Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

Towards a standard in assessment of bone cutting for total knee replacement.

Arthroplasty outcome is influenced by the 'quality' of bone preparation for implant insertion. Surgeons face increasing choices of technique and instrumentation, yet clinical scoring methods assess the overall outcome and patient satisfaction but not the bone cuts directly. 'Quality management' of bone reshaping is needed to evaluate different bone cutting methods and computer assisted orthopaedic surgery (CAOS) systems. Analyses and experiments in this study were formulated for measurement and computation of four quantitative characteristics of bone preparation 'quality' and produced a highly condensed index for each. These represented (a) surface finish of cuts, (b) implant fit/looseness possible with the cut shape, (c) implant location/misalignment, and (d) accuracy of individual planar cuts. Assessment of synthetic bone cuts verified the robustness of the method for wide application in arthroplasty intraoperatively, in vitro and for comparing navigation systems.

Adherence of Staphylococcus epidermidis to biomaterials is augmented by PIA.

Staphylococcus epidermidis is the most common cause of orthopaedic prosthetic device infections. Polysaccharide intercellular adhesin (PIA) is important in the pathogenesis of intravascular catheter-associated infection, and has an essential role in cellular aggregation and biofilm formation. However, the role of PIA in orthopaedic infections is less well understood. We used genetically defined strains of S. epidermidis in an in vitro adherence assay to assess the importance of PIA in the adherence to various orthopaedic biomaterials. On all biomaterials tested (zirconia, ultra-high molecular weight polyethylene, polymethylmethacrylate, cobalt chromium, titanium, stainless steel, and silastic), PIA-positive S. epidermidis 1457 exhibited greater levels of adherence thanS. epidermidis 1457 M10, an isogenic icaA Tn917 mutant. PIA appears to play a critical role in the adherence of S. epidermidis to orthopaedic biomaterials, and may serve as an important virulence determinant in orthopaedic prosthetic device infections.

Ceramic-on-polyethylene bearing surfaces in total hip arthroplasty. Seventeen to twenty-one-year results.

BACKGROUND: Polyethylene wear debris, and the resulting inflammatory response leading to osteolysis and loosening, is the primary mode of failure limiting the longevity of total hip replacements. Alternative bearing surfaces, including ceramic-on-polyethylene, have been investigated in an effort to decrease the amount of polyethylene wear debris. The purpose of this study was to evaluate the seventeen to twenty-one-year results of the use of ceramic-on-polyethylene total hip prostheses. METHODS: Sixty-four total hip prostheses were implanted with cement, by one surgeon, in fifty-six patients from 1978 to 1981. The average age at the index arthroplasty was sixty-nine years (range, fifty-one to eighty-four years). The components consisted of a cemented Charnley-Müller stem with a 32-mm modular alumina femoral head and a cemented all-polyethylene acetabular component. All patients who retained the index prosthesis were assessed clinically with use of Harris hip scores and were evaluated radiographically at the time of the latest follow-up. RESULTS: At the time of this latest follow-up, of the original sixty-four implants, eighteen (28%) were still in place and five (8%) had been revised. The remaining forty-one implants were in patients who had died and were functioning well until the patient's death. No patient was lost to follow-up. Of the eighteen hips with an intact prosthesis in the surviving patients, seven had an excellent clinical result; nine, a good result; and two, a fair result. One asymptomatic hip had definite radiographic evidence of femoral loosening. No hip had definite signs of acetabular loosening or evidence of osteolysis. Survivorship analysis revealed that the probability of survival of the prostheses without revision was 95% at five years, 95% at ten years, 89% at fifteen years, and 79% at twenty years. The mean linear and volumetric polyethylene wear rates were 0.034 mm/yr and 28 mm(3)/yr, respectively. There were no fractures of the ceramic heads. CONCLUSIONS: Outstanding long-term clinical and radiographic results were attained despite the use of what are now considered substandard techniques (an inferior stem design, a 32-mm head, and first-generation cementing techniques). The wear rates in this study are lower than previously reported metal-on-polyethylene wear rates and are consistent with the lowest reported in vivo ceramic-on-polyethylene wear rates. These findings support the consideration of ceramic-on-polyethylene bearing surfaces in total hip arthroplasty.

