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PubMed2005

Two forms of apatite deposited during mineralization of the hen tendon.

Old hen tendon provides a model suitable for the study of calcification in an extracellular matrix. In the present study, we observed the mineralizing substances of hen tendon by scanning electron microscopy of plasma-osmium-coated specimens and by transmission electron microscopy of those processed by a plasma-polymerization film replica method. The mineralizing front area revealed a number of elliptical particles fused to each other and forming rod-like structures oriented parallel to collagen fibrils. The area of advanced mineralization possessed non-mineralizing cavities, in which tendon cells were likely to exist. At this site, we recognized a second form of mineral structure, one in which the crystals had a scale-like morphology and were deposited onto the major first-form mineral component. This crystal form was similar to hydroxyapatite synthesized under wet reaction conditions. These findings strongly suggest that the second form of mineral formed independent of collagen fibrils existed together with the predominant, collagen-dependent form of mineral. We speculate that cell membranes and an extremely slow mineralization process may contribute to the formation of this form of mineral during the mineralization process in the hen tendon.

Animals↗
PubMed2001

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution.

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the 'linear model' we assumed a linear relation between mineral content and Young's modulus of the tissue. In the 'exponential model' we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 microm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.

Adult↗
PubMed1996

Phase-Dependent effects of transforming growth factor beta 1 on osteoblastic markers of human osteoblastic cell line sV-HFO during mineralization.

A human osteoblastic cell line (SV-HFO) established in our laboratory expresses osteoblastic markers, including mineralization in vitro, in response to differentiation-inducing agents such as dexamethasone. In this study, we examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the mineralization of SV-HFO cells and show that TGF-beta 1 inhibited the mineralization of the cells via down regulation of tetranectin and alkaline phosphatase without influencing other osteoblastic markers. To examine precisely the effects of TGF-beta 1 on the process of mineralization, we tentatively divided the whole process of mineralization into four phases: induced ALP activity (days 0-5), maximal ALP activity (days 5-10), early mineralization (days 10-15), and progressive mineralization (days 15-20). These inhibitory effects of TGF-beta 1 on the expression of tetranectin and alkaline phosphatase, like that on mineralization, were observed only when TGF-beta 1 was applied in the early phase of the process of mineralization. On the other hand, the other osteoblastic markers were not influenced by treatment with TGF-beta 1. These results suggest that TGF-beta 1 may inhibit mineralization of osteoblasts by the downregulation of tetranectin and alkaline phosphatase expression in the early phase. Thus, TGF-beta 1 has phase-dependent effects on a human osteoblastic cell line during the process of mineralization.

Alkaline Phosphatase↗
PubMed1997

Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes.

Matrix vesicles have a critical role in the initiation of mineral deposition in skeletal tissues, but the ways in which they exert this key function remain poorly understood. This issue is made even more intriguing by the fact that matrix vesicles are also present in nonmineralizing tissues. Thus, we tested the novel hypothesis that matrix vesicles produced and released by mineralizing cells are structurally and functionally different from those released by nonmineralizing cells. To test this hypothesis, we made use of cultures of chick embryonic hypertrophic chondrocytes in which mineralization was triggered by treatment with vitamin C and phosphate. Ultrastructural analysis revealed that both control nonmineralizing and vitamin C/phosphatetreated mineralizing chondrocytes produced and released matrix vesicles that exhibited similar round shape, smooth contour, and average size. However, unlike control vesicles, those produced by mineralizing chondrocytes had very strong alkaline phosphatase activity and contained annexin V, a membrane-associated protein known to mediate Ca2+ influx into matrix vesicles. Strikingly, these vesicles also formed numerous apatite-like crystals upon incubation with synthetic cartilage lymph, while control vesicles failed to do so. Northern blot and immunohistochemical analyses showed that the production and release of annexin V-rich matrix vesicles by mineralizing chondrocytes were accompanied by a marked increase in annexin V expression and, interestingly, were followed by increased expression of type I collagen. Studies on embryonic cartilages demonstrated a similar sequence of phenotypic changes during the mineralization process in vivo. Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro-osseous mineralizing border exhibited expression of both annexin V and type I collagen. These findings reveal that hypertrophic chondrocytes can qualitatively modulate their production of matrix vesicles and only when induced to initiate mineralization, will release mineralization-competent matrix vesicles rich in annexin V and alkaline phosphatase. The occurrence of type I collagen in concert with cartilage matrix calcification suggests that the protein may facilitate crystal growth after rupture of the matrix vesicle membrane; it may also offer a smooth transition from mineralized type II/type X collagen-rich cartilage matrix to type I collagen-rich bone matrix.

