Roger N. Levy

Cathepsin K Is a Critical Protease in Synovial Fibroblast-Mediated Collagen Degradation

Synovial fibroblasts (SFs) play a critical role in the pathogenesis of rheumatoid arthritis (RA) and are directly involved in joint destruction. Both SF-resident matrix metalloproteases and cathepsins have been implicated in cartilage degradation although their identities and individual contributions remain unclear. The aims of this study were to investigate the expression of cathepsin K in SFs, the correlation between cathepsin K expression and disease severity, and the contribution of cathepsin K to fibroblast-mediated collagen degradation. Immunostaining of joint specimens of 21 patients revealed high expression of cathepsin K in SFs in the synovial lining and the stroma of synovial villi, and to a lesser extent in CD68-positive cells of the synovial lining. Cathepsin K-positive SFs were consistently observed at sites of cartilage and bone degradation. Expression levels of cathepsin K in the sublining and vascularized areas of inflamed synovia showed a highly significant negative correlation with results derived from the Hannover Functional Capacity Questionnaire (r = 0.78, P = 0.003; and r = 0.70, P = 0.012, respectively) as a measure of the severity of RA in individual patients. For comparison, there was no correlation between Hannover Functional Capacity Questionnaire and cathepsin S whose expression is limited to CD-68-positive macrophage-like synoviocytes. The expression of cathepsin K was also demonstrated in primary cell cultures of RA-SFs. Co-cultures of SFs on cartilage disks revealed the ability of fibroblast-like cells to phagocytose collagen fibrils whose intralysosomal hydrolysis was prevented in the presence of a potent cathepsin K inhibitor but not by an inhibitor effective against cathepsins L, B, and S. The selective and critical role of cathepsin K in articular cartilage and subchondral bone erosion was further corroborated by the finding that cathepsin K has a potent aggrecan-degrading activity and that cathepsin K-generated aggrecan cleavage products specifically potentiate the collagenolytic activity of cathepsin K toward type I and II collagens. This study demonstrates for the first time a critical role of cathepsin K in cartilage degradation by SFs in RA that is comparable to its well-known activity in osteoclasts.

Outcome and long-term results following total hip replacement in elderly patients

The authors reviewed the preoperative and postoperative charts and radiographs of 100 patients who were at least 80 years old when they underwent total hip arthroplasty. Seventy-six of these patients were available for further reexamination and evaluation. The average patient age was 85.2 years old (range, 80-97 years). The average followup period was 59.4 months (range, 26-146 months). The female to male ratio was 4 to 1. Osteoarthritis was the most common diagnosis. Hospital stay ranged from 12 to 39 days. Preoperative Charnley pain and walking scores averaged 5.1 points of a possible 12 points, and postoperative scores averaged 10.6 points. Eighty-eight percent of patients remained community walkers, and 60% used a cane. Four percent of the patients had 1 dislocation. There were no instances of mechanical loosening and no deaths. Subjective satisfaction was high. The level of independent living was maintained in 96% of patients at long-term followup. A satisfactory and cost-effective health outcome can be anticipated after total hip arthroplasty in octogenarian and nonagenarian patients.

Surgical management of metastatic disease of bone at the hip.

Concordant advances in cancer chemotherapy, radiotherapy, and surgical technique have been of apparent benefit to many cancer patients suffering from skeletal involvement at the hip. Consideration of the effects of underlying disease and prior treatment must be evaluated prior to developing a surgical plan. Acetabular involvement can be treated by either conventional or augmented total hip arthroplasty using protrusio rings and acetabular meshes, depending upon minor or major degrees of tumor destruction. Girdlestone resection arthroplasty for massive degrees of acetabular involvement yields only modest results. Femoral neck fractures can be treated by endoprosthetic replacement. However, the association of acetabular disease should be considered, and if present, total hip arthroplasty should be performed. Intertrochanteric fractures can be stabilized with the use of a stout tubeplate nail device plus cement. Subtrochanteric fractures can be stabilized with a Zickel nail device plus cement. The goals of treatment are to relieve pain and restore function by using a device with an anticipated fatigue life which should exceed the patients life expectancy.

Inflammatory bowel disease related osteonecrosis: report of a large series with a review of the literature

Background : Osteonecrosis is a major complication of inflammatory bowel disease usually associated with steroid use. There are few large series available detailing the specifics of affected patients.

