Subchondral bone circulation in osteoarthritis of the human knee.

OBJECTIVE: The hypothesis of this study is that human subchondral bone exhibits abnormal patterns of perfusion in osteoarthritis (OA) that can be characterized by kinetic parameters of blood flow using dynamic contrast enhanced (DCE) MRI. DESIGN: Fifteen subjects with advanced OA of the knee and seven control subjects without OA were studied at 1.5 T with DCE-MRI. Region of interest (ROIs) analysis of pharmacokinetic perfusion parameters were used to examine initial uptake and washout of the contrast agent in the lateral tibial plateau. RESULTS: Arterial and venous perfusion kinetics were abnormal in subchondral OA bone compared to those of normal controls. Time-intensity curves (TIC) exhibited delayed contrast clearance in OA knees compared to normal. Quantitatively, changes were observed in the kinetic parameters, kep, Akep, and kel. The mean kep and Akep were reduced in OA, compared to normal bone, indicating a reduction of arterial inflow and delayed signal enhancement. The kel in OA bone was lower than in normal bone, the negative kel indicating a reduction in venous outflow. The area under the TIC (AUC60) indicated greater residual contrast in OA bone. CONCLUSIONS: DCE-MRI can quantitatively assess subchondral bone perfusion kinetics in human OA and identify heterogeneous regions of perfusion deficits. The results are consistent with venous stasis in OA, reflecting venous outflow obstruction, and can affect intraosseous pressure, reduce arterial inflow, reduce oxygen content, and may contribute to altered cell signaling in, and the pathophysiology of, OA.

Passage-dependent relationship between mesenchymal stem cell mobilization and chondrogenic potential.

OBJECTIVE: Galvanotaxis, the migratory response of cells in response to electrical stimulation, has been implicated in development and wound healing. The use of mesenchymal stem cells (MSCs) from the synovium (synovium-derived stem cells, SDSCs) has been investigated for repair strategies. Expansion of SDSCs is necessary to achieve clinically relevant cell numbers; however, the effects of culture passage on their subsequent cartilaginous extracellular matrix production are not well understood. METHODS: Over four passages of SDSCs, we measured the expression of cell surface markers (CD31, CD34, CD49c, CD73) and assessed their migratory potential in response to applied direct current (DC) electric field. Cells from each passage were also used to form micropellets to assess the degree of cartilage-like tissue formation. RESULTS: Expression of CD31, CD34, and CD49c remained constant throughout cell expansion; CD73 showed a transient increase through the first two passages. Correspondingly, we observed that early passage SDSCs exhibit anodal migration when subjected to applied DC electric field strength of 6 V/cm. By passage 3, CD73 expression significantly decreased; these cells exhibited cell migration toward the cathode, as previously observed for terminally differentiated chondrocytes. Only late passage cells (P4) were capable of developing cartilage-like tissue in micropellet culture. CONCLUSIONS: Our results show cell priming protocols carried out for four passages selectively differentiate stem cells to behave like chondrocytes, both in their motility response to applied electric field and their production of cartilaginous tissue.

Subchondral fluid dynamics in a model of osteoarthritis: use of dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: The hypothesis of this study is that changes in fluid dynamics in subchondral bone bear a functional relationship to bone remodeling and cartilage breakdown in osteoarthritis (OA). We have utilized dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to extract kinetic parameters of bone perfusion at various stages in the development of OA in the Dunkin-Hartley guinea pig. DESIGN: Animals of four different ages (6, 9, 12 and 15 months), representing various stages in the development of OA, were studied. All animals underwent DCE MRI and perfusion data were analyzed based on the Brix two-compartment pharmacokinetic model. Regions of interest were studied at the medial and lateral tibial plateaus and compared to histological-histochemical scores of articular cartilage and subchondral bone plate thickness. RESULTS: A decrease in perfusion as well as outflow obstruction was observed in animals between 6 and 9 months of age, only in the medial tibial plateau subchondral bone. The eventual cartilage and bone lesions of OA occurred also in the medial tibia. Changes in perfusion occurred in the lateral tibia but not until OA lesions were established. Kinetic parameters of inflow were unchanged in both the medial and lateral plateaus. CONCLUSIONS: DCE MRI can be used to extract kinetic information on bone perfusion in an animal model of OA. The signal enhancement in subchondral bone temporally precedes and spatially localizes at the same site of the eventual bone and cartilage lesions. Time-intensity curves suggest outflow obstruction as an underlying mechanism.