Animals↗
PubMed1997

Trace mineral metabolism in the avian embryo.

Trace mineral metabolism in the developing avian embryo begins with the formation of the egg and the trace mineral stores contained within it. Vitellogenin, the yolk precursor protein, serves as a trace mineral transporting protein that mediates the transfer of these essential nutrients from stores within the liver of the hen to the ovary and developing oocyte, and hence, to the yolk of the egg. Lipovitellin and phosvitin, derived from intraoocytic proteolytic processing of vitellogenin, are also trace mineral binding proteins that form important storage sites within the granule subfraction of yolk. The mobilization and uptake of egg trace mineral stores is mediated by the extra-embryonic membranes, principally the yolk sac membrane. The yolk sac also serves as a short-term storage site for trace minerals. Because it is an important site of plasma protein synthesis, the yolk sac has the ability to regulate the export of trace minerals to the embryo during development. Within the embryo, specific metaloproteins function in the interorgan transport cellular uptake, and intracellular storage of trace minerals. Thus, embryonic trace mineral homeostasis is established through the coordinated actions of the yolk sac, which mobilizes and exports trace minerals derived from egg stores; the vitelline circulation, which transports them to the embryo; and the liver, which accumulates trace minerals and distributes them to the rest of the tissues of the embryo via the embryonic circulation.

Animals↗
PubMed1994

Pedicle screws and bone mineral density.

STUDY DESIGN: Thirty-five consecutive patients who underwent surgeries for decompression, and one-level fusions with Cotrel-Dubousset pedicle screws for spinal canal stenosis were included in this study. The relationship between bone mineral density of the lumbar spine and the rate of successful fusion and screw problems was studied. OBJECTIVES: Bone mineral density of the third lumbar vertebral body was measured by quantitative computed tomography preoperatively, and the degree of osteoporosis was graded by radiographic films of lumbar spines. The films were followed with anteroposterior and lateral dynamic radiographic examinations of lumbar spines. These examinations were evaluated clinically after surgery. Follow-up duration was at least 19 months, with a mean of 28 months. SUMMARY OF BACKGROUND DATA: The mean bone mineral density of all the patients was 117.1 mg/mL (SD = 42.5). The rate of successful fusion was 88.6%, the non-union rate was 5.7%, and the rate of fusions that were undetermined was 5.7%. The incidence of screw loosening occurred in 5.7% of the patients, screw breakage occurred in 5.7% of patients, and symptomatic screws related to non-union were present in 5.7% of patients. The degree of bone mineral density or radiographic gradings of osteoporosis and the successful fusion or the incidence of symptomatic screws, which were defined as screws related to non-union, were not related. METHODS: The patients were divided into two groups. One group consisted of 12 patients who had less than 100 mg/mL of bone mineral density, with a mean of 72.0 mg/mL (SD = 21.2). The other group consisted of 23 patients who had more than 100 mg/mL of bone mineral density, with a mean of 140.6 mg/mL (SD = 30.0). The rate of successful fusion or non-union and the rate of screw problems such as screw loosening or screw breakage were compared in the two groups. The presence of bony trabeculation in grafted bone is the most important criterion for successful fusion. RESULTS: A statistical difference did not occur between the two groups. Non-union, screw breakage, and screw loosening were observed in patients with both increased and decreased bone mineral density and those with increased and decreased grade osteoporosis. Radiographic grading of osteoporosis was not correlated to bone mineral density, but patients with unexpected bone mineral density were frequent in this series. CONCLUSIONS: The use of decompression and pedicle screws for spinal canal stenosis due to degenerative lumbar disorders can be done safely with one-level fusion in patients with decreased bone mineral density if patients with grade III osteoporosis are excluded. Bone mineral density is more reliable than radiographic grading to evaluate the degree of osteoporosis and should be included in the preoperative evaluation of patients with osteoporosis.

