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D B Burr

Publications and source records attributed to D B Burr.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles.

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT). The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally. The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry. The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02). This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone.

Animals↗
PubMed2001

Effects of human parathyroid hormone (1-34), LY333334, on bone mass, remodeling, and mechanical properties of cortical bone during the first remodeling cycle in rabbits.

We have previously shown that parathyroid hormone (PTH) increases cortical bone mass and mechanical strength of female rabbits after 140 days of treatment. However, cortical porosity was also shown to increase. If cortical porosity increases prior to the change in geometry, there may be a transient decrease in cortical bone strength that could make the bone more susceptible to fracture in the early phase of treatment. The purpose of this study is to examine the effects of PTH on the remodeling dynamics and mechanical properties of cortical bone in rabbits, which exhibit haversian remodeling, during the first remodeling cycle after the initiation of treatment. Fifty 9-month-old intact female New Zealand white rabbits were randomized into five groups. A baseline control group was killed at the start of the experiment. The two PTH-treated groups were given human PTH(1-34) at 10 microg/kg daily subcutaneously for 35 (P35) or 70 (P70) days. Two respective age-matched control groups (V35, V70) were injected with vehicle. Histomorphometry of the cortical bone in the tibial midshaft showed that, although intracortical activation frequency was significantly increased by PTH at 35 days, there was no significant increase of cortical porosity in the first remodeling cycle (70 days). Moreover, stimulation of cortical surface bone formation in the treated animals led to significantly greater cortical area and greater bone strength in both P35 and P70. We conclude that, although intracortical remodeling increases within the first remodeling period (70 days) in animals treated with 10 microg/kg PTH, the greater cortical area due to acceleration of bone formation on cortical surfaces increases cortical bone strength. There is no mechanical risk during the first remodeling cycle associated with intermittent PTH treatment in animals with normal bone mass.

Alkaline Phosphatase↗
PubMed2001

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, 1 year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment. Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulation, but that osteoid accumulation reduces production of microdamage.

Animals↗
PubMed2001

Recovery periods restore mechanosensitivity to dynamically loaded bone.

Bone cells are capable of sensing and responding to mechanical forces, but mechanosensitivity begins to decline soon after the stimulus is initiated. Under continued stimulation, bone is desensitized to mechanical stimuli. We sought to determine the amount of time required to restore mechanosensitivity to desensitized bone cells in vivo by manipulating the recovery time (0, 0.5, 1, 2, 4 or 8 h) allowed between four identical daily loading bouts. We also investigated the osteogenic effectiveness of shorter-term recovery periods, lasting several seconds (0.5, 3.5, 7 or 14 s), introduced between each of 36 identical daily loading cycles. Using the rat tibia four-point bending model, the right tibia of 144 adult female Sprague-Dawley rats was subjected to bending, sham bending or no loading. In the rats receiving recovery periods between loading bouts, histomorphometric measurements from the endocortical surface of the loaded and nonloaded control (left) tibiae revealed more than 100 % higher relative bone formation rates in the 8 h recovery group than in the 0 and 0.5 h recovery groups. Approximately 8 h of recovery was sufficient to restore full mechanosensitivity to the cells. In the rats allowed time to recover between load cycles, 14 s of recovery resulted in significantly higher (66-190 %) relative bone formation rates compared to any of the three shorter recovery periods. In both experiments, bone formation in the sham-bending animals was similar to that in the nonloaded control group. The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens.

Animals↗
PubMed2001

Intermittently administered human parathyroid hormone(1-34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys.

