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Biomedical subjects

D B Burr

Publications and source records attributed to D B Burr.

At least 73 records · Page 4Linked to original sources

Dynamic bone remodeling in later Pleistocene fossil hominids.

Histomorphometric analysis of femoral and tibial diaphyseal fragments from seven Late Archaic and three Early Modern humans are compared with those of the Pecos, a pre-Columbian Native American population. The ten samples, from Broken Hill (EM-793), Shanidar 2, 3, 4, 5, and 6, Tabun 1, and Skhul 3, 6, and 7, provide age-at death results consistent with earlier estimates for most individuals. The Pleistocene groups exhibit less bone turnover and smaller osteons than Recent populations. Resorption and formation were both coupled and balanced in these Pleistocene populations, but the overall vigor of individual cells from both the osteoclast and osteoblast cell lines was less than in Recent populations. Thus the greater bone mass in Later Pleistocene members of the genus Homo is not the result of higher levels of bone turnover, at least among adults.

Age Determination by Skeleton↗

Mineral anisotropy in mineralized tissues is similar among species and mineral growth occurs independently of collagen orientation in rats: results from acoustic velocity measurements.

It has been reported that the mineral crystals in long bones have their c-axis aligned with the bone axis, presumably because collagen fibrils in bone also align with the bone axis. However, the predominant collagen orientation in bone often does not appear to be aligned with the mineral crystals, especially in rat primary bone. We hypothesized that mineral orientation in bone is not necessarily related to collagen orientation. An acoustic microscope was used to measure elastic constants of mineralized tissues from rat, cow, monkey, and human bone, and mineralized turkey leg tendon (MTLT). Measurements were made before and after demineralization with 10% ethylenediaminetetraacetic acid (EDTA) or decollagenization with 7% sodium hypochlorite. The elastic anisotropy ratio (AR) was defined as the ratio of the elastic coefficient in the longitudinal direction to the elastic coefficient in the transverse direction. Anisotropy ratios of mineralized tissues were not affected by formalin fixation or plastic embedding. An evaluation of tissues from the different species showed that the AR after decollagenization was not significantly different (p > 0.4, analysis of variance) among the groups, while AR after demineralization varied from 1.04 (rat bone) to 1.51 (MTLT). There was no correlation between AR after demineralization and AR after decollagenization (r = 0.13, p = 0.5). This showed that the elastic anisotropy of collagen is more variable than mineral anisotropy in bone and MTLT. Another experiment showed that mineralization of turkey leg tendon changes the elasticity of the collagen matrix, making it less anisotropic. A final, prospective experiment was performed in which tibiae of rats were subjected to mechanical loading for 16 weeks. After 12 days, new periosteal woven bone was observed on the tibiae and, after 16 weeks, this new bone was consolidated and mineralized. Mineral in the newly formed woven bone was virtually isotropic (AR = 1.07) after 12 days of loading, then became more anisotropic (AR = 1.52) after 16 weeks of mechanical loading, as the mineral density of the new bone increased. This increase in anisotropy of bone mineral occurred even though the collagen matrix was woven and had no measureable fibril orientation. We conclude that (1) collagen anisotropy and mineral anisotropy are not necessarily correlated in mineralized tissues, (2) mineralization can affect the collagen matrix elasticity of mineralized tissues, and (3) an organized mineral structure can form in the absence of an organized collagen matrix.

Acoustics↗

Resistance to crack growth in human cortical bone is greater in shear than in tension.

