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Relation of ligament damage with site specific cartilage loss and osteophyte formation in collagenase induced osteoarthritis in mice.

OBJECTIVE: To investigate the correlation between initial ligament damage and development of subsequent osteoarthritic changes. METHODS: Collagenase was injected intraarticularly into the knee joint of mice of strain C57B16 or C57B110. After 3 days, ligament damage was evaluated by measurements of knee laxity in the anterior-posterior direction as a measure of cruciate ligament function, and in the varus-valgus direction as a measure of collateral ligament function. The amount and location of cartilage loss and osteophyte formation were determined at Day 42. RESULTS: Significant correlations between the amount of laxity changes and the severity of cartilage loss (r = 0.78), the amount of laxity changes and the size of osteophytes (r = 0.87), and between the severity of cartilage loss and osteophyte size (r = 0.94) were demonstrated. The amount of cartilage loss and the degree of osteophyte formation at the medial side of the joint depended mainly on the severity of cruciate ligament damage. This is contrast to changes at the lateral side of the joint, which appeared not to be associated with the severity of ligament damage. CONCLUSION: A strong relationship exists between the severity of cruciate ligament damage and the severity of osteoarthritic changes on the medial side of the joint. In the lateral joint compartment, prone to spontaneous osteoarthritis in the mouse strain studied, this relation is absent.

Animals↗

Correlation between ossification of the stylohyoid ligament and osteophytes of the cervical spine.

OBJECTIVE: To investigate the correlation between ligamentous ossification or osteophytes of the cervical spine and ossification of the styloid process and stylohyoid ligament, and to determine any relation between diffuse idiopathic skeletal hyperostosis (DISH) of the thoracic spine and ossification of the styloid process and stylohyoid ligament. METHODS: Four patients having cervical spine DISH, an elongated styloid process and/or variable patterns of stylohyoid ligament ossification, and clinical findings compatible with Eagle's syndrome are described. Cervical computed tomography scans of 100 patients who also had lateral radiographs of the thoracic spine were reviewed. Point biserial and Spearman rank correlation analysis, McNemar test, chi-squared test, and Fisher's exact test were used to determine correlation between elongation of the styloid process and/or ossification of the stylohyoid ligament and (1) ligamentous ossification or osteophytes of the cervical spine (the characteristic spinal manifestation of DISH), and/or (2) DISH of the thoracic spine. RESULTS: (1) Elongation of the styloid process and variable patterns of ossification of the proximal, middle, and distal parts of the stylohyoid ligament, and (2) enlargement of this ligament were significantly correlated with transverse and anteroposterior dimensions of ligamentous ossification or osteophytes of the cervical spine at various levels. The prevalence of such abnormalities of this process and ligament was not significantly different between the patients with and without thoracic spine DISH. CONCLUSION: Variable types of styloid process-stylohyoid ligament complex abnormalities have significant correlation with ligamentous ossification and osteophytes of the cervical spine.

Aged↗

Vertebral osteophyte formation in experimental disc degeneration. Morphologic and proteoglycan changes over time.

Experimental intervertebral disc degeneration produced in rabbits by ventral nuclear herniation reliably produces vertebral osteophytes. Osteophytes arise from proliferating inner annular fibers which undergo metaplasia into cartilage, calcify, and proceed through an endochondral ossification sequence. Proteoglycans extracted from the osteophytes reveal that the degree of aggregation, molecular size of the monomer, and the chondroitin sulfate/keratin sulfate ratio are directly related to the cartilage state of the tissue.

Animals↗

The effect of marginal osteophytes on reduction of varus-valgus instability in osteoarthritic knees.

The varus-valgus stability of 20 knees with unicompartmental osteoarthritis was studied in vivo at the time of total knee replacement. Intact osteoarthritic knees had an average of 11.0 degrees of varus-valgus motion. Removal of osteophytes from the osteoarthritic compartment significantly increased the motion to 13.1 degrees (P less than 0.05), while subsequent removal of osteophytes from the nonosteoarthritic compartment further increased motion to 14.7 degrees (P less than 0.025). In primarily unicompartmental osteoarthritis, marginal osteophytes appear to stabilize osteoarthritic knees, but can cause fixed deformity.

Aged↗

Joint reaction to polyethylene implantation: a method for inducing osteoarthritic change and osteophyte formation in the rabbit knee joint.

