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Biomedical subjects

D B Burr

Publications and source records attributed to D B Burr.

At least 55 records · Page 3Linked to original sources
PubMed1999

Development of a fluorescent light technique for evaluating microdamage in bone subjected to fatigue loading.

A new method using fluorescent light microscopy has been developed to visualize and evaluate bone microdamage. We report the findings of two different experiments with a common aim of comparing the fluorescent light technique to the brightfield method for quantifying microdamage in bone. In Experiment 1, 36 canine femurs were tested in four-point cyclic bending until they had lost between 5 and 43% of their stiffness. The loaded portion of the bone was stained en bloc with basic fuchsin for the presence of damage. Standard point counting techniques were used to calculate fractional damaged area (Dm.Ar = Cr.Ar/B.Ar, mm2/mm2) under brightfield and fluorescent microscopy. In Experiment 2, bone microdamage adjacent to endosseous implants, subjected to fatigue loading (150,000 cycles, 2 Hz and 37 degrees C) ex vivo was examined. The bone around the implant was either allowed to heal (adapted specimen) for 12 weeks after placement in dog mid-femoral diaphyses prior to testing or was loaded immediately to simulate non-healed bone surrounding endosseous implants (non-adapted). Crack numerical density (Cr.Dn = Cr.N/B.Ar, #/mm2), crack surface density (Cr.S.Dn = Tt.Cr.Le/B.Ar, mm/mm2) and fractional damaged area were calculated separately by both techniques in the adapted and non-adapted specimens. In both Experiments 1 and 2, significantly more microdamage was detected by the fluorescent technique than by the brightfield method. Also, there was a trend towards higher intraobserver repeatability when using the fluorescent method. These results suggest that the brightfield technique underestimates microdamage accumulation and that the fluorescent technique better represents the actual amounts of microdamage present. The results demonstrate that the fluorescent method provides an accurate and precise approach for bone microdamage evaluation, and that it improves the prediction of stiffness loss from damage accumulation.

Animals↗
PubMed1999

Microdamage adjacent to endosseous implants.

Intense remodeling occurs in lamellar bone adjacent to osseointegrated endosseous implants. The purpose of this study was to compare microdamage accumulation subsequent to ex vivo fatigue loading of bone that surrounds an endosseous implant, (a) immediately after placement (nonadapted bone) and (b) following a 12 week healing period after placement (adapted bone). We hypothesize that there is less microdamage in the more compliant adapted bone than in the older nonadapted bone. Nonthreaded titanium plasma sprayed (TPS)-coated endosseous implants were placed into dog mid-femoral diaphyses and allowed to heal for 12 weeks. Block sections of bone, each containing one implant, were cut anteroposteriorly, resulting in an implant containing lateral cortex, and a medial cortex that was used for testing the nonadapted specimens. Control specimens (n = 14 each for adapted and nonadapted) were loaded at 0 N. Experimental specimens (n = 13, adapted; n = 14, nonadapted) were loaded at 100 N in cantilever bending for 150,000 cycles at 2 Hz, at 37 degrees C on a Bionix 858 testing machine. Specimens were bulk stained with basic fuchsin and 120-140 microm sections were obtained. Crack numerical density (Cr.Dn = Cr.N/ B.Ar, #/mm2), crack surface density (Cr.S.Dn = Tt.Cr.Le/ B.Ar, mm/mm2), and percent damage area (Dm.Ar = Cr.Ar x 100/B.Ar, mm2/mm2) were measured at x 250. Statistically significant differences (p < 0.0001) were seen for Cr.Dn, Cr.S.Dn, and Dm.Ar on the compressed cortices suggesting that adapted bone near the implant accumulated significantly less microdamage than nonadapted bone. Also, the adapted nonloaded control specimens had approximately 20-fold less damage than the respective nonadapted specimens. This study suggests that the compliant adapted bone adjacent to endosseous implants is relatively resistant to fatigue loads. The high success rates of endosseous implants may be due to the presence of a rapidly remodeling region that maintains tissue compliance and limits microdamage initiation.

Animals↗
PubMed1999

Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits.