Demineralized bone matrix as a biological scaffold for bone repair.

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.

Emerging multiresistant strains: recommended precautions in the emergency room and surgical setting.

The current success in treatment of surgical site infections may be jeopardized by the continued emergence of antibiotic resistance in bacteria common to these infections. The effectiveness of vancomycin against methicillin-resistant staphylococci may decrease as more cases of VISA emerge. No currently available antimicrobial is consistently effective against certain strains of VRE and the potential emergence of VRSA. Orthopaedic surgeons soon may be in the undesirable position of having to eradicate organisms resistant to all available antibiotics. Several new antibiotics show promising activity and may be useful against these multidrug-resistant bacteria. However, as the history of bacterial resistance has taught us, it likely only will be a matter of time until these organisms adapt mechanisms of resistance to these new drugs. The key then lies, as it always has, in preventive measures. Surgeons, and all physicians, must adhere to the precautionary guidelines recently set forth by the CDC and HICPAC. Chief among these guidelines is the elimination of inappropriate antibiotic usage, especially inappropriate vancomycin use.

Preoperative autologous donation for total joint arthroplasty. An analysis of risk factors for allogenic transfusion.

BACKGROUND: While autologous blood is commonly predonated to provide replacement of blood lost in orthopaedic procedures, few studies of patients managed with total joint replacement have addressed the problem of which patients are likely to benefit from an autologous blood-donation program. METHODS: A retrospective analysis of 489 consecutive patients who had had a total joint arthroplasty was performed to identify the risk factors for allogenic transfusion and to further define the indications for preoperative autologous blood donation. The operations included 247 total knee replacements (157 unilateral primary, thirty-two revision, and twenty-nine one-stage bilateral primary procedures) and 271 total hip replacements (163 primary and 108 revision procedures). Fifty-four percent (264) of the 489 patients donated a total of 527 units of blood (average, 2.0 units per patient) preoperatively. RESULTS: One hundred and ninety-one patients (39 percent) required a transfusion of autologous blood or allogenic blood, or both. One hundred and thirty-one patients (27 percent) received autologous blood, and eighty-two patients (17 percent) received a transfusion of allogenic blood; twenty-two patients (4 percent) received both autologous and allogenic blood. Neither form of transfusion caused serious complications. Fifty-six percent (295) of the 527 units of autologous blood were discarded. Autologous donation significantly decreased the requirements for allogenic transfusion (relative risk, 0.1; p<0.0001). It also caused the level of hemoglobin to decrease an average of 12.2 grams per liter from the time before donation to the time before the operation (p<0.0001). Factors that increased the risk for allogenic transfusion were a revision knee or hip procedure or a one-stage bilateral primary knee replacement (relative risk, 5.7; p<0.0001), an initial hemoglobin level of less than 130 grams per liter (relative risk, 5.6; p<0.0001), and an age of sixty-five years or older (relative risk, 2.8; p = 0.02). None of the sixty-seven patients who had a primary knee or hip arthroplasty and an initial hemoglobin level of 150 grams per liter or more required an allogenic transfusion. In addition, none of the sixty-three patients who had a primary arthroplasty, an initial hemoglobin level of between 130 and less than 150 grams per liter, and an age of less than sixty-five years required an allogenic transfusion. Eighty-three percent (115) of the 138 autologous units donated by the seventy patients in these two groups were discarded. These wasted units accounted for 39 percent of the 295 discarded units for the entire study sample. CONCLUSIONS: The efficiency of collection of autologous blood can be improved by identifying patients who have a very low risk of transfusion according to the type of arthroplasty, the initial level of hemoglobin, and age. Patients who have an initial hemoglobin level of at least 150 grams per liter or an initial hemoglobin level of between 130 and 150 grams per liter and an age of less than sixty-five years have a minimal risk of needing a transfusion during or after a primary total joint replacement. These patients should be apprised of their low risk so that they can make an informed decision regarding preoperative autologous donation.

