David S. Hungerford

Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes

The search for biocompatible materials that can support the growth and phenotypic expression of osteoblasts and chondrocytes is a major challenge in the application of tissue engineering techniques for the repair of bone and cartilage defects. Chitosan, a copolymer of glucosamine and N-acetylglucosamine, may provide an answer to this search. Chitosan is the deacetylated product of chitin, a ubiquitous biopolymer found in the exoskeleton of insects and marine invertebrates. Little is known about the utility of chitosan in propagating human osteoblasts and chondrocytes. In this study, we test the hypothesis that chitosan promotes the survival and function of osteoblasts and chondrocytes. Chitosan (4%, w/v in 2% HAc) was coated onto plastic coverslips that had been fitted into 24-well plates. Human osteoblasts and articular chondrocytes were seeded on either uncoated or chitosan-coated coverslips at 1 x 10(5)/cells per well. Cultures were incubated at 37 degrees C, 5% CO(2) for a period of 7 days. Cell viability was assessed at that time using a fluorescent molecular probe. The phenotypic expression of osteoblasts and chondrocytes was analyzed by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Osteoblasts and chondrocytes appeared spherical and refractile on chitosan-coated coverslips. In contrast, greater than 90% of cells on plastic coverslips were elongated and spindle shaped after 7 days of culture. Similar to cells propagated on uncoated control wells, greater than 90% of human osteoblasts and chondrocytes propagated on chitosan remained viable. Human osteoblasts propagated on chitosan films continued to express collagen type I whereas chondrocytes expressed collagen type II and aggrecan, as shown by reverse transcriptase-polymerase chain reaction analysis and immunostaining. The present in vitro work demonstrates the biocompatibility of chitosan as a substrate for the growth and continued function of human osteoblasts and chondrocytes. Chitosan may have potential use as a tissue engineering tool for the repair of osseous and chondral defects.

Nontraumatic osteonecrosis of the femoral head: ten years later.

The etiology of osteonecrosis of the hip may have a genetic basis. The interaction between certain risk factors and a genetic predisposition may determine whether this disease will develop in a particular individual. The rationale for use of joint-sparing procedures in the treatment of this disease is based on radiographic measurements and findings with other imaging modalities. Early diagnosis and intervention prior to collapse of the femoral head is key to a successful outcome of joint-preserving procedures. The results of joint-preserving procedures are less satisfactory than the results of total hip arthroplasty for femoral heads that have already collapsed. New pharmacological measures as well as the use of growth and differentiation factors for the prevention and treatment of this disease may eventually alter our treatment approach, but it is necessary to await results of clinical research with long-term follow-up of these patients.

Biomechanics of the patellofemoral joint.

The patellofemoral joint contains 2 complex mechanisms for ameliorating forces transmitted across it, namely increasing extensor lever arm-r in the important range of flexion 30 degrees-70 degrees and increasing contact area with increasing flexion. In this range the patella bears sole responsibility for transmitting resultant flexion of quadriceps force to the femur. Here lies the thickest cartilage in the body and perhaps not surprisingly, the most frequent site of cartilage degeneration. The Q-angle and valgus vector explain the predominance of the pathologic lesions on the lateral side of the joint as well as the associated dislocations, subluxations, lateral pressure syndromes, and patellofemoral arthrosis. Extension exercises against resistance produce non-physiologic loading of patellar articular cartilage. Even relatively small loads which are commonly used in physical therapy departments produce pressures far in excess of normal activities, such as stair climbing or squatting. Patients who are placed on such exercise programs are often made worse and develop symptoms which they did not have before. Straight leg raising with weights, on the other hand, maximally stresses the quadriceps muscle without any patellofemoral compression since the patella is out of contact, proximal to the trochlea.

Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus

In this prospective study, 28 (52 percent) of 54 patients with systemic lupus erythematosus (SLE) had ischemic necrosis of bone in 93 sites. All but two of the patients had multiple sites of involvement, with hips, knees, and shoulders affected in decreasing order of frequency. Demographic, clinical, and laboratory features were comparable in patients with and without ischemic necrosis of bone except for cushingoid changes in 24 (86 percent) of the 28 patients with ischemic necrosis of bone versus four (15 percent) of the 26 patients without ischemic necrosis of bone (p less than 0.0001). The duration of steroid therapy, total cumulative steroid dose, and the mean daily prednisone dose for the first one, three, six, and 12 months of therapy were not significantly different between the two groups. Mean daily prednisone dose for the highest single month as well as the highest consecutive three, six, and 12 months of therapy was significantly higher in patients with ischemic necrosis of bone. The mean daily dose of prednisone for the highest month of therapy was greater than 40 mg per day in 93 percent and greater than 20 mg per day in all patients with ischemic necrosis of bone. In patients with ischemic necrosis of bone, there was a statistically significant correlation between higher mean prednisone dose at all time intervals and increased number of bony sites involved. A lower mean dose of prednisone was required to produce ischemic necrosis of bone in patients with Raynauds phenomenon.

Osteonecrosis : etiology, diagnosis, and treatment

Purpose of reviewThis review provides an update of the recent progress in etiology, pathogenesis, diagnosis, and treatment of osteonecrosis. Recent findingsConcerning pathogenesis, there is evidence that there is a genetic predilection for those who are exposed to the two leading etiologic associations for osteonecrosis: corticosteroids and alcohol. Studies concerning the treatment of osteonecrosis indicate that most preservative (ie, joint-sparing) procedures available today have better results in the precollapse stages of the disease and in smaller lesions. Therefore, researchers continue to develop and modify diagnostic techniques, particularly relating to MRI, for the identification and quantification of osteonecrotic lesions. Advances concerning bone grafting and arthroplasty procedures have resulted in improved clinical outcomes for this patient population. The future treatment of osteonecrosis may involve genetic or cell-based therapies. SummaryAlthough progress has been made, considerably more research is needed before we fully understand this disease. Hopefully, such research will lead to effective measures for saving the femoral head or, better yet, preventing osteonecrosis.

the Outcome of Total Knee Arthroplasty in Obese Patients

BACKGROUND Evidence linking increased body weight to osteoarthritis of the knee and the high prevalence of obesity underscore the importance of defining the outcome of total knee arthroplasty in obese patients. The purpose of this study was to compare the clinical and radiographic results of total knee arthroplasties performed in obese patients with those of total knee arthroplasties performed in nonobese patients. METHODS Clinical and radiographic data on seventy-eight total knee arthroplasties in sixty-eight obese patients were compared with data on a matched group of nonobese patients. The analysis was also performed after stratification of the obese group for the degree of obesity. All patients had the same prosthesis. The clinical data that were analyzed included the Knee Society objective and functional scores, patellofemoral symptoms, activity level, and complications. RESULTS The percentage of knees with a Knee Society score of > or =80 points at an average of eighty months was 88% in the obese group, which was significantly lower than the 99% rate in the nonobese group at the same time. The morbidly obese subgroup had a significantly higher revision rate than did the nonobese group (p = 0.02). CONCLUSIONS The results of the present study suggest that any degree of obesity, defined as a body mass index of > or =30, has a negative effect on the outcome of total knee replacement.

Variation of rotation moment arms with hip flexion.

Excessive flexion and internal rotation of the hip is a common gait abnormality among individuals with cerebral palsy. The purpose of this study was to examine the influence of hip flexion on the rotational moment arms of the hip muscles. We hypothesized that flexion of the hip would increase internal rotation moment arms and decrease external rotation moment arms of the primary hip rotators. To test this hypothesis we measured rotational moment arms of the gluteus maximus (six compartments), gluteus medius (four compartments), gluteus minimus (three compartments) iliopsoas, piriformis, quadratus femoris, obturator internus, and obturator externus. Moment arms were measured at hip flexion angles of 0, 20, 45, 60, and 90 degrees in four cadavers. A three-dimensional computer model of the hip muscles was developed and compared to the experimental measurements. The experimental results and the computer model showed that the internal rotation moment arms of some muscles increase with flexion; the external rotation moment arms of other muscles decrease, and some muscles switch from external rotation to internal rotation as the hip is flexed. This trend toward internal rotation with hip flexion was apparent in 15 of the 18 muscle compartments we examined, suggesting that excessive hip flexion may exacerbate internal rotation of the hip. The gluteus maximus was found to have a large capacity for external rotation. Enhancing the activation of the gluteus maximus, a muscle that is frequently underactive in persons with cerebral palsy, may help correct excessive flexion and internal rotation of the hip.