Bone Density↗
PubMed2001

An experimental study on the interface strength between titanium mesh cage and vertebra in reference to vertebral bone mineral density.

STUDY DESIGN: Using human cadaver spines, the authors investigated mechanical properties of the interface between titanium mesh cage and vertebra in respect to vertebral bone mineral density. OBJECTIVES: The objective of this study is to examine the effects of the size of the mesh cage and an internal end ring system on interface mechanical properties in reference to vertebral bone mineral density. SUMMARY OF BACKGROUND DATA: A titanium mesh cage has recently been developed for anterior spinal reconstruction. The cage provides immediate postoperative stability and facilitates bony union with cancellous bone packed in the cage itself. Mechanical properties of the interface between the cage and vertebra, however, are yet to be clarified in osteoporotic spine. METHODS: Twenty-five lumbar vertebrae harvested from embalmed human cadavers (n = 20) were used. The vertebrae were divided into four experimental groups according to the applied cage conditions: Phi25 mm cage without internal end ring (L-), Phi19 mm cage without internal end ring (S-), Phi25 mm cage with internal end ring (L+), and Phi19 mm cage with internal end ring (S+). Bone mineral density of whole vertebral body was measured by dual energy radiograph absorptiometer (DXA). Peripheral quantitative computed tomography was used to determine local bone mineral density of subchondral cancellous bone of vertebral body. Each cage was compressed on vertebral endplate via a specially designed device connected to a material testing machine. Maximum load and stiffness of the interface between the cage and vertebra were measured from load-deformation data in quasi-static compression loading with a loading rate of 0.5 mm/min. Relationships between the mechanical properties and vertebral bone mineral densities were evaluated. In 11 specimens acoustic emission during compression loading was measured and simultaneously recorded in load-deformation data. After the mechanical test microradiograms of midsagittal sections of the vertebrae were taken to observe failure patterns of endplate or trabecular bone. RESULTS: Vertebrae compressed with large cages (group: L- or L+) showed greater maximum load than those compressed with small cages (group: S- or S+). The internal end ring contributed to higher maximumload. The size of the cage or the internal end ring, however, did not have any effect on stiffness. Maximum load and stiffness were positively correlated with whole vertebral bone mineral density measured by dual energy radiograph absorptiometer or local cancellous bone mineral density of subchondral bone measured by peripheral quantitative computed tomography. Correlation coefficient and P value were more significant in the association of the mechanical properties and subchondral bone mineral density measured by peripheral quantitative computed tomography than in the association of the parameters and whole vertebral bone mineral density measured by DXA. A load-deformation curve with an acoustic emission event count rate showed that significant acoustic emission signals were generated around maximum load. On microradiographic study most vertebrae compressed with the cage showed encroachment of the cage spikes into the endplate or trabecular structure, preserving structures of the most central portion of the vertebrae. CONCLUSION: A titanium mesh cage with larger diameter and/or augmentation of internal end ring produces a significant increase of the interface strength between the cage and the vertebra. A positive correlation between the interface strength and vertebral bone mineral density suggests that vertebral bone mineral density is an important parameter for successful spinal reconstruction, and also implies that in severe osteoporotic spine the stability of the cage is declined, and other instrumentation should be combined.

