Biomedical subjects

M D Grynpas

Publications and source records attributed to M D Grynpas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effect of material geometry on cartilagenous tissue formation in vitro.

The effect of material geometry, as defined by average pore size, on chondrocyte phenotype and cartilagenous tissue formation in vitro was examined. Bovine articular chondrocytes were plated on porous titanium alloy (Ti6Al4V) discs of different average pore sizes (13, 43, and 68 microm) and grown in culture for 4 weeks. Chondrocyte phenotype was maintained as indicated by the synthesis of large proteoglycans (Kav +/- SD: 13 microm = 0.28 +/- 0.01; 43 microm = 0.29 +/- 0.01; 68 microm = 0.27 +/- 0.02) and type II collagen. Light microscopical examination of histological sections of the composites showed that cartilagenous tissue had formed on all discs. The cartilagenous tissue on the discs of the smallest average pore size (13 microm) was significantly thicker than the tissue on the discs of larger average pore sizes and also had greater amounts of proteoglycan [mean glycosaminoglycan content +/- SD microg/disc): 13 microm = 246.9 +/- 7.8; 43 microm = 190.4 +/- 10.2; 68 microm = 156.6 +/- 25.8, p = 0.002] and DNA [mean DNA content +/- SD microg/disc): 13 microm = 12.5 +/- 0.6; 43 microm = 8.3 +/- 0.2; 68 microm = 9.3 +/- 0.9, p = 0.0008]. However, the amount of proteoglycan accumulated per cell was similar in the tissues generated on the discs of different average pore sizes. In contrast, the amount of collagen in the cartilagenous tissues showed no significant differences between the different pore sizes, but the amount of collagen accumulated per cell was less in the tissue formed on the smallest pore size disc (13 microm) as compared with the tissue formed on the discs of the larger pore sizes [mean hydroxyproline content/DNA (microg/microg) +/- SD: 13 microm = 1.56 +/- 0.2; 43 microm = 2.19 +/- 0.2; 68 microm = 2.3 +/- 0.3]. These results suggest that material geometry, as defined by pore size, can affect the amount and composition of the cartilagenous tissue that forms.

Alloys↗

PubMed2001

Porous calcium polyphosphate scaffolds for bone substitute applications -- in vitro characterization.

Porous structures were formed by gravity sintering calcium polyphosphate (CPP) particles of either 106-150 or 150-250 microm size to form samples with 30-45 vol% porosity with pore sizes in the range of 100 microm (40-140 microm). Tensile strength of the samples assessed by diametral compression testing indicated relatively high values for porous ceramics with a maximum strength of 24.1 MPa for samples made using the finer particles (106-150 microm). X-ray diffraction studies of the sintered samples indicated the formation of beta-CPP from the starting amorphous powders. In vitro aging in 0.1 M tris-buffered solution (pH 7.4) or 0.05 M potassium hydrogen phthalate buffered solution (pH 4.0) at 37 degreesC for periods up to 30d indicated an initial rapid loss of strength and P elution by 1 d followed by a more gradual continuing strength and P loss resulting in strengths at 30d equal to about one-third the initial value. The observed structures, strengths and in vitro degradation characteristics of the porous CPP samples suggested their potential usefulness as bone substitute materials pending subsequent in vivo behaviour assessment.

Bone Substitutes↗

PubMed2001

Effect of acidosis on urine supersaturation and stone formation in genetic hypercalciuric stone-forming rats.

BACKGROUND: We have successively inbred over 45 generations a strain of rats to maximize urine calcium excretion. The rats now consistently excrete 8 to 10 times as much calcium as controls and uniformly form poorly crystalline calcium phosphate kidney stones. In humans with calcium nephrolithiasis, consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones; however, the effect of this diet on urinary supersaturation with respect to the common solid phases found in kidney stones has not been determined. METHODS: To determine the effect of the addition of an acid precursor on urine ion excretion, supersaturation, and stone formation, we fed these genetic hypercalciuric stone-forming (GHS) rats 13 g/day of a 1.2% calcium diet with 0.0, 0.5, 1.0, or 1.5% NH4Cl in the drinking water for 14 weeks (N = 8 for each). Urine was collected and analyzed every two weeks. RESULTS: As expected, the addition of dietary NH4Cl led to a progressive fall in urine pH and urine citrate, while urine ammonium increased. Urine calcium and phosphorus increased, while urine oxalate fell. Increasing dietary NH4Cl led to a fall in supersaturation with respect to CaHPO4 (brushite) and CaOx and a rise in supersaturation with respect to uric acid. In spite of differences in supersaturation, most rats in each group formed stones that contained calcium phosphate and not calcium oxalate. CONCLUSIONS: Thus, while the provision of additional dietary acids alters urinary ion excretion and lowers supersaturation with respect to CaHPO4 and CaOx, it does not change the character or rate of stone formation in the GHS rats.

