Jari Arokoski

Normal and pathological adaptations of articular cartilage to joint loading.

Joints are functional units that transmit mechanical loads between contacting bones during normal daily or specialized activities, e.g., sports. All components of the joint, i.e. articular cartilage, bone, muscles, ligaments/tendons and nerves, participate in load transmission. Failure in any of these components can cause joint malfunction, which, in turn, may lead to accumulation of damage in other joint components. Mechanical forces have great influence on the synthesis and rate of turnover of articular cartilage molecules, such as proteoglycans (PGs). Regular cyclic loading of the joint enhances PG synthesis and makes cartilage stiff. On the other hand, loading appears to have less evident effects on the articular cartilage collagen fibril network. Continuous compression of the cartilage diminishes PG synthesis and causes damage of the tissue through necrosis. The prevailing view is that osteoarthrosis (OA) starts from the cartilage surface through PG depletion and fibrillation of the superficial collagen network. It has also been suggested that the initial structural changes take place in the subchondral bone, especially when the joint is exposed to an impact type of loading. This in turn would create an altered stress pattern on joint surfaces, which leads to structural damage and mechanical failure of articular cartilage. The importance of the neuromuscular system to the initiation and progression of OA is still poorly understood. Many surgical extra‐ and intra‐articular procedures have been used for the treatment of OA. Although some of the new methods, such as autologous chondrocyte transplantation and mosaicplasty, have given good clinical results, it is reasonable to emphasize that the methods still are experimental and more controlled studies are needed.

Osteoarthritis in the carpometacarpal joint of the thumb. Prevalence and associations with disability and mortality.

BACKGROUND This study was designed to investigate the prevalence of osteoarthritis in the carpometacarpal joint of the thumb in adults thirty years of age or older in Finland. METHODS Between 1978 and 1980, a representative population sample of 8000 Finns thirty years of age or older were invited to have a comprehensive health examination; 90% accepted. Hand radiographs were made of 3595 subjects. Since the examination, the subjects have been followed systematically to assess work disability and mortality by reviewing registers covering the whole population. RESULTS The age-adjusted prevalence of thumb carpometacarpal osteoarthritis of Kellgren grade 2, 3, or 4 was 7% for men and 15% for women. After adjustment for age, sex, and other alleged risk factors, body mass index was found to be directly proportional to the prevalence of thumb carpometacarpal osteoarthritis in both sexes. The adjusted odds ratio was 1.29 (95% confidence interval, 1.15 to 1.43) per 5-kg/m(2) increment in body mass index. No significant association was found between the physical workload history and thumb carpometacarpal osteoarthritis. Restricted mobility of the thumb and local tenderness and swelling were frequently found in conjunction with radiographic evidence of thumb carpometacarpal osteoarthritis. Advanced (grade-3 or 4) thumb carpometacarpal osteoarthritis predicted the total mortality rate in men (adjusted relative risk, 1.32; 95% confidence interval, 1.03 to 1.69). Radiographic signs of thumb carpometacarpal osteoarthritis did not predict work disability. CONCLUSIONS and CLINICAL RELEVANCE Obesity is a strong determinant of thumb carpometacarpal osteoarthritis in both sexes. The effect of thumb carpometacarpal osteoarthritis on disability and mortality in the general population is modest. Because of the rarity of ensuing disability, carpometacarpal osteoarthritis of the thumb is likely to be underdiagnosed in clinical practice.

Osteoarthritis of finger joints in Finns aged 30 or over: prevalence, determinants, and association with mortality

Background: Prevalence and risk factors of osteoarthritis (OA) in finger joints have been amply explored in previous studies. However, no study has focused on finger joint OA as a predictor of mortality. Objective: To investigate finger joint OA for its associations with alleged risk factors and with life expectancy in an extensive health survey. Methods: From 1978 to 1980 a representative population sample of 8000 Finns aged 30 years or over was invited to participate in a comprehensive health examination; 90% accepted. Hand radiographs were taken from 3595 subjects. By the end of 1994, 897 of these had died. Results: The prevalence of OA of Kellgren’s grade 2 to 4 in any finger joint and in at least two symmetrical pairs of distal interphalangeal joints (DIPs) was 44.8% and 16.0%, respectively. Age and body mass index were significant determinants for OA both in any finger joint and in symmetrical DIP OA. The history of physical workload in women showed a positive association with OA in any finger joint. Smoking in men seemed to protect against symmetrical DIP OA. As adjusted for the determinants above, symmetrical DIP OA predicted mortality in women (relative risk (RR), 1.23; 95% confidence interval (95% CI) 1.01 to 1.51), but not in men (RR 0.89; 95% CI 0.68 to 1.16). In men, however, OA in any finger joint significantly predicted cardiovascular deaths (RR 1.42; 95% CI 1.05 to 1.92). Conclusion: OA in any finger joint and symmetrical DIP OA have different risk factor profiles and predict mortality in different patterns between men and women.

