High dietary fat and the development of osteoarthritis in a rabbit model.

OBJECTIVE: Osteoarthritis (OA) is associated with obesity, although this relationship remains unclear. Proposed etiologies of OA in obesity include mechanical loading of malaligned joints and possible toxicity of dietary fat. The hypothesis tested in the present study was that increased dietary fat worsens OA in both malaligned and normal joints, detected by biochemical and histological cartilage markers. METHOD: 83 New Zealand white rabbits were divided among two conditions related to OA: bowing of the knee and a 14%kcal vs 47.8%kcal fat diet. Rabbit weights and knee angles were compared throughout the experiment. At 28 and 38 weeks, intra-articular forces were measured, animals sacrificed, and knee cartilage examined for histological changes, glycosaminoglycan content, 35S uptake, and aggrecanase-1 expression. RESULTS: There were no differences in animal weights or intra-articular forces between the two diets. Despite increased fat content in their diet, animals on the 47.8%kcal fat diet did not gain excess weight. Representative histology showed atypical shearing of articular cartilage among animals on the high fat diet. Animals on the 47.8%kcal fat diet had suppression of protein synthesis compared to the 14%kcal fat diet: lower glycosaminoglycan content and aggrecanase-1 expression in all knee compartments at both times, and lower 35S uptake at 38 weeks. CONCLUSION: These results suggest dietary fat, independent of animal weight, results in altered chondrocyte function. Increased dietary fat was associated with changes in rabbit cartilage in vivo and appears to be a risk factor for the development of OA.

Weight-bearing alters the expression of collagen types I and II, BMP 2/4 and osteocalcin in the early stages of distraction osteogenesis.

This study was performed to investigate the effect of loading on the biology of newly forming bone during limb lengthening. Unilateral 2.0 mm femoral lengthenings were performed in 20 male Sprague Dawley rats. Half (n = 10) of the animals were allowed to bear weight freely, while the other half were prevented from weight-bearing via an ipsilateral through-knee amputation. The animals in each group were sacrificed after one (n = 5) or four (n = 5) days of consolidation (post-operative days seven and 10, respectively). In situ hybridization for osteocalcin and collagen I, and antibody staining for collagen II and BMP 2/4 were used to evaluate the molecular influence of loading. There was more new bone in the distraction gap of the weight-bearing animals than there was in the non-weight-bearing animals. BMP 2/4 expression, and the messages for collagen I and osteocalcin, were more abundant in tissue from the weight-bearing animals; collagen II was higher in the non-weight-bearing animals. This suggests that early regenerate tissue is capable of responding to loading, and that weight-bearing appears to stimulate intramembranous ossification. These findings support the concept of early weight-bearing after limb lengthening.

A paradigm for the age-related treatment of knee dislocations in Larsen's syndrome.

Three cases of Larsen's syndrome in siblings are presented to illustrate a paradigm for the age-related treatment of deformity. Each child presented at a different age, with differing degrees of deformity and growth disturbance. Both growth and remodeling potential influenced the choice of treatment and outcome. The surgeon who undertakes the correction or prevention of these deformities must face the problem of and, it is hoped, use, growth potential from open physes and the progressive loss of remodeling capacity with advancing age.

RGD-coated titanium implants stimulate increased bone formation in vivo.

Numerous studies have demonstrated that peptide modified surfaces influence short- and long-term cell responses such as attachment, shape and function in vitro. These responses are mediated via cell receptors known as integrins which bind specifically to short peptide sequences from larger proteins. Integrins transduce information to the nucleus through several cytoplasmic signalling pathways. Little is known, however, about the ability of peptide-coated surfaces to influence cell responses in vivo. The present study was designed to evaluate the quality and quantity of the new bone formed in response to titanium rods surface-coated with the peptide sequence Arg-Gly-Asp-Cys (RGDC) using gold-thiol chemistry and implanted in rat femurs. Histomorphometric analysis of cross-sections perpendicular to the implant long axis showed a significantly thicker shell of new bone formed around RGD-modified versus plain implants at 2 weeks (26.2 +/- 1.9 vs. 20.5 +/- 2.9 microm; P < 0.01). A significant increase in bone thickness for RGD implants was also observed at 4 weeks while bone surrounding controls did not change significantly in thickness (32.7 +/- 4.6 vs. 22.6 +/- 4.0 microm; P < 0.02). Mechanical pull-out testing conducted at 4 weeks revealed the average interfacial shear strength of peptide modified rods was 38% greater than control rods although this difference was not statistically significant. These pilot data suggest that an RGDC peptide coating may enhance titanium rod osseointegration in the rat femur. Long-term studies and evaluation of other peptides in larger animal models are warranted.