Emerging antibiotic-resistant bacteria. Their treatment in total joint arthroplasty.

Successful treatment of an infected total joint arthroplasty can be achieved in approximately 90% of cases. This outcome may be jeopardized by the emergence of antibiotic resistance in bacteria common to these infections. Staphylococci are the most frequently isolated bacteria in total joint infections, and the prevalence of antibiotic resistance in these organisms among all nosocomial and community-acquired infections has been increasing. As many as 46.7% of Staphylococcus aureus strains and 85.7% of coagulase-negative staphylococci strains are methicillin-resistant. Enterococci also are commonly isolated from infected total joint arthroplasties. The prevalence of vancomycin-resistant enterococci among all enterococci strains is estimated at 23%. As the prevalence of these resistant bacteria continues to increase among all infections, it is anticipated that they will be encountered more regularly in total joint infections. Knowledge of the mechanisms of resistance of these bacteria and currently available and newly developed antimicrobials is key to preventing the expansion of antimicrobial resistance and ensuring the future successful treatment of total joint infections.

Repair of segmental bone defects in the rat: an experimental model of human fracture healing.

Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study, the relevance of a recently developed segmental defect model in rat fibula to human fracture healing was investigated by evaluating temporal progression of rigidity of the fibula, mineral content of the repair site, and histological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DBM) by inserting it over the cut ends of the fibula. The temporal increase in rigidity of the healing fibula demonstrated a pattern similar to biomechanical healing curves measured in human fracture healing. This pattern was characterized by a short phase of rapidly rising rigidity during weeks 4-7 after surgery, associated with a sharp increase in the mineral content of the repair tissue. This was preceded by a phase of nearly zero rigidity and followed by a phase of slow rate of increase approaching a plateau. Histologically, chondroblastic and osteoblastic blastema originating from extraskeletal and subperiosteal (near fibula-graft junction) regions, infiltrated the DBM graft during the first 2 weeks. The DBM graft assumed the role of a "bridging callus." By weeks 6-8, most of the DBM was converted to new woven and trabecular bone with maximal osteoblastic activity and minimal endochondral ossification. Medullary callus formation started with direct new bone formation adjacent to the cortical and endosteal surfaces in the defect and undifferentiated cells in the center of the defect at 3 weeks. The usual bone repair process in rodents was altered by the presence of the DBM graft to recapitulate the sequential stages of human fracture healing, including the formation of a medullary callus, union with woven and lamellar bone, and recreation of the medullary canal.

Molecular diagnostics for the detection of musculoskeletal infection.

The last decade has seen the crossover of basic molecular research techniques toward clinical application. The use of molecular diagnostics originally was driven by the desire to identify unculturable or fastidious pathogens. Success in this setting has led to new applications aimed at identifying organisms involved in musculoskeletal infection. Recently, polymerase chain reaction techniques have been investigated as to their efficacy in diagnosing septic arthritis and periprosthetic infection. This paper will offer an introduction to molecular diagnostics, a brief review of several techniques, and update their status in the diagnosis of musculoskeletal infection.

Femoral preparation in cemented total hip arthroplasty: reaming or broaching?

Surgical techniques continue to be refined to improve the results of primary cemented total hip arthroplasty. Although there has been much research in the areas of cementation and implant design, little work has specifically addressed how bone preparation can be optimized on the femoral side. On the basis of available scientific data, it appears that the broach-only system has several potential advantages over the traditional ream-and-broach technique. Broaching is usually faster, leaves behind more bone stock, and may improve both microinterlock and macrointerlock. Additionally, the excess bone resulting from broaching without reaming does not seem to compromise fixation at the bone-cement interface. Such differences may become even more important as the indications for cemented hip arthroplasty broaden to include increasingly younger and more active patients, because revision in these individuals is likely. In most cases, reaming is probably counterproductive, although it may be advantageous when used to open the femoral canal, to prevent varus stem orientation, and to manage sclerosis or deformity of bone due to a preexisting hip disorder or the presence of internal fixation devices. Regardless of which method is chosen, good bone surface cleansing and cement penetration remain paramount. More studies comparing reamed and nonreamed preparation are necessary to resolve this controversial issue definitively.