Acidosis↗

PubMed2001

Sequential analysis of kidney stone formation in the Aprt knockout mouse.

BACKGROUND: We have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified in kidney sections from male and female mice (strain 129) aged one day to eight months and this parameter was correlated with changes in renal histopathology. Aprt heterozygous and wild-type mice were used as controls. METHODS: Following anesthesia, the left kidney was removed and immediately frozen in dry ice. Unstained cryosections were examined by polarized light to determine total area of birefringent particles. The right kidney was perfused and embedded in plastic, and stained sections were viewed by light microscopy to examine the histopathology and to determine the location of the birefringent particles. A pathological score was assigned to the histological findings. The scores from the right kidney were compared with crystal/particle area in the left kidney, and the data were analyzed using two-way analysis of variance. The chemical composition of the particles was determined by x-ray diffraction analysis. Several stone fragments from the bladder were also examined by scanning electron microscopy (SEM). RESULTS: Crystals were detected in kidney sections from one- to two-day-old Aprt knockout mice. The crystal burden remained low in both sexes throughout the study except in males at the 120- to 240-day period. Furthermore, there was a substantial degree of renal pathology, primarily seen as interstitial fibrosis, in those males with a very high level of stone formation. The crystalline material was identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM indicated that the crystals were spherical, with a diameter of 10 to 20 microm. Tissue staining and fixation procedures dramatically reduced the amount of birefringent material in kidney sections. Aprt heterozygotes of both sexes had low levels of crystalline material in the kidneys and no pathology. Birefringent material or pathological changes were not seen in kidneys from wild-type mice. CONCLUSIONS: Both male and female Aprt knockout mice accumulate DHA. However, the area occupied by DHA crystals was significantly greater in 120- to 240-day-old males compared with the females of similar age. Also, substantial renal pathology was detected in kidneys of male mice that had very high levels of stone material.

Adenine↗

PubMed2000

Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago.

This cross-sectional study investigates metabolic bone disease and the relationship between age and bone mineral density (BMD) in males and females of a large, well-documented skeletal population of free-ranging rhesus monkeys (Macaca mulatta), from the Caribbean Primate Research Center Museum collection from Cayo Santiago, Puerto Rico. The sample consists of 254 individuals aged 1.0-20+ years. The data consist of measurements of bone mineral content and bone mineral density, obtained from dual-energy X-ray absorptiometry (DEXA), of the last lumbar vertebra from each monkey. The pattern of BMD differs between male and female rhesus macaques. Females exhibit an initial increase in BMD with age, with peak bone density occurring around age 9.5 years, and remaining constant until 17.2 years, after which there is a steady decline in BMD. Males acquire bone mass at a faster rate, and attain a higher peak BMD at an earlier age than do females, at around 7 years of age, and BMD remains relatively constant between ages 7-18.5 years. After age 7 there is no apparent effect of age on BMD in the males of this sample; males older than 18.5 years were excluded due to the presence of vertebral osteophytosis, which interferes with DEXA. The combined frequency of osteopenia and osteoporosis in this population is 12.4%. BMD values of monkeys with vertebral wedge fractures are generally higher than those of virtually all of the nonfractured osteopenic/osteoporotic individuals, thus supporting the view that BMD as measured by DEXA is a useful but imperfect predictor of fracture risk, and that low BMD may not always precede fractures in vertebral bones. Other factors such as bone quality (i.e., trabecular connectivity) should also be considered. The skeletal integrity of a vertebra may be compromised by the loss of key trabeculae, resulting in structural failure, but the spine may still show a BMD value within normal limits, or within the range of osteopenia.

Absorptiometry, Photon↗

PubMed2000

The effect of androstenedione/estrone supplementation on cortical and cancellous bone in the young intact female monkey: a model for the effects of polycystic ovarian disease on the skeleton?

