Search PubMed⌕ Search

Biomedical subjects

D R Sumner

Publications and source records attributed to D R Sumner.

At least 37 records · Page 2Linked to original sources

Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury.

The purposes of the present study were to determine if recombinant human transforming growth factor-beta-2 (rhTGF-beta2) enhances bone ingrowth into porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-beta2 in buffer at a dose per implant of 1.2 microg (n = 6), 12 microg (n = 7), or 120 microg (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF-beta treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15%, of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF-beta treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 microg/implant group (a 2.2-fold increase over the paired internal control (P = 0.004) and a 4-fold increase over the external control (P < 0.001)). The TGF-beta treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 microg groups (1.8-fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8-fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9-fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7-fold increase. P = 0.008). Thus, application of rhTGF-beta2 to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor.

Animals↗

A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

Aged↗

Accuracy and precision of radiostereometric analysis in the measurement of THR femoral component translations: human and canine in vitro models.

Radiostereometric analysis (RSA) is used to measure translations of joint replacement components with respect to the host bone in vivo. We used two cadaveric models of hip arthroplasty, one human and one canine, to evaluate the accuracy and precision of RSA-based estimates of translations of the femoral component with respect to the femur under ideal conditions. The femoral components were attached rigidly to a micrometer stage that provided standard displacements in increments of 25 and 50 microm in the interval from zero to 500 microm along three orthogonal axes. Radiostereometric examinations were performed for each increment. Accuracy was calculated as the 95% prediction intervals from regression analyses between the measured and actual displacements. Precision was evaluated as the standard deviation of five repeated measurements of a 200 microm displacement along each axis. Both accuracy and precision were best along the longitudinal axis, with a prediction interval of +/-47 microm in the human model and +/-45 microm in the canine model and a standard deviation of 30 microm in the human model and 40 microm in the canine model. The use of only the prosthetic head as a landmark (as opposed to three markers placed on the femoral stem) led to a 3-fold larger prediction interval in the human model and a 2-fold greater prediction interval in the canine model.

Animals↗

Bone graft harvesting from the distal radius, olecranon, and iliac crest: a quantitative analysis.

The purpose of this study was to quantify the volume and density of cancellous bone available from 3 commonly used bone graft sites in upper extremity surgery: the distal radius, olecranon process, and anterior iliac crest. Sixteen cadavers (age range, 59-98 years) with no prior history of bone harvest or metabolic conditions affecting bone were used. Cancellous graft was obtained using standardized techniques designed to simulate the clinical setting. Packed cancellous bone volume was determined as the volume occupied by the harvested bone after compression packing with a uniform load. Defect volume was determined by measuring the volume of the site from which bone was harvested. The distal radius and olecranon provided similar volumes of packed cancellous bone (2.7 and 2.8 cc, respectively). The anterior iliac crest provided approximately twice this amount (5.3 cc). The packed cancellous bone volume/defect volume ratio was not different between the 3 sites studied. Male gender was associated with a significantly greater amount of packed cancellous bone volume for all sites. We believe the olecranon to be an alternative to the distal radius as a source of bone graft for upper extremity procedures. We suggest using the anterior iliac crest when a large volume of cancellous bone is required.

Aged↗

Bone density, dynamic joint loading and joint degeneration. A review.

Increased joint loading and elevated bone density may be involved in the initiation or progression of osteoarthritis. Here, we provide an introduction to the literature on this topic and describe recent studies from our laboratories on several cohorts of subjects who had or were scheduled to have a total hip replacement for unilateral end-stage osteoarthritis. This population is very useful for studying the development and progression of osteoarthritis because of the known higher incidence of osteoarthritis in the contralateral hip than in a normal population. Separate studies of the asymptomatic contralateral hip in these subjects have shown that radiographic signs of early osteoarthritis are associated with increased bone mineral density and some of the gait adaptations typically found in subjects with end-stage osteoarthritis. We have also shown in separate studies of similar populations that elevated bone mineral density is associated with a subsequent accelerated joint space narrowing rate and that elevated hip joint loads during gait are similarly associated with an accelerated narrowing rate. Major questions yet to be answered are how joint loading and bone density interact in the development and progression of joint degeneration.

