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R B Martin

Publications and source records attributed to R B Martin.

At least 19 recordsLinked to original sources
PubMed2007

On sampling bones for microcracks.

This paper addresses the problem of designing experiments to measure microcrack density in cortical bone. Microcracks are relatively scarce in bone cross-sections, and their size requires microscope settings having small fields of view. Thus, substantial time is required to count cracks in each cross-section. Consequently, most studies evaluate a relatively small cross-sectional area from each specimen, the chance of finding a crack in any given field is small, and there is a significant chance of not finding even one crack in the specimens representing a particular subject. Therefore, a statistical model for microcrack counting was created to develop guidelines for sampling bones for microcracks. Three questions were addressed. 1) What are the relationships of sample size to variability in microcrack density results and the probability of crackless specimens? 2) How can sample size be chosen a priori so as to reduce the probability of crackless specimens and the associated variability in the data to an acceptable level? 3) What are the confidence intervals for the mean density of microcracks measured using microscopic counting? Using a Poisson model for the distribution of microcracks within microscope fields the total area (mm(2)) that should be examined for each specimen is given by A(s)=-ln(F)/Cr.Dn, where Cr.Dn is the expected microcrack density for an individual sample and F is the desired probability (expressed as a fraction) that the individual sample will contain no microcracks. This equation is validated against 8 results from three different experiments.

Animals↗
PubMed2005

Osteonal effects on elastic modulus and fatigue life in equine bone.

We hypothesized that recently formed, incompletely mineralized, and thus, relatively deformable osteons in the equine third metacarpus enhance in vitro load-controlled fatigue life in two ways. Macroscopically, there is a compliance effect, because reduced tissue elastic modulus diminishes the stress required to reach a given strain. Microscopically, there is a cement line effect, in which new osteons and their cement lines more effectively serve as barriers to crack propagation. We studied 18 4 x 10 x 100 mm beams from the medial, lateral, and dorsal cortices of metacarpal bones from 6 thoroughbred racehorses. Following load-controlled fatigue testing to fracture in 4 point bending, a transverse, 100 microm thick, basic fuchsin-stained cross-section was taken from the load-bearing region. The number and diameter of all intact (and thus recently formed/compliant) secondary osteons in a 3.8 x 3.8 mm region in the center of the section were determined. The associated area fraction and cement line length of intact osteons were calculated, and the relationships between these variables, elastic modulus (E), and the logarithm of fatigue life (logN(F)) were analyzed. As expected, logN(F) was negatively correlated with E, which was in turn negatively correlated with intact osteon area fraction and density. (LogN(F))/E increased in proportion to intact osteon density and nonlinearly with cement line density (mm/mm(2)). These results support the hypothesis that remodeling extends load-controlled fatigue life both through the creation of osteonal barriers to microdamage propagation and modulus reduction.

Animals↗
PubMed2004

Classifying disease chromosomes arising from multiple founders, with application to fine-scale haplotype mapping.

The availability of high-density haplotype data has motivated several fine-scale linkage disequilibrium mapping methods for locating disease-causing mutations. These methods identify loci around which haplotypes of case chromosomes exhibit greater similarity than do those of control chromosomes. A difficulty arising in such mapping is the possibility that case chromosomes have inherited disease-causing mutations from different ancestral chromosomes (founder heterogeneity). Such heterogeneity dilutes measures of case haplotype similarity. This dilution can be mitigated by separating case chromosomes into subsets according to their putative mutation origin, and searching for an area with excessive haplotype similarity within each subset. We propose a nonparametric method for identifying subsets of case chromosomes likely to share a common ancestral progenitor. By simulation studies and application to published data, we show that the method accurately identifies relatively large subsets of chromosomes that share a common founder. We also show that the method allows more precise estimates of the disease mutation loci than obtained by other fine-scale mapping methods.

Algorithms↗
PubMed2004

Do microcracks decrease or increase fatigue resistance in cortical bone?

Fatigue of cortical bone produces microcracks; it has been hypothesized that these cracks are analogous to those occurring in engineered composite materials and constitute a similar mechanism for fatigue resistance. However, the numbers of these linear microcracks increase substantially with age, suggesting that they contribute to increased fracture incidence among the elderly. To test these opposing hypotheses, we fatigued 20 beams of femoral cortical bone from elderly men and women in load-controlled four point bending having initial strain ranges of 3000 or 5000 microstrain. Loading was stopped at fracture or 10(6) cycles, whichever occurred first, and microcrack density and length were measured in the loaded region and in a control region that was not loaded. We studied the dependence of fatigue life and induced microdamage on initial microdamage, cortical region, subject gender and age, and several other variables. When the effect of modulus variability was controlled, longer fatigue life was associated with higher rather than lower initial crack density, particularly in the medial cortex. The increase in crack density following fatigue loading was greater in specimens from older individuals and those initially having longer microcracks. Crack density increased as much in specimens fatigued short of the failure point as in those that fractured, and microcracks were, on average, shorter in specimens with greater numbers of resorption spaces, a measure of remodeling rate.

