviewed for fracture and DJD in 209 women (mean age 62.6±6.7). The severity of DJD findings was
W. Yu; C.-C. Glüer; T. Fuerst; S. Grampp; J. Li; Y. Lu; H. K. Genant
Hip joints (280) from 140 human fetuses, obtained from abortions and deaths in the perinatal period, were studied. The fetuses ranged from 8.7 to 40 cm in crown-rump length and are believed to be between 12 and 42 weeks in age. The joints were dissected, morphology inspected, and measurements taken of the depth and diameter of the acetabulum, the diameter of the femoral head, length and width of the ligament of the head, the neck-shaft, and torsion angles of the proximal femur. Regression models were fitted to determine which would best predict the growth pattern. Multivariate analysis of variance showed no significant differences between males and females or between the right and left sides. Acetabular depth was shown to be the slowest-growing hip variable, increasing less than fourfold in the period studied. Acetabular indices less than 50 percent indicate a shallow socket at term. Femoral head and acetabular diameter demonstrated a strong relationship (r = 0.860) and in many joints the femoral head diameter exceeded that of the acetabulum. Considerable variability was demonstrated in both femoral angles. The femoral angles showed only low correlation with the other hip variables. These observations indicate that soft tissue structures about the joint must play an important role in neonatal joint stability. The explanation of greater female and left side involvement in congenital hip disease must lie in factors other than growth changes of hip dimensions. Neither angle appears to be a useful indicator of normal joint development. Images FIG. 2 FIG. 3 FIG. 4 FIG. 10 FIG. 11 FIG. 13
Walker, J. M.; Goldsmith, C. H.