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Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte formation.

OBJECTIVE: To examine the nitric oxide (NO) production relevant to chondrocyte cell death in order to elucidate the mechanism of chondro-osteophyte formation in osteoarthrotic joints. DESIGN: Human chondro-osteophytes were obtained during total hip arthroplasty. Expression of inducible nitric oxide synthase (iNOS) mRNA was determined by in-situ hybridization. Localization of iNOS and nitrotyrosine at protein level were examined by immunohistochemistry. Cell death of chondrocytes were confirmed by both TUNEL method and transmission electron microscopy. RESULTS: The various populations of proliferative and hypertrophic chondrocytes expressed iNOS mRNA and iNOS as well as nitrotyrosine protein. Approximately 30% of hypertrophic chondrocytes forming chondro-osteophyte showed positive reaction to TUNEL staining. Electron microscopy confirmed both disintegrated and apoptotic chondrocytes in these zones. In the deep hypertrophic zone calcification was seen around each of the matrix vesicles and some masses of cell debris. CONCLUSION: Chondro-osteophyte formation involves NO production by chondrocytes. The expression and localization of iNOS and nitrotyrosine in chondro-osteophytes suggest the significant role of NO in chondrocyte hypertrophy and apoptosis.

Aged↗

Kellgren & Lawrence grade 1 osteophytes in the knee--doubtful or definite?

The most universally accepted methods of classification of radiographic osteoarthritis (OA) is the Kellgren & Lawrence (K&L) grading system. However, there have been many criticisms of this including the grading of a doubtful osteophyte as a grade 1. We report the natural history of a given prevalent grade 1 osteophyte in a 10-year follow-up knee study. 62% of women graded at baseline with a doubtful osteophyte went on to develop true osteophytic knee OA compared with only 22% of controls with no sign of disease. So called 'doubtful' osteophytes appear to be 'real' and significantly related to OA knee and therefore cannot be ignored or classified as normal.

Chondrocytes↗

[Marginal osteophytes as a radiological and clinical indicator of patellofemoral arthrosis (author's transl)].

Radiological and pathological comparisons carried out on patellae at autopsy have shown a statistical relationship between the size of marginal patellar osteophytes and radiologically invisible ulceration of the joint cartilage. Patellar osteophytes greater than 2 mm. show a 100% association with cartilage ulcers. The detritus originating from the ulcerated cartilage is a potent irritant of the synovial membrane. The radiological demonstration of marginal patellar osteophytes therefore provides evidence concerning the severity of the arthrosis; the larger the patellar marginal osteophytes, the greater is the need for treatment of the painful arthrosis. The lateral and upper margins of the patella are the sites of predelection for the osteophytes. The medial patellar facet is the site of predelection for the cartilagenous ulcers.

Adult↗

Anterior cervical osteophyte causing dysphagia as a complication of laminectomy.

Asymptomatic osteophytes of the anterior margins of the cervical vertebral bodies (VB) may occur in 20 - 30% of the population. On rare occasions, dysphagia or dyspnoea may be caused by such cervical osteophytes. We present the case of a 27-year-old woman with progressive dysphagia caused by a voluminous osteophyte secondary to chronic cervical instability after a laminectomy performed 8 years before. Progressive growth of the osteophyte was observed in sequential roentgenograms. As far as we know, this complication of cervical laminectomy has never been reported before. After resection of the osteophyte and arthrodesis of the affected segment the patient was cured.

Adult↗

Bone formers: osteophyte and enthesophyte formation are positively associated.

OBJECTIVE: To test the hypothesis that enthesophyte formation and osteophyte growth are positively associated and to look for associations between bone formation at different sites on the skeleton so that a simple measure of bone formation could be derived. METHODS: Visual examination of 337 adult skeletons. All common sites of either enthesophyte or osteophyte formation were inspected by a single observer who graded bone formation at these sites on a 0-3 scale. The total score for each feature was divided by the number of sites examined to derive an enthesophyte and an osteophyte score. Cronbach's alpha and principal components analysis were used to identify groupings. RESULTS: Enthesophyte formation was associated with gender (M > F) and age. There was a positive correlation between enthesophytes and osteophytes (r = 0.65, 95% confidence interval, 0.58 to 0.71) which remained after correction for age and gender. Principal components analysis indicated four different groupings of enthesophyte formation. By choosing one site from each group a simple index of total skeletal bone formation could be derived. CONCLUSIONS: Osteophytes and enthesophytes are associated, such that a proportion of the population can be classified as "bone formers". Enthesophyte groupings provide some clues to aetiopathogenesis. Bone formation should be investigated as a possible determinant of the heterogeneity of outcome and of treatment responses in common musculoskeletal disorders.