Adult↗
PubMed2003

Equine cortical bone exhibits rising R-curve fracture mechanics.

Previous studies of the fracture properties of cortical bone have suggested that the fracture toughness increases with crack length, which is indicative of rising R-curve behavior. Based on this indirect evidence and the similarity of bone to ceramic matrix composites, we hypothesized that bone would exhibit rising R-curve behavior in the transverse orientation and that the characteristics of the R-curves would be regionally dependent within the cortex due to variations in bone microstructure and toughening mechanisms. To test these hypotheses, we conducted R-curve experiments on specimens from equine third metacarpal bones using standard fracture mechanics testing methods. Compact type specimens from the dorsal and lateral regions in the middle of the diaphysis were oriented for crack propagation transverse to the longitudinal axis of the bone. The test results demonstrate that equine cortical bone exhibits rising R-curve behavior during transverse crack propagation as hypothesized. Statistical analyses of the crack growth initiation toughness, K0, the peak toughness, Kpeak, and the crack extension at peak toughness, deltaa, revealed significant regional differences in these characteristics. Specifically, the lateral cortex displayed higher crack growth initiation and peak toughnesses. The dorsal cortex exhibited greater crack extension at the peak of crack growth resistance. Scanning electron microscopy revealed osteon pullout on fracture surfaces from the dorsal cortex and but not in the lateral cortex. Taken together, the significant differences in R-curves and the SEM fractography indicate that the fracture mechanisms acting in equine cortical bone are regionally dependent.

Animals↗
PubMed2003

Osteon pullout in the equine third metacarpal bone: effects of ex vivo fatigue.

An important concept in bone mechanics is that osteons influence mechanical properties in several ways, including contributing to toughness and fatigue strength by debonding from the interstitial matrix so as to "bridge" developing cracks. Observations of "pulled out" osteons on fracture surfaces are thought to be indicative of such behavior. We tested the hypothesis that osteon pullout varies with mode of loading (fatigue vs. monotonic), cortical region, elastic modulus, and fatigue life. Mid-diaphseal beams from the dorsal, medial, and lateral regions of the equine third metacarpal bone were fractured in four point bending by monotonic loading to failure under deflection control, with or without 10(5) cycles of previous fatigue loading producing 5000 microstrain (15-20% of the expected failure strain) on the first cycle; or sinusoidal fatigue loading to failure, under load or deflection control, with the initial cycle producing 10,000 microstrain (30-40% of the expected failure strain). Using scanning electron microscopy, percent fracture surface area exhibiting osteon pullout (%OP.Ar) was measured. Monotonically loaded specimens and the compression side of fatigue fracture surfaces exhibited no osteon pullout. In load-controlled fatigue, pullout was present on the tension side of fracture surfaces, was regionally dependent (occurring to a greater amount dorsally), and was correlated negatively with elastic modulus and positively with fatigue life. Regional variation in %OP.Ar was also significant for the pooled (load and deflection controlled) fatigue specimens. %OP.Ar was nearly significantly greater in deflection controlled fatigue specimens than in load-controlled specimens (p=0.059). The data suggest that tensile fatigue loading of cortical bone eventually introduces damage that results in osteonal debonding and pullout, which is also associated with increased fatigue life via mechanisms that are not yet clear.

Animals↗
PubMed2003

Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta.

Alendronate, a bisphosphonate drug, has shown promise in reducing remodeling and bone loss in postmenopausal osteoporosis. Alendronate acts directly on the osteoclast, inhibiting its resorption capability. This inhibition of osteoclast activity has led to the use of bisphosphonates in the treatment of the osteogenesis imperfecta condition. Treatment of osteogenesis imperfecta with bisphosphonates enhances bone strength, but the consequences on linear bone growth are not well defined. Using the oim mouse model for type III osteogenesis imperfecta, two doses of alendronate, low (0.125 mg/kg/wk) and high (2.5 mg/kg/wk) were administered weekly via intraperitoneal injection starting at 4 weeks of age and ending at 12 weeks of age to assess the effects of alendronate on humerus and ulna length. The higher dose of alendronate reduced humerus and ulna length in the oim/wt and wt/wt genotypes for both sexes (P < 0.05). The oim/oim humerus and ulna were not significantly affected by the higher dose of alendronate in females, but reduced bone length in males (P < 0.0085). Proximal humerus growth plate area was affected by both genotype and alendronate dose and growth plate diameter was increased at the chondro-osseous junction by both alendronate doses (P < 0.011). Genotype and alendronate dose affected growth plate height. The oim/oim genotype displayed taller growth plates. The high dosage of alendronate increased overall growth plate height, particularly within the hypertrophic zone, which suggests a failure of vascular invasion-induced apoptosis in the hypertrophic cells. In conclusion, these results indicate that high doses of alendronate (>2.5 mg/kg/wk) inhibit long bone length in mice through alteration of the growth plate and possibly reduced resorption at the chondro-osseous junction.

