Laurence E. Dahners

Effect of cefazolin and vancomycin on osteoblasts in vitro.

The effect of cefazolin and vancomycin on osteoblast-like cells was studied. Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 Ug/ml. For cefazolin, a second interval was performed between 100 and 1000 ug/ml to define toxic levels more accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined. The results of this study show that local levels of vancomycin of 1000 μg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 μg/ml cause cell death. Concentrations of cefazolin of 100 μg/ml and less have little or no effect on osteoblast replication, 200 μg/ml significantly decrease cell replication, and 10,000 μg/ml cause cell death. The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections.

The effect of combinations of growth factors on ligament healing

Platelet-derived growth factor, basic fibro-blast growth factor, and insulin-like growth factor Type 1 have demonstrated chemotactic and mitogenic properties in vitro that could benefit healing ligaments. These growth factors also have demonstrated in vivo effects when used in skin wound-healing models. In a previous study, bFGF and IGF-1, used alone, failed to improve healing. The authors wished to test the hypothesis that platelet-derived growth factor alone or combinations of platelet-derived growth factor plus insulin-like growth factor Type 1, platelet-derived growth factor plus basic fibroblast growth factor, or basic fibroblast growth factor plus insulin-like growth factor Type 1 would increase the healing efficiency of ligaments because of their effects on different parts of the cell replication cycle and their abilities to induce chemotaxis. Ligaments receiving platelet-derived growth factor alone were 73% ± 55% stronger than their contralateral internal controls (p < 0.0025). Stiffness increased 94% ± 63% over controls (p < 0.0025), and breaking energy was 101% ± 104% > controls (p < 0.1). Ligaments treated with a combination of platelet-derived growth factor plus insulin-like growth factor Type 1 and platelet-derived growth factor plus basic fibroblast growth factor also had increases in rupture force, stiffness, and breaking energy over internal controls. Ligaments treated with a combination of basic fibroblast growth factor plus insulin-like growth factor Type 1 also appeared to have some improved healing; the results, however, did not prove to be statistically significant. Synergistic effects of growth factor combinations were not evident.

Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing.

Nonsteroidal anti-inflammatory drugs continue to be prescribed as analgesics for patients with healing fractures even though these drugs diminish bone formation, healing, and remodeling. Inhibition of bone formation can be clinically useful in preventing heterotopic ossification in selected clinical situations. In this regard, naproxen may be more efficacious than the traditional indomethacin, and short-term administration is as effective as long-term. When fracture healing or spine fusion is desired, nonsteroidal anti-inflammatory drugs should be avoided. Some nonsteroidal anti-inflammatory drugs have a positive effect on soft-tissue healing; they stimulate collagen synthesis and can increase strength in the early phases of repair during skin and ligament healing. Cyclooxygenase-2 inhibitors have an adverse effect on bone healing and may have an adverse effect on ligament healing. Therefore, further investigation is necessary to confirm that traditional nonsteroidal anti-inflammatory drugs may be preferable for the healing of collagenous tissues.

Bone toxicity of locally applied aminoglycosides.

Summary: The effect of tobramycin on osteoblasts was studied. Osteoblast-like cells from the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and exposed to concentrations of tobramycin: first at order of magnitude intervals between 0 and 10,000 μg/ml, and then at closer intervals between 100 and 1,000 μg/ml to more accurately define toxic levels. Cell number and 3H-thymidine incorporation at 0, 24 and 72 h were determined. Similarly, primary cultures of rat osteoblasts were exposed to the same concentrations of tobramycin to confirm the validity of the MG-63 cell line as a model for nontransformed cells. The results of this study demonstrate that local levels of tobramycin of ≤200 μg/ml have little or no effect on osteoblast replication. Concentrations of 400 μg/ml significantly decreased cell replication, and concentrations of 10,000 μg/ml caused cell death. Results obtained with primary rat osteoblast cultures were similar to those obtained from the MG-63 cultures at the tested tobramycin concentrations.

