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Biomedical subjects

C H Turner

Publications and source records attributed to C H Turner.

At least 127 records · Page 7Linked to original sources
PubMed1994

Mechanotransduction in bone: do bone cells act as sensors of fluid flow?

When compact bone is subjected to bending loads, interstitial fluid in the bone matrix flows away from regions of high compressive stress. The amount of interstitial fluid flow is strongly influenced by the loading rate in a dose-dependent fashion. We hypothesize that interstitial fluid flow affects bone formation, and we tested this hypothesis indirectly by measuring the effect of different loading frequencies on bone formation rate in vivo. The right tibiae of adult female rats were subjected to applied bending at frequencies of 0.05, 0.1, 0.2, 0.5, 1.0, and 2.0 Hz for a 2-wk period. The rats were then killed and histomorphometric measurements of bone formation were made of the midshaft of the tibia. Bending of the tibia increased bone formation rate in the higher-frequency (0.5 to 2.0 Hz) loading groups as much as fourfold, yet no increase in bone formation rate was observed for loading frequencies below 0.5 Hz. In a separate experiment, we found stress-generated potentials (SGP) in the rat tibia to increase monotonically with increasing loading frequency. The dose-response relationship between loading frequency and the bone formation response closely resembles the relationship between loading frequency and SGP within bone. The qualitative similarity between these two relationships suggests that increased bone formation is associated with increased SGP, which are caused by interstitial fluid flow. Bone cells are known to be sensitive to electric fields and may respond directly to SGP. Also, fluid shear forces have been shown to stimulate bone cells in culture, so it is possible that increased interstitial fluid flow directly affects bone formation.

Animals↗
PubMed1994

Raloxifene preserves bone strength and bone mass in ovariectomized rats.

We investigated the effects of raloxifene, a nonsteroidal benzothiophene, on bone strength in ovariectomized rats and compared them with estrogen treatment. Sixty ovariectomized Sprague-Dawley rats were divided into three groups for treatment with orally dosed raloxifene (3 mg/kg), ethynyl estradiol (EE, 0.1 mg/kg), or vehicle. A fourth group of 20 rats that underwent sham ovariectomies and received vehicle was used for comparison. Treatments began 3 days after ovariectomy and continued for 6 months. Raloxifene treatment resulted in greater bone strength in the lumbar vertebrae (P < 0.05) and femoral neck (P < 0.01) and greater bone mineral density at the proximal tibia (P < 0.001) and lumbar vertebrae (P < 0.001) when compared with vehicle-treated ovariectomized animals. The positive effects on bone biomechanical properties from raloxifene treatment were not different than those associated with EE treatment. Raloxifene did not cause a significant increase in uterine weight, whereas EE treatment resulted in uterine weight increased 4-fold over vehicle-treated ovariectomized controls. Therefore, in rats, raloxifene has beneficial effects on bone biomechanics that are equivalent to those of EE treatment without substantial effects on the uterus.

Animals↗
PubMed1993

A mathematical model for fluoride uptake by the skeleton.

A mathematical model was developed that predicts fluoride accumulation and clearance from the skeleton based upon fluoride bioavailability, bone remodeling rate, and the fluoride binding characteristics of bone. It was assumed that fluoride binds to bone in a nonlinear fashion such that a smaller percentage of fluoride is bound to bone if fluoride intake is increased to high levels. Bone resorption rate was assumed to be proportional to the solubility of hydroxyfluoroapatite which is inversely related to bone fluoride content. The predictions made by the model compared favorably with experimental results from fluoride uptake and clearance studies. Parametric studies done using the model showed the following: (1) fluoride can be cleared from the skeleton by bone remodeling, but fluoride clearance takes over four times longer than does fluoride uptake; and (2) fluoride uptake by the skeleton was positively associated with bone remodeling rate. However, the concentration of fluoride in newly formed bone does not decrease with reduced remodeling rates and surpasses 10,000 ppm for intakes of fluoride greater than 9 mg/day. For osteoporosis, daily dose and duration of fluoride treatment should be selected to avoid reaching a toxic cumulative bone fluoride content.

Apatites↗
PubMed1993

Young's modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements.