Alendronate↗
PubMed2002

Compliance calibration for fracture testing of equine cortical bone.

An experimental compliance calibration method for measuring crack length in fracture toughness tests of cortical bone was developed. Calibration tests were conducted on twenty compact type fracture specimens machined from the mid-diaphysis of five pairs of equine third metacarpal bones. Specimens were oriented for crack propagation in a direction transverse to the longitudinal axis of the bone. Specimen compliance was determined from the load vs. crack opening displacement record over a range of crack lengths from 0.48 to 0.75 times the specimen width. The results demonstrate that the compliance calibration method developed for isotropic materials can be used to determine crack length in bone, which is transversely isotropic. However, specimens from lateral and dorsal regions exhibited significantly different compliance calibrations even after differences in elastic modulus were taken into account in the normalized compliance.

Animals↗
PubMed2002

Is all cortical bone remodeling initiated by microdamage?

There is increasing interest in the degree to which bone remodeling, particularly in cortical bone, is "targeted" at fatigue microdamage. The theory that microdamage initiates remodeling in close proximity to microcracks, thereby removing them, and that this accounts for a significant fraction of the overall remodeling activity, has been gaining acceptance. However, the association between the initial, resorptive stage of remodeling and microcracks in histologic sections of cortical bone is far from complete; indeed, the great majority of resorption spaces are not spatially associated with microcracks. This observation has maintained support for the older concept that most remodeling occurs primarily for such metabolic purposes as calcium homeostasis. To gain further insight regarding the degree to which microdamage governs remodeling, this study presents a mathematical analysis based on the unorthodox hypothesis that all cortical bone remodeling is initiated by, and in close proximity to, microcracks. Equations are derived showing that, because remodeling basic multicellular units (BMUs) travel several millimeters beyond their point of initiation, the relative numbers of resorption spaces and microcracks found in close spatial proximity or isolated from one another are consistent with the hypothesis. The results also predict the degree to which the spatial association between resorption spaces and microcracks should exceed that due to chance alone. There are as yet very limited experimental data suitable for testing this model, but the existing data closely correspond to the model's predictions.

Animals↗
PubMed2002

Bone morphogenetic protein-7 selectively enhances mechanically induced bone formation.

The responses of bone cells to skeletal loading are clearly an important factor in bone biology, but much remains to be learned about the role of these responses in skeletal development, maintenance, and tissue repair. Bone morphogenetic proteins (BMPs) are key regulators of bone formation. We examined the effect of BMP-7 on periosteal and endosteal bone formation in response to increased mechanical loading using the rat tibial bending model. Female Sprague-Dawley rats were divided into four groups of six rats each. Three groups received four point bending loading at 60 N force; the fourth group received sham loading at the same force. The right tibia received 36 cycles of loading on Monday, Wednesday, and Friday for 2 weeks; the left tibia served as a nonloaded control. Just prior to loading, the three loaded groups were injected intraperitoneally with vehicle only or 10 microg/kg or 100 microg/kg of recombinant human BMP-7. Half the sham group received vehicle, and half were given 100 microg/kg of BMP-7. Bone forming surfaces were labeled twice in vivo with calcein, and histomorphometry was performed to quantify periosteal and endosteal bone formation in the loaded and control tibiae. BMP-7 had no effect on periosteal or endosteal bone formation in control or sham-loaded tibiae. Loading produced significantly more woven bone on the periosteal surface than sham loading, but BMP-7 treatment had no effect on this response. Endosteal bone formation was entirely lamellar, and loading (but not sham loading) increased the endosteal mineral apposition and bone formation rates. The higher BMP-7 dose more than doubled the load-induced increase in endosteal lamellar bone formation rate, primarily by increasing the amount of bone forming surface.

Animals↗
PubMed2002

Size, structure and gender: lessons about fracture risk.