Joint lesions were induced by implantation of a rigid piece of polyethylene sutured under the patella and quadriceps tendon of the rabbit's right knee. Compared to the left sham-operated knee, follow-up studies revealed progressive changes that consisted of early and transient synovial hyperemia and proliferation and late osteoarthritis. By day 7 after surgery, soft synovial-like tissue proliferated around the implant and the articular margins of the femoral trochlea indicating primitive "osteophytic" protuberances (synoviophytes). By day 15 after surgery, the synoviophytes had acquired a more solid consistency and were composed mostly of fibrocartilage covered by a fibro-cellular synovial lining (chondrophytes). By that time, this tissue was invaded with vascular channels; signs of ossification were already present in the deepest layer adjacent to bone. Between the 2nd and 12th weeks, this fibro-cartilaginous tissue, except for the surface fibrous or fibrocartilaginous layer, was progressively replaced by immature bone (osteophyte). Secondary bone remodeling started soon after the first lamellae of immature bone were deposited. Complete integration of the osteophyte into the distal femur occurred during the 2nd and 3rd month.

Animals↗

Keratan sulfate content in the superficial and deep layers of osteophytic and nonfibrillated human articular cartilage in osteoarthritis.

Very thin slices of the superficial and deep layers of osteophytic and apparently normal articular cartilage from six human osteoarthritic femoral heads were digested with papain. The digests were analyzed for keratin sulfate content using an enzyme-linked immunosorbent assay (ELISA) with inhibition step, and for chondroitin sulfate and collagen contents using biochemical assays. Although there were marked differences in Safranin-O staining of the superficial and deep layers of osteophytic cartilage, these two layers had identical high ratios of chondroitin sulfate/collagen. Keratan sulfate was present only in small amounts in osteophytic cartilage. However, the deeper layer contained significantly more of this glycosaminoglycan. The deeper layer of articular cartilage contained approximately twice as much chondroitin sulfate and six times more keratan sulfate relative to collagen than the superficial layer. The results of this study showed that this new sensitive approach, which requires as little as 200 micrograms wet cartilage as starting material, provides important qualitative and quantitative information about the major constituents of the matrix.

Cartilage, Articular↗

The role of osteophytic growth in hip osteoarthritis.

We studied the appearance and frequency of the medial epiarticular osteophyte in human femoral heads. Specimens were sampled from 24 men and 31 women who underwent total hip arthroplasty. On radiography, medial epiarticular osteophytes were present in two thirds of the cases. However, histological examination revealed endochondral ossification in all. Presumably, the bone formation was preceded by the formation of canals and cavities containing vessels. Due to the ossification around these canals and cavities, the histological picture frequently featured two layers of cartilage with bone in the middle. Also in the marginal osteophytes, bone was formed by endochondral ossification. However, this bone appeared more irregular. The new bone formation most likely indicates a reactivated growth as an attempt to repair the osteoarthritic lesions rather than a process of degradation.

Aged↗

Dysphagia and dyspnea due to an anterior cervical osteophyte.

Hypertrophic anterior cervical osteophytes have been reported as a cause of dysphagia, with about 100 cases described in the literature; on the other hand, chronic or acute dyspnea due to edema of the laryngeal inlet or bilateral vocal cord adduction-fixation is rare. We report a 57-year-old patient with a 2-year history of dysphagia and episodic dyspnea, who suffered sudden, severe respiratory distress necessitating emergency tracheotomy. A voluminous anterior cervical osteophyte at the C5 level was diagnosed by computed tomography (CT) and barium swallow test and removed by an anterior approach to the cervical spine, with clinical remission. The incidence, pathogenetic mechanisms, radiological diagnosis, and surgical indications of anterior cervical osteophytes associated with dysphagia and dyspnea are discussed. We advise examining cervical spine patients with dysphagia and/or dyspnea by radiography and CT when other investigations are not conclusive for a digestive or respiratory pathology.

Cervical Vertebrae↗

Clonal chromosome aberrations are present in vivo in synovia and osteophytes from patients with osteoarthritis.

We have previously reported recurrent clonal chromosomal aberrations in synovia, osteophytes and articular cartilage from patients with osteoarthritis (OA). In particular, gain of chromosomes 5 and 7 was found to be strongly associated with OA. In order to exclude the possibility of in vitro artefacts, we studied three to four parallel, independent cultures from ten samples of synovia and three samples of osteophytes from ten women with primary OA. In all, 40 cultures were cytogenetically analysed, 39 of which had clonal chromosomal aberrations. The most common aberrations were +7 and +5 which were found in 38 and 12 cultures, respectively. There were striking karyotype similarities among the parallel cultures from each case. Out of a total of 83 clones, only 11 were unique for one culture, 7 from synovia and 4 from osteophytes. The genetic homogeneity among different cultures from the same patients excludes the possibility of in vitro artefacts and indicates a widespread distribution of the cytogenetically aberrant clones in vivo.

