Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population. Received: March 30, 2001 / Accepted: May 7, 2001     

Trabecular microfracture

Healing trabecular microfractures are a common feature in cancellous bone. These lesions, when observed in macerated cancellous bone slices, measure about 500 m in diameter and surround fractures in trabeculae with microcallus. Whether microcallus is a structure acting primarily as a transient brace, preventing relative movement of the fragmented segments and enabling the trabecula to heal, or whether it is a permanent buttress reducing the stress on the fractured strut, preventing the healing process, is not known. Microfractures are the result of normal physical activity. Hence, the widespread occurrence of trabecular microfracture in cancellous bone implies that a reasonable rate of microfracture is physiologically tolerable. There are three putative effects for trabecular microfracture. One is that, in response to impulse loading, cancellous subchondral bone increases its rigidity due to osteosclerosis resulting from bone formed around microfractures. Another hypothesis is that, if sufficient trabecular microfractures occur, they will compromise the trabecular structure of the vertebra and the proximal femur leading to osteoporotic fracture. By inducing remodeling changes, microfractures have an effect on the maintenance of joint structure. There are two histological patterns for microfractures: an early stage, when actively forming woven bone is bridging the fracture; and a more common late stage, when woven bone is inactive. Femoral studies fail to demonstrate that an increasing number of healed or healing microfractures in osteoarthrosis causes the increase of bone in the head of femur. Only one study has reported a significant increase in the number of trabecular microfractures in osteoarthrotic femoral heads compared with normal controls. This significant increase was in patients taking antiinflammatory drugs. In osteoporotic fracture, sufficient trabecular microfracture may lead to femoral fracture. The bone loss in the vertebral bodies is by a loss of horizontal trabeculae. This loss reduces the resistance of vertical elements to deformation under load and creates the conditions for trabecular fracture. Coincident with this observation, microfracture is most prevalent on the vertical structure. The increase of microfractures with increasing age has three possible explanations: (l) the incidence of microfracture increases as trabeculae become thinner; (2) the incidence of microfracture is constant but the rate of healing decreases; or (3) these two factors combine to increase the number of microfractures. The occurrence of trabecular microfracture has been shown to correlate with factors such as physical activity, age, bone viability and remodeling potential, cancellous bone volume, bone mineral content, bone fatigue properties, and the direction of cancellous bone loading. As trabecular microfracture is not an event that initiates a pathological process, a number of important questions need to be addressed. Whatever the answers to these questions, trabecular microfracture is intimately linked to the nature of cancellous bone structure, and the conditions under which microfracture will compromise this structure are fundamental to the question of bone quality.Presented at the NIA Workshop on Aging and Bone Quality, September 3–4, 1992, Bethesda, Maryland     

Changes in proteoglycans of ageing and osteoarthritic human articular cartilage: An electron microscopic study with polyethyleneimine

Background: Ageing and osteoarthritic (OA) cartilage show characteristic alterations in chondrocyte morphology and in the composition and content of matrix proteoglycans (PGs). Data concerning matrix components are mostly of biochemical nature. Ultrastructural histochemistry is needed to gain more information about distribution of these altered matrix components. Methods: We used the cationic dye polyethyleneimine (PEI) to visualize at the EM level alterations in the distribution and dimensions of PGs of human healthy young, healthy aged, and OA articular cartilage. Results: Young cartilage contained PEI-positive granules in the superficial layer and big winding PEI-positive structures in the deeper layers. In the healthy aged tissue, PEI-positive granules were observed throughout the matrix and smaller winding structures were present in the deeper layer. In OA cartilage both types of PEI-positive structures were absent in the superficial layer. Deeper in the matrix PEI-positive granules could be demonstrated. Moreover, PEI-positive angular structures were observed in the deeper zones. Conclusions: The differences in PEI-positive structures are a good reflection of the differences in PGs between young, ageing, and OA cartilage as demonstrated in biochemical studies. PEI, used at the EM level, gave more precise information concerning the localized changes in quality, quantity, and location of PGs in articular cartilage during ageing and disease. © 1994 Wiley-Liss, Inc.     

保留股骨颈型人工全髋关节置换术初步观察

目的:探讨保留股骨颈型人工全髋关节置换的近期疗效.方法:采用保留股骨颈型人工全髋关节置换术治疗髋关节骨关节病 20例(24髋).结果:本组经过0.5～5 a随访,24个人工髋关节临床效果良好.人工髋关节的活动和其后关节功能良好,影像学检查显示人工髋关节位置良好,假体无松动和下沉.结论:保留股骨颈型人工全髋关节置换治疗髋关节骨关节病近期疗效较好,尤其适用于可能需要行假体翻修的中青年患者.     