The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient.

The control of postoperative pain in the pediatric orthopaedic patient is a challenging endeavor. Several studies have shown the efficacy of ketorolac tromethamine in the pediatric general surgical population, but its efficacy in the pediatric orthopaedic population remains unproven. Twenty-seven consecutive patients (age 6 months to 18 years) who underwent long-bone osteotomies or foot procedures by a group of three pediatric orthopaedic surgeons were given a ketorolac protocol (1 mg/kg loading, 0.5 mg/kg every 6 h for 24 h). Breakthrough pain was managed with morphine until the patient was able to take oral pain medication, as was any pain after the 24-h period for ketorolac expired. Thirty-seven age- and case-matched patients were used as retrospective controls. The patients in the study who received ketorolac required significantly fewer doses of morphine than did the control group (2.29 +/- 3.98 vs. 10.02 +/- 3.39; p < 0.05). In addition the patients on the ketorolac protocol experienced fewer gastrointestinal side effects (4% vs. 32%; p < 0.05). Finally, the patients in the ketorolac group had a significantly shorter length of stay (3.63 +/- 1.64 days vs. 4.74 +/- 1.76 days; p < 0.05). There were no bleeding complications in either group. Ketorolac is thus a safe and effective means of controlling postoperative pain in the pediatric orthopaedic population while avoiding the troubling maleffects seen with the exclusive use of morphine.

Long-term patient-oriented outcome study of a modified Evans procedure.

More than 50 surgical procedures have been described for treatment of chronic lateral ankle instability. Anatomic repairs have come into favor in the recent literature based on short-term studies, which have used objective measures for outcome. A long-term (range, 7-20 years; average, 12.6) patient-oriented outcome analysis was performed on 20 patients that underwent a modified Evans procedure for chronic lateral ankle instability by the senior author over a 13-year period. There was a 91% follow-up on all located patients (20 of 22). All patients had mechanical and functional instability, and all had failed conservative therapy. A questionnaire, based on the outcomes questionnaire developed by the American Academy of Orthopaedic Surgeons was used to determine functional stability. The patient's ability to perform recreational or competitive sporting activities at specific time intervals were also assessed (preinjury, 1 year postoperatively, present time). Overall result was considered satisfactory if five criteria were met: patents (a) were happy with the outcome of surgery, (b) were able to perform desired level of activities, (c) had functional stability, (d) were pain free performing desired level activities, (e) would undergo procedure again. The entire cohort demonstrated satisfactory results in 19 (95%) of 20 respondents at 1 year and 17 (85%) at present time. Grouping patients into competitive (12 cases) and recreational (eight cases) athletes demonstrated six of 12, and seven of eight reached their preinjury level (p = 0.074). In this study, we showed that surgical reconstruction using a modified Evans procedure is a reliable and effective treatment for chronic lateral instability. This procedure has proved to stand the test of time, as demonstrated by a patient-oriented outcome analysis. The elite athlete may be better served by a procedure using the principles of anatomic rather than augmented repair; however, the long-term data to our knowledge has yet to be published.

Pediatric throwing injuries about the elbow.

Pediatric elbow injuries that result from repetitive throwing-type activities are common. These injuries differ from those seen in adults, because of anatomic differences. The purpose of this paper is twofold: first, to review the anatomy of the elbow and the mechanics of the throwing motion about the elbow, and second, to discuss the diagnosis, treatment, rehabilitation, and prevention of pediatric throwing injuries of the elbow.