It has been proposed that longitudinal shear stresses create bone microdamage, which suggests that bone is weak in shear and may not be adapted to prevent crack growth under shear loading. However, based on the similarities between bone and other fiber-reinforced composites that are tough, i.e. resistant to crack growth, we hypothesized that resistance of human bone to crack growth under shear loading is greater than under tensile loading. Because bone from older individuals and women has demonstrated increased propensity to fracture, we also hypothesized that bone from these individuals has less resistance to crack growth under shear and tension loading. Using compact shear and compact tension specimens, the critical strain energy release rate (Gc) of human bone was measured for longitudinally oriented cracks under tension (mode I) and shear (mode II) loading for male and female cadavers ranging from 55 to 89 y. Average tensile fracture toughness (GIc) of male and female human bone was 339 Nm-1 (S.D. = +/- 132). Average shear fracture toughness (GIIc) of human bone over the same range was 4200 Nm-1 (S.D. = +/- 2516 Nm-1). Shear toughness was greater than tensile toughness (approximately 13 times), which is consistent with other fibrous composite materials. Fracture toughness decreased with age, but the fits were weak and significant for shear loading only. Tension and shear toughness did not depend on gender. We concluded that the resistance to crack propagation under shear loading is greater than under tensile loading, a finding which suggests that bone adapts to prevent crack growth in shear. We also found that bone toughness is equivalent in men and women and that bone toughness gradually decreases with age between 55 and 89 y.

Age Factors↗

In vivo measurement of human tibial strains during vigorous activity.

Our understanding of mechanical controls on bone remodeling comes from studies of animals with surgically implanted strain gages, but in vivo strain measurements have been made in a single human only once. That study showed that strains in the human tibia during walking and running are well below the fracture threshold. However, strains have never been monitored in vivo during vigorous activity in people, even though prolonged strenuous activity may be responsible for the occurrence of stress fractures. We hypothesized that strains > 3000 microstrain could be produced on the human tibial midshaft during vigorous activity. Strains were measured on the tibiae of two subjects via implanted strain gauges under conditions similar to those experienced by Israeli infantry recruits. Principal compressive and shear strains were greatest for uphill and downhill zigzag running, reaching nearly 2000 microstrain in some cases, about three times higher than recorded during walking. Strain rates were highest during sprinting and downhill running, reaching 0.050/sec. These results show that strain is maintained below 2000 microstrain even under conditions of strenuous activity. Strain rates are higher than previously recorded in human studies, but well within the range reported for running animals.

Analysis of Variance↗

Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis.

OBJECTIVE: To determine whether oral administration of doxycycline, in a dose that inhibits cartilage breakdown in a canine cruciate deficiency model of osteoarthritis (OA), affected formation or resorption of subchondral bone. METHODS: Ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament. Five were given doxycycline, 3.5 mg/kg/day, orally, from the day after surgery until they were sacrificed 6 weeks later; the other 5 dogs served as positive OA controls. Three weeks before sacrifice, each dog was given an intravenous injection of the fluorochrome label, calcein, on each of 2 consecutive days; 10 days later, the injection regimen was repeated. At sacrifice, samples of bone from the medial femoral condyle of both knees of each dog were obtained for staining with Villanueva tetrachrome to localize the fluorochrome label and McNeal's tetrachrome for measurement of osteoid and cell counts. RESULTS: Cruciate deficiency resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. CONCLUSION: Doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.

Administration, Oral↗

Advantages of raloxifene over alendronate or estrogen on nonreproductive and reproductive tissues in the long-term dosing of ovariectomized rats.

For the first time, raloxifene or alendronate was administered to rats immediately after ovariectomy for 10 months and compared with estrogen to elucidate mechanisms behind the raloxifene effects observed in nonreproductive and reproductive tissues. Specifically, 75-day-old rats were randomly selected as sham controls (Sham), ovariectomized controls (Ovx) or ovariectomized rats treated with fully efficacious doses of raloxifene (RA), 17 alpha-ethynyl estradiol (EE2) or alendronate (ABP). Lumbar vertebrae and proximal tibiae were examined by computed tomography (QCT) and by histomorphometry. Histomorphometry showed differences in bone architecture between groups when QCT densities were similar, but tibial trabecular bone analysis by QCT correlated with histomorphometry with r = .86 to .93, depending on the parameter. Both techniques confirmed that Ovx had substantially less bone than Sham, with greater loss of trabecular bone in the proximal tibia than vertebrae. Both techniques showed that RA had effects similar to but not identical with EE2 in preventing bone loss in vertebrae and tibiae. ABP partially prevented loss of bone in L-5, but was not significantly different from Ovx in the proximal tibia. This may be caused by ABP suppression of bone apposition, beyond effects observed for EE2 or RA. RA appeared to be more similar to EE2 because ABP significantly depressed bone formation (bone formation rate, mineral apposition rate) to below RA or EE2 levels, especially in L-5. Mechanical loading to failure of L-6 vertebrae showed a rank order of vertebral strength of Sham > RA > EE2 > Ovx > ABP, although significant differences were not observed between treatment groups. These data show that ABP suppression of bone formation can affect bone quality with long-term treatment. In other tissues, RA had minimal uterine effects, while significantly lowering serum cholesterol to below EE2-treated levels. Both EE2 and RA rats had significantly lower body weights than the other groups. ABP had no effect on serum lipids, uterine weight or body weight. Therefore, RA appears to have a broader range of desirable effects on bone, body weight, uteri and cholesterol than ABP or EE2 in ovariectomized rats.