Cortical porosity in patients with hyperparathyroidism has raised the concern that intermittent parathyroid hormone (PTH) given to treat osteoporotic patients may weaken cortical bone by increasing its porosity. We hypothesized that treatment of ovariectomized (OVX) cynomolgus monkeys for up to 18 months with recombinant human PTH(1-34) [hPTH(1-34)] LY333334 would significantly increase porosity in the midshaft of the humerus but would not have a significant effect on the strength or stiffness of the humerus. We also hypothesized that withdrawal of PTH for 6 months after a 12-month treatment period would return porosity to control OVX values. OVX female cynomolgus monkeys were given once daily subcutaneous (sc) injections of recombinant hPTH(1-34) LY333334 at 1.0 microg/kg (PTH1), 5.0 microg/kg (PTH5), or 0.1 ml/kg per day of phosphate-buffered saline (OVX). Sham OVX animals (sham) were also given vehicle. After 12 months, PTH treatment was withdrawn from half of the monkeys in each treatment group (PTH1-W and PTH5-W), and they were treated for the remaining 6 months with vehicle. Double calcein labels were given before death at 18 months. After death, static and dynamic histomorphometric measurements were made intracortically and on periosteal and endocortical surfaces of sections from the middiaphysis of the left humerus. Bone mechanical properties were measured in the right humeral middiaphysis. PTH dose dependently increased intracortical porosity. However, the increased porosity did not have a significant detrimental effect on the mechanical properties of the bone. Most porosity was concentrated near the endocortical surface where its mechanical effect is small. In PTH5 monkeys, cortical area (Ct.Ar) and cortical thickness (Ct.Th) increased because of a significantly increased endocortical mineralizing surface. After withdrawal of treatment, porosity in PTH1-W animals declined to sham values, but porosity in PTH5-W animals remained significantly elevated compared with OVX and sham. We conclude that intermittently administered PTH(1-34) increases intracortical porosity in a dose-dependent manner but does not reduce the strength or stiffness of cortical bone.

Animals↗
PubMed2001

Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location.

Bone tissue responds to elevated mechanical loading with increased bone formation, which is triggered either directly or indirectly by the mechanical strain engendered in the bone tissue. Previous studies have shown that mechanical strain magnitude must surpass a threshold before bone formation is initiated. The objective of this study was to estimate the strain thresholds at three different locations along the ulna of adult rats. We hypothesized that the strain threshold would be greater in regions of the ulna habitually subjected to larger mechanical strains. New bone formation was measured on the periosteal and endocortical surfaces of the ulnar diaphysis in adult female rats exposed to controlled dynamic loading. Axial, compressive loading was applied daily at five different magnitudes for a period of 2 weeks. Bone formation rate (BFR) was measured, using double-label histomorphometry at the ulnar middiaphysis and at locations 3 mm proximal and 3 mm distal to the middiaphysis. Loading induced lamellar bone formation on the periosteal surface that was greater at the distal ulnar location and lower at the proximal location when compared with the middiaphysis. Likewise, peak strains on the periosteal surface were greatest distally and less proximally. There was a significant dose-response relationship between peak strain magnitude and periosteal new bone formation when the mechanically induced strain surpassed a threshold. The strain threshold varied from 1343 microstrain (mu strain) proximally to 2284 mu strain at the midshaft to 3074 mu strain distally. Unlike the periosteal response to mechanical loading, there was not a clear dose-response relationship between applied load and bone formation on the endocortical surface. Endocortical strains were estimated to be < 20% of periosteal strains and may not have been sufficient to initiate a bone formation response. Our results show that the osteogenic response on the periosteal surface of the ulna depends on peak strain level once a strain threshold is surpassed. The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower.

Animals↗
PubMed2001

Modeling fatigue damage evolution in bone.

A simple analytical model for damage evolution of bone fatigue is presented. A probabilistic method for characterizing the damage accumulation in terms of microcracks for bone fatigue was developed. The crack numerical density distributions were obtained from the Monte Carlo simulations with a Weibull distribution fit in this study. The results predicted from the present model are compared with existing experimental data and discussed. The quantitative relationship between stiffness loss, loading cycles and microdamage parameter developed in this study may be useful for fatigue life and failure stress predictions.

Animals↗
PubMed2001

Skeletal loading in animals.