Fracture healing in a rat osteopenia model.

Fracture healing is influenced by mechanical and biologic factors. The capacity for fracture repair has been reported to decrease with age, although the risk of fracture increases with age. Fracture healing in an animal model of postmenopausal osteoporosis or osteopenia would provide a useful technique to evaluate and develop new treatment protocols. The authors examined the tensile and bending properties of healing femoral fractures in normal and ovariectomized rats. Mechanical data from tensile and bending tests indicate ovariectomy impairs fracture healing, which was confirmed through histologic study. Bending and tensile data provide useful information concerning the mechanical properties of the healing fracture. Tensile tests were noted to be sensitive indicators of the properties of the healing fracture.

Aggregate degradation by growth plate proteases.

For long bone growth to occur, calcification of the matrix must begin in the lower hypertrophic zone of the growth plate. It generally is accepted that physeal proteoglycans help regulate mineralization, and that, at least in vitro, smaller proteoglycan fragments are less inhibitory of mineral formation. It also has been shown that proteoglycan degrading enzymes are concentrated in the hypertrophic zone, where calcification occurs. Thus, one can hypothesize that these enzymes are involved in the calcification process. Proteoglycans appear mainly as the aggregate form in the physis, and this study demonstrates the ability of the naturally occurring physeal enzymes to degrade proteoglycan aggregate, without first disaggregating it. Because the matrix constituents probably limit hypertrophic cell size and shape, this degradation may have some relationship to the rate of growth of the physis.

Management of the completely stiff pediatric knee.

The purpose of this study was to ascertain whether aggressive surgical treatment of ankylosed knees, followed by immediate continuous passive motion (CPM), can restore acceptable function in children. A retrospective analysis was performed on five children operated on for severely contracted knees. In all cases, extensive intraarticular pathology was present, and lysis of adhesions, tendon lengthenings, and capsular releases were performed in each case. Cruciate ligament release, drilling of subchondral bone, and patellectomy or meniscectomy or both also were performed in certain cases. Surgery was followed by immediate CPM for 6 weeks. Knee motion improved significantly from a preoperative mean of 7 degrees (range, 0-20 degrees) to 63 degrees (range, 15-90 degrees) at final follow-up, and all patients were satisfied with the result. The mean follow-up interval was 4.6 years. The regenerative properties of articular cartilage as well as the physis in the skeletally immature may permit a radically different approach from that accepted in adults. Such an approach can spare the native joint and restore acceptable function.

Incidence of deep vein thrombosis after arthroscopic knee surgery: a prospective study.

Deep vein thrombosis (DVT) with subsequent pulmonary emboli (PE) is the most life-threatening complication of knee arthroscopy. Although the incidence of clinically diagnosed DVT after arthroscopy is low, clinical examination is less sensitive and specific than other diagnostic modalities for the detection of venous clot. This study used compression ultrasound to prospectively evaluate patients before and after arthroscopic surgery for the presence of DVT. Preoperatively, patients were screened for DVT risk factors. Eighty-five patients completed the study. Three asymptomatic "silent" DVTs were identified, for an incidence of 3.5%. There was no statistically significant difference between those with and without risk factors for the development of DVT.

Effects of local injection of corticosteroids on the healing of ligaments. A follow-up report.

One hundred and one skeletally mature New Zealand White rabbits were used to study the long-term effects of a single injection of corticosteroid on the biomechanical, histological, and biochemical properties of ligament-healing. Two steroid doses were studied, as previously described. The injections were made into a fascial pocket immediately after transection of the ligament. The animals were killed forty-two and eighty-four days after the injury. In our previous investigation, in which we examined the early (inflammatory and proliferative) phases of ligament-healing, the specimens that had been injected with a dose of steroids equivalent to that given to humans demonstrated significantly inferior biomechanical properties and histological organization relative to controls that had not received an injection. In the current study, we examined the later (remodeling and maturation) phases of ligament-healing and found that the tensile strength (the ultimate stress) of the specimens that had been injected with the steroids returned to a value that was equal to that of the controls that had not received an injection; however, the peak load of the specimens that had been injected with steroids remained inferior to that of the controls. This was accompanied by a lag in the histological maturation.