Adaptation, Physiological↗

Animal models relevant to cementless joint replacement.

This review focuses on animal models used to study certain aspects of 'cementless' joint replacement. Implants used in this application are designed to become attached to the host skeleton through either bone ingrowth into porous surfaces or bone apposition (ongrowth) onto other types of surfaces. Biological fixation of cementless joint replacement implants relies on intramembranous bone regeneration. We describe a framework for understanding research design in light of the type of research questions now being asked. In particular, species choice, implant design and placement, and experimental endpoints are described in some detail. We provide a summary of recent studies specifically focused on implant fixation, demonstrating that most work is still at the morphological and biomechanical levels with little understanding at the molecular level. We also provide a more comprehensive listing of studies using hip and knee replacement models, demonstrating that most work is focused on the interface, and responses of the immediately adjacent trabecular bone and the more distant cortical bone. We conclude by encouraging investigators to design their experiments so that there is enough power to answer a limited number of questions as opposed to providing limited data on a broader number of issues.

Journal Article↗

Sensitivity of periprosthetic stress-shielding to load and the bone density-modulus relationship in subject-specific finite element models.

Subject-specific finite element (FE) computer models of the proximal femur in hip replacement could potentially predict stress-shielding and subsequent bone loss in individual patients. Before such predictions can be made, it is important first to determine if between subject differences in stress-shielding are sensitive to poorly defined parameters such as the load and the bone material properties. In this study we investigate if subject-specific FE models provide consistent stress-shielding patterns in the bone, independent of the choice of the loading conditions and the bone density-modulus relationship used in the computer model. FE models of two right canine femurs with and without implants were constructed based on contiguous computed tomography (CT) scans so that subject-specific estimates of stress-shielding could be calculated. Four different loading conditions and two bone density-modulus relationships were tested. Stress-shielding was defined as the decrease of strain energy per gram bone mass in the femur with the implant in place relative to the intact femur. The analyses showed that for the four loading conditions and two bone density-modulus relationships the difference in stress-shielding between the two subjects was essentially constant (1% variation) when the same loading condition and density-modulus relationship was used for both subjects. The severity of stress-shielding within a subject was sensitive to these input parameters, varying up to 20% in specific regions with a change in loading conditions and up to 10% for a change in the assumed density-modulus relationship. We conclude that although the choice of input parameters can substantially affect stress-shielding in an individual, this choice had virtually no effect on the relative differences in femoral periprosthetic stress-shielding between individuals. Thus, while care should be taken in the interpretation of the absolute value of stress-shielding calculated with these type of models, subject-specific FE models may be useful for explaining the variation in bone adaptation responsiveness between different subjects in experimental or clinical studies.

Animals↗

Contributions of bone density and geometry to the strength of the human second metatarsal.

We investigated, at the whole bone level, the contribution of bone density and geometry to the fracture load of the second metatarsal, a bone that is prone to stress fracture. Dual-energy X-ray absorptiometry (DXA) was used to determine the areal bone mineral density (BMD), projected area of bone, and bone mineral content. Peripheral quantitative computed tomography (pQCT) was used to determine the volumetric cortical bone mineral density (vCtBMD) and cross-sectional moment of interia. Various metatarsal linear dimensions were also measured. The load at failure in cantilever bending was determined. The only linear dimension that had a significant correlation with load at failure was the height of the metatarsal base (r(2) = 0.30, p = 0.008). Utilizing all of the information provided by DXA gave no greater indication of whole bone strength than just BMD alone (adjusted r(2) = 0.40, p = 0.001). Using all of the information provided by pQCT gave no greater indication of whole bone strength than just vCtBMD alone (r(2) = 0. 46, p < 0.001). Volumetric cortical density and BMD were strongly correlated (r(2) = 0.81, p < 0.001). Our data suggest that, in the human second metatarsal, a variable such as material strength (as inferred from cortical density), and not geometry, may be the major factor in determining cantilever load to failure.

Absorptiometry, Photon↗

Parallel plate model for trabecular bone exhibits volume fraction-dependent bias.

Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods. Both thickness and spacing calculated using the plate model were well correlated to the direct three-dimensional measures (r(2) = 0. 77-0.92). The correlation between trabecular number and connectivity density varied greatly (r(2) = 0.41-0.94). Whereas trabecular thickness was consistently underestimated using the plate model, trabecular spacing was underestimated at low volume fractions and overestimated at high volume fractions. Use of the plate model resulted in a volume-dependent bias in measures of thickness and spacing (p < 0.001). This was a result of the fact that samples of low volume fraction were much more "rod-like" than those of the higher volume fraction. Our findings indicate that the plate model provides biased results, especially when populations with different volume fractions are compared. Therefore, we recommend direct thickness measures when three-dimensional data sets are available.

Adolescent↗

Bone mineral density varies as a function of the rate of joint space narrowing in the hip.

OBJECTIVE: To determine whether patients with a rapid rate of joint space narrowing (JSN) in the hip have higher initial bone mineral density (BMD) in the proximal femur and/or lumbar spine than corresponding patients with a slow rate of JSN. METHODS: Twenty-eight patients undergoing unilateral total hip replacement (THR) for osteoarthritis (OA), but whose contralateral hips were asymptomatic and had minimal or no radiographic OA, were evaluated. The contralateral proximal femur (i.e., non-operated hip) and lumbar spine were scanned by dual energy x-ray absorptiometry at baseline (prior to THR) and at 2 years. The rate of JSN was determined by serial longitudinal quantification of the joint spaces over the 2 year period following THR from conventional radiographs, and the patients were divided into a group with a slow rate of JSN (< or = 0.2 mm/yr, n = 20) and a group with a rapid rate of JSN (> 0.2 mm/yr, n = 8). RESULTS: The baseline BMD z and t scores at the femoral neck, Ward's triangle, and lumbar spine of the patients with subsequent rapid rates of JSN were significantly higher than those of patients with slower rates (p < 0.05). There was no difference between the rapid and slow narrowers at the greater trochanter (p > 0.2). Age, sex, weight, height, body mass index, Kellgren- Lawrence scores, and initial joint space width were not significantly different between the 2 groups. CONCLUSION: Patients with a rapid rate of JSN of the asymptomatic hip after unilateral THR are characterized by elevated local and remote BMD. The local elevation in BMD implies that increased local bone density may contribute to or serve as a marker for increased risk of development of OA (assuming that JSN can be used as a predictive marker). The presence of elevated BMD in the spine suggests that there are systemic as well as local aspects of OA pathogenesis, at least in patients with one THR and rapid JSN in the contralateral hip.

Absorptiometry, Photon↗

The pattern of bone mineral density in the proximal femur and radiographic signs of early joint degeneration.

OBJECTIVE: To determine if the presence of early radiographic signs of degenerative changes in the hip is associated with the pattern of bone mineral density (BMD) in the proximal femur. METHODS: Twenty-eight patients scheduled for unilateral hip replacement were placed into one of 2 groups based on the preoperative radiographic findings in the asymptomatic hip: Group 1 (no changes) or Group 2 (doubtful or minimal changes). Both femora and the lumbar spine were scanned by dual energy x-ray absorptiometry. RESULTS: The BMD z scores of the asymptomatic hip were significantly higher at the neck and Ward's triangle sites in Group 2 compared to Group 1 (p < 0.05). There were no differences between the groups in the symptomatic hip except at Ward's triangle, where Group 2 had higher z scores than Group 1 (p < 0.05). The lumbar BMD z scores were elevated in both groups (p < 0.05). CONCLUSION: Proximal femur BMD in the asymptomatic hip of patients scheduled for unilateral hip replacement is elevated when there are early radiographic signs of hip osteoarthritis (OA), consistent with the idea that early OA involves bone as well as cartilage.

Absorptiometry, Photon↗

Dimensional characteristics of uncomplicated autopsy-retrieved acetabular polyethylene liners by ultrasound.