A number of in vivo skeletal loading models have been developed to test specific hypotheses addressing the key mechanical and biochemical signals involved in bone's adaptive response to loading. Exercise protocols, osteotomy procedures, loading of surgically implanted pins, and force application through the soft tissues are common approaches to alter the mechanical environment of a bone. Although each animal overload model has a number of assets and limitations, models employing extrinsic forces allow greater control of the mechanical environment. Sham controls, for both surgical intervention (when performed) and loading, are required to unequivocally demonstrate that responses to loading are mechanically adaptive. Collectively, extrinsic loading models have fostered a greater understanding of the mechanical signals important for stimulating bone cells, and highlighted the roles of key signaling molecules in the adaptive response.

Journal Article↗
PubMed2000

Changes in geometry and cortical porosity in adult, ovary-intact rabbits after 5 months treatment with LY333334 (hPTH 1-34).

The purpose of this study was to determine if the increased cortical bone porosity induced by intermittently administered parathyroid hormone (PTH) reduces bone strength significantly. Mature ovary-intact New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 or 40 microg/kg/day for 140 days. Geometry of the femoral midshaft was measured to evaluate changes in the cross-sectional moment of inertia (CSMI). Cortical porosity was measured in the midshaft of the tibia by dividing cortical area into three zones based on equal divisions of cortical diameter: near endocortical (Zone I), near intermediate (Zone II), and near periosteal (Zone III) regions. Total cortical porosity significantly increased after PTH treatment from 1.4% in the controls to 6.3% in the higher dose group, but the location of the new porosities was not randomly distributed. In the controls, porosity of Zones I and II (both 1.7%) was almost twice as much as that of Zone III (0.9%). In the lower dose group, cortical porosity of Zone I (5.5%) and II (1.8%) was greater than in Zone III (0.9%), but these differences were not statistically significant. In the higher dose group, cortical porosity of Zone I (11.5%) and II (6. 1%) significantly increased compared with Zone III (1.4%) (P < 0. 0005). Histomorphometric measurements showed that bone formation rate on both periosteal and endocortical surfaces increased, resulting in increased bone area and cortical area in the higher dose group. A model was developed to evaluate the effect of the changes in geometry and porosity on CSMI in the different zones. This simulation model indicated that CSMI in the higher dose group was significantly greater than in the other two groups, despite the increased porosity. We speculate the reason to be that porosity increased near the endocortical surface, where its mechanical effect is small. This increase was more than offset by apposition of new bone on the periosteal surface. These data suggest that (1) PTH increases cortical porosity in a dose-dependent manner, primarily near endocortical surfaces; (2) because of this nonhomogeneous distribution, the mechanical effect of increased porosity is small; (3) the increased cortical porosity associated with PTH treatment is more than offset by periosteal apposition of new bone, causing an overall increase in the bending rigidity of cortical bone; and (4) these changes cannot be accurately evaluated using noninvasive methods of bone densitometry, which cannot account for the location of bone gain and bone loss.

Animals↗
PubMed2000

Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation?

One plausible purpose of bone turnover is to repair bone microdamage. We hypothesized that suppression of bone turnover impairs bone quality by allowing accumulation of microdamage. We investigated the effect of high-dose etidronate (EHDP) on bone's mechanical properties and microdamage accumulation. Skeletally mature beagles, 1-2 years old at the beginning of the study, were treated with daily injections of vehicle or EHDP at 0.5 mg/kg per day or 5.0 mg/kg per day for 1 year. X-rays were taken at baseline and monthly from 7 to 12 months. Bones were taken upon sacrifice and biomechanical tests, histomorphometry, and microdamage analyses were performed. Fractures of ribs and/or thoracic spinous processes were found in 10 of 11 dogs treated with the higher dose EHDP. Only one fracture of a thoracic spinous process was found in dogs treated with the lower dose EHDP, and no fractures were found in the vehicle controls. Biomechanical tests showed reduced mechanical strength in ribs and lumbar vertebrae, but not in the femoral diaphysis or thoracic spinous process in the higher dose EHDP group. Histomorphometric measurements showed a significant reduction of cancellous bone turnover in both EHDP-treated groups compared with controls. In dogs treated with the higher dose EHDP, activation frequency was reduced to zero in both cortical and cancellous bone. Osteoid volume increased significantly, especially in trabecular bone, resulting in reduced mineralized bone volume in the higher dose EHDP group. Microcrack numerical density (Cr.Dn) increased significantly only in the lumbar vertebral body in the higher dose EHDP group, but not in the rib or thoracic spinous process where fractures occurred. These findings show that suppression of bone turnover using high doses of EHDP is associated with fractures of the ribs and spinous processes in dogs. This is most likely the result of excessive amounts of unmineralized bone produced by the inhibition of mineralization at these high doses, rather than by the accumulation of microdamage.

