Joseph A. Buckwalter

Aging and degeneration of the human intervertebral disc.

Human intervertebral discs undergo age-related degenerative changes that contribute to some of the most common causes of impairment and disability for middle aged and older persons: spine stiffness, neck pain, and back pain. Potential causes of the age-related degeneration of intervertebral discs include declining nutrition, loss of viable cells, cell senescence, post-translational modification of matrix proteins, accumulation of degraded matrix molecules, and fatigue failure of the matrix. The most important of these mechanisms appears to be decreasing nutrition of the central disc that allows accumulation of cell waste products and degraded matrix molecules, impairs cell nutrition, and causes a fall in pH levels that further compromises cell function and may cause cell death. Although aging changes of the disc appear to be inevitable, identification of activities and agents that accelerate these changes may help decrease the rate and severity of disc degeneration; and recent work suggests that methods can be developed that will regenerate disc tissue.

Mapping Early Brain Development in Autism

Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions.

The impact of osteoarthritis: implications for research.

Homeostasis of articular cartilage depends in part on mechanical loads generated during daily activity whereas inappropriate joint loads result in focal degeneration of cartilage, as occurs in osteoarthritis. We will review results of a series of questions regarding the effects of two types of mechanical loads—intermittent hydrostatic pressure and shear stress—on adult human articular chondrocytes in high-density monolayer culture. Intermittent hydrostatic pressure increased aggrecan and Type II collagen gene expression in normal chondrocytes and induced changes in the cell-associated proteins of normal and osteoarthritic chondrocytes. Hydrostatic pressure also counteracted inhibitory effects of bacterial lipopolysaccharide on matrix protein expression by cultured chondrocytes. Application of shear stress to osteoarthritic chondrocytes increased the release of the proinflammatory mediator, nitric oxide, decreased aggrecan and Type II collagen expression, and induced molecular changes associated with apoptosis whereas hydrostatic pressure increased matrix macromolecule expression. The findings show that the types of load comprising the mechanical loading environment of articular cartilage considerably alter chondrocyte metabolism and suggest that mechanical stimulation may be used for in vitro or in vivo approaches for cartilage engineering.

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Articular Cartilage. Part II: Degeneration and Osteoarthrosis, Repair, Regeneration, and Transplantation*†

Joint pain and loss of mobility are among the most common causes of impairment in middle-aged and older people36,134. In many instances, the degeneration of articular cartilage and alterations in other joint tissues that result from the loss of structure and function of articular cartilage cause the pain and the loss of motion28,46,47,85,118,150. This occurs most frequently in the clinical syndrome of idiopathic or primary osteoarthrosis, but it may also result from joint injury or from developmental, metabolic, and inflammatory disorders that destroy the articular surface, causing secondary osteoarthrosis28,46,118. An understanding of the degeneration of articular cartilage, osteoarthrosis, and the potential for restoring an articular surface depends to a large extent on an appreciation of the biological behavior and the responsiveness of articular cartilage to injury and disease. Of considerable importance is the observation, first reported centuries ago and confirmed by multiple investigators over the last fifty years, that adult articular cartilage does not have the capacity to repair structural damage resulting from injury or disease29,32,71. This observation has contributed to the view that adult articular cartilage is an inert bearing surface, like high-density polyethylene or metal, and that degeneration of the articular surface with age is the result of mechanical wear with inevitable, irreversible loss of structure and mechanical performance resulting from joint use62. The implication of this view is that, other than limiting joint use or loading, little or nothing can be done to prevent the degeneration of articular cartilage, and the most appropriate treatment for advanced degeneration of cartilage leading to the clinical syndrome of osteoarthrosis is replacement of the articular surface. Alternatively, if articular cartilage is …

Articular Cartilage Injuries

The acute and repetitive impact and torsional joint loading that occurs during participation in sports can damage articular surfaces causing pain, joint dysfunction, and effusions. In some instances, this articular surface damage leads to progressive joint degeneration. Three classes of chondral and osteochondral injuries can be identified based on the type of tissue damage and the repair response: (1) damage to the joint surface that does not cause visible mechanical disruption of the articular surface, but does cause chondral damage and may cause subchondral bone injury; (2) mechanical disruption of the articular surface limited to articular cartilage; and (3) mechanical disruption of articular cartilage and subchondral bone. In most instances, joints can repair damage that does not disrupt the articular surface if they are protected from additional injury. Mechanical disruption of articular cartilage stimulates chondrocyte synthetic activity, but it rarely results in repair of the injury. Disruption of subchondral bone stimulates chondral and bony repair, but it rarely restores an articular surface that duplicates the biologic and mechanical properties of normal articular cartilage. In selected patients, surgeons have used operative treatments including penetrating subchondral bone, soft tissue grafts, and cell transplants and osteochondral autografts and allografts to restore articular surfaces after chondral injuries. Experimental studies indicate that use of artificial matrices and growth factors also may promote formation of a new joint surface. However, an operative treatment of an articular surface injury that will benefit patients must not just provide a new joint surface, it must produce better long-term joint function than would be expected if the injury was left untreated or treated by irrigation and debridement alone. Therefore, before selecting a treatment for a patient with an articular cartilage injury, the surgeon should define the type of injury and understand its likely natural history.