Long-term results of total joint arthroplasty in elderly patients who are frail.

Many studies of joint replacement in the aged population include a wide spectrum of geriatric patients ranging from relative healthy and otherwise vigorous younger-elderly to small numbers of much older patients with many comorbid problems. To clarify the latter patient subset we assessed the results of total hip and knee arthroplasties done on a group of frail elderly patients. We retrospectively reviewed the preoperative and postoperative charts and radiographs of 130 patients who were at least 80 years when they had a total joint arthroplasty. One hundred arthroplasties (70 hips, 30 knees) were done. On a subjective grading scale, 95% of the patients were very satisfied, 5% reported satisfactory outcomes and no patients considered their results poor. After surgery, 90% of the patients became community walkers without assistance. The level of independent living was maintained in 97% of patients at long-term followup. Causes of morbidity included two infections, one dislocation, and one leg-length discrepancy. This study specifically addresses the outcomes of total joint replacement in elderly patients who are frail. We show that satisfactory and cost-effective health outcomes can be anticipated after total joint arthroplasties in this age group.

Metastatic Disease of Bone in Orthopedic Surgery

Metastases to the skeleton are the most common of all bone neoplasms. More than 80% of bone metastases are from the breast, prostate, lung and kidney. Approximately 15%-20% of patients with metastatic disease will develop detectable skeletal metastases during their life. Autopsy studies show that occult metastases to the skeleton probably approaches 7 0 % ~ ~ ~ Metastases to bone commonly are associated with pain. Pathologic fracture will occur in approximately 10%15% of patients with radiographic evidence of skeletal metastases. In general, lytic lesions are more probable to fracture than are blastic lesions. Metastatic lesions in carcinoma of the breast may be lytic, mixed, or predominantly blastic. Purely lytic metastases are usually associated with carcinoma of the lung, kidney, breast, thyroid, gastrointestinal tract and neuroblastoma, in order of decreasing

Giant cell reaction of small bones.

A radiographically nonspecific lytic lesion in the middle phalanx of the index finger with microscopic evidence of a benign fibrous stroma with giant cells and osteoid was investigated in an 18-year-old man. Giant cell reaction is a rare, benign lesion of the small bones of the hands and feet. Trauma as the cause of a giant cell lesion poses an interesting question.

Does cost containment create conflict in the care of the elderly patient

Ethical aspects of care of geriatric patients with orthopaedic disorders include patient autonomy, beneficence, and nonmaleficence. Advance directives and surrogate decision-makers are required if the patient has lost decisional capacity. Investor-owned health plans have captured the major share of the United States medical market, but have been shown to deliver lower quality of care than competing methods. A deeply imbedded fear of a government-run health plan with good intentions expressed as bad policy exists. Ageism is one example of how ethical principles may be trampled. The orthopaedic surgeon has a responsibility to maintain and fight for these ethical standards.

Lepromatous Leprosy Mimicking Systemic Lupus Erythematosus

Keywords leprosy.anthiphospholipidantibodyCase PresentationA 29-year-old Brazilian woman was referred for manage-ment of systemic lupus erythematosus (SLE) withantiphospholipid antibodies (aPL). Her symptoms were1 year of intermittent fever and diffuse, tender, erythe-matosus, and nodular rash that began during her firstpregnancy. She was treated with short course of low-dose corticosteroids, with resolution; however, she suf-fered an embryonic loss at 7 weeks. Six months prior toadmission, she had recurrence of the nodular rash withnew onset arthralgia; a skin biopsy showed panniculitis.Tests done at that time showed lupus anticoagulant(LA), anticardiolipin antibody (aCL) IgM >150 U (nor-mal 0–7 U), anti-β

The location of the level of femoral neck transection for prosthetic hip arthroplasty.

The proper level of transection of the femoral neck for hip arthroplasty can be ascertained by using the proximal tip of the intact greater trochanter as a reference point. A transverse line projected medially from this point will cross the true level of the center of rotation of the femoral head for that hip. Placement of a trial prosthesis in accordance with this level will locate the point at which the femoral neck should be cut. By placing the femoral component so that its center of rotation is bisected by the same line, the level of the calcar flange can be marked on the neck of the femur. This is the level at which the femoral neck should be cut.