Animals↗
PubMed2000

Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18-31 years of age.

Women who exercise during their second and third decades may increase their peak bone mass and lower their eventual risk for postmenopausal fracture. However, the effects of exercise in younger women can be modulated by the use of oral contraceptives, which may prevent the normal accretion of bone mass that would otherwise occur. We hypothesized that exercise intervention in young adult women would significantly increase both bone mass and the bending rigidity of the femoral neck. We further hypothesized that exercise intervention in the presence of oral contraceptive use would have a negative effect on bone mass and bending rigidity. Women 18-31 years of age (n = 123) were classified by oral contraceptive use (OC, NOC) and age (18-23, 24-31 years), and then randomized into exercise or nonexercise groups. The exercise protocol consisted of three sessions/week of aerobic and nonaerobic exercises, and continued for 2 years. Each 6 months, the femoral neck of each subject was scanned using a Lunar dual-energy X-ray absorptiometry (DEXA) scanner, and bone mineral content, density and geometric information were used to calculate estimated stresses and bending rigidity at the hip. Percent changes from baseline were analyzed using two-way analysis of variance (ANOVA) at 6, 12, 18, and 24 months. Women who neither exercised nor took oral contraceptives (NE/NOC) had the greatest percentage increases in cross-sectional area (4.98 +/- 2.29%), cross-sectional moment of inertia (9.45 +/- 2.37%), total bone mineral density (2.07 +/- 2.09%), fracture index (8.03 +/- 2.03%), and safety factor (20.03 +/- 5.79%) over the 24 month exercise program. Women who exercised and did not take oral contraceptives (E/NOC) declined on most variables related to femoral strength and bone mass, whereas those women who took oral contraceptives were usually intermediate between NE/NOC and E/NOC, whether they exercised or not. These data show that either exercise or OC use is associated with a suppression of the normal increase in bone mass and mechanical strength in the femoral neck in women 18-31 years old, but the combination of exercise and OC use appears to have a less suppressive effect.

Absorptiometry, Photon↗
PubMed2000

Ca(2+) regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts.

Osteoblasts subjected to fluid shear increase the expression of the early response gene, c-fos, and the inducible isoform of cyclooxygenase, COX-2, two proteins linked to the anabolic response of bone to mechanical stimulation, in vivo. These increases in gene expression are dependent on shear-induced actin stress fiber formation. Here, we demonstrate that MC3T3-E1 osteoblast-like cells respond to shear with a rapid increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) that we postulate is important to subsequent cellular responses to shear. To test this hypothesis, MC3T3-E1 cells were grown on glass slides coated with fibronectin and subjected to laminar fluid flow (12 dyn/cm(2)). Before application of shear, cells were treated with two Ca(2+) channel inhibitors or various blockers of intracellular Ca(2+) release for 0. 5-1 h. Although gadolinium, a mechanosensitive channel blocker, significantly reduced the [Ca(2+)](i) response, neither gadolinium nor nifedipine, an L-type channel Ca(2+) channel blocker, were able to block shear-induced stress fiber formation and increase in c-fos and COX-2 in MC3T3-E1 cells. However, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, an intracellular Ca(2+) chelator, or thapsigargin, which empties intracellular Ca(2+) stores, completely inhibited stress fiber formation and c-fos/COX-2 production in sheared osteoblasts. Neomycin or U-73122 inhibition of phospholipase C, which mediates D-myo-inositol 1,4,5-trisphosphate (IP(3))-induced intracellular Ca(2+) release, also completely suppressed actin reorganization and c-fos/COX-2 production. Pretreatment of MC3T3-E1 cells with U-73343, the inactive isoform of U-73122, did not inhibit these shear-induced responses. These results suggest that IP(3)-mediated intracellular Ca(2+) release is required for modulating flow-induced responses in MC3T3-E1 cells.