Alendronate↗

Fracture toughness of human bone under tension.

The longitudinal fracture toughnesses of human cortical bone were compared to those of bovine cortical bone to test the hypothesis that although human osteonal bone is significantly weaker and more compliant than primary (plexiform) bone, it is not less tough than primary bone. The fracture toughness indices, critical strain energy release rate (Gc) and critical stress intensity factor (Kc), were determined for human Haversian bone and bovine bone under tension (Mode I) loading using the compact tension method. The effects of thickness, crack growth range and anisotropy on fracture indices for slow stable crack growth in cortical bone were determined. Plane strain assumptions required for application of linear elastic fracture mechanics (LEFM) to bone were investigated. Longitudinal oriented fracture toughness tests were used to assess the crack inhibiting effect of human bone microstructure on fracture resistance. Human bone Kc calculated from the stress concentration formula for 2 and 3 mm thick specimens equaled 4.32 and 4.05 MN m-3/2, respectively. Human bone Gc calculated from the compliance method equaled 827 N m-1 for 2 mm thick specimens and 595 N m-1 for 3 mm thick specimens. It was found that crack growth range, thickness and material assumptions affect fracture toughness. Kc calculated from Gc using an anisotropic relation provided the lowest estimate of Kc and equaled 3.31 MN m-3/2 for 2 mm thick specimens and 2.81 MN m-3/2 for 3 mm thick specimens. Both Kc and Gc were significantly reduced after being adjusted to ASTM standard thickness using ratios determined from bovine bone. The fracture toughness of bovine bone relative to human bone ranged from 1.08 to 1.66. This was compared to the longitudinal strength of bovine bone relative to the longitudinal strength of human bone which is approximately equal to 1.5. We found that even though human bone is significantly weaker than bovine bone, relative to its strength, the toughness of human and bovine bone are roughly similar, but the data were not sufficiently definitive to answer the question of which is tougher.

Aged↗

High frequency components of bone strain in dogs measured during various activities.

Rubin et al. [J. Biomechanics 23, 43-54 (1990)] proposed that high frequency bone strains in the 15-30 Hz range might have significant influence on the morphological adaptation of bone tissue. We sought to further their findings by determining the magnitude of high frequency strains during various activities. We measured strains in the forelimbs of dogs during walking, standing and with their limbs unweighted. As negative controls, we measured strains while the dogs were tranquilized and after sacrifice. Strains in the 15-30 Hz range were not significantly greater than controls for any activity except walking, in which they were less than 4% as large as in the 0-15 Hz range. The high frequency strains observed during walking seemed to occur prior to footfall, suggesting that they were not the result of foot strike. The biological significance of high frequency bone strains has yet to be determined, but may be less than originally proposed because of the relatively small magnitude of these strains.

Adaptation, Physiological↗

Risedronate treatment does not increase microdamage in the canine femoral neck.

