Biological responses of human mesenchymal stem cells to titanium wear debris particles.

Wear debris-induced osteolysis is a major cause of orthopedic implant aseptic loosening, and various cell types, including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. We recently showed that mesenchymal stem/osteoprogenitor cells (MSCs) are another target, and that endocytosis of titanium (Ti) particles causes reduced MSC proliferation and osteogenic differentiation. Here we investigated the mechanistic aspects of the endocytosis-mediated responses of MSCs to Ti particulates. Dose-dependent effects were observed on cell viability, with doses >300 Ti particles/cell resulting in drastic cell death. To maintain cell viability and analyze particle-induced effects, doses <300 particles/cell were used. Increased production of interleukin-8 (IL-8), but not IL-6, was observed in treated MSCs, while levels of TGF-ß, IL-1ß, and TNF-α were undetectable in treated or control cells, suggesting MSCs as a likely major producer of IL-8 in the periprosthetic zone. Disruptions in cytoskeletal and adherens junction organization were also observed in Ti particles-treated MSCs. However, neither IL-8 and IL-6 treatment nor conditioned medium from Ti particle-treated MSCs failed to affect MSC osteogenic differentiation. Among other Ti particle-induced cytokines, only GM-CSF appeared to mimic the effects of reduced cell viability and osteogenesis. Taken together, these results strongly suggest that MSCs play both responder and initiator roles in mediating the osteolytic effects of the presence of wear debris particles in periprosthetic zones.

A prospective study of the nonoperative treatment of degenerative meniscus tears.

This prospective study was designed to evaluate a nonoperative-based treatment protocol for patients with the clinical diagnosis of a degenerative medial meniscus tear and to determine if a significant percent of patients with degenerative medial meniscus tears improve with nonoperative treatment and do not elect operative treatment. Twenty-six patients were followed for 37 months and evaluated clinically, radiographically, and with standardized, validated Modified Lysholm Knee Scoring System (MLKS) and Standardized Activities of Daily Living Scale of the Knee (SADL) questionnaires. Patients were initially treated with 4 weeks of nonsteroidal anti-inflammatory drugs. After 4 weeks, they were offered arthroscopic partial meniscectomy or continued nonoperative treatment. Forty-six percent of patients (12 of 26) declined operative treatment. The mean length of time between enrollment and surgery was 3 months (range, 1-13 months). Both groups improved significantly over baseline (P<.05). The initial and final SADL and initial MLKS scores of the 2 groups were not significantly different (P>.05). The final MLKS score of the operative treatment group was significantly greater than the nonoperative group (P=.04). Both the nonoperative and operative treatment groups improved significantly at 3-year follow-up. Forty-six percent of the patients received nonoperative treatment and improved to a functional level that allowed them to avoid surgery. Therefore, we recommend an initial course of nonoperative treatment for all patients with a clinical diagnosis of degenerative medial meniscus tears prior to considering surgery.

The effectiveness of self-adjustable custom and off-the-shelf bracing in the treatment of varus gonarthrosis.

BACKGROUND: A recent development in valgus-producing knee braces has been the adjustable "unloader" brace. The purpose of this study was to compare the effectiveness of off-the-shelf and custom-made patient-adjustable, valgus-producing knee unloader braces in relieving pain, reducing stiffness, and improving function and in reducing varus angulation and the peak adduction moments about the knee during gait and stair-stepping in patients with painful varus gonarthrosis of the knee. METHODS: Ten adult patients served as their own controls for the measurement of baseline values and then wore each of the two braces, one after the other, for four to five weeks in a random order. Pain, stiffness, and function were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index. Gait and stair-stepping were evaluated with a three-dimensional motion analysis system and multicomponent force platform. Full-length (hip, knee, and ankle) standing anteroposterior radiographs were used to determine alignment of the knee. RESULTS: Both braces significantly reduced pain and stiffness (p<0.05), with the custom brace reducing stiffness significantly more than the off-the-shelf brace (p=0.030). The custom brace significantly improved function (p=0.010) and reduced the peak knee adduction moments during gait (p=0.033) and stair-stepping (p=0.002) compared with baseline values and compared with the off-the-shelf brace (p=0.029 and p=0.027, respectively). The custom brace significantly reduced varus angulation of the knee by 1.5 degrees compared with baseline (p=0.001) and by 1.3 degrees compared with the off-the-shelf brace (p=0.009). The off-the-shelf brace did not significantly reduce the varus angle. CONCLUSIONS: We investigated only the short-term effects of custom and off-the-shelf patient-adjustable valgus-producing knee "unloader" braces and found that patients with varus gonarthrosis of the knee may benefit significantly with respect to pain relief and reduced stiffness from use of either brace. However, such patients may experience additional significant benefit in improved function and reduced stiffness, varus angulation, and medial compartment loading of the knee from use of the custom-made patient-adjustable brace.