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Biomedical subjects

C T Rubin

Publications and source records attributed to C T Rubin.

At least 55 records · Page 3Linked to original sources

Characterizing bone strain distributions in vivo using three triple rosette strain gages.

Three triple-element rosette strain gages were attached to the equine third metacarpal midshaft to record site-specific strains engendered by locomotion. The distribution of strains acting upon the midshaft cross section were characterized using a combined beam theory and finite element model analysis that did not presume the manner by which the bone was inertially loaded. A medium-speed trot (3.6 ms-1) was chosen as a representative speed and gait, with normal and shear strains, and strain energy density (SED) distributions determined throughout the stance and subsequent swing phase. Importantly, the sites of maximum compression (-2400 mu epsilon), tension (810 mu epsilon), shear (1500 mu epsilon), and SED (54 kPa) were not located at any of the gage attachment sites, emphasizing that a minimum of three rosette gages are necessary to resolve the peaks and locations of functionally induced normal and shear strains. Considering the nonuniform strain distributions across the cortex, we conclude that the third metacarpal is subject to a complex loading milieu comprised of bending, axial compression, end shear, and torsion. As this complex manner of loading was consistent through the entire stance phase, it would appear that, at least during the trot, specific sites within the same cross section are subject to vastly different magnitudes of strain stimulus.

Animals↗

The effect of low-frequency electrical fields on osteogenesis.

An in vivo animal model of disuse osteopenia was used to determine the osteogenic potential of specific components of electrical fields. The ability of a complex pulsed electrical field to inhibit loss of bone was compared with the remodeling response generated by extremely low-power, low-frequency (fifteen, seventy-five, and 150-hertz) sinusoidal electrical fields. The left ulnae of thirty adult male turkeys were functionally isolated by creation of distal and proximal epiphyseal osteotomies and then were exposed, for one hour each day, to an electrical field that had been induced exogenously by means of magnetic induction. After a fifty-six-day protocol, the remodeling response was quantified by a comparison of the cross-sectional area of the mid-part of the diaphysis of the functionally isolated ulna with that of the intact contralateral ulna. Disuse resulted in a 13 per cent mean loss of osseous tissue, which was not significantly different than the 10 per cent loss that was caused by disuse treated with inactive coils. Exposure to the pulsed electrical fields prevented this osteopenia and stimulated a 10 per cent mean increase in the bone area. The osteogenic influence of the sinusoidal electrical fields was strongly dependent on the frequency; the 150, seventy-five, and fifteen-hertz sinusoidal fields, respectively, generated a -3 per cent, + 5 per cent, and + 20 per cent mean change in the bone area. These results suggest a tissue sensitivity that is specific to very low-frequency sinusoidal electrical fields, and they imply that the induced electrical fields need not have complex waveforms to be osteogenic. Since the frequency and intensity range of the sinusoidal fields producing the greatest osteogenic response are similar to the levels produced intrinsically by normal functional activity, these results support the hypothesis that electricity plays a role in the retention of the normal remodeling balance within mature bone.

Animals↗

Frequency specific modulation of bone adaptation by induced electric fields.

A frequency specificity for the response of bone tissue to a physical stimulus is proposed. This is obtained by comparing the spectral power of exogenously induced electric fields to the efficacy of those fields to inhibit immobilization induced bone loss in an in vivo model of skeletal adaptation. Analysis of a family of related waveforms shows that the effectiveness of the induced electric fields could be related to the induced spectral power below approximately 75 Hz. The analysis suggests that bone tissue may be extremely sensitive to induced power levels at or below this frequency, as amplitude variations of less than a factor of two within this range correspond to significantly different bone remodeling responses. The analysis also suggests that bone tissue may be strongly frequency selective, with bone capable of responding specifically to induced power in this osteogenic frequency band, even though the band includes less than 0.1% of the total induced power. As normal functional activity generates strain components encompassing this osteogenic frequency band, a distinct frequency selectivity may indicate that the tissue response is tuned to a specific endogenous stimulus. A detailed characterization of the frequency response of bone tissue could well point to the primary source for the control of the cells responsible for functional adaptation in the skeleton.

Adaptation, Physiological↗

Metabolic modulation of disuse osteopenia: endocrine-dependent site specificity of bone remodeling.