An ultrasonic technique and microtensile testing were used to determine the Young's modulus of individual trabeculae and micro-specimens of cortical bone cut to similar size as individual trabeculae. The average trabecular Young's modulus measured ultrasonically and mechanically was 14.8 GPa (S.D. 1.4) and 10.4 (S.D. 3.5) and the average Young's modulus of microspecimens of cortical bone measured ultrasonically and mechanically was 20.7 GPa (S.D. 1.9) and 18.6 GPa (S.D. 3.5). With either testing technique the mean trabecular Young's modulus was found to be significantly less than that of cortical bone (p < 0.0001). However, the specimens were dried before microtensile testing so Young's modulus values may have been greater than those of trabeculae in vivo. Using Young's modulus measurements obtained from 450 cubes of cancellous bone and 256 cubes of cortical bone, Wolff's hypothesis that cortical bone is simply dense cancellous bone was tested. A multiple regression analysis that controlled for group membership showed that Young's modulus of cortical bone cannot be extrapolated from the Young's modulus vs density relationship for cancellous bone, yet the Young's modulus of trabeculae can be predicted by extrapolation from the relationship between Young's modulus vs density of the cancellous bone. These results suggest that when considered mechanically, cortical and trabecular bone are not the same material.

Aged↗
PubMed1992

The effects of fluoridated water on bone strength.

Fluoride from fluoridated water accumulates not only in the enamel of teeth but also in the skeleton. The effects of fluoridated water on the skeleton are not well understood, yet there is some evidence that fluoridated water consumption increases the incidence of fractures. In the present study, femoral bending strength was measured in rats on fluoride intakes that ranged from low levels to levels well above natural high fluoride drinking water. Bone strength followed a biphasic relationship with bone fluoride content. Fluoride had a positive effect on bone strength for lower fluoride intakes and a negative influence on bone strength for higher fluoride intakes. The vertebral fluoride content at which femoral strength was maximum was between 1,100 and 1,500 ppm. The increase in femoral strength at this fluoride level was not accompanied by an increase in femoral bone density. The optimal fluoride content is within the range of bone fluoride contents found in persons living in regions with fluoridated water (1 ppm) for greater than 10 years.

Animals↗
PubMed1992

Characterization of in vivo strain in the rat tibia during external application of a four-point bending load.

This paper describes a technique for characterizing strains and stresses induced in vivo in the rat tibia during application of an external four-point bending load. An external load was applied through the muscle and soft tissue with a four-point bending device, to induce strain in a 11 mm section of the right tibiae of ten adult female Sprague-Dawley rats. Induced strains were measured in vivo on the lateral surface of the tibia. Inter-rat difference, leg positioning and strain gage placement were evaluated as sources of variability of applied strains. Beam bending theory was used to predict externally induced in vivo strains. Finite element analysis was used to quantify the magnitude of shear stresses induced by this type of loading. There was a linear relationship between applied load and induced in vivo strains. In vivo strains induced by external loading were linearly correlated (R2 = 0.87) with the strains calculated using beam bending theory. The finite element analysis predicted shear stresses at less than 10% of the longitudinal stresses resulting from four-point bending. Strains predicted along the tibia by finite element analysis and beam bending theory were well-correlated. Inter-rat variability due to tibia size and shape difference was the most important source of variation in induced strain (CV = 21.6%). Leg positioning was less important (CV = 9.5%).

Animals↗
PubMed1992

On Wolff's law of trabecular architecture.

Several studies suggest that the yield strain in cancellous bone may be uniformly distributed and isotropic. Yield strain was reported to be independent of textural anisotropy in bovine cancellous bone [Turner, J. biomech. Engng 111, 1-5 (1989)] and it is plausible that yield strain is isotropic in human cancellous bone as well. In this paper, it is hypothesized that uniform, isotropic strain represents a goal of cancellous bone adaptation, i.e. cancellous bone alters its structure to maintain uniform, isotropic peak strains. Therefore, textural anisotropy must exactly cancel the anisotropy of the peak principal stresses imposed upon cancellous bone. When evaluating the relationships between mechanical properties of cancellous bone and trabecular architecture, it was found that over 90% of the variance of yield strength can be explained by one term--rho 2H3 (where rho is apparent density and H is the normalized anisotropy (fabric) constant). Furthermore, this single term explains 70-78% of the variance in Young's modulus of cancellous bone. Based upon these findings, it was postulated that fabric adaptation goes as Hi/Hj = [ sigma i/sigma j[, where Hi and Hj are fabric eigenvalues in the i- and the j-direction and sigma i and sigma j are peak principal stresses.