Aged↗
PubMedDate not supplied

An integrated epidemiologic and radiographic algorithm for canine urocystolith mineral type prediction.

Research involved 2 databases. One database (occurrence frequency) comprised the age, breed, gender and urocystolith mineral type (pure chemical types only) from 2041 canine patients submitted to the Minnesota Urolith Center. The other database (imaging) comprised the maximum size, surface (rough, smooth, and smooth with blunt tips), shape (faceted, irregular, jackstone, ovoid, and round) and internal architecture (lucent center, random-nonuniform, and uniform) from 434 canine patients imaged in a urinary bladder phantom. The imaging database was a partial subset of the occurrence frequency database. Imaging techniques simulated were survey radiography and double contrast cystography. The databases were compared using multivariate analysis techniques. Equations were developed to use clinically-relevant characteristics (age, breed, gender, maximum size, surface, shape, and internal architecture) to predict urocystolith mineral types. The goal was to assess the accuracy of the various techniques in predicting the urocystolith mineral types. The combination of signalment (age, breed, gender) and simulated survey radiographic findings does not improve mineral type prediction accuracy (average across all mineral types is 69.9%) beyond that achievable with signalment alone (average across all mineral types is 69.8%). However, the combination of signalment and double contrast cystography does improve mineral type prediction accuracy (average across all mineral types is 75.3%). For comparison, mineral type prediction accuracy without signalment from survey radiographs only was 65.7% across all mineral types. The clinical utility of the algorithm is the option to distinguish urocystolith mineral types requiring surgical vs. medical treatment.

Algorithms↗
PubMed2005

Elastic deformation of mineralized collagen fibrils: an equivalent inclusion based composite model.

Mineralized collagen fibrils are the basic building blocks of bone tissue at the supramolecular level. Several disease states, manipulation of the expression of specific proteins involved in biomineralization, and treatment with different agents alter the extent of mineralization as well as the morphology of mineral crystals which in turn affect the mechanical function of bone tissue. An experimental assessment of mineralized fibers' mechanical properties is challenged by their small size, leaving analytical and computational models as a viable alternative for investigation of the fibril-level mechanical properties. In the current study the variation of the elastic stiffness tensor of mineralized collagen fibrils with changing mineral volume fraction and mineral aspect ratios was predicted via a micromechanical model. The partitioning of applied stresses between mineral and collagen phases is also predicted for normal and shear loading of fibrils. Model predictions resulted in transversely isotropic collagen fibrils in which the modulus along the longer axis of the fibril was the greatest. All the elastic moduli increased with increasing mineral volume fraction whereas Poisson's ratios decreased with the exception of v12 (=v21). The partitioning of applied stresses were such that the stresses acting on mineral crystals were about 1.5, 15, and 3 times greater than collagen stresses when fibrils were loaded transversely, longitudinally, and in shear, respectively. In the overall the predictions were such that: (a) greatest modulus along longer axis; (b) the greatest mineral/collagen stress ratio along the longer axis of collagen fibers (i.e., greatest relief of stresses acting on collagen); and (c) minimal lateral contraction when fibers are loaded along the longer axis. Overall, the pattern of mineralization as put forth in this model predicts a superior mechanical function along the longer axis of collagen fibers, the direction which is more likely to experience greater stresses.

Animals↗
PubMed1985

Growth of phenol-mineralizing microorganisms in fresh water.