Results of total knee arthroplasty after failed proximal tibial osteotomy for osteoarthritis

The cases of twenty-one consecutive patients who had a minimally constrained total knee arthroplasty (six of whom had a cemented and fifteen, an uncemented prosthesis) after a failed proximal tibial osteotomy for osteoarthritis were compared with those of a non-consecutive group of twenty-one patients who had had a primary total knee arthroplasty for osteoarthritis. The groups were matched according to age and sex of the patient, type of prosthesis and fixation, and length of follow-up. At an average length of follow-up of 2.9 years, a good or excellent result was obtained in 81 per cent of the patients who had had a previous osteotomy. At an average length of follow-up of 2.8 years, a good or excellent result was obtained in 100 per cent of the patients who had had a primary arthroplasty. Two patients in the osteotomy group and none in the primary arthroplasty group required additional surgery. At the time of arthroplasty, technical difficulties in exposing the proximal part of the tibia were noted in three patients in the group that had undergone an osteotomy. The results of total knee arthroplasty after failed proximal tibial osteotomy approached but did not equal the results after primary total knee arthroplasty.

Multiple irrigation, debridement, and retention of components in infected total knee arthroplasty

The results of 24 infected total knee arthroplasties (22 patients) that were treated by irrigation, debridement, and retention of the prosthetic components were prospectively studied. Strict criteria were used for the selection of this method of treatment. Patients had to be less than 30 days after index arthroplasty (postsurgical group) or had to have less than 30 days of knee symptoms (hematogenous group). In addition, there had to be no radiographic signs of osteitis or evidence of a loose prosthetic component. Patients had one to three irrigation and debridement procedures depending on systemic signs, knee symptoms, or the results of knee aspirations. All of the immediate postsurgical infections (10 knees) and 10 of the 14 (71%) late hematogenously infected knees retained the prosthesis without further evidence of infection at the final follow-up visit at 48 months (range, 24-140 months). This study shows that in selected circumstances, irrigation, debridement, and retention of the components can result in low morbidity with high success rates.

Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection: A comparison-group study

Background: Two-stage reimplantation has proven to be highly successful in the treatment of patients with infection at the site of a total knee arthroplasty. However, up to 20 percent of patients have a recurrence of infection following this treatment. The purpose of our study was to determine whether aspiration of the affected joint and culture of the specimen, performed before reimplantation and after discontinuation of antibiotic therapy, would help to identify patients who might have a recurrent infection.Methods: We prospectively followed sixty-nine patients who were treated for a culture-proven deep infection at the site of a total knee arthroplasty. Group I consisted of thirty-five patients who were treated with removal of the prosthetic components and irrigation and débridement of the joint, followed by six weeks of antibiotic therapy and reimplantation of a prosthesis. Group II was composed of thirty-four patients who were treated with removal of the components and irrigation and débridement of the joint, six weeks of antibiotic therapy, and then repeat culture four weeks after the antibiotic course had ended. If the culture was negative, the patient was managed with a second-stage reimplantation of a prosthesis. If the culture was positive, the protocol was repeated, beginning with irrigation and débridement. The two groups were similar with regard to male-to-female ratio, age, preoperative Knee Society scores, time since primary surgery, types of infectious organisms, duration of symptoms, duration of follow-up, and number of previous revisions. All of the patients were evaluated clinically with use of the objective scoring system of the Knee Society and were followed with serial radiographs. Success was defined as no infection and a functional prosthesis, with a Knee Society score of at least 75 points at the last (thirty-six-month-minimum) follow-up evaluation.Results: Of the thirty-five patients in Group I, five (14 percent) had recurrence of infection. One of the patients was managed with a successful second-stage revision, three were managed with arthrodesis of the knee, and one continued dwith chronic antibiotic suppressive treatment. Of the thirty-four patients in Group II, three (9 percent) had a positive culture after the course of antibiotics. The protocol was repeated for all three, and they subsequently had a successful second revision. One other patient (3 percent) in Group II, who had a negative culture, had a recurrent infection and was eventually managed with arthrodesis of the knee.Conclusions: Prerevision cultures, grown after discontinuation of antibiotic treatment and before reimplantation of the components, helped to identify the patients with infection at the site of a total knee arthroplasty in whom the infection might recur. The performance of aspiration and cultures resulted in a substantial improvement in the clinical outcome.