Cortical and trabecular bone from the femoral neck of 24 adult female beagle dogs was examined for microdamage following 2 years of treatment with risedronate (NE-58095). Specimens of the femoral neck, sectioned between the femoral head and the intertrochanteric groove, were bulk stained in 1% basic fuchsin in graded alcohols and embedded in methylmethacrylate. Five transverse sections of 100 microns from each specimen were examined for microdamage and measurement of cortical and trabecular area, and three sections from each specimen were measured for calculation of trabecular and cortical bone activation frequency (Ac.f) and bone formation rate (BFR/BV) in the superior and anterior regions of the femoral neck. Although no statistical differences were observed among groups for numerical density or length of microcracks, Kruskal-Wallis analysis showed differences among groups for both cortical and trabecular bone area (p < 0.05). Ac.f was significantly lower in both cortical bone (p < 0.05) and trabecular bone (p < 0.005) of the femoral neck at all dosage levels. No significant difference was observed among groups for trabecular mean wall thickness. The hypothesis that microdamage accumulation increases following reduction in Ac.f was not supported for the canine femoral neck in this experiment. This result could be explained by the fact that microdamage does not accumulate following treatment; that transient increases in microdamage at the beginning of the study period had been repaired; or finally, that the canine femoral neck does not reflect weight-bearing conditions of clinical relevance to humans for assessment of microdamage.

Animals↗

Elastic properties of osteoporotic bone measured by scanning acoustic microscopy.

A combination of low bone mass and decreased bone quality underlies osteoporotic fracture. We used scanning acoustic microscopy, a nondestructive method for assessing bone elasticity at a resolution of about 60 microns, to estimate the quality of biopsied iliac bones. We compared the acoustic velocities and bone volumes among premenopausal normal (n = 10), osteoporotic (n = 20), and postmenopausal normal (n = 10) subjects, the latter age-matched to the osteoporotic subjects. The acoustic measurements were highly reproducible (coefficient of variation = 0.32%). Bone volume of osteoporotic subjects (BV/TV = 13.3%) was lower than that of premenopausal and age-matched normals (BV/TV = 22.8%, p = 0.0007; BV/TV = 24.8%, p = 0.0004, respectively). Acoustic velocity of osteoporotic bone was 6.2% lower than that of age-matched normal bone (p < 0.02), but 3.4% higher than that of bone from premenopausal normal women. The lower acoustic velocity of osteoporotic bone than that of age-matched normal subjects implies that osteoporosis involves altered tissue elasticity. However, the lowest acoustic velocities were measured in premenopausal normal subjects. This unexpected result may indicate a complex relationship between tissue level properties and fragility in bone.

Aged↗

Alterations to the en bloc basic fuchsin staining protocol for the demonstration of microdamage produced in vivo.

En bloc staining with basic fuchsin has become the method of choice to demonstrate bone microdamage produced in vivo. Several alterations have recently been made to the protocol. This technical note presents the new protocols, which include staining through a graded series of alcohols under vacuum, and eliminating the original evaporation stage in the staining protocol. Reasons for variations in staining quality can be related to inadequate dehydration, failure to stain under vacuum, the source of the basic fuchsin, or the solubility of basic fuchsin in water. The most common reasons for over- or understanding are the time left in stain, and the density of the bone. Limitations to the technique include the fact that probably not all cracks are stained by the technique, and the technique is not useful for studies that involve bone with highly variable densities in a single section.

Animals↗

Recovery of dynamic muscle function following isokinetic fatigue testing.

This study was designed to evaluate recovery of dynamic muscle function following muscle fatigue produced by isokinetic testing. Sixteen physically active males (age = 29.2) performed fatigue and recovery tests on an isokinetic dynamometer (KIN-COM 500H). The fatigue test involved concentric contractions of the quadriceps femoris performed until force output fell below 50% MVC for 3 consecutive contractions. This test was repeated 3 times, with 1 minute rest between sets. Recovery of force output was measured during the following 8 minutes. Following post hoc analysis, subjects were grouped into 1 of 3 groups based on their time to recovery of 80% MCV; Recovery immediately following fatigue exercise (Group 1), between 3 and 6 minutes (Group 2), or no recovery during the 8 minute period (Group 3). Analysis revealed a significant decline in peak force between bouts of a three-bout fatigue test for Groups 2 and 3 (p < 0.001), and no decline in Group 1. There was a significant relationship between decline in force output and time to recovery. Thus, subjects developing a greater amount of muscle fatigue took longer to recover following this isokinetic test. It was concluded that an isokinetic fatigue test to 50% MVC, repeated 3 times, is an appropriate fatigue generating protocol for most active males; that recovery time following isokinetic fatigue exercise varies among active males; and recovery may be directly related to decline in force output between bouts of a three-bout fatigue test.