Adaptation, Physiological↗
PubMed1992

Functional determinants of bone structure: beyond Wolff's law of bone transformation.

Frost has suggested that functional loading controls bone mass and form as a thermostat controls temperature--by homeostatic regulation (i.e., by negative feedback). Yet, the literature contains many results that appear incompatible with the "mechanostat" hypothesis. We propose that a different type of regulation--epigenetic--is important in many aspects of bone adaptation. Epigenetic regulation, as we describe it, involves positive feedback loops and promotes differentiation as it forces elements of a system to choose between two extreme levels called attractors. Our review of bone adaptation data suggests that lamellar bone formation is regulated homeostatically, whereas the formation of woven-fibered bone or fracture callus is regulated epigenetically, that is, woven bone formation is brought about by a positive feedback loop that stimulates osteoblasts to a state of greater individual activity. This positive feedback loop may involve transforming growth factor beta (TGF beta), for which autocrine induction has been demonstrated in vivo, as well as other factors, including insulin-like growth factor (IGF) and prostaglandin E2 (PGE2). The importance of this model is that it provides a mechanism for many unexplained nonlinear events that have been observed in bone adaptation experiments. Furthermore, it provides insights into the genesis of woven bone, which is a critical step in the process of bone healing and regeneration.

Animals↗
PubMed1992

Structural changes in rat bone subjected to long-term, in vivo mechanical loading.

Woven bone formation is commonly observed when grossly altered loading conditions are imposed upon living bone tissue. The fate of this woven bone with time has not been fully characterized. In this study, rats underwent daily bending of the right tibia for a period of 3 to 14 weeks. New bone was formed in the region of maximum bending stresses on the right tibiae of all rats that underwent daily loading. The new bone was at first poorly mineralized with disorganized collagen structure. With time, the new bone consolidated into a well mineralized primary bone structure similar in appearance to pre-existing nonlamellar bone within the tibial cortex. Using the data from this study and previous studies, we were able to outline the sequence of events that occur during bone adaptation in the rat tibia loading model. Explosive new woven bone formation began to occur five days after the initial four-point bending session, and the amount of woven bone reached a peak after about 15 days. After the third week the new bone began to consolidate. Rapid mineralization occurred during the third and fourth weeks, with less rapid mineralization occurring for several weeks thereafter. After the 14 weeks, the new bone was fully mineralized, and new bone formation had stopped.

Animals↗
PubMed1991

Toward a cure for osteoporosis: reversal of excessive bone fragility.

While estrogen replacement therapy and calcium supplementation appear to be effective at preventing postmenopausal osteoporosis, therapy for established osteoporosis is far less effective. The reduction of bone fragility should be a goal of a treatment for established osteoporosis. To this end, increases in cortical bone mass by subperiosteal new bone formation may produce the greatest mechanical advantage. Anti-resorptive drugs, such as etidronate, have shown potential for reducing the incidence of osteoporotic fracture in the short term, but their ability to produce a long-term benefit may be limited. An alternative approach might be to develop drug therapies that substantially increase cortical bone strength, namely by stimulating periosteal bone formation. Although sodium fluoride has proved to be problematic, there are several other potential osteoporosis therapies. They include treatment with anabolic hormones (e.g. growth hormone and anabolic steroids) and targeted delivery of growth factors. Also, anti-resorptive and formation-stimulating drugs might be combined in a new form of ADFR (coherence) therapy where the new acronym means: Activate-Depress-Formation stimulation-Repeat.

Bone Remodeling↗
PubMed1991

Ultrasonic velocity as a predictor of strength in bovine cancellous bone.

Ultrasonic methods measure properties intrinsic to bone's structure that are not necessarily dependent on bone mass. Therefore, ultrasound may prove to be a useful tool for diagnosing bone fragility and osteoporosis. The goal of this study was to determine the relationship between apparent velocity of ultrasound (AVU) measured using the OsteoTechnology prototype I machine and cancellous bone yield strength (sigma y). AVU correlated well with sigma y (r = 0.753). Consistent with theory, the best predictor of cancellous bone strength was the combination of apparent density (rho a) and AVU, rho a (AVU)2, which had an r2 of 77.4%.

Animals↗
PubMed1991

A noninvasive, in vivo model for studying strain adaptive bone modeling.

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.

Adaptation, Physiological↗