A method was developed to enumerate the procaryotic and eucaryotic phenol-mineralizing microorganisms present in samples of fresh water. Sixty-five percent or greater mineralization of [U-14C]phenol was considered a positive tube (contained phenol-mineralizing microorganisms) in the most-probable-number technique. Replicate most-probable-number tubes contained no microbial inhibitors, streptomycin and tetracycline, or cyclohexamide and nystatin plus 200 pg to 100 micrograms of phenol per ml. Phenol mineralization rates were obtained by measuring the amount of exogenous phenol that disappeared from solution over time in the presence or absence of the microbial inhibitors. Initially, less than 100 phenol-mineralizing bacteria per ml and 1 phenol-mineralizing fungus per ml were present at both 200 pg and 100 micrograms of phenol per ml. Phenol mineralization rates were 6.3 times greater for the mineralizing bacteria than for the fungi at 200 pg of phenol per ml. Phenol concentrations above 10 micrograms/ml were inhibitory to the microorganisms capable of mineralizing phenol. The phenol mineralizers grew in the water samples in the absence of phenol, indicating that there were sufficient indigenous nutrients in the lake water to support growth. There was no difference in the growth rate of these microorganisms in the presence or absence of 1 ng of phenol per ml, whereas the growth rate was more rapid at 1 microgram of phenol per ml than in its absence. There was a correlation between microbial growth and the amount of phenol mineralized at 1 microgram but not at 1 ng of phenol per ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed2001

Sorption of Fe (hydr)oxides to the surface of Shewanella putrefaciens: cell-bound fine-grained minerals are not always formed de novo.

Shewanella putrefaciens, a gram-negative, facultative anaerobe, is active in the cycling of iron through its interaction with Fe (hydr)oxides in natural environments. Fine-grained Fe precipitates that are attached to the outer membranes of many gram-negative bacteria have most often been attributed to precipitation and growth of the mineral at the cell surface. Our study of the sorption of nonbiogenic Fe (hydr)oxides revealed, however, that large quantities of nanometer-scale ferrihydrite (hydrous ferric oxide), goethite (alpha-FeOOH), and hematite (alpha-Fe(2)O(3)) adhered to the cell surface. Attempts to separate suspensions of cells and minerals with an 80% glycerin cushion proved that the sorbed minerals were tightly attached to the bacteria. The interaction between minerals and cells resulted in the formation of mineral-cell aggregates, which increased biomass density and provided better sedimentation of mineral Fe compared to suspensions of minerals alone. Transmission electron microscopy observations of cells prepared by whole-mount, conventional embedding, and freeze-substitution methods confirmed the close association between cells and minerals and suggested that in some instances, the mineral crystals had even penetrated the outer membrane and peptidoglycan layers. Given the abundance of these mineral types in natural environments, the data suggest that not all naturally occurring cell surface-associated minerals are necessarily formed de novo on the cell wall.

Adsorption↗
PubMed2006

Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women.

UNLABELLED: Long-term effects of risedronate on bone mineralization density distribution in triple transiliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate increased the degree and homogeneity of mineralization without producing hypermineralization. These changes at the material level of bone could contribute to risedronate's antifracture efficacy. INTRODUCTION: Risedronate, a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone mineralization density distribution (BMDD) in humans. MATERIALS AND METHODS: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium and vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline and 3 and 5 years. BMDD was measured in these biopsies using quantitative backscattered electron imaging, and the data were also compared with a normal reference group. RESULTS: At baseline, both risedronate and placebo groups had a lower degree and a greater heterogeneity of mineralization as well as an increase in low mineralized bone compared with the normal reference group. The degree of mineralization increased significantly in the risedronate as well as in the placebo group after 3- and 5-year treatment compared with baseline. However, the degree of mineralization did not exceed that of normal. Three-year treatment with risedronate significantly increased the homogeneity of mineralization and slightly decreased low mineralized bone compared with placebo. Surprisingly with 5-year risedronate treatment, heterogeneity of mineralization increased compared with 3-year treatment, which might indicate an increase in newly formed bone. CONCLUSIONS: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix. These changes at the material level of the bone matrix may contribute to risedronate's antifracture efficacy in osteoporotic patients.

Biopsy↗
PubMed2002

Cell-type-dependent up-regulation of in vitro mineralization after overexpression of the osteoblast-specific transcription factor Runx2/Cbfal.