Intermittent administration of parathyroid hormone (PTH) has an anabolic effect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim of this study was to determine the effects of biosynthetic human PTH(1-34) on the histology and mechanical properties of cortical bone in rabbits, which exhibit Haversian remodeling. Mature New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 micrograms/kg/day or 40 micrograms/kg/day for 140 days. Body weight in rabbits treated with PTH did not change significantly over the experimental period. Serum calcium and phosphate were within the normal range, but a 1 mg/ml increase in serum calcium was observed in rabbits given the higher dose of PTH. Histomorphometry of cortical bone in the midshaft of the tibia showed significant increases in periosteal and endocortical bone formation in these rabbits. Intracortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, stiffness, and work to failure of the midshaft of the femur of rabbits given the 40 micrograms dose of PTH were significantly greater than those in the control group, whereas elastic modulus was significantly lower than that in the rabbits given the 10 micrograms dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption without increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied by concurrent increases in bone at the periosteal and endocortical surfaces. The combination of these phenomena resulted in an enhancement of the ultimate stress, stiffness, and work to failure of the femur.

Animals↗
PubMed1999

Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis.

OBJECTIVE: To examine the effect of the bisphosphonate NE- 10035 on bone histomorphometry and bone dynamics in dogs after transection of the anterior cruciate ligament (ACL), and to determine, in a placebo controlled trial, whether treatment modified the severity of pathologic changes of osteoarthritis (OA) in the unstable joint. METHODS: Ten adult male mongrel dogs underwent ipsilateral ACL transection. Five dogs then received daily subcutaneous injections of NE-10035 on 5 days per week for 12 weeks beginning the day after surgery. The other 5 dogs served as concurrent OA controls and received subcutaneous injections of saline on the same schedule. At sacrifice, 12 weeks after ACL transection, the articular cartilage and synovium of both knees of each dog were evaluated grossly and histologically and the water content and uronic acid concentration of the articular cartilage was determined. Fifteen days before sacrifice, each dog was injected with the fluorochrome label calcein. The injection regimen was repeated 10 days after the initial date. At sacrifice, static and dynamic variables of bone formation were assessed and bone resorption was quantified. RESULTS: In the OA knee of the control group, bone formation and resorption were markedly increased. NE-10035 markedly reduced both formation and resorption of cancellous subchondral bone, but had no effect on osteophyte formation or pathologic changes of OA in the articular cartilage, which were mild in both treatment groups. Water content of the OA cartilage was increased by about 8% in both treatment groups. However, among the controls, the mean uronic acid concentration of the OA cartilage was increased by about 30% in comparison with values for the contralateral knee, while in the NE-10035 treatment group the mean uronic acid concentration of OA knee cartilage was about 15% lower in the active treatment group than in cartilage from the contralateral knee (p = 0.003 for the difference in OA knee uronic acid concentration between the 2 treatment groups, relative to that in the contralateral knee). CONCLUSION: The antiresorptive agent employed in this study effectively reduced turnover of subchondral bone in the OA joint, consistent with the coupling of bone formation to bone resorption at that site. Nonetheless, over the 12 week period of the study it had no effect on osteophyte formation, in which bone formation occurs via enchondral ossification and is not linked to bone resorption, and, despite the clear inhibition of bone turnover in the OA knee of the active treatment group, did not affect the severity of cartilage changes of OA. It should be noted, however, that although treatment with this antiresorptive agent did not affect the level of chondropathy, the cartilage changes in both treatment groups were relatively mild and the sample size relatively small. Additional studies with a larger number of animals and a longer period of observation (to increase the severity of pathology) are warranted to determine whether the inhibition of bone turnover and the decrease in proteoglycan concentration that resulted from therapy will affect articular cartilage degeneration in the OA joint.

Animals↗
PubMed1998

En bloc staining of bone under load does not improve dye diffusion into microcracks.

Microdamage accumulation in bone has been implicated in the pathogenesis of some bone fractures, and in implant loosening. Standard techniques for staining microcracks may not allow all cracks to be stained. We tested the hypothesis that crack closure in bone cortices after removal of a bending load may prevent diffusion of stain to sites of microcrack nucleation. Following cyclic loading, 26 canine femurs were divided into a group stained en bloc while applying a four point bending load, and another group stained without an applied load. No differences in number or length of microcracks were observed, indicating that crack closure does not prevent diffusion of stain to the crack location. Staining under load is unnecessary.

Animals↗
PubMed1998

Does microdamage accumulation affect the mechanical properties of bone?