Direct comparison of contact areas, contact stress and subchondral mineralization in human hip joint specimens

 X-ray densitometric and CT osteoabsorptiometric findings suggest that in the human hip subchondral mineralization patterns change from bicentric to monocentric as a function of age. It has been hypothesized that these changes indicate an alteration in the geometric configuration of the joint from incongruous to congruous, possibly associated with the onset of osteoarthrosis. The purpose of this study was therefore to directly compare contact areas, contact stress and subchondral mineralization in the hip joint. Twelve specimens without cartilage lesions (ages 34–86 years) were investigated. Simulating the mid-stance phase, the contact areas were determined by polyether casting and the contact stress with Fuji film. The distribution of subchondral mineralization was assessed non-invasively with CT osteoabsorptiometry. At small loads the load-bearing areas were located at the periphery of the lunate surface. In some joints they were found in the acetabular roof and expanded, with higher loads, to the center of the lunate surface and the anterior and posterior horns. In other joints, the contact areas were recorded at lower loads in the anterior and posterior horns, and only at higher forces they merged in the acetabular roof. The maximal contact stress ranged from 8 to 9 MPa at 300% body weight. Maxima of subchondral mineralization were recorded in the acetabular roof, in the anterior and posterior horns, or in all three locations. There was no clear correlation between the distribution of contact and pressure, and the pattern of subchondral bone density. Incongruity is shown to strongly affect the distribution of contact and pressure in the human hip joint. However, the pattern of subchondral mineralization cannot be readily explained in terms of the contact areas and contact stress during mid-stance. Incongruity may give rise to tensile stresses in the subchondral bone, and the construction of the pelvis as a whole may play an important role in subchondral bone loads and adaptation. Accepted: 19 September 1996     

The experience of knee arthritis in athletic young and middle-aged adults: An heuristic study

Objective . To gain a better understanding of the experience of living with tibiofemoral osteoarthritis (OA) as young and middle-aged adults. Methods . Heuristic qualitative research methods were used. Four informants between the ages of 25 and 45 years diagnosed with tibiofemoral OA were purposively sampled. Informants were white, college educated, middle class, and physically active. Informants were interviewed for 4 hours. Interviews were transcribed verbatim and analyzed according to a van Kaam method modified by Moustakas. Results . Living with tibiofemoral OA involved pain, fear, isolation, helplessness, and loss of function, identity, and perceived control. The informants struggled with adapting to their pathology. Behavior change and activity modification were difficult and seemed to be related to the physical, sociologic, and psychologic aspects of pathology. Conclusions . A biopsychosocial model of chronic pathology was developed that may guide health professionals in treating and developing interventions for younger adults with arthritis.     

Proteoglycan and collagen sensitive MRI evaluation of normal and degenerated articular cartilage.

Quantitative magnetic resonance imaging (MRI) techniques have earlier been developed to characterize the structure and composition of articular cartilage. Particularly, Gd-DTPA(2-)-enhanced T1 imaging is sensitive to cartilage proteoglycan content, while T2 relaxation time mapping is indicative of the integrity and arrangement of the collagen network. However, the ability of these techniques to detect early osteoarthrotic changes in cartilage has not been demonstrated. In this study, normal and spontaneously degenerated bovine patellar cartilage samples (n=32) were investigated in vitro using the aforementioned techniques. For reference, mechanical, histological and biochemical properties of the adjacent tissue were determined, and a grading system, the cartilage quality index (CQI), was used to score the structural and functional integrity of each sample. As cartilage degeneration progressed, a statistically significant increase in the superficial T2 (r=0.494, p<0.05) and a decrease in superficial and bulk T1 in the presence of Gd-DTPA(2-) (r=-0.681 and -0.688 (p<0.05), respectively) were observed. Gd-DTPA(2-)-enhanced T1 imaging served as the best predictor of tissue integrity and accounted for about 50% of the variation in CQI. The present results reveal that changes in the quantitative MRI parameters studied are indicative of structural and compositional alterations as well as the mechanical impairment of spontaneously degenerated articular cartilage.     

不同关节腔给药方法治疗KOA的临床疗效观察

目的:探讨关节腔给药方法治疗探讨膝关节骨性关节炎的临床疗效,阐明其可能存在的作用机制。方法:抽取我科2005年以来的住院病例,在1年后进行随访,根据不同治疗方法分为复方丹参注射液冲洗组、生理盐水冲洗组、玻璃酸钠注射组、复方丹参注射液冲洗+玻璃酸钠注射组、生理盐水冲洗+玻璃酸钠注射组,每组病例各30例,对其近期及远期疗效分别进行分析。结果:复方丹参注射液冲洗+玻璃酸钠注射治疗KOA的近远期疗效优于其他各组。结论:关节腔冲洗与关节内HA注射的治疗方法,用于治疗膝骨关节炎时具有协同作用。可能是通过减少炎症反应、润滑关节软骨、改善临床症状等途径来实现的。     

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson''s trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.