A femoral component inserted without cement in total hip arthroplasty. A study of the Tri-Lock component with an average ten-year duration of follow-up.

Seventy-four total hip arthroplasties in sixty-six patients were performed, between 1983 and 1986, with use of a Tri-Lock femoral component inserted without cement. This tapered cobalt-chromium component has a fixed head and a circumferential proximal porous coating. Follow-up was conducted with use of a questionnaire, physical examination, and radiographic analysis. At the time of the latest follow-up, fifteen patients (eighteen hips) had died, three patients (four hips) had been lost to follow-up, and one patient (one hip) had refused to participate in the follow-up study; however, the status of fifteen hips at the time of death could be verified. Thus, clinical follow-up data were available for sixty-six of the original seventy-four hips. The average age at the time of the operation was sixty-two years (range, seventeen to eighty-four years), and the average interval between the operation and the latest follow-up evaluation was 10.0 years (range, 8.3 to 11.6 years). The Harris hip score was determined for forty-three hips (forty-one patients) in which the prosthesis was in situ at the time of the latest follow-up. The score was good for thirteen hips and excellent for twenty-eight, so the rate of clinical success was 95 per cent. Two patients had a fair result. One of them had persistent pain and the other had limited motion, but neither had radiographic evidence of loosening of the femoral or acetabular component. All forty-one patients were satisfied with the result. The probability (with standard error) of survival of the femoral component at ten years, with revision as the end point, was 0.95 +/- 0.03. The rate of revision of the femoral component because of aseptic loosening was one (2 per cent) of sixty-six. The overall rate of aseptic loosening of the femoral component in the hips that were followed radiographically was two (4 per cent) of forty-seven. Only one (2 per cent) of the forty-seven acetabular cups had evidence of aseptic loosening. There was no radiographic evidence of distal osteolysis around the prostheses that were well fixed. Proximal osteolysis was present in five (11 per cent) of forty-seven hips, but none of the lesions compromised the stability of the prosthesis or the bone and there were no associated fractures. At an average of ten years postoperatively, the Tri-Lock femoral component functioned well overall and patient satisfaction was high.

Preoperative physical therapy in primary total knee arthroplasty.

In order to evaluate the efficacy of preoperative physical therapy for patients undergoing elective primary total knee arthroplasty, 10 patients completed 6 weeks of physical therapy before surgery (PT group). Ten patients served as controls (C group). Subjects were tested at baseline (PT only), before surgery, 6 weeks after surgery, and 3 months after surgery using the Hospital for Special Surgery knee rating scale, range of motion, thigh circumference, walking speed, Cybex II isokinetic knee flexion, and extension testing, and computed tomography scanning for cross-sectional muscle area. Hospital stay and need for physical therapy after inpatient rehabilitation were also compared. Physical therapy produced modest gains in isokinetic flexion strength in these severely arthritic knees but no difference in extension strength. The decrease in isokinetic strength after surgery was not affected by preoperative physical therapy. Muscle area did not decrease significantly for the PT group, but it did decrease for the C group after surgery. While postoperative strength differences could not be demonstrated, preoperative physical therapy preserved thigh muscle area after surgery. The clinical significance of this finding is uncertain. Consequently, this study failed to support the routine use of preoperative physical therapy in knee replacement surgery.

Arthrodesis of the knee with a modular titanium intramedullary nail.