Functional expression of the transcriptional activator Runx2/Cbfal is essential for osteoblastic differentiation and bone formation and maintenance. Forced expression of Runx2 in nonosteoblastic cells induces expression of osteoblast-specific genes, but the effects of Runx2 overexpression on in vitro matrix mineralization have not been determined. To examine whether exogenous Runx2 expression is sufficient to direct in vitro mineralization, we investigated sustained expression of Runx2 in nonosteoblastic and osteoblast-like cell lines using retroviral gene delivery. As expected, forced expression of Runx2 induced several osteoblast-specific genes in NIH3T3 and C3H10T1/2 fibroblasts and up-regulated expression in MC3T3-E1 immature osteoblast-like cells. However, Runx2 expression enhanced matrix mineralization in a cell-type-dependent manner. NIH3T3 and IMR-90 fibroblasts overexpressing Runx2 did not produce a mineralized matrix, indicating that forced expression of Runx2 in these nonosteogenic cell lines is not sufficient to direct in vitro mineralization. Consistent with the pluripotent nature of the cell line, a fraction (25%) of Runx2-expressing C3H10T1/2 fibroblast cultures produced mineralized nodules in a viral supernatant-dependent manner. Notably, bone sialoprotein (BSP) gene expression was detected at significantly higher levels in mineralizing Runx2-infected C3H10T1/2 cells compared with Runx2-expressing cultures which did not mineralize. Treatment of Runx2-infected C3H10T1/2 cultures with dexamethasone enhanced osteoblastic phenotype expression, inducing low levels of mineralization independent of viral supernatant. Finally, Runx2 overexpression in immature osteoblast-like MC3T3-E1 cells resulted in acceleration and robust up-regulation of matrix mineralization compared with controls. These results suggest that, although functional Runx2 is essential to multiple osteoblast-specific activities, in vitro matrix mineralization requires additional tissue-specific cofactors, which supplement Runx2 activity.

3T3 Cells↗
PubMed2003

Congenic strains of mice for verification and genetic decomposition of quantitative trait loci for femoral bone mineral density.

Peak femoral volumetric bone mineral density (femoral bone mineral density) in C57BL/6J (B6) 4-month-old female mice is 50% lower than in C3H/HeJ (C3H) and 34% lower than in CAST/EiJ (CAST) females. Genome-wide analyses of (B6 x C3H)F2 and (B6 x CAST)F2 4-month-old female progeny demonstrated that peak femoral bone mineral density is a complex quantitative trait associated with genetic loci (QTL) on numerous chromosomes (Chrs) and with trait heritabilities of 83% (C3H) and 57% (CAST). To test the effect of each QTL on femoral bone mineral density, two sets of loci (six each from C3H and CAST) were selected to make congenic strains by repeated backcrossing of donor mice carrying a given QTL-containing chromosomal region to recipient mice of the B6 progenitor strain. At the N6F1 generation, each B6.C3H and B6.CAST congenic strain (statistically 98% B6-like in genomic composition) was intercrossed to obtain N6F2 progeny for testing the effect of each QTL on femoral bone mineral density. In addition, the femoral bone mineral density QTL region on Chr 1 of C3H was selected for congenic subline development to facilitate fine mapping of this strong femoral bone mineral density locus. In 11 of 12 congenic strains, 6 B6.C3H and 5 B6.CAST, femoral bone mineral density in mice carrying c3h or cast alleles in the QTL regions was significantly different from that of littermates carrying b6 alleles. Differences also were observed in body weight, femoral length, and mid-diaphyseal periosteal circumference among these 11 congenic strains when compared with control littermates; however, these latter three phenotypes were not consistently correlated with femoral bone mineral density. Analyses of eight sublines derived from the B6.C3H-1T congenic region revealed two QTLs: one located between 36.9 and 49.7 centiMorgans (cM) and the other located between 73.2 and 100.0 cM distal to the centromere. In conclusion, these congenic strains provide proof of principle that many QTLs identified in the F2 analyses for femoral bone mineral density exert independent effects when transferred and expressed in a common genetic background. Furthermore, significant differences in femoral bone mineral density among the congenic strains were not consistently accompanied by changes in body weight, femur length, or periosteal circumference. Finally, decomposition of QTL regions by congenic sublines can reveal additional loci for phenotypes assigned to a QTL region and can markedly refine genomic locations of quantitative trait loci, providing the opportunity for candidate gene testing.