Aged↗

The 'anvil' osteophyte-a primary cause of fixed flexion of the knee?

Three cases are reported in which clinical presentation was with arthritic symptoms and inability to straighten the knee. An unusually prominent anterior tibial osteophyte, whose shape is remarkably suggestive of a blacksmith's anvil, appeared to be a contributory factor through its apparent impingement with the femoral trochlea at the limit of extension. The osteophyte was radically removed arthroscopically in each case as an isolated gesture, and the patients were followed up with particular emphasis on fixed flexion deformity. At clinical review, after a mean follow-up period of 5.3 years, it was concluded that there had not been a convincing or sustained improvement in knee function, although the fixed flexion deformities had not increased significantly. Our conclusion is that the 'anvil' osteophyte may simply be a part of a more diffuse degenerative process and that it was probably not, in itself, the primary cause of fixed flexion deformity in these cases.

Adult↗

Peroneal nerve compression resulting from fibular head osteophyte-like lesions.

BACKGROUND: The anatomical relationship of the fibular head with the fibular nerve is a critical point in regard to injuries of peripheral nerves in the lower extremities. In this location, the peroneal nerve may be injured due to several mechanisms, and osteophyte-like lesions can be considered as a differential diagnosis. METHODS: The suitable literature concerning this association is reviewed and a case is presented. A 15-year-old adolescent boy presented with right peroneal nerve palsy on admission. The radiological examinations (computed tomography and magnetic resonance imaging) demonstrated an osteophytic lesion in the head of the right fibula. The patient underwent surgical decompression of the nerve and resection of the lesion. Postoperatively, there was a complete recovery of the deficits. CONCLUSIONS: The association of osteophyte-like bone changes and peroneal nerve palsy is rare. The differential diagnoses of these lesions include cartilaginous exostoses and osteochondromas, which may be related to hereditary multiple exostoses syndrome. The timing of the treatment plays an important role in the neurological recovery.

Adolescent↗

Acute urinary retention associated with fractured osteophyte.

A 24-year-old man presented to our hospital twice with acute urinary retention in March 2002. Myelographic computed tomography demonstrated a posterior osteophyte. The preoperative urodynamic study indicated detrusor overactivity and detrusor sphincter dyssynergia 30 days after the first occurrence of urinary retention. During osteophyte resection and laminoplasty, the osteophyte, which was found to be fractured and to press on the cauda equina, was removed. The postoperative urodynamic study showed that detrusor overactivity remained and detrusor sphincter dyssynergia had disappeared. The patient was regularly followed up as an outpatient, and no dysuria had been noted by January 2003.

Acute Disease↗

The significance of osteophytes on lumbar vertebral bodies in relation to discographic findings.

Marginal osteophytes of the lumbar vertebral bodies have been related to the discographic findings in lumbar disc spaces. Every case of Scheuermann's anterior marginal epiphysitis was associated with a direct communication with the disc nucleus. Eleven per cent of discs with related 'traction' spurs were discographically normal Forty-three per cent of discs with related 'claw-type' osteophytes appeared normal with discography. It is concluded that when reported radiographs of the lumbosacral spine with osteophytes, particularly those of the claw-type, it is incorrect to describe these changes as representative of disc degeneration in the absence of unequivocal disc space narrowing.

Humans↗

The mechanical 'quality' of osteophytes.

Intrinsic mechanical properties of osteophytes have been compared with those of normal articular cartilage by obtaining force-indentation curves. The cartilage of the osteophyte was found to be thinner than articular cartilage. The mean stiffness of osteophytes was 272.8 (+/- 78.8) N/mm and the mean stiffness of articular cartilage was 1412 (+/- 917.3) N/mm.

Aged↗

An unusual case of stridor due to osteophytes of the cervical spine: (Forestier's disease).

Stridor is a noisy breathing caused by compromised airway in the larynx and trachea. The causes can either be due to intrinsic or extrinsic compression. Stridor resulting from extrinsic compression due to anterior cervical osteophytes is rare. We report an unusual case of acute stridor due to an osteophytic mass in the cervical vertebrae resulting in a mechanical upper airway obstruction. The underlying pathology was Forestier's disease or diffuse idiopathic skeletal hyperostosis (DISH). Stridor is a rare manifestation of DISH and it certainly represents the most life-threatening one. Only a few cases have been reported in the English literature and are mainly secondary to impaired function of the vocal folds, or postcricoid ulceration and oedema. We present such a case, in that stridor was the result of direct airway obstruction by the osteophytic mass and an emergency tracheostomy had to be performed to establish an airway.