The Effects of Common Anti-Inflammatory Drugs on the Healing Rat Patellar Tendon

Background Tendon injuries that occur at the osteotendinous junction are commonly seen in clinical practice and range from acute strain to rupture. Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of these conditions, but the effect that these agents may have on the healing response at the bone-tendon junction is unclear. Hypothesis In response to an acute injury at the osteotendinous junction, the healing patellar tendon will have inferior biomechanical properties with administration of anti-inflammatory drugs as compared with acetaminophen and control. Study Design Controlled laboratory study. Methods A total of 215 Sprague-Dawley rats underwent transection of the patellar tendon at the inferior pole of the patella, which was subsequently stabilized with a cerclage suture. The animals were then randomized into 7 groups and administered 1 of the following analgesics for 14 days ibuprofen, acetaminophen, naproxen, piroxicam, celecoxib, valdecoxib, or control. At 14 days, all animals were sacrificed, and the extensor mechanism was isolated and loaded to failure. Biochemical analysis of the repair site tissue was performed. Animal activity throughout the study was monitored using a photoelectric sensor system. Results The control group demonstrated greater maximum load compared with the celecoxib, valdecoxib, and piroxicam groups (P < .05). The acetaminophen and ibuprofen groups were also significantly stronger than the celecoxib group (P < .05) but not statistically different than the control group. A total of 23 specimens had failure of the cerclage suture with the following distribution control (0/23), ibuprofen (0/23), acetaminophen (0/24), naproxen (3/24), piroxicam (4/24), celecoxib (6/22), and valdecoxib (10/24). The difference in distribution of the failures was significant (P < .001). Conclusions Anti-inflammatory drugs, with the exception of ibuprofen, had a detrimental effect on healing strength at the bone-tendon junction as demonstrated by decreased failure loads and increased failures of the cerclage suture. Acetaminophen had no effect on healing strength. The biomechanical properties paralleled closely with the total collagen content at the injury site, suggesting that these agents may alter healing strength by decreasing collagen content. Clinical Relevance Selective and nonselective cyclooxygenase (COX) inhibitors should be used judiciously in the acute period after injury or surgical repair at the bone-tendon junction.

An in vivo model of degenerative disc disease.

Although the precise etiology of low back pain is disputed, degeneration of the intervertebral disc is believed to play an important role. Many animal models have been described which reproduce the changes found in degenerative disc disease, but none allow for efficient, large‐scale testing of purported therapeutic agents. The purpose of this study was to develop a simple animal model resembling degenerative disc disease using the intervertebral discs found in the tails of rats. The proximal two intervertebral discs in the tails of 20 rats were injected with either chondroitinase ABC or control (phosphate buffered saline, PBS). The tails were harvested at 2 weeks, and measurements were made of intervertebral disc height (measured radiographically and histologically), biomechanics (stiffness, hysteresis, and residual deformation), and histologic appearance. Treatment with chondroitinase ABC resulted in a significant loss in intervertebral disc height (radiographic intervertebral disc height, p < 0.001; histologic intervertebral disc height, p < 0.001) and significant increases in all biomechanical parameters (stiffness, p < 0.001; hysteresis, p < 0.006; residual deformation, p < 0.004) compared to PBS controls. Intervertebral discs treated with chondroitinase ABC had significantly lower histologic grades for each grading category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining) compared to controls. The results of injury with chondroitinase ABC were similar to the findings in degenerative disc disease: reduced intervertebral disc height, diminished proteoglycan content, loss of NP cells, and increased stiffness of the disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo evaluation of proposed treatments for degenerative disc disease.

A Cyclooxygenase-2 Inhibitor Impairs Ligament Healing in the Rat

Celecoxib was the first of a new class of nonsteroidal antiinflammatory drugs, the cyclooxygenase-2 (COX-2) specific inhibitors, marketed as having the same antiinflammatory efficacy as other nonsteroidal antiinflammatory drugs without their increased risk of gastrointestinal ulceration. Among the widest uses of nonsteroidal antiinflammatory drugs is in the treatment of acute soft tissue injuries. Although the benefits of celecoxib have been shown when used for rheumatoid arthritis and osteoarthritis, we are unaware of any studies concerning its effect on soft tissues. We used the surgically incised medial collateral ligament of male Sprague-Dawley rats as an experimental model for acute ligament injuries to investigate the effects of celecoxib on ligament healing. Fifty rats underwent surgical transection of the right medial collateral ligament. Postoperatively, half were given celecoxib for the first 6 days of recovery, the other half were not. The animals were sacrificed 14 days after the operation, and both the injured and uninjured medial collateral ligaments were mechanically tested to failure in tension. Celecoxib-treated/injured ligaments were found to have a 32% lower load to failure than untreated/ injured ligaments. The results of this study do not support use of cyclooxygenase-2 specific inhibitors in the treatment of ligament injuries.