Posttraumatic osteoarthritis : A first estimate of incidence, prevalence, and burden of disease

Although posttraumatic osteoarthritis (OA) is a common and important entity in orthopedic practice, no data presently exist regarding its prevalence or its relative burden of disease. A population-based estimate was formulated, based on one large institutions experience in terms of its fraction of patients with OA presenting to lower-extremity adult reconstructive clinics with OA of posttraumatic origin. The relative proportion of these patients undergoing total joint replacement provided a basis for extrapolating institutional experience with posttraumatic OA to a populationwide estimate because the numbers of lower-extremity total joint arthroplasty procedures performed were reliably tabulated both within the institution and populationwide. By this methodology, approximately 12% of the overall prevalence of symptomatic OA is attributable to posttraumatic OA of the hip, knee, or ankle. This corresponds to approximately 5.6 million individuals in the United States being affected by posttraumatic OA sufficiently severe to have caused them to present for care by an orthopedic lower-extremity adult reconstructive surgeon. Further, based on the relative prevalence of OA versus rheumatoid arthritis, and their relative impacts as assessed by the SF-36 (Short-Form 36) lower-extremity physical composite scores, about 85.5% of the societal costs of arthritis are attributable to OA. The corresponding aggregate financial burden specifically of posttraumatic OA is

Injury and Repair of the Musculoskeletal Soft Tissues

3.06 billion annually, or approximately 0.15% of the total U.S. health care direct cost outlay.

Athletics and Osteoarthritis

This reference work summarises current knowledge in all of the musculoskeletal soft-tissue areas and focuses on the structural aspects of soft-tissue injury.

Post‐traumatic osteoarthritis: Improved understanding and opportunities for early intervention

Athletes, and an increasing number of middle aged and older people who want to participate in athletics, may question whether regular vigorous physical activ ity increases their risk of developing osteoarthritis. To answer this, the clinical syndrome of osteoarthritis must be distinguished from periarticular soft tissue pain associated with activity and from the development of osteophytes. Sports that subject joints to repetitive high levels of impact and torsional loading increase the risk of articular cartilage degeneration and the resulting clinical syndrome of osteoarthritis. However, moderate habitual exercise does not increase the risk of osteo arthritis ; selected sports improve strength and mobility in older people and people with mild and moderate osteoarthritis. People with abnormal joint anatomy or alignment, previous significant joint injury or surgery, joint instability, above-average body weight, distur bances of joint or muscle innervation or inadequate muscle strength probably have increased risk of osteo arthritis. These people and those with early osteoar thritis can benefit from regular physical activity, but they should have a careful evaluation of their joint structure and function before participation. They should consider measures that decrease the intensity and frequency of impact and torsional loading of joints, including use of sports equipment that decreases joint impact loading, maintaining or improving muscle strength, tone, and general conditioning so that muscle contractions help protect joints from injury and high impact, and decreasing body weight.

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Articular Cartilage. Part I: Tissue Design and Chondrocyte-Matrix Interactions*†

Even with current treatments of acute joint injuries, more than 40% of people who suffer significant ligament or meniscus tears, or articular surface injuries, will develop osteoarthritis (OA). Correspondingly, 12% or more of all patients with lower extremity OA have a history of joint injury. Recent research suggests that acute joint damage that occurs at the time of an injury initiates a sequence of events that can lead to progressive articular surface damage. New molecular interventions, combined with evolving surgical methods, aim to minimize or prevent progressive tissue damage triggered by joint injury. Seizing the potential for progress in the treatment of joint injuries to forestall OA will depend on advances in (1) quantitative methods of assessing the injury severity, including both structural damage and biologic responses, (2) understanding of the pathogenesis of post‐traumatic OA, taking into account potential interactions among the different tissues and the role of post‐traumatic incongruity and instability, and (3) application of engineering and molecular research to develop new methods of treating injured joints. This paper highlights recent advances in understanding of the structural damage and the acute biological response following joint injury, and it identifies important directions for future research.