A relationship between mechanically-induced changes in serum cartilage oligomeric matrix protein (COMP) and changes in cartilage thickness after 5 years.

OBJECTIVE: To evaluate the hypothesis that a mechanical stimulus (30-min walk) will produce a change in serum concentrations of cartilage oligomeric matrix protein (COMP) that is associated with cartilage thickness changes on magnetic resonance imaging (MRI). METHODS: Serum COMP concentrations were measured by enzyme-linked immunosorbent assay in 17 patients (11 females, age: 59.0±9.2 years) with medial compartment knee osteoarthritis (OA) at study entry immediately before, immediately after, 3.5 h, and 5.5 h after a 30-min walking activity. Cartilage thickness changes in the medial femur and medial tibia were determined from MR images taken at study entry and at 5-year follow-up. Relationships between changes in cartilage thickness and COMP levels, with post-activity concentrations expressed as a percentage of pre-activity levels, were assessed by the calculation of Pearson correlation coefficients and by multiple linear regression analysis, with adjustments for age, sex, and body mass index (BMI). RESULTS: Changes in COMP levels 3.5 h and 5.5 h post-activity were correlated with changes in cartilage thickness in the medial femur and tibia at the 5-year follow-up. The results were strengthened after analyses were adjusted for age, sex, and BMI. Neither baseline pre-activity COMP levels nor changes in COMP levels immediately post-activity were correlated with cartilage thickness changes. CONCLUSIONS: The results of this study support the hypothesis that a change in COMP concentration induced by a mechanical stimulus is associated with cartilage thinning at 5 years. Mechanically-induced changes in mechano-sensitive biomarkers should be further explored in the context of stimulus-response models to improve the ability to assess OA progression.

Meniscectomy alters the dynamic deformational behavior and cumulative strain of tibial articular cartilage in knee joints subjected to cyclic loads.

OBJECTIVE: Meniscectomy-induced osteoarthritis may be mechanically based. We asked how meniscectomy alters time-dependent deformation of physiologically loaded articular cartilage. We hypothesized that meniscectomy alters nominal strain in tibial articular cartilage, and that meniscectomy affects cartilage thickness recovery following cessation of loading. METHODS: A cyclic load simulating normal gait was applied to four sheep knees. A custom device was used to obtain MR images of cartilage at 4.7T during cyclic loading. Articular cartilage thickness and nominal strain were measured every 2.5 min during 1h of cyclic loading, and during 2.5h after cessation of loading. RESULTS: Following meniscectomy the loaded joints rapidly developed high strain centrally and minimal strain peripherally. Maximum nominal strains after 1h of loading were about 55% in the intact knees and 72% in the meniscectomized knees. Nominal strains in the peripheral tibial cartilage were significantly reduced in the meniscectomized knees. Strain recovery was markedly prolonged in the meniscectomized knees. CONCLUSIONS: With meniscectomy, tibial articular cartilage in the central load bearing region remains chronically deformed and dehydrated, even after cessation of loading. Post-meniscectomy osteoarthritis may be initiated in this region by direct damage to the cartilage matrix, or by altering the hydration of the tissue. In peripheral regions, reduced loading and strain may facilitate subchondral vascular invasion, and endochondral ossification. This is consistent with the central fibrillation and peripheral osteophyte formation seen in post-meniscectomy osteoarthritis.

Articular cartilage MR imaging and thickness mapping of a loaded knee joint before and after meniscectomy.

OBJECTIVE: We describe a technique to axially compress a sheep knee joint in an MRI scanner and measure articular cartilage deformation. As an initial application, tibial articular cartilage deformation patterns after 2 h of static loading before and after medial meniscectomy are compared. METHODS: Precision was established for repeated scans and repeated segmentations. Accuracy was established by comparing to micro-CT measurements. Four sheep knees were then imaged unloaded, and while statically loaded for 2 h at 1.5 times body weight before and after medial meniscectomy. Images were obtained using a 3D gradient echo sequence in a 4.7 T MRI. Corresponding 3D cartilage thickness models were created. Nominal strain patterns for the intact and meniscectomized conditions were compared. RESULTS: Coefficients of variation were all 2% or less. Root mean squared errors of MR cartilage thickness measurements averaged less than 0.09 mm. Meniscectomy resulted in a 60% decrease in the contact area (P=0.001) and a 13% increase in maximum cartilage deformation (P=0.01). Following meniscectomy, there were greater areas of articular cartilage experiencing abnormally high and low nominal strains. Areas of moderate nominal strain were reduced. CONCLUSIONS: Medial meniscectomy resulted in increased medial tibial cartilage nominal strains centrally and decreased strains peripherally. Areas of abnormally high nominal strain following meniscectomy correlated with areas that are known to develop fibrillation and softening 16 weeks after medial meniscectomy. Areas of abnormally low nominal strain correlated with areas of osteophyte formation. Studies of articular cartilage deformation may prove useful in elucidating the mechanical etiology of osteoarthritis.