Decreased birefringence of the superficial zone collagen network in the canine knee (stifle) articular cartilage after long distance running training, detected by quantitative polarised light microscopy.

OBJECTIVE: To investigate the effects of a one year programme of running training (up to 40 km/day for 15 weeks) on the spatial orientation pattern of collagen and glycosaminoglycans in articular cartilage in different parts of the knee (stifle) and shoulder joints of young beagle dogs. METHODS: Area specific measurements of the optical path difference (= retardation, gamma) and the cartilage zone thickness were performed using conventional procedures and a new computer based quantitative polarised light microscopy method. Transmission electron microscopy was used to determine the zonal volume density of collagen fibrils. The concentrations of collagen and hydroxypyridinium crosslinks were investigated biochemically. RESULTS: Running training decreased gamma by 24-34% (p < 0.05) in the superficial zone of the lateral femoral condyle articular cartilage and at the centre of the tibial condyles. Gamma of glycosaminoglycans decreased by 26% (p < 0.05) in the superficial zone of the lateral condyle of the femur, but at the same site the volume density of collagen fibrils was unchanged. Neither the collagen concentration nor the concentration of hydroxypyridinium crosslinks was altered as a result of running. In both control and runner dogs, the thickness and gamma values of the superficial zone were greater in the humerus and the femur than in the tibia. CONCLUSION: Endurance type running exercise in beagles caused a reduction in the superficial zone birefringence of the articular cartilage, which indicates either a disorganisation or a reorientation of the superficial zone collagen network. Articular cartilage showed marked variability of collagen network organisation over the different knee (stifle) joint articular surfaces.

Importance of the superficial tissue layer for the indentation stiffness of articular cartilage

Indentation testing is a widely used technique for nondestructive mechanical analysis of articular cartilage. Although cartilage shows an inhomogeneous, layered structure with anisotropic mechanical properties, most theoretical indentation models assume material homogeneity and isotropy. In the present study, quantitative polarized light microscopy (PLM) measurements from canine cartilage were utilized to characterize thickness and structure of the superficial, collageneous tissue layer as well as to reveal its relation to experimental indentation measurements. In addition to experimental analyses, a layered, transversely isotropic finite element (FE) model was developed and the effect of superficial (tangential) tissue layer with high elastic modulus in the direction parallel to articular surface on the indentation response was studied. The experimental indentation stiffness was positively correlated with the relative thickness of the superficial cartilage layer. Also the optical retardation, which reflects the degree of parallel organization of collagen fibrils as well as collagen content, was related to indentation stiffness. FE results indicated effective stiffening of articular cartilage under indentation due to high transverse modulus of the superficial layer. The present results suggest that indentation testing is an efficient technique for the characterization of the superficial degeneration of articular cartilage.

Back and hip extensor muscle function during Therapeutic exercises

BACKGROUND Therapeutic exercises are widely used in the treatment of low back problems. Clinical knowledge about targeting the load in these exercises, however, is insufficient. This study assessed the L2 and L5 level paraspinal and gluteus maximus muscle activities in different therapeutic exercises. Intramuscular and surface electromyography (EMG) measurements were obtained to study whether surface EMG measurements can be used in the assessment of multifidus muscle function. METHODS Eleven healthy subjects (5 men, 6 women) 21 to 38 years of age volunteered for the study. The subjects performed 18 different therapeutic exercises. During the exercises paraspinal EMG was recorded using fine wire and surface electrodes. The normalized peak and average muscle EMG activities (percentage of amplitude in maximal voluntary contraction [MVC]) during each task were determined. RESULTS The correlations between the average intramuscular and surface activities of the normalized EMG (% of MVC) at the L2 and L5 levels were .928 and .950, respectively. The peak and average EMG amplitudes of the exercises were below 50% and 25% of MVC, respectively. At the L5 level, the multifidus peak and average EMG amplitudes (% MVC) were higher in women than in men, whereas no significant difference was found at the L2 level. In women, the normalized multifidus EMG amplitude was higher at the L5 level than at the L2 level, whereas no significant difference was found in men. In both sexes, the normalized EMG amplitude was higher in the multifidus than in the longissimus muscle. CONCLUSION Surface EMG measurements may be used in the assessment of multifidus muscle function. Simple therapeutic exercises are effective in activating the lumbar paraspinal muscles.