The differences in age-related fracture risks among men and women must reflect gender differences in the relevant variables. We are concerned here with gender differences in structural variables that relate to the size and shape of bones. As children grow, their bones grow in diameter through periosteal modeling. Studies show that radial growth is driven by mechanical forces and is not just "genetically programmed". Moving bone mass farther from the center of the diaphysis makes it more effective in resisting bending and twisting forces, and disproportionately so in comparison to changes in bone mass. Gender differences in long bone structure appear to arise because the bone cells of males and females function in different hormonal environments which affect their responses to mechanical loading. In girls, bone formation on the metacarpal periosteal surface essentially stops at puberty, and is replaced by formation on the endosteal surface, reducing endosteal diameter until about age 20. Bone strength is 60% greater in male metacarpals than in those of females because bone is added periosteally in boys and endosteally in girls. At menopause endosteal resorption resumes, accompanied by slow periosteal apposition, weakening cortical structure. Similar phenomena occur in such critical regions as the femoral neck. Another fundamental gender difference in skeletal development is that whole body bone mineral content increases in linear proportion to lean body mass throughout skeletal maturation in boys, but in girls there is a distinct increase in the slope of this relationship at puberty, when estrogen rises. Frost's hypothesis is that this reflects an effect of estrogen on bone's mechanostat set point, and this is increasingly supported by data showing that estrogen and mechanical strain act through a common pathway in osteoblast-like cells. If Frost's hypothesis is correct, the mechanostat is set for maximal effect of mechanical loading on bone gain during the 2-3 years preceding menarche. During the childbearing years, the set point is at an intermediate level, and at menopause, it shifts again to place the skeleton into the metabolic equivalent of a disuse state. The most direct approach to resolving this problem would be to simulate the putative effect of estrogen on the set point itself.

Journal Article↗
PubMed2001

Stabilities and isomeric equilibria in solutions of monomeric metal-ion complexes of guanosine 5'-triphosphate (GTP4-) and inosine 5'-triphosphate (ITP4-) in comparison with those of adenosine 5'-triphosphate (ATP4-).

Under experimental conditions in which the self-association of the purine-nucleoside 5'-triphosphates (PuNTPs) GTP and ITP is negligible, potentiometric pH titrations were carried out to determine the stabilities of the M(H;PuNTP) and M(PuNTP)2-complexes where M2+ = Mg2+, Ca2+, Sr2+. Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ (I = 0.1 M, 25 degrees C). The stabilities of all M(GTP)2- and M(ITP)2- complexes are significantly larger than those of the corresponding complexes formed with pyrimidine-nucleoside 5'-triphosphates (PyNTPs), which had been determined previously under the same conditions. This increased complex stability is attributed, in agreement with previous 1H MNR shift studies, to the formation of macrochelates of the phosphate-coordinated metal ions with N7 of the purine residues. A similar enhanced stability (despite relatively large error limits) was observed for the M(H;PuNTP) complexes, in which H+ is bound to the terminal y-phosphate group, relative to the stability of the M(H;PyNTP)- species. The percentage of the macrochelated isomers in the M(GTP)2- and M(ITP)2- systems was quantified by employing the difference log KMM(PuNTP)-log KMM(PyNTP); the lowest and highest formation degrees of the macrochelates were observed for Mg(ITP)2- and Cu(GTP)2- with 17 +/- 11% and 97 +/- 1%, respectively. From previous studies of M(ATP)2- complexes, it is known that innersphere and outersphere macrochelates may form; that is, in the latter case a water molecule is between N7 and the phosphate-coordinated M2+. Similar conclusions are reached now by comparisons with earlier 1H MNR shift measurements, that is, that Mg(GTP)2- (21 +/- 11%), for example, exists largely in the form of an outersphere macrochelate and Zn(GTP)2- (68 +/- 4%) as an innersphere one. Generally, the overall percentage of macrochelate falls off for a given metal ion in the order M(GTP)2- > M(ITP)2- > M(ATP)2-; this is in accord with the decreasing basicity of N7 and the steric inhibition of the (C6)NH2 group in the adenine residue. Furthermore, although the absolute stability constants of the previously studied M(GMP), M(IMP), and M(AMP) complexes differ by about two to three log units from the present M(PuNTP)2- results, the formation degrees of the macrochelates are astonishingly similar for the two series of nucleotides for a given metal ion and purine-nucleobase residue. The conclusion that N7 of the guanine residue is an especially favored binding site for metal ions is also in accord with observations made for nucleic acids.

Adenosine Triphosphate↗
PubMed2001

Effects of chair restraint on the strength of the tibia in rhesus monkeys.