The remodeling response of bone tissue to disuse in four normal adult male turkeys and four adult males metabolically altered by castration was compared by functionally isolating the left ulna of each animal via transverse epiphyseal osteotomies. The right ulna in each animal was left intact and served as a control. After 8 weeks, the animals were euthanized, the ulnae harvested, and 100 microns undecalcified cross sections of the midshaft microradiographed. Areal properties, osteon mineral apposition rates from in vivo fluorochrome labels, and the number and ratios of bone-forming and bone-resorbing foci were quantitated. Compared to their control ulnae, the magnitude of bone resorbed from the functionally isolated ulnae of normal versus castrated males was not significantly different (-12.8 +/- 3.7 versus -10.7 +/- 3.5%, respectively). However, in the functionally isolated ulnae of normal birds, 94% of the total bone loss resulted from expansion of the corticoendosteal envelope, and 97% of the decrease in cross-sectional areas of the ulnae in the castrated birds was due to intracortical porosity. Furthermore, there was a significant interaction between disuse and castration, increasing the total number of intracortical remodeling events (9.4 +/- 0.9) when compared to disuse alone (4.7 +/- 1.4, p less than 0.01), or to the intact ulnae of castrated (2.1 +/- 0.5) and normal adult males (2.0 +/- 1.1). This work emphasizes that the manner in which the bone tissue responds to local changes in its physical environment is directly dependent on the status of the organism's metabolic milieu.

Animals↗

A reduced-modulus acrylic bone cement: preliminary results.

Excessive local contact stress is implicated as an important factor in the initiation of the loosening process after total joint arthroplasties. A reduced-modulus acrylic bone cement, which decreases the bone-cement interface stresses, was developed to test this hypothesis. The formulation consists of butylmethacrylate beads, having a glass transition temperature of 27 degrees C, in a methylmethacrylate matrix. This cement, polybutylmethylmethacrylate (PBMMA), has an elastic modulus one-eighth that of standard PMMA bone cement, 0.27 vs. 2.1 GPa, at body temperature. In vivo use in a pilot study using the sheep total hip arthroplasty model shows a reduction in the rate of loosening of femoral components when compared both radiographically and mechanically with PMMA controls.

Acrylic Resins↗

Functional strains and cortical bone adaptation: epigenetic assurance of skeletal integrity.

The skeleton's ability to withstand the extremes of physical activity is achieved in large part by its capacity to perceive and respond to small changes in its mechanical environment. Strains generated by functional activity would represent an efficient, epigenetic parameter by which the bone cell population could assess the skeleton's structural effectiveness, and subsequently use this information to influence its morphology. However, contrary to our normal interpretation of Wolff's Law, minimizing strain does not appear to be the paramount goal of adaptation, but rather skeletal morphology interacts with functional activity to generate a certain, perhaps cytologically beneficial, type of strain. Three sections are used to address the epigenetic impact on bone morphology: (a) at the level of the organ, the strains generated by functional activity; (b) at the level of the tissue, osteoregulatory parameters of the strain environment; and (c) at the level of the cell, the mechanisms by which physical information is translated to an adaptive response. Only when we understand the mechanisms and objectives of tissue adaptation in the normal skeleton can our perspective and treatment of functionally influenced skeletal pathologies (e.g. osteopenias, fractures) be enhanced.

Adaptation, Physiological↗

Toward an identification of mechanical parameters initiating periosteal remodeling: a combined experimental and analytic approach.

The ability of bone to adapt to its mechanical environment is well recognized, although the specific mechanical parameters initiating or maintaining the adaptive responses have yet to be identified. Recently introduced mathematical models offer the potential to aid in the identification of such parameters, although these models have not been well validated experimentally or clinically. We formulated a complementary experimental/analytic approach, using an animal model with a well-controlled mechanical environment combined with finite element modeling (FEM). We selected the functionally isolated turkey ulna, since the loading could be completely characterized and the periosteal adaptive responses subsequently monitored and quantified after four and eight weeks of loading. Known loads input into a three-dimensional, linearly elastic FEM of the ulna then permitted full-field mechanical characterization of the ulna. The FEM was validated against a normal strain-gaged turkey ulna, loaded in vivo in an identical fashion to the experimental ulnae. Twenty-four candidate mechanical parameters were then compared to the quantified adaptive responses, using statistical techniques. The data supported strain energy density, longitudinal shear stress, and tensile principal stress/strain as the mechanical parameters most likely related to the initiation of the remodeling response. Model predictions can now suggest new experiments, against which the predictions can be supported or falsified.

Adaptation, Physiological↗

Cement line staining in undecalcified thin sections of cortical bone.

A technique for demonstrating cement lines in thin, undecalcified transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.

Animals↗

Cement line staining in undecalcified thin sections of cortical bone.