Adult↗

Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the tibiofemoral joint.

OBJECTIVE: To assess the correlation between the presence of radiographically diagnosed osteophytes in the tibiofemoral joint (TFJ) and (1) magnetic resonance (MR) detected cartilage defects and meniscal lesions in the same joint and (2) knee pain. METHODS: Fifty-nine people, 29 men and 30 women, with chronic knee pain (aged 41-58 years, mean 50 years) were examined with posteroanterior weightbearing radiograms in semiflexion of both TFJ. The presence and grade of marginal and central osteophytes were assessed. On the same day, an MR examination was performed of the signal knee with proton density and T2 weighted turbo spin-echo sequences on a 1.0 T imager. Cartilage defects and meniscal abnormalities in the TFJ were noted. The subjects were questioned for current knee pain for each knee. RESULTS: Marginal osteophytes had a sensitivity of 77%, specificity of 83%, and positive predictive value of 87% for MR detected cartilage defects in the TFJ and a sensitivity of 71%, specificity of 68%, and positive predictive value of 71% for meniscal abnormalities. A correlation (p < 0.05) between osteophytes at the medial tibial condyle and knee pain was found. CONCLUSIONS: With the presence of marginal osteophytes in the TFJ there is a high prevalence of MR detected cartilage defects in the same joint whether joint space narrowing (< 3 mm) is present or not.

Adult↗

Distribution of distal femoral osteophytes in a human skeletal population.

OBJECTIVES: To examine objectively spatial patterns of osteophytes around the distal end of the femur and to identify distinct subgroups. METHODS: A sample of 107 human femora from a large skeletal population were selected for study. These femora included subjects with evidence of late stage osteoarthritis (that is, with eburnation present) and those with no such evidence. The location of osteophytes was recorded using a video camera and digitised computer images were extracted. Multidimensional scaling was used to identify clusters of femora based upon osteophyte location. RESULTS: A distinct subgroup of femora was identified with osteophytes present only within the intercondylar notch region. None of these subjects had any evidence of eburnation. CONCLUSIONS: This finding adds to an earlier study based on radiographs. Osteophytes located within the intercondylar notch of the femur appear to be a distinct subset, which may occur either as an early stage of knee osteoarthritis or for some independent reason.

Adult↗

UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.

OBJECTIVES: (1) To estimate the prevalence of chondrocalcinosis (CC) in the community and to characterise its compartmental distribution within the knee. (2) To investigate the associations between CC and individual radiographic features of osteoarthritis (OA) at the tibiofemoral joint (TFJ) and patellofemoral joint (PFJ). METHODS: From three community questionnaire studies investigating the prevalence of knee pain, standing anteroposterior and skyline radiographs were obtained on 1727 subjects (1084 women, 643 men; mean age 63.7; 999 (58%) with knee pain). A single observer recorded the presence and site of CC and graded osteophyte and joint space narrowing (JSN) using a line atlas. "OA" was globally defined as the presence of definite osteophyte and definite JSN. Minimum joint space width (JSW) was measured to 0.1 mm with a metered dial caliper RESULTS: (1) The crude prevalence of CC was 7.0% (95% confidence interval (CI) 5.8 to 8.2). This showed a strong association with age. The age adjusted odds ratio (aOR) for CC in women v men was 0.79 (95% CI 0.52 to 1.12). The age, sex, and knee pain standardised estimate for those aged >40 in Nottingham, UK was 4.5%. Patellofemoral CC was seen in only nine cases, all with tibiofemoral CC. (2) The age-sex aOR for the association between CC and OA was 2.08 at the PFJ (1.38 to 3.12) and 2.00 (1.11 to 3.60) at the TFJ. There was no association between measured JSW and CC at either the PFJ or TFJ. Both total osteophyte score and total number of sites with osteophyte were positively associated with CC; aOR for the upper quartile was 2.40 (1.48 to 3.90) and 1.94 (1.15 to 3.26), respectively. An association between CC and diuretic use was also demonstrated (aOR=2.07, 1.02 to 4.19). CONCLUSIONS: In this large UK community study the age, sex, and knee pain adjusted prevalence of CC was 4.5%. There was a strong age association, but no sex predisposition. Patellofemoral CC was uncommon. An association between OA and CC was confirmed, but this appears to operate through an association with osteophyte rather than JSN. The new association between CC and diuretic use might theoretically be explained by diuretic induced hypomagnesaemia.