To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was 4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

Adaptation, Physiological↗
PubMed2001

Overload arthrosis: strain patterns in the equine metacarpal condyle.

An overload arthrosis occurs consistently in the palmar region of the metacarpal condyle of the equine fetlock (metacarpophalangeal) joint characterized by subchondral bone sclerosis, devitalization and mechanical failure leading to collapse of the overlying articular cartilage. Samples were selected of joints with mild, moderate, and severe subchondral sclerosis, in which cartilage collapse had not yet occurred. An additional group that had severe sclerosis with focal rarefaction suggesting impending collapse was also studied (n=5/group). Parasagittal slices were milled to 2.0 mm thickness and subjected to palmar forces 50 to 200% of those applied by the sesamoid bone at angles corresponding to early, mid and late stance support phases of the gait cycle. From contact radiographs in the loaded and unloaded samples, strains were determined by recognizing displacements in the trabecular patterns using texture correlation analysis. Failure did not occur in any of the samples. Strains were generally proportional to the forces applied and greatest at midstance. Strain patterns varied between samples and with the different loading positions. With increased subchondral bone sclerosis there was greater shear strain in overlying trabeculae. Strain patterns were not consistently different within the sclerotic bone at the site of failure. Focally higher strains at the surface were sometimes related to the edge of the platen which was molded to mimic the sesamoid bone in vivo. These results indicate that sclerotic thickening of subchondral bone transmits stresses to overlying trabeculae. No consistent strain pattern was recognized where devitalization and mechanical failure occurs. Focally higher strains related to the edge of the opposing sesamoid bone may play a role.

Journal Article↗
PubMed2000

Bone strain and microcracks at stress fracture sites in human metatarsals.

Microcracks in bone have been implicated in the development of stress fractures. The goal of this study was to evaluate bone strain and microcracks at locations where stress fractures are common (second metatarsal diaphysis) and rare (fifth metatarsal diaphysis) in an attempt to increase our understanding of the pathogenesis of stress fractures. A dynamic gait simulator was used to simulate normal walking with cadaver feet. The feet were loaded over the entire stance phase of gait and diaphyseal strains were recorded in second and fifth metatarsals. Microcrack density (Cr.Dn) and surface density (Cr.S.Dn) were determined in metatarsal cross sections from the contralateral feet. Bone strain was significantly higher in second metatarsals (-1897 +/- 613 microstrain) than in fifth metatarsals (-908 +/- 503 microstrain). However, second metatarsal Cr.Dn (0.23 +/- 0.15 #/mm(2)) was not significantly different from fifth metatarsal Cr.Dn (0.35 +/- 0.19 #/mm(2)). There was also no significant difference between Cr.S.Dn in second (17.64 +/- 10.99 microm/mm(2)) and fifth (26.70 +/- 15.53 microm/mm(2)) metatarsals. There were no significant relationships between the microcrack parameters and peak strain in either metatarsal. Cracks that occurred in trabecular struts (92 +/- 33 microm) were significantly longer than those found ending at cement lines (71 +/- 15 microm) and within osteons (57 +/- 16 microm). There were no significant relationships between the microcrack parameters and age in either metatarsal. Peak strain was more than twofold greater in second metatarsals than in fifth metatarsals for simulations of normal walking; however, microcrack parameters were unable to explain the greater incidence of second metatarsal stress fractures.

Adult↗
PubMed2000

Toward a unifying theory of bone remodeling.

A theory is developed to resolve several inconsistencies between current concepts and observations about bone remodeling. For example, the observation that remodeling increases both when mechanical loading is excessively low, that is, in a disuse state, and when it is excessively high, producing substantial fatigue damage, is contrary to the widely held assumption that a signal generated by osteocytes in proportion to mechanical loading stimulates bone lining cells to activate remodeling. The new theory resolves this disparity by assuming that lining cells are inclined to activate remodeling unless restrained by an inhibitory signal, and that the mechanically provoked osteocytic signal serves this inhibitory function. Consequently, remodeling is elevated when signal generation declines due to reduced loading, or when signal generation or transmission is interrupted by damage due to excessive loading. Otherwise, remodeling is kept at a relatively low level by inhibitory signals produced through physiologic loading. Furthermore, the inhibitory signal is postulated to be identical to that proposed by Marotti as the mechanism for conversion of osteoblasts to osteocytes, and responsible for the diminishment of apposition rate during refilling of osteonal basic multicellular units. Consequently, a single, mechanically derived signal, produced in the osteocytic syncytium, may control osteoblast and bone lining cell functions, and thereby a variety of important phenomena in bone biology.

Animals↗