A technique for demonstrating cement lines in thin, undecalcified, transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.

Animals↗

The in vivo biodynamic properties of the intact equine linea alba.

Liquid metal strain gauges (LMSG) were implanted surgically at three locations on the intact linea alba (LA) in eight horses. LA strain, strain rate, change in strain and stress were recorded during general anaesthesia, recovery from anaesthesia, standing, vocalisation, rectal palpation and at the walk, trot and canter. LA stress was quantitated using an in vitro tensiometric technique. Stress-strain responses differed significantly (P < 0.05) with location, but each described a characteristic relationship for viscoelastic tissues. Maximum peak stress, peak strain and change in strain occurred during anaesthetic recovery. Maximum strain rate occurred at the canter. An abdominal bandage provided no consistent change in strain magnitude. The caudal LA experienced greater stress and strain than the cranial LA. LA strain varied cyclically with cadence. It was concluded that: LMSGs provide a suitable technique for recording LA biodynamics; the dynamic properties of the LA are not homogenous throughout its length; the LA is suited to accommodate the rapid acceleration/deceleration forces associated with strenuous activity which might otherwise cause injury to abdominal viscera; and LA resultant strain alters significantly with phase of stride. It was implied that the likelihood of incisional dehiscence is reduced by minimising exercise and rectal palpation post operatively. The data will permit a more accurate representation of physiological conditions for future laboratory studies.

Abdominal Muscles↗

Prevention of osteoporosis by pulsed electromagnetic fields.

Using an animal model, we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent the osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, we noted a loss of bone of 13.0 per cent compared with the intact contralateral control ulnae over an eight-week experimental period. Using a treatment regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum osteogenic effect between 0.01 and 0.04 tesla per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intracortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new-bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone-remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading.

Animals↗

Ultrasonic measurement of immobilization-induced osteopenia: an experimental study in sheep.

An animal model was used to examine the use of noninvasive transmission ultrasound to measure changes in bone mass which occur following disuse. Unilateral achilles tenectomy was performed on the left leg of eight adult sheep. Following a 12-week period of nonweight bearing, presacrifice transmission ultrasound measurements were taken across the calcanei of the intact and the experimental limbs and compared with those values taken postoperatively. Following specimen harvest, cross-sectional areas of the bones were quantified by microradiography and stereology, and compared with the in vivo ultrasound measurements. There was an average of 8.6% less total bone area, and 18.0% less trabecular volume fraction in the experimental nonweight-bearing limbs as compared with control intact calcanei. The difference in bone mass was associated with a 9.0% decrease in the velocity of sound from the postoperative to the presacrifice ultrasound measurements taken from the experimental calcanei, and a 2.3% increase in the control calcanei. The velocity of sound was found by the Student's t test to be a highly reliable discriminator between the experimental and control limbs.

Animals↗

The cellular basis of Wolff's law. Transduction of physical stimuli to skeletal adaptation.

The cellular milieu responsible for skeletal homeostasis is extremely complex, comprised of many elements, and serves to accomplish both structural and metabolic responsibilities. From one perspective, it is the interactions of the cells loosely grouped as "osteoregulatory" which must retain many of the mineral and metabolic levels of the body. From another view, the coordinated formation and resorption of mineralized tissues, relegated by this same population of cells, is predominantly responsible for achieving and retaining the structural integrity of the skeleton. Unfortunately, the predominant focus of much research is asympathetic to the multifaceted role of the skeleton; it is perceived either as a mineral reservoir or as a structural entity. The skeleton, however, is both of these things. It is not until we acknowledge the dual responsibility of bone that we will be able to understand what parameters, systemic or local, control its regulation. Considered within the context of a three-dimensional movie, with metabolic roles cast in red and structural ones in green, neither the impact nor depth of the film can be appreciated until viewed through the glasses which consider the intricate balance between both the mechanical and mineral dimensions.

Adaptation, Physiological↗

Kappa Delta Award paper. Osteoregulatory nature of mechanical stimuli: function as a determinant for adaptive remodeling in bone.

The capacity for functional adaptation within the skeleton was studied using the functionally isolated turkey ulna preparation. The results of this study would suggest that adaptive bone remodeling is extremely sensitive to alterations in both the magnitude and distribution of the strain generated within the bone tissue. At present, it appears that a loading regime can only influence bone remodeling when it is dynamic in nature. The full osteogenic potential of its influence is then achieved after only an extremely short exposure to this stimulus. The potency of the stimulus appears to be proportional to the magnitude of the strain engendered. As strain levels that are acceptable in one location induce adaptive remodeling in others, it would appear that each region of each bone is "genetically programmed" to accept a particular amount and pattern of intermittent strain as "normal." Deviation from this "optimal strain environment" will stimulate changes in the bone's remodeling balance, resulting in adaptive increases or decreases in its mass.