Human osteoblasts in culture metabolize both 1 alpha, 25-dihydroxyvitamin D3 and its precursor 25-hydroxyvitamin D3 into their respective lactones.

1 alpha, 25-Dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3], the hormonal form of vitamin D3, is further metabolized in the kidney and intestine through the carbon 24 (C-24) oxidation pathway initiated by C-24 hydroxylation, and the carbon 23 (C-23) oxidation pathway initiated by C-23 hydroxylation. The C-24 oxidation pathway leading to the formation of calcitroic acid has been previously reported to be present in bone cells, but the C-23 oxidation pathway leading to the formation of 1 alpha, 25-(OH)2D3-26,23-lactone has not been described in bone cells, even though 1 alpha, 25-(OH)2D3-26,23-lactone is noted to have a significant effect on bone formation. Therefore, in the present study, we investigated the production of 1 alpha, 25-(OH)2D3-26,23-lactone in normal human osteoblasts, and our studies revealed that human osteoblasts possess the activity of both 24- and 23-hydroxylases constitutively. Thus, 1 alpha, 24(R),25-(OH)3D3, 1 alpha, 25-(OH)2-24-oxo-D3, 1 alpha, 23(S), 25-(OH)3-24-oxo-D3, 1 alpha, 23-(OH)2-24,25,26,27-tetranor D3, and calcitroic acid formed through the C-24 oxidation pathway and 1 alpha, 23(S),25-(OH)3D3 and 1 alpha, 25-(OH)2D3-26,23-lactone formed through the C-23 oxidation pathway were detected under basal conditions. Also, the synthesis of these metabolites was increased significantly when the cells were treated with 1 alpha, 25-(OH)2D3 (50 nM) for 24 h before incubation with the tracer. As 25-hydroxyvitamin D3 (25OHD3) follows similar side-chain modifications as 1 alpha, 25-(OH)2D3, the metabolism of 25OHD3 in normal human osteoblasts was studied under basal conditions. We found that 25OHD3 was also metabolized through both C-24 and C-23 oxidation pathways, resulting in significant synthesis of 24(R),25-(OH)2D3 along with 25OH-24-oxo-D3, 23(S),25-(OH)2-24-oxo-D3, 23(S),25-(OH)2D3, and 25OHD3-26,23-lactone. Under the same experimental conditions, we looked for 1 alpha, 25-(OH)2D3 synthesis, as earlier studies have shown production of 1 alpha, 25-(OH)2D3 in human bone cells. During a time-course study ranging from 1-24 h, we found that by 2 h, the 24(R), 25-(OH)2D3 concentration rose and accumulated considerably during the following 24 h, but 1 alpha, 25-(OH)2D3 did not accumulate at any time. However, other 1-hydroxylated metabolites, 1 alpha, 23(S),25-(OH)3D3, 1 alpha, 23(S),25-(OH)3-24-oxo-D3, as well as 1 alpha, 25-(OH)2D3-26,23-lactone were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of a delayed steroid injection on ligament healing using a rabbit medial collateral ligament model.

Corticosteroids are known to inhibit collagen synthesis in vitro as well as having a deleterious effect on ligament healing when applied immediately following injury. An acute injection of betamethasone into a transected rabbit medial collateral ligament significantly impaired the biomechanical and histological properties compared to non-injected transected ligaments. Differences in mechanical, histological and biochemical properties were observed up to 3 months following injury and an acute steroid injection. The present study explored the effects of a corticosteroid (betamethasone) injection 7 days following the initial injury. Biomechanical and histomorphometric analyses were carried determine if the previously observed deleterious effects of a corticosteroid injection immediately following injury can be linked to an interference in the inflammatory phase of healing due to the presence of the corticosteroid.

Remodeling of articular step-offs. Is osteoarthrosis dependent on defect size?