Age Distribution↗

Morphology of tibiotalar osteophytes in anterior ankle impingement.

The purpose of this study was to document radiographic trends in the size and location of osteophytes occurring in patients who have undergone surgical treatment of bony anterior ankle impingement. All patients over a period of 31 months who had undergone surgical excision of anterior ankle osteophytes were identified. 9 patients (10 ankles) in whom preoperative CT scans were available were selected as the study group. This group was retrospectively reviewed in terms of basic preoperative characteristics (age, sex, symptomatology, sports history, systemic disease, passive dorsiflexion). Osteophyte size was measured on plain lateral radiographs, and axial CT images were used to determine both tibial and talar osteophyte location by referencing them to the midline of the talar dome. 95% confidence intervals demonstrated that the talar spur peak lies medial to the midline, the tibial spur peak lies lateral to the midline, and the spurs typically do not overlap each other. Further, the tibial spur is wider than the talar spur, and the talar spur usually protrudes medially off the medial edge of the talar neck. Thus, there is evidence that anterior tibiotalar osteophytes may have a relatively consistent pattern of formation, with the talar spur occurring on the medial aspect of the talar neck, and the tibial spur peaking lateral to the midline.This information, if substantiated with additional patients, may provide insight into the pathophysiology of anterior ankle impingement, as well as facilitate the open and arthroscopic approaches toward resection of these lesions.

Adult↗

[Relationship between cervical osteophytes and globus sensation--a study based on altered swallowing function].

The swallowing function of ten patients showing marked cervical osteophytes were studied by double contrast pharyngogram and manometric examinations. In five cases in which the pharyngeal clearance was B type according to Shuzaki's classification, a significant increase in the maximal swallowing pressure value on the oral side ipsilateral to the osteophytes was often observed. In five cases in which the pharyngeal clearance showed A + A' type (marked impairment), the frequency of significantly decreased maximal swallowing pressure on the oral side ipsilateral to the osteophytes and abnormal waveforms of the swallowing pressure were high. However, no definite correlation was noted between these changes in swallowing function and osteophyte site. Therefore, there are two possible outcomes of the changes in swallowing function caused by cervical osteophytes: one is a compensatory increase in pharyngeal constriction aimed at maintaining relatively good pharyngeal clearance, the other is impaired pharyngeal constriction and the pharyngeal clearance. These changes in swallowing function would impact on globus sensation.

Aged↗

Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair.

Osteoarthritis has as main characteristics the degradation of articular cartilage and the formation of new bone at the joint edges, so-called osteophytes. In this study enhanced expression of TGF-beta1 and -beta3 was detected in developing osteophytes and articular cartilage during murine experimental osteoarthritis. To determine the role of endogenous TGF-beta on osteophyte formation and articular cartilage, TGF-beta activity was blocked via a scavenging soluble TGF-beta-RII. Our results clearly show that inhibition of endogenous TGF-beta nearly completely prevented osteophyte formation. In contrast, treatment with recombinant soluble TGF-beta-RII markedly enhanced articular cartilage proteoglycan loss and reduced the thickness of articular cartilage. In conclusion, we show for the first time that endogenous TGF-beta is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss.

ADAM Proteins↗

Chronic obstructive pneumonia caused by a vertebral body osteophyte.

Osteophytes associated with spondylosis have been implicated as a cause of multiple extraspinal manifestations. Symptoms are more likely to occur with the large osteophytes associated with diffuse idiopathic skeletal hyperostosis. In the thoracic region, osteophytes have been reported infrequently as a cause of extraspinal complications. We report a case in which an anterior thoracic vertebral osteophyte was responsible for chronic obstructive pneumonia due to obstruction of the right main stem bronchus. The patient's condition improved considerably after surgical resection of the compressing thoracic osteophyte.

Aged↗

[Dysphagia due to giant cervical osteophytes].

We reported a patient with isolated dysphagia due to an esophageal canal stenosis compressed by focal cervical spondylotic osteophytes. The patient was a 63-year-old male who developed swallowing disturbance of predominantly solid materials. The neurological examination showed subjectively isolated dysphagia unassociated with any significant cranial nerve signs. Cervical magnetic resonance imaging and X-ray demonstrated giant cervical spurs focally at the ventral portion of the C 5/6 vertebral bodies, protruding ventrally and compressing mildly to the esophageal canal. The intervertebral disc formation was relatively preserved between the osteophytes. At the neck flexion portion, the esophagus was severely compressed between the osteophytes and the epiglottis. Videofluoroscopic examination of swallowing function showed a congestion of the contrast medium at the portion of the epiglottic vallecula, unassociated with aspiration into the trachea. The endoscopic examination showed erosion of the posterior wall of the esophagus at the portion compressed by the osteophytes. The anti-inflammatory medication improved the symptom of dysphagia, and the patient has been carefully followed-up without a surgical procedure. The presence of giant osteophyte should be considered in the differential diagnosis of subjectively isolated dysphagia unassociated with any significant cranial nerve signs.