A new, in vitro ultrasound-based method to measure the thickness of acetabular polyethylene components was developed and applied to 26 uncomplicated autopsy retrieved components and 40 unused components. The average age at total hip arthroplasty was 62 years and the average time in service of the retrieved components was 49 months. The clinical notes indicated that each of the arthroplasties was functioning well at the time of the patients death. Thickness distributions in the retrieved components had two distinct patterns. Eighteen of the retrieved components (69%) had their thinnest areas self-contained and located near the polar point. In the other 8 retrieved components (31%) the areas of minimum thickness were adjacent to the rim. Thickness distribution in the unused cups was predominately concentric with the thinnest area located near the polar point (85% of the cups). Detection limits for dimensional change were established based on the variability found in the unused liners. Fifteen of the 26 retrieved components (58%) had areas of reduced thickness which exceeded the detection limits; the average thickness reduction rate for these components was 0.076 mm per year. The other 11 retrieved components (42%) lacked such areas. The 15 cups with areas of reduced thickness had a longer time in service (63 +/- 18 months) than the 11 cups without areas of reduced thickness (32 +/- 25 months) (p = 0.003), but no other clinical factor (age, gender, Harris hip score, size and inclination of the cup, type of femoral fixation) was associated with these 15 cups. Cylindrical models to estimate volumetric change tended to underestimate the actual changes, suggesting that the actual particulate burden may be greater than previously appreciated. Finding that the pattern of thickness reduction can vary suggests that distinctive hip loading modes may be present postoperatively in patients with total hip arthroplasty. The wear rates of these components are consistent with wear rates calculated from radiographic data for well-functioning implants and are considerably lower than wear rates calculated for surgically-retrieved implants, indicating that autopsy-derived retrievals may be more representative of the majority of components currently in service than surgically-derived retrievals.

Aged↗

Dynamic knee loads during gait predict proximal tibial bone distribution.

This study tested the validity of the prediction of dynamic knee loads based on gait measurements. The relationship between the predicted loads at the knee and the distribution of bone between the medial and lateral sides of the tibia was examined. The motion and external forces and moments at the knee were measured during gait and a statically determinate muscle model was used to predict the corresponding forces on the medial and lateral tibial plateaus. In particular, the relationship between the knee adduction moment during gait and the ratio or distribution of medial to lateral tibial bone mineral content was studied. Bone mineral content was measured with dual energy X-ray absorptiometry in four regions, two proximal regions 20 mm in height, one medial and one lateral and two distal regions 20 mm in height, one medial and one lateral. The best single predictor of the medial lateral ratio of proximal bone mineral content (bone distribution) was the adduction moment (R2=0.31, p=0.003). Adding weight (negative coefficient. p=0.0004) and the ratio of the average predicted peak force on the medial plateau to the predicted peak force on the lateral plateau (positive coefficient, p=0.0033) to the regression model significantly increased the ability to predict the proximal medial lateral bone distribution (R2=0.72, p=0.0001). Distally neither the subject characteristics nor the gait moments and predicted forces were significant predictors of the bone distribution. The lack of a correlation distally may be reflective of the forces being more evenly distributed further from the tibial plateau. While it has long been suggested that the adduction moment is the primary determinate of the distribution of load between the medial and lateral plateaus, this is the first evidence of its relationship to the underlying bone distribution.

Absorptiometry, Photon↗

Functional adaptation and ingrowth of bone vary as a function of hip implant stiffness.

The purpose of the present study was to test the hypothesis that cortical bone loss, trabecular bone density and the amount of bone ingrowth vary as a function of stem stiffness in a canine cementless hip replacement model. The study was motivated by the problem of cortical bone atrophy in the proximal femur following cementless total hip replacement. Two stem stiffnesses were used and both designs were identical in external geometry and porous coating placement. The high stiffness stem caused approximately 26% cortical bone stress-shielding and the low stiffness stem caused approximately 7.5% stress-shielding, as assessed by beam theory. Each group included nine adult, male canines who received unilateral arthroplasties for a period of six months. The animals with the low stiffness stems tended to lose less proximal cortical bone than the animals with high stiffness stems (4% +/- 9 as opposed to 11% +/- 14), but the difference was not statistically significant (p = 0.251). However, the patterns of bone ingrowth into the implant and change in medullary bone density adjacent to the implant were fundamentally different as a function of stem stiffness (p < 0.01). Most importantly, while the high stiffness group had peaks in these variables at the distal end of the stem, the low stiffness group had peak values proximally. These different patterns of functional adaptation are consistent with the idea that reduced stem stiffness enhances proximal load transfer.