We retrospectively studied the results of arthrodesis of the knee with a modular titanium intramedullary nail that couples at the knee. The study group consisted of thirteen patients who had a malignant tumor around the knee, five who had failure of a total knee arthroplasty, and three who had a locally destructive benign tumor about the knee. All of the patients were followed for a minimum of two years. Through a single incision at the knee, one nail was inserted retrograde into the femur and the other, antegrade into the tibia; the two nails were joined at the level of the knee by a conical couple and were secured with locking screws. The diameters of the nails were different, to accommodate the dissimilar sizes of the tibial and femoral intramedullary canals. A solid osseous fusion was achieved in nineteen (90 per cent) of the twenty-one patients (sixteen who had had resection of a tumor and three who had had a failed arthroplasty), at an average of 8.4 months (range, three to nineteen months) after the operation. One patient had a delayed union, but fusion was achieved after additional bone-grafting. Of the sixteen patients who were available for clinical and radiographic evaluation at the time of the study, fifteen were satisfied with the over-all outcome and thirteen had either less pain or the same amount of pain as they had had preoperatively. There were no mechanical failures of the implant and no recurrences of tumor. Complications occurred in eight (38 per cent) of the twenty-one patients: three patients had a stress fracture, three had a peroneal nerve palsy (one of which was transient), one had a superficial wound infection, and one had reflex sympathetic dystrophy.

The role of a composite, demineralized bone matrix and bone marrow in the treatment of osseous defects.

The efficacy of demineralized bone matrix (DBM) used alone and with bone marrow as a graft material in the treatment of osseous defects was evaluated in 48 patients. Of these 48 patients, 39 were available to follow up and review. Follow up averaged 19 months for all patients. In the entire series, 30 of 39 patients demonstrated osseous union for a 77% success rate. Patients with fracture nonunion represented the most recalcitrant group clinically, with union achieved in only 61% of these cases. Overall, the 39 patients grafted with DBM demonstrated healing that was comparable to results achieved with standard iliac crest bone graft. The results indicate the DBM and marrow composite grafting is a suitable alternative to autologous iliac crest bone graft for use in certain clinical situations, such as bone defects in children, comminuted fractures with associated bone loss, nonunited fractures, or to augment an intended arthrodesis site.

Evolution of the quadriceps snip.

Between May 1990 and December 1992, the quadriceps snip was used to assist in the surgical exposure of the knee in 16 patients (4 women and 12 men) who underwent knee surgery at the average age of 65 years (range, 50-73 years). The original diagnoses included osteoarthritis (12 patients), traumatic arthritis (2 patients), rheumatoid arthritis (1 patient), and psoriatic arthritis (1 patient). The surgical exposure was done in the treatment of aseptic loosening of a total knee prosthesis in 8 patients, septic loosening in 2 patients, and primary knee arthroplasty in 6 patients with fibrous ankylosis. Using the Hospital for Special Surgery Scoring System, the authors rated the knees of 10 patients as excellent and those of 6 patients as good at postoperative evaluation. The range of motion was improved in all knees by an average of 30 degrees. Cybex testing revealed significant weakness of the knee in extension when compared with the contralateral normal side at test speeds of 60 degrees and 180 degrees per second but no difference compared with the opposite knee that had been replaced. In the authors' experience, the surgical technique of a quadriceps snip has been safe and simple, has not required special equipment, and postoperatively the patient's physical therapy has not had to be altered. Clinically, the quadriceps strength was very good, although weaker than that of a contralateral normal leg when measured by Cybex testing.

Acetabular fractures.

Acetabular fractures are not uncommon injuries of the pelvis. They are most frequently associated with high energy trauma such as that seen in a motor vehicle accident. Management of patients with acetabular fractures includes careful attention to ATLS (advanced Trauma Life Support) protocols and delayed operative treatment of the acetabular fractures. Diagnostic evaluation with plain radiography and CT is used to plan the treatment approach. Treatment includes not only the recognition of the fracture but avoidance of early and late complications. Emergent treatment includes closed reduction of associated hip dislocations followed by skeletal traction. Delayed reconstruction at four days after the injury decreases intraoperative blood loss by allowing retroperitoneal hemorrhage to subside. Final outcome after acetabular trauma depends not only on the reconstruction of the fracture, but the avoidance of complications. Acetabular fractures are becoming an increasingly common orthopedic injury. Fractures of the acetabulum (or hip socket) are most commonly seen after motor vehicle accidents. Young patients (18 to 30 years old) are typically affected. A frequent mechanism of injury is a direct blow to the anterior aspect of the knee with the hip flexed such as a dashboard injury in an automobile accident. Other mechanisms of injury include direct blows to the lateral aspect of the hip as in a fall from a height or a side impact automobile collision.