Articular cartilage superficial zone collagen birefringence reduced and cartilage thickness increased before surface fibrillation in experimental osteoarthritis

OBJECTIVES To investigate articular cartilage collagen network, thickness of birefringent cartilage zones, and glycosaminoglycan concentration in macroscopically normal looking knee joint cartilage of young beagles subjected to experimental slowly progressive osteoarthritis (OA). METHODS OA was induced by a tibial 30° valgus osteotomy in 15 female beagles at the age of 3 months. Fifteen sisters were controls. Cartilage specimens were collected seven (Group 1) and 18 months (Group 2) postoperatively. Collagen induced optical path difference and cartilage zone thickness measurements were determined from histological sections of articular cartilage with smooth and intact surface by computer assisted quantitative polarised light microscopy. Volume density of cartilage collagen fibrils was determined by image analysis from transmission electron micrographs and content of glycosaminoglycans by quantitative digital densitometry from histological sections. Results—In the superficial zone of the lateral tibial and femoral cartilage, the collagen induced optical path difference (birefringence) decreased by 19 to 71% (p < 0.05) seven months postoperatively. This suggests that severe superficial collagen fibril network deterioration took place, as 18 months postoperatively, macroscopic and microscopic OA was present in many cartilage areas. Thickness of the uncalcified cartilage increased while the superficial zone became thinner in the same sites. In operated dogs, glycosaminoglycan content first increased (Group 1) in the lateral tibial condyle and then decreased (Group 2) (p < 0.05). Conclusion—In this OA model, derangement of the superficial zone collagen network was the probable reason for birefringence reduction. This change occurred well before macroscopic OA.

Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteoarthritis—a population-based study with a follow-up of 22 years

OBJECTIVE Several studies have shown that knee OA is associated with obesity, physical stress at work, traumatic knee injuries, heredity and female gender. However, the body of such evidence comes from cross-sectional or case-control studies, and from only a few follow-up studies, mostly of short duration. Based on the nationwide Mini-Finland Health Survey, we analysed the potential risk factors for prediction of incident knee OA in the long term. METHODS Focused on major health problems, the survey was carried out in 1978-80 in a sample of 8000 subjects, representative of the Finnish population aged > or =30 years. Altogether 823 subjects free from knee OA at the baseline were re-examined in 2000-01, and after the intervening 22 years 94 new cases of knee OA were found. Knee OA was diagnosed on both occasions by physicians using information on disease histories, symptoms and standardized clinical examinations. RESULTS The risk of developing knee OA was strongly associated with BMI (kg/m(2)); adjusted for age and gender and other covariates, and compared with the reference category (BMI < 25.0); the relative odds ratios (ORs) with 95% CIs were 1.7 (95% CI 1.0, 2.8) and 7.0 (95% CI 3.5, 14.10) for subjects with BMIs 25.0-29.9 and > or =30.0, respectively. Similarly, the adjusted OR for the heaviest category of physical stress at work was 18.3 (95% CI 4.2, 79.4) compared with the lightest category, and 5.1 (95% CI 1.4, 19.0) for permanent complaints due to past knee injury. CONCLUSIONS This prospective study confirms the roles of obesity, heavy work load and knee injury in the aetiology of knee OA.

Remobilization does not fully restore immobilization induced articular cartilage atrophy.

The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage.

Specimen preparation and quantification of collagen birefringence in unstained sections of articular cartilage using image analysis and polarizing light microscopy

To establish an optimal method for analysis of the collagen structures from unstained tissue sections, a computerized image analysis system using a charge coupled device camera coupled to a polarizing light microscope was used. Retardation values of birefringence, which are proportional to the content and fibril orientation of collagen in the extracellular matrix of articular cartilage, were determined from sections prepared in different ways. In the superficial zone of articular cartilage, the highest retardation values were recorded from sections cut parallel to the so-called split lines indicating the anisotropic arrangement of collagen. Complete digestion of glycosaminoglycans reduced the retardation value by approximately 6.0%, suggesting a minor, but not insignificant, contribution of glycosaminoglycans to the birefringence of the matrix. The use of a mounting medium with a refractive index close to that of the collagen (e.g. DPX) increased the specificity of the method, since the optical anisotropy of collagen derives predominantly from the intrinsic (structural) birefringence. In conclusion, analysis of unstained sections after careful removal of paraffin and glycosaminoglycans from the tissues provides a sensitive and rapid quantitative assessment of oriented collagen structures in articular cartilage