Adaptation, Physiological↗

The use of ultrasound in vivo to determine acute change in the mechanical properties of bone following intense physical activity.

The velocity of ultrasound was measured transcutaneously across the patella and tibia in 98 volunteers both before and after running the 26 mile Boston Marathon. Absolute sound velocities were 2.9% higher in those runners finishing before 3 h when compared to runners finishing after 3 h. Tibial velocities in males were 8.8% higher than in female runners. The mean velocity across the patella of three wheelchair racers was 28% lower than the mean combined patella velocity measured in all runners. These data suggest that 'faster' velocities are associated with bone that is better suited for high functional demands. Surprisingly, when pre- and post-race velocities were compared in each runner, there was a 1.6% increase in ultrasonic velocity across the tibia, and a 3.5% increase across the patella. An increase in ultrasonic velocity following extreme physical activity suggests that adaptive mechanisms exist in healthy bone to withstand, or possibly avoid, the microdamage which might be caused by repetitive cyclic loading.

Adult↗

Modulation of bone loss during calcium insufficiency by controlled dynamic loading.

Changes in the midshaft cross-sectional area of the ulna were measured in egg-laying turkeys on a diet insufficient in calcium. Left:right comparisons were used to assess the bone loss over a six-week period due to 1) calcium insufficiency, 2) calcium insufficiency plus disuse, and 3) calcium insufficiency and disuse interrupted by a short daily period of intermittent loading applied from an external device. Calcium insufficiency alone in the intact ulna resulted in a 15% reduction in cross-sectional area. In the functionally deprived bones this loss was increased to 32%. In bones where the disuse was interrupted by a single short daily period of loading, the degree of bone loss was significantly modified (P less than 0.006) to 25%. No significant difference in the modulating effect of loading was achieved by varying the peak strain from 0.0015 to 0.003, the strain rate from 0.01 to 0.05, or the duration of the single loading period from 100 sec per day to 25 minutes. All the loading regimes employed had been demonstrated to be osteogenic in mature male birds on a diet sufficient in calcium.

Animals↗

Regulation of bone mass by mechanical strain magnitude.

The in vivo remodeling behavior within a bone protected from natural loading was modified over an 8-week period by daily application of 100 consecutive 1 Hz load cycles engendering strains within the bone tissue of physiological rate and magnitude. This load regime resulted in a graded dose:response relationship between the peak strain magnitude and change in the mass of bone tissue present. Peak longitudinal strains below 0.001 were associated with bone loss which was achieved by increased remodeling activity, endosteal resorption, and increased intra-cortical porosis. Peak strains above 0.001 were associated with little change in intra-cortical remodeling activity but substantial periosteal and endosteal new bone formation.

Animals↗

Dynamic strain similarity in vertebrates; an alternative to allometric limb bone scaling.

Galileo (1638) observed that "nature cannot grow a tree nor construct an animal beyond a certain size, while retaining the proportions which suffice in the case of a smaller structure". However, subsequent measurement has shown that limb bone dimensions are scaled geometrically with body size (Alexander et al., 1979a), and that the material properties of their constituent bone tissue are similar in animals over a wide range of body weight (Sedlin & Hirsch, 1966; Yamada, 1970; Burstein et al., 1972; Biewener, 1982). If, as suggested in previous scaling arguments (McMahon, 1973; Biewener, 1982), vigorous locomotion involved the same proportional forces over a wide range of animal size, this would create a paradox since large animals would be in far greater danger of skeletal failure than small ones. However, in vivo strain gauge implantations have shown that, during high speed running, axial force as a proportion of body weight (G) in the limb bones of animals decreases as a function of body size from 6.9 G in a 7 kg turkey to 2.8 G in a small (130 kg) horse. Estimates of axial force in larger animals suggest that this is further reduced to 0.8 G in a 2500 kg elephant. Nevertheless, it appears that, regardless of animal size or locomotory style, the peak stresses in the bones of these animals are remarkably similar. Therefore, throughout the range of animals considered (350 times differences in mass), we suggest that similar safety factors to failure are maintained, not by allometrically scaling bone dimensions, but rather by allometrically scaling the magnitude of the peak forces applied to them during vigorous locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