It has never been demonstrated that microcrack accumulation in bone leads to impaired mechanical properties. We hypothesized that microdamage accumulation is positively and linearly correlated with a reduction in bone's elastic modulus. We also tested the hypothesis that damage accumulates more rapidly in tensile cortices, but crack growth is greater in compressive cortices. Canine femurs (n = 26) were tested in four-point cyclic bending under load control until they had lost between 5 and 43% of their stiffness. Ten femurs were used as nonloaded controls. The loaded portion of the bone was stained en bloc with basic fuchsin to detect the presence of microdamage. The number of stained microcracks, their lengths and the area of damaged bone were measured under the microscope. Crack numerical density, surface density, mean crack length, and the percentage of damaged area were calculated. Significant microdamage accumulation was not detected until the bone had lost 15% of its elastic modulus. The relationship between crack density and stiffness loss was approximately quadratic, but the relationship between damaged area and stiffness loss was linear. There were significantly more microcracks in tensile cortices, but on average cracks were significantly longer in compressive cortices. We conclude that microcrack accumulation impairs the mechanical properties of bone by reducing its elastic modulus. We also conclude that damage accumulates more rapidly in tensile cortices, but crack growth is greater in compressive cortices.

Animals↗
PubMed1998

The importance of subchondral bone in osteoarthrosis.

This article reviews evidence that subchondral bone plays a role in the degeneration of cartilage in osteoarthrosis. Whether the bony changes precede the cartilage degeneration remains unproven but may best be considered necessary for progression of the disease. Epidemiologic studies clearly show increasing subchondral sclerosis with disease progression. Recent evidence demonstrates specific architectural changes in the subchondral trabecular bone in osteoarthrosis that are consistent with an acceleration of bone turnover, which appears to be a part of the pathophysiologic process in progression of the disease. The now well-documented acceleration of bone turnover in osteoarthrosis decreases the stiffness of the bone as a material, but because of structural modifications in both trabecular bone (i.e., increased trabecular number and reduced separation) and subchondral bone (i.e., increased plate thickness), the stiffness (rigidity) of the structure as a whole undoubtedly increases. There is no evidence that growth factors, cytokines, or enzymes play any role in the bony changes associated with the disease, other than as the naturally occurring sequelae of normal bone remodeling processes.

Biomechanical Phenomena↗
PubMed1998

Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions.

Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

Actin Cytoskeleton↗
PubMed1997

The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence.

This paper reviews evidence for the role of subchondral bone and calcified cartilage in the initiation and progression of osteoarthrosis (OA). There is consensus that OA is characterized by subchondral sclerosis, but disagreement about whether bone changes are concurrent with, primary to, or secondary to cartilage deterioration. Clinical observation suggests that bone density and cartilage fibrillation are inversely related. Evidence from the rabbit impulsive loading model is consistent with early bone changes, but evidence from other models of subchondral stiffening, such as the sheep metallic implant model, do not strongly support this idea. However, evidence from tibial angulation models and from the Pond-Nuki (anterior cruciate ligament resection) model show evidence that bone changes precede cartilage fibrillation temporally, and are associated spatially within a single joint. Evidence is also presented for the importance of calcified cartilage changes in pre-disposing the joint towards progression to OA. Microdamage accumulation and repair by vascular invasion may be a component of the pathogenesis of OA in some cases, but more work is needed to demonstrate this conclusively. We conclude that changes in the subchondral mineralized tissues are not required for initiation of cartilage fibrillation, but may be necessary for progression, and that only changes in bone and calcified cartilage close to the joint are significant to the disease process.

Animals↗
PubMed1997

A method suitable for in vivo measurement of bone strain in humans.

Strain gages are the gold-standard for measurement of bone strains in vivo. The use of strain gages in humans, however, is limited by the need for surgery to implant them and by the use of cyanoacrylate adhesives to bond them to bone. Cyanoacrylate adhesives are not FDA approved for implantation in humans, making it difficult to justify their use in experimental procedures. To surmount this difficulty, a method was developed to bond strain gages to bone using an approved substance: polymethylmethacrylate (PMMA). The technique and the validating experiments are presented. The PMMA bonding method gave strain gage readings within an average of 0.25% (range 0-5%) of those found using cyanoacrylate bonding in a side by side comparison on cast acrylic. On bone, the PMMA bonding method produced results comparable to extensometer readings. This method of strain gage application is accurate and straightforward. It is currently being successfully used for in vivo strain measurements in both humans and animals for up to several days following gage application.

Biomechanical Phenomena↗
PubMed1997

Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures.