Measurement of perioperative flexion-extension mechanics of the knee joint.

Perioperative knee mechanics currently are evaluated Perioperative knee mechanics currently are evaluated by measuring range of motion. This is an incomplete measurement, however, because the torque applied to achieve the motion is not measured. We hypothesized that a custom goniometer and force transducer could measure the torque required to passively flex a knee through its full range of motion. This measurement was done in the operating room immediately before and after surgery in 20 knees having total knee arthroplasty and 9 having surgery on another limb. Surgery changed the mechanics of 8 knees, whereas unoperated knees remained unchanged. This measurement technique is safe, easy, and repeatable. It improves on the current standard of perioperative knee measurement and can be applied to investigate the effects of surgery and rehabilitation on ultimate knee motion.

Continuous passive motion (CPM): theory and principles of clinical application.

Stiffness following surgery or injury to a joint develops as a progression of four stages: bleeding, edema, granulation tissue, and fibrosis. Continuous passive motion (CPM) properly applied during the first two stages of stiffness acts to pump blood and edema fluid away from the joint and periarticular tissues. This allows maintenance of normal periarticular soft tissue compliance. CPM is thus effective in preventing the development of stiffness if full motion is applied immediately following surgery and continued until swelling that limits the full motion of the joint no longer develops. This concept has been applied successfully to elbow rehabilitation, and explains the controversy surrounding CPM following knee arthroplasty. The application of this concept to clinical practice requires a paradigm shift, resulting in our attention being focused on preventing the initial or delayed accumulation of periarticular interstitial fluids.

Coincident development of sesamoid bones and clues to their evolution.

Sesamoid bones form within tendons in regions that wrap around bony prominences. They are common in humans but variable in number. Sesamoid development is mediated epigenetically by local mechanical forces associated with skeletal geometry, posture, and muscular activity. In this article we review the literature on sesamoids and explore the question of genetic control of sesamoid development. Examination of radiographs of 112 people demonstrated that the relatively infrequent appearances of the fabella (in the lateral gastrocnemius tendon of the knee) and os peroneum (in the peroneus longus tendon of the foot) are related within individuals (P < 0.01). This finding suggests that the tendency to form sesamoids may be linked to intrinsic genetic factors. Evolutionary character analyses suggest that the formation of these sesamoids in humans may be a consequence of phylogeny. These observations indicate that variations of intrinsic factors may interact with extrinsic mechanobiological factors to influence sesamoid development and evolution.

Mechanobiology of skeletal regeneration.

Skeletal regeneration is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, endochondral ossification, and bone remodeling. It has been shown that all these processes are influenced strongly by the local tissue mechanical loading history. This article reviews some of the mechanobiologic principles that are thought to guide the differentiation of mesenchymal tissue into bone, cartilage, or fibrous tissue during the initial phase of regeneration. Cyclic motion and the associated shear stresses cause cell proliferation and the production of a large callus in the early phases of fracture healing. For intermittently imposed loading in the regenerating tissue: (1) direct intramembranous bone formation is permitted in areas of low stress and strain; (2) low to moderate magnitudes of tensile strain and hydrostatic tensile stress may stimulate intramembranous ossification; (3) poor vascularity can promote chondrogenesis in an otherwise osteogenic environment; (4) hydrostatic compressive stress is a stimulus for chondrogenesis; (5) high tensile strain is a stimulus for the net production of fibrous tissue; and (6) tensile strain with a superimposed hydrostatic compressive stress will stimulate the development of fibrocartilage. Finite element models are used to show that the patterns of tissue differentiation observed in fracture healing and distraction osteogenesis can be predicted from these fundamental mechanobiologic concepts. In areas of cartilage formation, subsequent endochondral ossification normally will proceed, but it can be inhibited by intermittent hydrostatic compressive stress and accelerated by octahedral shear stress (or strain). Later, bone remodeling at these sites can be expected to follow the same mechanobiologic adaptation rules as normal bone.

Mechanical influences on tissue differentiation at bone-cement interfaces.