Stimulation of experimental endochondral ossification by low-energy pulsing electromagnetic fields.

Pulsed electromagnetic fields (PEMFs) of certain configuration have been shown to be effective clinically in promoting the healing of fracture nonunions and are believed to enhance calcification of extracellular matrix. In vitro studies have suggested that PEMFs may also have the effect of modifying the extracellular matrix by promoting the synthesis of matrix molecules. This study examines the effect of one PEMF upon the extracellular matrix and calcification of endochondral ossification in vivo. The synthesis of cartilage molecules is enhanced by PEMF, and subsequent endochondral calcification is stimulated. Histomorphometric studies indicate that the maturation of bone trabeculae is also promoted by PEMF stimulation. These results indicate that a specific PEMF can change the composition of cartilage extracellular matrix in vivo and raises the possibility that the effects on other processes of endochondral ossification (e.g., fracture healing and growth plates) may occur through a similar mechanism.

Acceleration of experimental endochondral ossification by biophysical stimulation of the progenitor cell pool.

Endochondral ossification can be modulated by a number of biochemical and biophysical stimuli. This study uses the experimental model of decalcified bone matrix-induced endochondral ossification to examine the effect of one biophysical stimulus, an electromagnetic field, on chondrogenesis, calcification, and osteogenesis. A temporal acceleration and quantitative increase in sulfate incorporation, glycosaminoglycan content, and calcification suggests that the stimulation of endochondral ossification is due to an increase in extracellular matrix synthesis. The locus of that stimulation is identified in the mesenchymal stage of endochondral bone development, and stimulation at this stage is essential for accelerated bone formation. The data suggest that enhanced differentiation of mesenchymal stem cells present at this stage is most likely responsible for the increase in extracellular matrix synthesis and bone maturation.

Laterally comminuted fracture-dislocation of the ankle.

Laterally comminuted fracture-dislocations of the ankle are highly unstable injuries in which anatomical reduction of the talus and restoration of fibular length and rotation are difficult. To our knowledge, no descriptions of the fracture pattern of these injuries and the surgical technique for treating them are available, and surgical results with this fracture have been disappointing. Discontinuity of the fibula as a result of comminution makes accurate assessment of fibular length and rotation impossible if the fibula is reduced first. Anatomical stabilization of the talus beneath the tibia is achieved by reduction and fixation of the medial malleolus. The fibular malleolus is then anatomically positioned in the lateral articular facet of the talus and fixed in this position. The osseous discontinuity of the fibula is grafted with bone. Clinical and radiographic results of the technique were highly satisfactory after a mean length of follow-up of thirty-four months.

Survival analysis of hips treated with core decompression or vascularized fibular grafting because of avascular necrosis.

Avascular necrosis of the femoral head is a multifaceted process that leads to articular incongruity and subsequent osteoarthrosis of the joint. Clinicians concur that primary treatment should focus on preservation of the natural surface of the joint; however, there has not been a consensus on how best to accomplish this. While a number of therapeutic interventions have been reported, the efficacy has varied markedly and there have been few statistical comparisons. The purpose of the current study was to use statistical analysis to compare the results of two widely used procedures, vascularized fibular grafting (614 hips; 480 patients) and core decompression (ninety-eight hips; seventy-two patients), for the treatment of avascular necrosis. The patients were stratified according to age and the stage of disease, and a survival analysis was performed with total hip arthroplasty as the end point for failure. None of the eleven hips that had Ficat stage-I disease needed a total joint replacement after being treated with either regimen. Analysis of the hips that had stage-II disease revealed rates of survival, at fifty months, of 65 per cent (twenty-eight of forty-three hips) after core decompression and 89 per cent (ninety-nine of 111 hips) after vascularized fibular grafting. For the hips that had Ficat stage-III disease, the rates of survival at fifty months were 21 per cent (ten of forty-seven hips) after core decompression and 81 per cent (405 of 500 hips) after vascularized fibular grafting. Among the hips that had Ficat stage-II or III disease, the rate of eventual total joint arthroplasty after vascularized fibular grafting was significantly lower than that after core decompression (p < 0.0001). The results indicate that the increased morbidity associated with vascularized fibular grafting is justified by the associated delay in or prevention of articular collapse in hips that have stage-II or III disease.

Compression ultrasonography for the detection of deep venous thrombosis in patients who have a fracture of the hip. A prospective study.