Repetitive loading causes fragility and microdamage accumulation in the skeleton, but it is not clear whether microcracks accumulate with age in the human skeleton, or whether older women with femoral neck fractures have more microdamage than older women without fracture. This study tested the hypotheses that: (1) microcracks accumulate in the femoral head with age; and (2) older women with femoral neck fractures have significantly more microcracks than similar aged women without fractures. Nonosteoarthritic femoral heads from 9 young (16-66 years) and 12 old (73-88 years) female cadavers and those from 7 females with femoral neck fractures (56-90 years) were dissected. Midfrontal slabs were block stained with 1% basic fuchsin and 150-microm-thick specimens were measured histomorphometrically. Percent trabecular bone area (TbxAr) significantly decreased in older and fractured subjects compared with young subjects (p < or = 0.05). Microcrack density (CrxDn) was significantly higher in women older than 70 years compared with those younger than 70 (p = 0.005; Spearman's r = 0.41, p = 0.032), but was not different between older women with and without fractures. Osteocyte lacunar density (OtxDn) was significantly less in old and fractured subjects compared with young subjects (p < or = 0.01), and inversely correlated to crack density (r = -0.49, p = 0.011). CrxDn was higher in women with low TbxAr (Spearman's r = -0.56; p = 0.004), and varied inversely with OtxDn (Spearman's r = -0.47; p = 0.014). This is consistent with the idea that cracks accumulate more rapidly in women with low bone density. It is also consistent with the idea that the osteocyte network detects microcracks, and signals for their repair.

Adolescent↗
PubMed1997

Differences in muscle endurance and recovery between fallers and nonfallers, and between young and older women.

BACKGROUND: Significant morbidity and mortality are associated with falls in older adults. We tested the hypothesis that older women with a history of falls demonstrate decreased muscle endurance and longer recovery times following fatiguing exercise. METHODS: We evaluated dynamic endurance and recoverability of the quadriceps femoris of 29 young women (YW) (M age = 21.7), 26 older women with a history of falls (FA) (M age = 73.3), and 27 older women with no history of falls (NF) (M age = 71.2) using an isokinetic dynamometer. Subjects performed repeated maximal concentric knee extensions until the force output of two consecutive repetitions fell below 50% of their maximal voluntary contraction (MVC). Recovery was defined as the time required for the return of force output > or = 80% MVC for 2 consecutive repetitions, within a set consisting of 3 maximal contractions. One minute rest was allowed between sets. We collected electromyographic (EMG) data from the quadriceps during all testing to evaluate spectral shifts. RESULTS: ANOVA with a post-hoc Bonferroni-Dunn test revealed time to fatigue was significantly faster in FA than YW (p < .02) and in FA than NF (p < .05), but not different between YW and NF. Time to recovery was significantly slower in FA than YW (p = .01), but not different between YW and NF, or between FA and NF, EMG median frequency power shift (from the beginning to the end of the test) was significantly less in FA (p < .001) than either YW (p < .002) or NF (p < .05). CONCLUSIONS: Older women with a history of falls demonstrate decreased muscular endurance compared to YW and NF, and increased time to recover from fatiguing exercise when compared to young women.

Accidental Falls↗
PubMed1997

Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain.

Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.

3T3 Cells↗
PubMed1997

Bone microdamage and skeletal fragility in osteoporotic and stress fractures.

The accumulation of bone microdamage has been proposed as one factor that contributes to increased skeletal fragility with age and that may increase the risk for fracture in older women. This paper reviews the current status and understanding of microdamage physiology and its importance to skeletal fragility. Several questions are addressed: Does microdamage exist in vivo in bone? If it does, does it impair bone quality? Does microdamage accumulate with age, and is the accumulation of damage with age sufficient to cause a fracture? The nature of the damage repair mechanism is reviewed, and it is proposed that osteoporotic fracture may be a consequence of a positive feedback between damage accumulation and the increased remodeling space associated with repair.

Aged↗
PubMed1997

Application of artificial neural network for micro-crack and damage evaluation of bone.

This paper presents the reasoning and adaptive learning method of artificial neural network (ANN) for micro-crack assessment and damage accumulation due to stiffness loss of dog bone. The importance of using the alternative approach of ANN is that it avoids the complexity of modeling problems, overrides the consideration of simplified assumptions and can be developed directly from experimental data using adaptive learning mechanisms. The proposed artificial neural network model provides a relationship between microdamage accumulation, stiffness loss and number of fatigue cycles (Nf) to failure from an experimental study where stiffness loss and crack area (Cr.Ar., mm2/mm2) are evaluated. This preliminary study using ANN for microdamage evaluation shows that ANN accurately predicts the amount of damage accumulation from stiffness loss.

Animals↗