Adult↗

Effect of disc lesion on microdamage accumulation in lumbar vertebrae under cyclic compression loading.

A relationship between disc lesion and microdamage accumulation in adjacent vertebrae during fatigue loading was investigated in a canine model. Eighteen functional spinal units obtained from 6 skeletally mature mongrel dogs were divided into 3 groups: I, control (without loading) (n = 6); II, loading with normal disc (n = 6); and III, loading with disc lesion created by nucleotomy (n = 6). Physiologic cyclic compression was performed for 10(5) cycles, and fractional trabecular bone area and microcrack density in the vertebrae were measured. There was a significant difference in microcrack density among groups and regions (p < 0.0001) with significantly more microdamage in functional spinal units with disc lesions than in the other 2 groups (p < 0.0001). The microcracks were distributed predominantly in the vertebral region adjacent to the nucleotomized disc (p < 0.005). There was a negative association of microcrack density with fractional trabecular bone area (R2 = 0.236, p < 0.02). These results support the hypothesis that disc degeneration contributes to vertebral fragility by causing microdamage accumulation, especially in vertebrae with low bone mass.

Animals↗

Geometric structure of the femoral neck measured using dual-energy x-ray absorptiometry.

An algorithm was developed to estimate the strength of the femoral neck from data generated by the dual-energy x-ray absorptiometry (DXA). This algorithm considers shape of the proximal femur as well as cross-sectional moment of inertia (CSMI) in the estimate. Proximal femora (10) from cadavers of white adults and an aluminum step wedge were scanned with the Lunar DPX to validate the calculation of CSMI. After scanning, each femoral neck was sectioned at its narrowest portion for direct measurement of CSMI. Three healthy young women were scanned five times each to evaluate the reproducibility of geometric measurements using DXA. There was a strong linear association between the CSMI measured directly and using DXA in both cadaver bones (r2 = 0.96) and the aluminum step wedge (r2 = 0.99). The coefficient of variation for CSMI from repeated measurements using DXA was less than 3%. This indicates that it is possible to estimate reproducibly the bending rigidity of bone from DXA measurements. The data from 306 normal subjects were analyzed to investigate geometric changes in the femoral neck with age. Although there was no strong correlation between CSMI and age in normal subjects of either sex, safety factor (SF, an index of strength of the femoral neck during walking) and fall index (FI, an index of the strength of the femoral neck during a fall) decrease with age in both sexes. We observed an alteration of the geometric structure of the femoral neck with age that may increase the stress on the femoral neck and decrease SF and FI.

Absorptiometry, Photon↗

Do variations in hip geometry explain differences in hip fracture risk between Japanese and white Americans?

Despite lower femoral neck bone mass, Japanese women have a substantially lower incidence of hip fracture than North American whites. Reasons for this discrepancy were sought in a study of 57 Japanese and 119 white American women aged 50-79. All women were in good health. Bone mineral content (BMC) in the femoral neck, femoral neck length (NL), femoral neck angle (theta), cross-sectional moment of inertia (CSMI), safety factor (SF), and fall index (FI) were calculated using dual x-ray absorptiometry. Height and weight were greater in Americans than in Japanese (1.62 versus 1.52 m; p < 0.0001 and 66.0 versus 49.4 kg; p < 0.0001, respectively). Mean BMC in the femoral neck and CSMI were greater in Americans than in Japanese (3.91 versus 3.02 g; p < 0.0001 and 0.99 versus 0.57 cm4; p < 0.0001, respectively). NL was longer in Americans (5.6 versus 4.4 cm; p < 0.0001) and theta was larger in Americans (130 versus 128 degrees; p < 0.01), whereas SF and FI were less in Americans than in Japanese (3.41 versus 5.12; p < 0.0001 and 1.00 versus 1.40; p < 0.0001, respectively). These results indicate that despite lower bone mass, Japanese women have lower risks of structural failure in the femoral neck, attributable primarily to shorter femoral necks and, to a lesser degree, a smaller femoral neck angle. Geometric characteristics of the femoral neck in Japanese women are associated with their lower hip fracture risk, and the measurement of proximal femoral geometry, combined with bone mass, may provide further clinical information about the risk of hip fracture.