Retrieval studies have shown that tissue at the bone-cement or bone-implant interface can develop into fibrous tissue, fibrocartilage, and bone, and that tissue differentiation appears to be mechanically influenced. A prior histologic analysis of retrieved interface tissues supporting cemented Marmor unicondylar knee components found that beneath the central portion of these implants, a thick, mature layer of fibrocartilage consistently developed, whereas fibrous tissue formed beneath the prosthesis periphery and adjacent to the bone beneath the tibial spine. Finite-element analysis was used to model the interface tissue supporting a cemented Marmor tibial component and interpreted patterns of stress and strain generated in the interface according to a mechanically based tissue differentiation theory. Distortional strain and hydrostatic stress, mechanical stimuli that are hypothesized to be associated with fibrous matrix and cartilaginous matrix production, respectively, were found to correlate well with the previous histologic findings. Given the biologic environments in which the retrieved interface tissues developed, frequently applied hydrostatic stress of approximately 0.7 MPa may be sufficient to stimulate cartilaginous extracellular matrix production in the interface tissue, and frequently applied distortional strain of 10% may be sufficient to stimulate fibrous extracellular matrix production.

Cellular shape and pressure may mediate mechanical control of tissue composition in tendons.

In vivo studies have suggested that mechanical factors are involved in the regulation of the morphology and biochemical composition of tendons that wrap around bones. In these tendons, fibrocartilage is found in the segment wrapped around the bone, and tendon far from the bone displays normal tendon histomorphology. Recent in vitro studies have shown that intermittently loaded connective tissue cells are sensitive to changes in cellular shape and hydrostatic pressure: stretching and distortion of the cells enhances production of fibrous matrix and hydrostatic pressure enhances production of cartilaginous matrix. We used finite-element analysis to determine whether the regions of increased development of cartilaginous matrix in tendons that wrap around bones correspond to regions in which tendon cells are subjected to higher pressures, and whether the maintenance and rearrangement of fibrous extracellular matrix in these tendons is associated with regions of stretching and distortion of cells. We found that regions of cartilaginous matrix and fibrous matrix formation and turnover correlate well with patterns of hydrostatic compressive stress and distortional strain in the tendon. Although further experiments clearly are needed to establish the predictive value of our approach, hydrostatic stress and distortional strain history--parameters intimately related to changes in cellular pressure and shape, respectively--appear to be important tissue-level mechanical stimuli that regulate cartilaginous and fibrous matrix composition of connective tissues.

A comparison of unicortical and bicortical end screw attachment of fracture fixation plates.

Plate fixation is considered by many clinicians to be the treatment of choice for displaced diaphyseal fractures of the forearm. One possible complication associated with plate fixation is refracture with the plate in situ or after plate removal. With the plate in situ, refracture typically occurs through the last screw hole near the end of the plate. Some clinicians have advocated the use of unicortical end screws to minimize the risk of such refractures. In this study, we performed a series of in vitro tests to compare the breaking strength of plated bone analogues that used either unicortical or bicortical end screws. The plated constructs that used unicortical end screws were significantly weaker in the two most important physiologic loading modes. Based on these results, we conclude that the use of unicortical end screws may result in a greater risk of refracture with the plate in situ.

The influence of fixation peg design on the shear stability of prosthetic implants.

The variety of fixation peg designs existing on prosthetic implants indicates uncertainty regarding the optimum design of fixation pegs for the reduction of stress and relative motion at the bone-implant interface. Fixation pegs have a number of important functions on a prosthesis, one of which is to reduce shear stress and shear displacement at the bone-implant interface. This is a parametric study intended to identify trends in the shear stability of prostheses incorporating a range of fixation peg designs. The parameters varied included the number of fixation pegs on a surface, the size of the pegs, and the aspect ratio (length/diameter) of the pegs. Mechanical tests were performed on urethane foam blocks with mechanical properties comparable to trabecular bone. The results indicated the following: (a) Fixation pegs act independently in resisting shearing force if they are spaced sufficiently far apart. (b) For any given shear displacement, smaller pegs generate a greater resistive shear force per unit of peg projected area in the direction of the applied load than larger pegs having the same aspect ratio. (c) Smaller diameter pegs cause the supporting material to yield at lower displacements. (d) Pegs with a high aspect ratio provide high shear stability with a minimum amount of bone removed, but may bend if the aspect ratio becomes excessive. (e) Smaller, slender pegs generate a greater resistive shear force at a given displacement per unit of peg volume than larger, lower aspect ratio pegs.(ABSTRACT TRUNCATED AT 250 WORDS)