3T3 Cells↗
PubMed2000

Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib.

It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone.

Alendronate↗
PubMed2000

Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893.

Daily administration of parathyroid hormone (PTH) and PTH-related protein (PTHrP) peptides has been shown to increase bone mass and strength in animals and, for PTH, to increase bone mass in humans. Long-term direct comparison of multiple members of the PTH/PTHrP family in vivo has not been reported. We therefore selected three PTH/PTHrP molecules for direct comparison in vivo in an adult rat model of postmenopausal osteoporosis: PTH(1-34), PTHrP(1-36), and the PTH analog, SDZ-PTH 893 ¿Leu8, Asp10, Lys11, Ala16, Gln18, Thr33, Ala34 human PTH 1-34 [hPTH(1-34)]¿. A 6-month study was performed in which adult (6-month-old) vehicle-treated ovariectomized (OVX) and sham OVX rats were compared with OVX rats receiving 40 micrograms/kg per day of either PTH(1-34), PTHrP(1-36), or PTH-SDZ-893. Bone mass, as assessed by ash weight and densitometry, bone histomorphometry, biomechanical properties at trabecular and cortical sites, and indices of bone formation markedly increased in all three PTH/PTHrP peptide-treated groups as compared with controls. In general, this improvement followed a rank order of SDZ-PTH-893 > PTH > PTHrP. The adverse effect profile also was greatest with SDZ-PTH-893; these rats developed moderate hypercalcemia, marked renal calcium accumulation, and displayed a 13% mortality. These studies show that PTH(1-34), PTHrP(1-36), and PTH-SDZ-893 significantly and progressively increase bone mass and bone strength in this rat model of postmenopausal osteoporosis. The adverse effect profile correlates in general terms with efficacy. All three peptides show promise as skeletal anabolic agents. Further studies in humans will be required to define optimal efficacy-to-adverse effect ratios and relative efficacy for each peptide in human osteoporosis.

Animals↗
PubMed2000

Partitioning a daily mechanical stimulus into discrete loading bouts improves the osteogenic response to loading.

A single 3-minute bout of mechanical loading increases bone formation in the rat tibia. We hypothesized that more frequent, shorter loading bouts would elicit a greater osteogenic response than a single 3-minute bout. The right tibias of 36 adult female Sprague-Dawley rats were subjected to 360 bending cycles per day of a 54 N force delivered in 1, 2, 4, or 6 bouts on each of the 3 loading days. Rats in the 6-bouts/day group received 60 bending cycles per bout (60 x 6); rats in the 4-bouts/day group received 90 bending cycles per bout (90 x 4); the 2- and 1-bouts/day groups received 180 and 360 bending cycles per bout, respectively (180 x 2 and 360 x 1). A nonloaded, age-matched control group (0 x 0) and two sham-bending groups (60 x 6 and 360 x 1) also were included. Fluorochrome labeling revealed a 10-fold increase in endocortical lamellar bone formation rate (BFR/bone surface [BS]) in the right tibia versus the left (nonloaded) side in the 60 x 6 bending group. Endocortical BFR/BS in the right tibia of the 4-, 2-, and 1-bout bending groups exhibited 8-, 4-, and 4-fold increases, respectively, over the control side. Relative (right minus left) values for endocortical BFR/BS, mineralizing surface (MS/BS), and mineral apposition rate (MAR) were 65-94% greater in the 90 x 4 and 60 x 6 bending groups compared to the 360 x 1 bending group. Sham-bending tibias exhibited relative endocortical bone formation values similar to those collected from the control (0 x 0) group. The data show that 360 daily loading cycles applied at intervals of 60 x 6 or 90 x 4 represent a more osteogenic stimulus than 360 cycles applied all at once, and that mechanical loading is more osteogenic when divided into discrete loading bouts. Presumably, bone cells become increasingly "deaf" to the mechanical stimulus as loading cycles persist uninterrupted, and by allowing a rest period between loading bouts, the osteogenic effectiveness of subsequent cycles can be increased.