Hip arthroscopy to remove loose bodies after traumatic dislocation

Objectives: This study was designed to review the incidence of arthroscopically detected intra-articular loose bodies found in patients after traumatic hip dislocation or small acetabular wall fracture which would not otherwise be treated without surgery. Design: Retrospective review. Setting: Level 1 academic trauma center. Patients: Thirty-six patients who sustained traumatic hip injuries and subsequently had 39 hip arthroscopies between November 1997 and January 2004 were reviewed. Intervention: All patients had standard AP pelvis x-rays and CT scans performed. At our institution, patients with hip dislocations or acetabular wall fractures not otherwise requiring surgery are routinely offered hip arthroscopy to remove loose bodies. The radiographs were reviewed to determine incidence of loose bodies or nonconcentric reduction before hip arthroscopy. Chart review provided incidence of loose bodies found during arthroscopy. Main Outcome Measurements: Comparison was made between radiographic data obtained preoperatively and operative findings. Results: Loose bodies were found in the hips of 33 of 36 patients (92%) who were arthroscoped. Loose bodies were found in 7 of 9 cases (78%) in which standard radiographic studies (AP pelvis x-rays and CT scan) found no loose bodies and a concentric reduction. Conclusions: Loose bodies are routinely present after closed treatment of hip dislocations or wall fractures not otherwise requiring surgery, even when radiographs are negative. Hip arthroscopy may be indicated for loose body removal when open treatment is not otherwise necessary.

Fixed-angle plate fixation in simulated fractures of the proximal humerus: a biomechanical study of a new device.

This study was performed to evaluate the biomechanical properties of a new device for displaced fractures of the proximal humerus. The device is a low-profile, fixed-angle plate specially designed for percutaneous application. With the use of embalmed cadaveric humeri, we simulated both noncomminuted and comminuted 2-part surgical neck fractures of the proximal humerus. Each humerus of a pair was then randomly fixed with either the new experimental device or the Association for the Study of Internal Fixation (ASIF) T-plate and mechanically tested to failure in an axial shear-loading model. The two fixation devices were evaluated in paired humeri with regard to mode of failure, stiffness, displacement at physiologic loads, and displacement, load, and energy at the point of ultimate load before failure. In the noncomminuted fracture trials the experimental device exhibited significantly greater stiffness (P <.001; P =.002 for normalized values) and ultimate load before failure (P =.015) and significantly less displacement at higher physiologic loads (P =.031). In the comminuted fracture trials the experimental device exhibited significantly greater stiffness (P =.048), ultimate load (P <.001) and energy absorbed (P =.048) before failure, and significantly less displacement at higher (P =.004) and lower physiologic loads (P =.011). The study demonstrates improved biomechanical properties for the new experimental device over the T-plate in simulated fractures of the proximal humerus. We extrapolate that these improved biomechanical properties may prove advantageous in future clinical investigation.

Correlating selection criteria with subsequent performance as residents.

The objective of this study was to determine which criteria in the residency application had the highest correlation with subsequent performance of orthopaedic residents. Data collected from the application files of 58 residents included scores on standardized tests, number of honors grades in the basic and clinical years of medical school, election to Alpha Omega Alpha, numbers of research projects and publications, and numbers of extracurricular activities. Measures of performance included scores on the Orthopaedic In-Training Examination and American Board of Orthopaedic Surgery Part I Examination, and faculty evaluations of overall, cognitive, affective, and psychomotor performance. The number of honors grades on clinical rotations was the strongest predictor of performance, whereas election to Alpha Omega Alpha was second. The only other significant correlation was between the number of fine motor activities and psychomotor performance. None of the predictor variables had a significant correlation with Orthopaedic In-Training Examination or American Board of Orthopaedic Surgery Examination scores. Consistency between faculty rankings in each of the four categories was supported by regression analysis. From the results of this study, it appears that academic performance in clinical clerkships in medical school is the most predictive of resident performance. Range restriction in the data available for orthopaedic residency applicants, however, likely precludes the development of a reliable model to assist in the selection of orthopaedic residents.