Cervical Vertebrae↗

Preliminary experience with a new surgical treatment for dysphagia due to anterior cervical osteophytes.

A technique for surgical treatment of anterior cervical osteophytes is presented. A midline trough is created in the osteophytes using a burr under fluoroscopy down to the anterior cervical line. A rongeur is used to remove the remaining osteophytes while protecting the lateral soft tissues. Two patients presented with symptoms of progressive dysphagia secondary to anterior cervical osteophytes. Each underwent surgical ostectomy without complication after failing conservative treatment. This technique provides a safe, effective method to remove anterior cervical osteophytes.

Aged↗

Osteophyte evolution: studies in an experimental partial meniscectomy model.

Osteophytes are considered characteristic manifestations of osteoarthritis (OA) but may be seen independent of structural cartilage erosive lesions. Etiopathogenic mechanisms for osteophyte formation may involve responses to synovial inflammation, stretching of the synovial membrane, general mechanical instability, and vascular metaplasia. Experimentally induced OA following partial menisectomy in rabbits demonstrates active cellular replication at the normal joint periphery. Vascular responses are seen late in parallel with osteophyte formation rather than preceding it. Osteophyte ossification is primarily endochondral. The parallel stimulatory response to perichondrium, cartilage, and bone allows speculation on the interplay of mechanical/electrical forces and chemical/hormonal transducers in the development of osteophytes.

Adrenal Cortex Hormones↗

[Osteophytes of the femur head].

The shape and size of osteophytes were studied in different parts of the head of femur (mediodistal, proximal and lateral, central). There was not found any dependence of osteophytes on the basic disease of joint which produced arthrosis. Osteophytes developed from the subchondral cortical lamella, most often at the margin of the joint cartilage. Original corticalis and joint cartilage persisted nearly always at least in remnants under mediodistal osteophyte. On the other hand, original corticalis and cartilage were found under proximal and lateral osteophytes rather exceptionally.

Aged↗

Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation.

OBJECTIVE: To investigate in vivo and in vitro whether macrophages have an intermediate role in transforming growth factor beta (TGFbeta)-induced osteophyte formation. METHODS: In vivo, synovial lining macrophages were selectively depleted by injection of clodronate-laden liposomes 7 days prior to injection of 20 ng or 200 ng of TGFbeta into murine knee joints 3 times, on alternate days. Total knee joint sections were obtained on day 7 after the last injection and stained with Safranin O. Production of bone morphogenetic protein 2 (BMP-2) and BMP-4 was determined by immunolocalization. The interaction between murine macrophages and mesenchymal cells (precursors with chondrogenic potential) was studied in vitro using a Transwell system in which RAW macrophages were cocultured with C3H10T1/2 mesenchymal cells. Spheroid neocartilage formation was quantified microscopically after staining with May-Grünwald-Giemsa. RESULTS: Triple injections of 20 ng or 200 ng of TGFbeta into normal murine knee joints induced significant osteophyte formation at the lateral and medial sites of the patella and femur on day 7 after the last injection. Strikingly, removal of synovial lining macrophages prior to TGFbeta injection resulted in a drastic reduction of osteophyte formation (by 70% and 64% after injection of 20 ng and 200 ng of TGFbeta, respectively). Synovial lining cells produced BMP-2 and BMP-4 after TGFbeta stimulation, whereas BMP-2 and BMP-4 were absent in the synovial tissue after macrophage depletion. In vitro, clustering and spheroid formation of C3H10T1/2 was induced by TGFbeta concentrations of >1 ng/ml. However, in the Transwell system, in the presence of murine macrophages, 0.5 ng/ml of TGFbeta was very effective in generating large spheroids, suggestive of macrophage-derived (co)factors. In coculture supernatants, TGFbeta concentrations were not elevated in the presence of macrophages, indicating generation of other growth factors involved in spheroid formation. CONCLUSION: These findings indicate that macrophages are crucial intermediate factors in osteophyte formation induced by TGFbeta, probably by inducing other chondrogenic signals.

Animals↗

Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage.

Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one-tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose-dependent protective effect in this model of chemically induced articular cartilage damage.

Animals↗