Adaptation, Physiological↗

Hip motion and moments during gait relate directly to proximal femoral bone mineral density in patients with hip osteoarthritis.

The present study examined the loads at the hip joint during gait and the bone mineral density of the proximal femur in 25 patients with end-stage hip osteoarthritis. Dual energy X-ray absorptiometry was used to determine the bone mineral density of the greater trochanter, femoral neck and Ward's triangle of the osteoarthritic group. The bone mineral density was normalized for the patient's age, gender, weight and ethnic origin (Z score). Gait analysis was used to determine the external hip joint moments and motion during walking for the osteoarthritic group and a control group of 21 normal subjects. The gait parameters of the osteoarthritic group which were significantly diminished compared to the normal group (p < 0.001) accounted for as much as 42% (p < 0.001) of the variation in the normalized bone mineral density. Specifically, the dynamic sagittal plane hip motion during gait (maximum flexion minus maximum extension) and peak external rotation and adduction moments were significantly correlated with greater trochanter (R = 0.429-0.648, p = 0.032-0.0001) and Ward's triangle (R = 0.418-0.532, p = 0.038-0.006) normalized bone mineral density while the adduction moment was also significantly correlated with the femoral neck normalized bone mineral density (R = 0.5394, p = 0.005). The normalized bone mineral density of the femoral neck and Ward's triangle was elevated while that of the greater trochanter was decreased as compared to normal reference values. The significant correlation between the hip joint moments during gait and femoral bone mineral density indicate that hip joint loads need to be included when explaining local variation in bone mineral density in hip osteoarthritis.

Absorptiometry, Photon↗

Nondestructive measurements of implant-bone interface shear modulus and effects of implant geometry in pull-out tests.

Push-out and pull-out tests are used for destructive evaluation of implant-bone interface strength. Because nondestructive mechanical tests would allow maintenance of an intact interface for subsequent morphological study, we developed such a test to determine the shear modulus of the interface by measuring the shear deformation of a thin layer adjacent to the implant. A polyurethane foam model was used to test the experimental setup on a group of nine cylindrical implants with three different lengths (15-48 mm) and three different diameters (5-9.7 mm). The shear modulus of the interface, as calculated from the pull-out test, was validated against the shear modulus of the foam derived from tensile tests. The two values of shear modulus were well correlated (R2 = 0.8, p < 0.001), thus encouraging further application of the setup for tests of implant-bone interface mechanics. In addition, we also examined the effects of implant length and diameter. The length of the implants had a significant influence on the interface shear modulus (p < 0.05), indicating that comparisons of the variable should only be made of implants with the same length. The length and diameter of the implants were not critical parameters for the ultimate fixation strength.

Biocompatible Materials↗

Maintenance of proximal cortical bone with use of a less stiff femoral component in hemiarthroplasty of the hip without cement. An investigation in a canine model at six months and two years.

A canine model of hemiarthroplasty of the hip was used to determine if the use of a less stiff femoral stem can reduce the amount of bone loss induced by stress-shielding. Two types of stem were used: the stiffer stems were made of a titanium alloy, and the less stiff stems were composed of a cobalt-chromium-alloy core with an outer polymer layer. The stems were identical in shape, and both types were circumferentially coated along their entire length (except for the distal five millimeters) with commercially pure titanium fiber metal. Ten dogs with each type of stem were followed for six months, and twelve dogs with each type of stem were followed for two years. Loss of cortical bone from the proximal part of the femur was associated with both types of stem, but typically 50 per cent less bone was lost with the less stiff implants. Most of the cortical loss occurred at the subperiosteal surface. The amount of medullary bone adjacent to the proximal and distal aspects of both types of stem increased; the less stiff stems were associated with a greater increase in the proximal region, and the stiffer stems were associated with a greater increase in the distal region. Similarly, there were peaks in the amount of bone growth into the proximal and distal portions of both types of stem, with a greater peak in proximal bone growth into the less stiff stems and a greater peak in distal bone growth into the stiffer stems.

Alloys↗