Alleles↗
PubMed2002

The role of osteocytes in bone regulation: mineral homeostasis versus mechanoreception.

Early work on the role of osteocytes in bone regulation suggested that the primary function of these cells was osteolysis. This lytic function was not precisely defined but included mineral homeostasis and at least the initiation of matrix remodeling, if not a primary role in remodeling. This paper is an attempt to promote the concept of osteocytic osteolysis as a method of systemic mineral homeostasis and to separate it from bone remodeling. Although recent investigations have pointed to mechanotransduction as a primary function of osteocytes, resulting in a general abandonment of the osteocytic osteolysis concept, the corpus of evidence suggests that osteocytes likely have a multipurpose role in the biology of bone. The osteocyte network represents an enormous surface area over which the cells interface with the surrounding matrix, useful for both strain detection and matrix mineral access. Osteocytes have been found to possess receptors for PTH, a known regulator of mineral ion homeostasis. Cultured osteocytes placed on dentin slices demonstrated no capacity to pit the dentin, but they were not treated with a regulating factor such as PTH, nor does mineral homeostasis require substantial bone volume removal. Scaling relationships suggest that osteocyte density is inversely proportional to body mass, R(2) = 0.86, and thus directly proportional to metabolic rate. Thus, species with higher metabolic rates (and therefore a greater demand for immediate access to minerals) have more osteocytes per bone volume. Finally, osteocytes express molecules typically associated with nerve cells and which are involved with glutamate neurotransmission. By this system, almost instantaneous messages may be transmitted throughout the network, an important feature in cells whose homeostatic function would be utilized on a scale of seconds, rather than hours or days. Experimental procedures for determining the role of the osteocyte in mineral homeostasis would require calcium mobilization from the bone matrix on a relatively immediate time scale. The experimental procedure would then be coupled with a high resolution histomorphometric analysis of lacunar radiographic area and mineral density. Added to this would be an in vitro study of mineral activation capacity via cultured osteocytes treated with PTH. Osteocytic osteolysis would be confirmed by an increase in the demineralized volume of osteocytic lacunae and the identification of a chemical mechanism by which osteocytes can readily access the mineral portion of their immediate bone matrix. It should also be true that a reverse capacity exists by which osteocytes can remineralize their immediate matrix utilizing alkaline phosphatase for example, a chemical which they, like osteoblasts, are known to generate. It is thus proposed that osteocytes are both mechanoreceptors and systemic mineral homeostasis regulators.

Journal Article↗
PubMed1976

Mineral imbalances in farm animals and their study and diagnosis with isotopic tracers.

Twenty-two mineral elements are known to be essential for animal life. These are calcium, phosphorus, sulphur, potassium, sodium, chlorine, magnesium, iron, iodine, copper, manganese, zinc, cobalt, molybdenum, selenium, chromium, tin, vanadium, fluorine, silicon, nickel and arsenic. Naturally occurring and man-made dietary imbalances of many of these elements and their interactions with other minerals are described and their functions and requirements by farm animals are outlined. The nature and importance of metabolic interactions among the mineral elements are discussed and the important concept stressed that there is no single minimum requirement or safe tolerance of a particular mineral, but a series of such minimum requirements and safe tolerances depending on the extent to which other minerals with which it interacts is present or absent from the diet. Radioactive tracer elements are shown to be of great value in the determination of mineral nutrient availability to the animal and for following mineral metabolic movements in the body. They are also shown to have considerable potential for the diagnosis of mineral imbalances. Various in vivo and in vitro techniques, involving both radioactive and stable tracers developed for the early diagnosis of mineral deficiencies are described and the strengths and weaknesses of such techniques in comparison with standard biochemical tests, are discussed. The need for further critical studies with isotopic tracers in the detection and diagnosis of mineral imbalances is emphasized. The main types of biochemical criteria used in the diagnosis of mineral deficiencies and excesses are given, with appropriate examples of their use.