The effectiveness of compression ultrasonography in the detection of femoral and popliteal venous thrombosis was determined in a prospective trial over a period of seven months. Forty-two patients who had an isolated intertrochanteric or femoral neck fracture participated, and forty of these patients completed the study. The average age of the patients was 81.6 years. Venography was the standard with which all ultrasonic studies were compared. A total of 112 ultrasonic studies were performed. The incidence of major venous thrombosis, as detected by venography, was 12.5 per cent. All patients were clinically asymptomatic. The compression ultrasonic technique had an accuracy of 97 per cent, a sensitivity of 100 per cent, and a specificity of 97 per cent. Compression ultrasonography appears to be a very effective technique for diagnosing venous thrombosis in patients who have a fracture of the hip. It is safe, well accepted by both patients and staff, and simply and quickly performed, and it carries no inherent risks. It also can be readily repeated, making it ideal for monitoring high-risk patients.

Hospital-acquired Aspergillus flavus infection in a surgical wound: a case report.

This report describes a case of hospitalacquired Aspergillus flavus subcutaneous inflammation. The infection developed in a surgical wound and was cured by repeated debridement and amphotericin B therapy.The rare occurrence of this inflammation is noted. Pressure and necrosis caused by casts may provide a favorable environment for the growth of Aspergillus organisms.

Electrical stimulation of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head in the adult is a progressive condition that, if untreated, usually results in femoral head collapse and secondary osteoarthritis. The experimental application of electrical and electromagnetic fields has been shown to favorably affect a number of biological processes pertinent to osteonecrosis of the femoral head and has led to several clinical trials. The condition has been treated by the application of electrical fields invasively by the surgical implantation of electrodes within the femoral head and noninvasively by capacitative or inductive coupling. This review describes results in osteonecrosis of the femoral head with these therapeutic techniques. Stimulation by means of inductive coupling with pulsed magnetic fields seems to be the most promising technique studied so far, but the optimal signal characteristics and device design are not yet known.

Noninvasive methods of measuring bone blood perfusion.

Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability within the bone was performed with small and macromolecular contrast media, using dynamic contrast-enhanced magnetic resonance imaging in models of osteoarthritis and the femoral head. Bone blood flow and remodeling was estimated using (18)F-Fluoride positron emission tomography in fracture healing and osteoarthritis. Multimodality assessment of bone blood flow, permeability, and remodeling by using noninvasive imaging techniques may provide information essential in monitoring subsequent rates of healing and response to treatment as well as identifying candidates for additional therapeutic or surgical interventions.

Supracondylar fracture of the femur after total knee arthroplasty.

In a review of 250 total knee arthroplasties, five patients with rheumatoid arthritis incurred supracondylar fractures of the femur. These fractures may be associated with a surgical encroachment of the anterior femoral cortex during resection of the patellar trochlea. Forty-two percent of patients with excessively deep resections of the patellar trochlea suffered fractures. No fractures occurred in patients without encroachment of the anterior femoral cortex. All patients with fractures also had significant osteoporosis, which may have predisposed them to fracture. A resection of the patellar trochlea that is made too deeply would interrupt the transmission of stresses through the cancellous bony trabeculae of the anterior femoral cortex and could predispose to fracture.

Therapeutic effects of electromagnetic fields in the stimulation of connective tissue repair.

The therapeutic effects of electric and magnetic fields have been studied largely for their promotion of connective tissue repair. The most widely studied application concerns bone repair and deals with acceleration of the healing of fresh fractures, delayed and non-unions, incorporation of bone grafts, osteoporosis, and osteonecrosis. More recently the effects of these fields upon the repair of cartilage and soft fibrous tissues have been described. In all these experimental systems and clinical applications an acceleration of extracellular matrix synthesis and tissue healing has been observed. A degree of specificity, in terms of the parameters of applied energy and biological response, is hypothesized.

Influence of electromagnetic fields on endochondral bone formation.

Endochondral ossification is a basic physiological process in limb development and is central to bone repair and linear growth. Factors which regulate endochondral ossification include several biophysical and biochemical agents and are of interest from clinical and biological perspectives. One of these agents, electric stimulation, has been shown to result in enhanced synthesis of extracellular matrix, calcification, and bone formation in a number of experimental systems and is the subject of this review. The effects of electric stimulation have been studied in embryonic limb rudiments, growth plates, and experimental endochondral ossification induced with decalcified bone matrix and, in all these models, endochondral ossification has been enhanced. It is not known definitively whether electric fields stimulate cell differentiation or modulate an increased number of molecules synthesized by committed cell population and this is a fertile area of current study.