One of the major unresolved questions in trauma repair concerns the degree of step-off that can be accepted in a joint surface. In answer to this question, a new rabbit model of femoral step-off was developed. Osteoarthrotic changes in cartilage and bone and the failure of repair responses were seen at 20 weeks in the presence of a 3-mm wide sagittal defect displaced 5 mm from the joint surface and spanning the anteroposterior extent of the medial femoral condyle. This study examined the effects of a similar defect, displaced 2 mm from the joint surface, to determine whether the development of osteoarthrosis is dependent on the size of the step-off. Defects were created in 18 New Zealand white rabbits. In a second group, the medial joint surface was osteotomized, but was not displaced. In contrast to th first study, cartilaginous and bony repair resulted in closure of the surgical defect and restoration of femoral congruity. Histologic and biochemical parameters did not differ significantly between groups. The results indicate that cartilage and bone possess the ability to remodel small articular step-offs and to restore joint congruity. Furthermore, the combined data suggest that the development of osteoarthrosis requires significant articular incongruity.

Correlation between ultrasound imaging and mechanical and physical properties of lengthened bone: an experimental study in a canine model.

The right tibias of 16 adult mongrel dogs were lengthened 2.5 cm using a uniplanar lengthening device (Orthofix). After the animals were killed in groups of 4 at 3, 6, 9, and 12 weeks postlengthening, ultrasound imaging and mechanical and physical testing was performed. There was a direct relationship between the percentage of intact cortices on ultrasound imaging and the mechanical and physical properties of lengthened bone. However, once 80-90% of all the cortices regained their continuity, the strength of the lengthened bone was only 50-60% that of the control. Ultrasound imaging, therefore, may be useful in predicting the mechanical and physical properties of lengthened bone in the early phases of limb lengthening. Once all the cortices become continuous, however, another method for assessment of the mechanical properties of lengthened bone should be used.

Evaluation of treatment modalities for septic arthritis with histological grading and analysis of levels of uronic acid, neutral protease, and interleukin-1.

We compared the effectiveness of antibiotics alone and in combination with arthroscopy, arthroscopy with debridement, arthrotomy, or needle aspiration for the treatment of septic arthritis. Each modality has its proponents, but, to our knowledge, no comparative studies have been conducted in animals. We used biochemical and histological analysis to compare these methods of treatment in an experimental model. The right hind knee of thirty goats was injected with 1 x 10(5) Staphylococcus aureus bacilli. The left hind knee was not inoculated and served as the normal control. Seventy-two hours after inoculation, a two-week course of treatment with intramuscular administration of cefuroxime sodium, either alone or in combination with another mode of treatment, was initiated in each of five groups. The cartilage was evaluated histologically with biochemical, enzymatic, and interleukin-1 analyses. Despite the early therapeutic intervention, on the average, there was a 25 per cent loss of uronic acid (t test, p < 0.001) and a 43 per cent increase in neutral protease activity (signed-rank test, p = 0.003) in the treatment groups. There were no significant intergroup differences with regard to the histochemical-histological rating or the levels of uronic acid, neutral protease, or interleukin-1.

Biomechanical and physical properties of lengthened bone in a canine model.

Reports on the mechanical and physical properties of lengthened bone after completion of the lengthening process remain scarce. Varied results of torsional testing of lengthened bone have been reported. Furthermore, torsional testing provides information on the shear properties of the tissue but does not reflect the elastic properties obtained from tensile, compressive, or bending tests. The present study evaluated the mechanical properties of lengthened bone at various time points, using a uniaxial tension test. Physical properties (density and ash weight) were determined as well. Results indicate that the tensile properties of the lengthened bone increase with time after the completion of lengthening, but they remain significantly weaker than controls (50%) even after 12 weeks. Density and ash weight measurements also increased with time, correlating with the increase in the tensile mechanical properties.

Radioulnar synostosis.

Radioulnar synostosis is a rare condition that exists in two forms: congenital and post-traumatic. Although both may involve either a bony or a fibrous union between the radius and ulna, they differ considerably in their etiologies, treatment, and prognosis. This article explores both of these conditions.