Absorptiometry, Photon↗

Contribution of collagen and mineral to the elastic anisotropy of bone.

It has long been thought that collagen fibers within the bone matrix are deposited in an aligned pattern that channels mineral growth. If this model of bone structure is correct, both organic and inorganic phases of bone should have similar elastic anisotropy. Using an acoustic microscope, we measured longitudinal and transverse acoustic velocities of cortical specimens taken from 10 dog femurs before and after removal of either the mineral (using 10% EDTA) or collagen phases (using 7% sodium hypochlorite) and calculated longitudinal (CL) and transverse (CT) elastic coefficients. The anisotropy ratio (CL/CT) decreased significantly after demineralization (1.61 before versus 1.06 after, P < 0.0001, paired t-test). However, there was no significant change after decollagenization (1.51 before versus 1.48 after, P = 0.617, paired t-test). We conclude that the orientation of mineral crystals is the primary determinant of bone anisotropy, and the collagen matrix within osteonal bone has little directional orientation.

Acoustics↗

The effects of muscle fatigue on bone strain.

There is anecdotal evidence that bone strains may increase to the point that bone becomes susceptible to rapid failure when muscles become fatigued. To determine whether neuromuscular response could be a factor in accelerating bone failure, we tested the hypothesis that muscle fatigue causes a significant increase in peak principal and shear strains in bone. Ten adult foxhounds were subjected to rigorous exercise that caused muscular fatigue while myoelectrical activity of the quadriceps and hamstrings and strain on the distal tibia were monitored simultaneously. Ground reaction forces on the dog hindlimbs were measured before and after strain gauges had been applied to the tibia. The data show a significant shift to lower median myoelectrical frequencies in the quadriceps, indicating muscular fatigue, following the 20 min exercise period. In conjunction with this shift, peak principal and shear strains increased on both compressive and tensile cortices of the tibia and shear strain on the tensile cortex increased significantly (P = 0.02). The largest changes were along the anterior and anterolateral surfaces of the tibia, where peak principal strain increased by an average of 26-35% following muscular fatigue. The cross-sectional strain distribution was calculated at the gauge site at peak strain at the beginning of the exercise period and at peak strain after 20 min of exercise. These data show a change in strain distribution when muscle becomes fatigued. Strains on the posterior cortex of the bone showed the greatest change. Correlation analysis demonstrated a significant inverse association between median myoelectrical frequency and bone strain after 20 min of exercise (Spearman r2 = 1.00; P = 0.05). These data show that muscle fatigue may be associated with increased bone strain.

Animals↗

Histomorphometric assessment of the mechanisms for rapid ingrowth of bone to HA/TCP coated implants.

The purpose of this work is to use dynamic histomorphometry to evaluate the basic biological mechanisms by which hydroxyapatite/tricalcium phosphate (HA/TCP) implant coatings accelerate bone formation rates. Twenty-five rabbits had an HA/TCP coated cylindrical titanium fiber metal mesh implant surgically placed in the subchondral bone of the proximal tibia and a noncoated implant placed in the contralateral tibia. Twenty-two of these animals had HA/TCP coated cylindrical solid titanium implants placed in the distal femur and an uncoated implant placed in the contralateral femur. The animals were double labeled with vital stains, and sacrificed at 3, 6, 16, or 26 weeks after surgery. Histomorphometric analyses were done of the bone implant interfaces. Both static and dynamic histomorphometric parameters indicate that HA/TCP coatings stimulate faster bone ingrowth to coated fiber metal implants through the early production of woven bone and by subsequent rapid lamellar bone formation rates. Coated fiber metal implants demonstrated significantly more bone ingrowth than noncoated implants through 16 weeks postimplantation, but not by 26 weeks. In solid implants, the differences between coated and noncoated implants are less pronounced and not statistically significant, although there is a trend toward increased bone apposition to the surface of the implants over the first 16 weeks following implantation. The clinical significance of these results is that coated implants may allow earlier return to normal weightbearing.

Alloys↗