Animals↗
PubMed1998

Lean tissue mass is a better predictor of bone mineral content and density than body weight in prepubertal girls.

PURPOSE AND METHODS: Body weight is the most extensively studied correlate of bone mass and is widely used as a covariate in statistical evaluations of bone mineral parameters. Lean tissue mass (LTM) also correlates with bone mass. We evaluated the correlations linking each of these two parameters with bone mineral content and bone mineral density in 41 prepubertal girls, including ten swimmers, 18 gymnasts and 13 nonathletes. Lean tissue mass, bone mineral content and bone mineral density were measured using dual-energy X-ray absorptiometry (Hologic QDR-1000/W; Hologic Inc., Waltham, MA, USA). Forward stepwise multiple regression was used to evaluate correlations linking bone mineral content or density (the dependent variables) to body weight or lean tissue mass (the independent variables). RESULTS: Body weight and lean tissue mass showed strong correlations with all bone mineral content and density measurements in the simple linear regression analysis, with lean tissue mass yielding the highest Pearson's correlation coefficients. In the multiple regression model, lean tissue mass consistently explained the largest proportion of the variance, whereas body weight had little influence or was eliminated from the model. The slopes of the regression lines of bone mineral content or density on body weight were significantly steeper in the subgroup of gymnasts (P < 0.001), whereas the slopes of the regression lines of bone mineral content or density on lean tissue mass were significantly less steep in the swimmers (P < 0.05). CONCLUSION: Our data indicate that lean tissue mass is a significant predictor of bone mass in prepubertal girls and explains a larger part of the variance of bone mineral content and density than body weight. Use of body weight as a covariate in studies of bone mineral density may lead to erroneous results in prepubertal girls.

Absorptiometry, Photon↗
PubMed2003

Scanning electron microscopic analysis of the mineralization of type I collagen via a polymer-induced liquid-precursor (PILP) process.

We have put forth the hypothesis that collagen is mineralized during bone formation by means of a polymer-induced liquid-precursor (PILP) process, in which a liquid-phase mineral precursor could be drawn into the gaps and grooves of the collagen fibrils by capillary action, and upon solidification, leave the collagenous matrix embedded with nanoscopic crystallites of hydroxyapatite. This hypothesis is based upon our observations of capillarity seen for liquid-phase mineral precursors generated with calcium carbonate. Here, we demonstrate proof-of-concept of this mechanism by mineralizing Cellagen sponges (type I reconstituted bovine collagen) in the presence of a liquid-precursor phase to calcium carbonate. Scanning electron microscopy (SEM) was used to examine the mineralized collagen, which in combination with selective etching studies, revealed the extent to which the mineral phase infiltrated the collagenous matrix. A roughly periodic array of disk-like crystals was found to be embedded within the collagen fibers, demonstrating that the mineral phase spans across the diameter of the fibers. Some of the morphological features of the mineralized fibers in our in vitro model system are similar to those seen in natural bone (albeit of a different mineral phase), lending support to our hypothesis that these non-equilibrium morphologies might be generated by a PILP process. SEM provides a different perspective on the morphology of bone, and has been useful here for examining the extent of mineralization in composite structures generated via the PILP process. However, further investigation is needed to examine the nanostructural arrangement of the crystallites embedded within the collagenous matrix.

Animals↗