Animals↗
PubMed2000

Fatigue data analysis of canine femurs under four-point bending.

When bone is subjected to fatigue loading, micro-cracks initiate and grow. This reduces the mechanical properties and quantitative relationships between stiffness loss and loading cycles may be derived. We developed the relationships between stiffness loss and loading cycles for whole canine femurs subjected to cyclic fatigue in four-point bending. The fatigue data from experiments followed Weibull statistics. When the stiffness loss is less than 15%, a linear relationship is best-fitted (R2 = 0.96, p < 0.0001) between the stiffness loss and loading cycles. However, when the stiffness loss is greater than 30%, a power law relationship is best-fitted (R2 = 0.97, p < 0.0001) between the stiffness loss and loading cycles. Thus, we conclude that the derived relationships between stiffness loss and loading cycles might be useful for the prediction of bone failure under cyclic bending subjected to an initial strain of 2700 microstrain.

Algorithms↗
PubMed1999

Elastic anisotropy and collagen orientation of osteonal bone are dependent on the mechanical strain distribution.

There is evidence that the collagen microarchitecture of bone is influenced by mechanical stresses or strains. We hypothesized that peak functional strains correlate with the elastic anisotropy and collagen orientation of bone tissue and that the bone anisotropy might be changed by altering the strain patterns in canine radii for 12 months. We tested these hypotheses in studies using nine adult foxhounds. The baseline group (n = 3) had three rosette strain gauges placed around the midshaft of the radius, and strain distributions were measured during walking. The osteotomy group (n = 3) had 2 cm of the ulna surgically removed, and the sham group (n = 3) received a sham osteotomy. The osteotomy and sham groups were allowed free movement in cages with runs for 12 months, after which strain distributions were measured on the radii during walking. Bone-tissue anisotropy and collagen architecture were measured in radii from which the in vivo longitudinal strain patterns had been measured. The collagen birefringence patterns were measured with use of a circularly polarized light technique, and the elastic anisotropy of the bone, mineral, and collagen matrix was evaluated with a novel acoustic microscopy technique. Peak longitudinal strains in the radius correlated with the normalized longitudinal structure index (a polarized light measure of collagen birefringence) and the tissue anisotropy ratio. The average anisotropy ratio was 1.28+/-0.01 in the posterior (compressive) cortex and 1.43+/-0.01 in the anterior (tensile) cortex (these values are significantly different at p < 0.0001). The ulnar osteotomy changed the strain pattern on the radius, causing increased tensile strains in the medial cortex by more than 5-fold that were associated with a significant increase in the anisotropy ratio in the bone tissue. The longitudinal structure index was strongly correlated (r = 0.62, p < 0.005) with the anisotropy ratio of demineralized bone but was not correlated with that of deproteinized bone; this indicates that it reflects collagen fibril orientation in the bone matrix. These results indicate that mechanical strains affect both collagen and mineral microarchitecture in bone tissue, i.e., tensile strains are associated with increased tissue anisotropy and compressive strains, with decreased anisotropy.

Animals↗