Aged↗

Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans.

Bone- and cartilage-derived morphogenetic proteins (BMPs and CDMPs), which are TGFbeta superfamily members, are growth and differentiation factors that have been recently isolated, cloned and biologically characterized. They are important regulators of key events in the processes of bone formation during embryogenesis, postnatal growth, remodelling and regeneration of the skeleton. In the present study, we used immunohistochemical methods to investigate the distribution of BMP-2, -3, -5, -6, -7 and CDMP-1, -2, -3 in human osteophytes (abnormal bony outgrowths) isolated from osteoarthritic hip and knee joints from patients undergoing total joint replacement surgery. All osteophytes consisted of three different areas of active bone formation: (1) endochondral bone formation within cartilage residues; (2) intramembranous bone formation within the fibrous tissue cover and (3) bone formation within bone marrow spaces. The immunohistochemistry of certain BMPs and CDMPs in each of these three different bone formation sites was determined. The results indicate that each BMP has a distinct pattern of distribution. Immunoreactivity for BMP-2 was observed in fibrous tissue matrix as well as in osteoblasts; BMP-3 was mainly present in osteoblasts; BMP-6 was restricted to young osteocytes and bone matrix; BMP-7 was observed in hypertrophic chondrocytes, osteoblasts and young osteocytes of both endochondral and intramembranous bone formation sites. CDMP-1, -2 and -3 were strongly expressed in all cartilage cells. Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption. Since a similar distribution pattern of bone morphogenetic proteins was observed during embryonal bone development, it is suggested that osteophyte formation is regulated by the same molecular mechanism as normal bone during embryogenesis.

Aged↗

Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation.

OBJECTIVE: To investigate the impact of a prolonged and constant active TGF-beta expression by the synovial lining cells on cartilage and ligamentous joint structures in vivo. DESIGN: An adenoviral vector (AdTGF-beta1(223,225)) was used for the overexpression of active TGF-beta1 in knee joints of C57Bl/6 mice. RESULTS: It was found that physiological relevant levels of active TGF-beta1 produced by the synovial lining layer resulted in histopathological changes: hyperplasia of synovium and chondro-osteophyte formation at the so-called chondro-synovial junctions. No histological changes were seen after intra-articular injection of an empty control vector (AdDL70-3) or by overexpression of latent TGF-beta1 (AdTGF-beta1). The predominant site of TGF-beta production in osteoarthritis (OA) and rheumatoid arthritis (RA) is the synovial lining layer. To address the question whether the TGF-beta-induced changes were related to the expression site in the synovial lining, the synovial lining layer was depleted by local treatment with liposomes encapsulating clodronate. Depletion of the lining resulted in a dramatic change of TGF-beta1-induced pathology: markedly reduced chondro-osteophyte formation and increased accumulation of extracellular matrix in the synovium. CONCLUSION: This study shows that overexpression of active TGF-beta1 in the knee joint results in OA-like changes and suggests the synovial lining cells contribute to the chondro-osteophyte formation.

Animals↗

Evidence of oncotic cell death and DNA fragmentation in human hypertrophic chondrocytes in chondro-osteophyte.

OBJECTIVE: To investigate the population and morphology of in situ terminal deoxynucleotidyle transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) stain positive non-apoptotic chondrocytes in hypertrophic zone of human chondro-osteophytes. MATERIALS AND METHODS: Chondro-osteophytes from osteoarthritic patients were obtained at joint replacement surgery. Apoptosis was verified by light microscopic examination of Safranin O stained sections and TUNEL stain. TUNEL staining was also performed on hydrophilic resin embedded semi-thin and ultra-thin sections combined with the treatment with streptavidin-gold conjugates, observed by light microscopy with silver enhancement technique (TUNEL-LM with SE) and transmission electron microscopy (TUNEL-TEM) respectively for the simultaneous evaluation of cellular structure and DNA fragmentation. RESULTS: In paraffin embedded sections (N=18), 31.5+/-6.1% of cells in the hypertrophic zone were TUNEL positive, but only 3.8+/-1.2% cells in this zone showed apoptotic appearances with cell shrinkage and nuclear condensation. Both in TUNEL-TEM and TUNEL-LM with SE, gold particles, which indicate DNA fragmentation, were observed within the nucleus of morphologically apoptotic chondrocytes, as well as of disintegrated, swollen chondrocytes. CONCLUSIONS: In human chondro-osteophytes, hypertrophic chondrocytes might die by oncotic cell death with DNA fragmentation, as well as apoptosis.

Adult↗