The goal of this study was to determine the effects of chronically elevated blood androstenedione and estrone levels on the quality and quantity of both cancellous (trabecular) and cortical bone in a young (mean age 9.4 years) female primate model (M. fascicularis). Thirteen intact female monkeys received continuous androstenedione/estrone supplementation via subcutaneous implants over a 24-month period to simulate the human condition known as polycystic ovarian disease (PCOD). A group of 16 untreated intact age-matched female monkeys served as controls. Lumbar spine and whole body bone mineral density (BMD) status was determined mid-study by dual photon absorptiometry (DPA); subsequent analysis of the bone related to data obtained following the 2-year treatment period without further BMD measurement. Bone markers, including serum acid phosphatase, total bone alkaline phosphatase, bone gla protein and tartrate-resistant acid phosphatase were measured at the end of the study. At necropsy, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone respectively and to compare these with the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio and mineral content (%Ca + %PO4) between control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry and image analysis. Cross-sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical parameters. There was a significant increase in BMD at the L2-L4 region in the treatment group compared with the control groups (p < 0.005) as measured at 1 year into the trial. Serum acid phosphatase was significantly lower (p < 0.05) in the treatment group compared with the controls near study termination. A nonsignificant shift in the mineralization profile of the vertebrae towards less dense bone was observed in the treatment group, while there was a significant shift in the mineralization profile towards more dense bone in the treated femora compared with controls (p < 0.05) after a 2-year period. There was no difference between treatment and control groups in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a significant increase in cancellous bone area (B.Ar.) (p < 0.02) and a significant increase (p < 0.05) in mean trabecular width with a corresponding decrease in trabecular separation (p < 0.03) in the experimental group compared with the controls. There were no significant changes in osteoid parameters (perimeter, area or width) or eroded perimeter measurements in the experimental group compared with the controls. In the experimental group, trabecular strut analysis showed a significant increase in the number of nodes (p < 0.02) and in the total strut length (p < 0.003) compared with the controls. There was also a significant increase in the node to node (p < 0.04) and node to terminus (p < 0.004) strut length in the treatment group compared with the controls. A significant increase in B.Ar. without concurrent indices of ongoing remodelling differing from controls suggests that cancellous bone of the vertebral body in the treated young female primate had been receptive to the anabolic stimulus of androstenedione/estrone supplementation over the 2-year period. In contrast, macroscopic parameters of cortical bone such as perimeter, area and width were preserved over the 2-year course, while intracortical remodeling was evident with increased percent porosity (p < 0.001), osteonal bone (p < 0.01) and osteonal density (p < 0.01) observed in the treatment group compared with the controls. The endocrine profile of both elevated androstenedione and estrone levels in an intact female primate of reproductive age may identify differential effects of the condition known as polycystic ovarian disease on the skeletal compartments.

Absorptiometry, Photon↗

PubMed2000

Relationships between bone protein and mineral in developing porcine long bone and calvaria.

Several proteins in the bone matrix have been implicated in the regulation of mineral crystal formation and growth. To investigate the relationships between these proteins and the mineral phase at various stages of mineral maturation, fetal porcine calvariae and long bones were fragmented and the particles (20 microm) separated by density gradient sedimentation into fractions of increasing density (1.8 to >2.2 g/cm3). Samples from each fraction were analyzed by X-ray diffraction to obtain the average crystal size/strain and chemical composition. Other samples were sequentially extracted, first with 4.0 mol/L guanidium hydrochloride (GuHCl) (G1), then with 0.5 mol/L ethylene-diamine tetraacetic acid (EDTA) (E), and again with 4.0 mol/L Gu-HCI (G2), for analysis of proteins in different tissue compartments. Based on the mineral density distribution and crystal size, fetal porcine bone protein content was determined for tissue residue and each extract and the protein composition analyzed by sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE). Although the insoluble organic matrix decreased with mineral density the collagen and protein content remained fairly constant, representing approximately 10% of the tissue weight, except in the highest density fraction. Whereas the total extractable protein, representing predominantly noncollagenous proteins, did not show density-related differences, differences were observed for individual proteins on SDS-PAGE. Consistent with their presence in osteoid, the content of bone sialoprotein (BSP), tyrosine-rich acidic matrix protein (TRAMP), and a series of small proteins with cell attachment properties in the G1 extract decreased with mineral density, whereas TRAMP and BSP were increased in G2 extracts. Mineral-associated proteins, including alpha2HS-glycoprotein, BSP, osteopontin (OPN), and osteocalcin, increased with mineral density, whereas secreted protein acidic and rich in cysteine (SPARC)/osteonectin, and some minor proteins, appeared to decrease. Differences of individual proteins within and between the calvarial and long bones could be related to the role of these proteins in the formation and maturation of hydroxyapatite crystals. Collectively, these studies demonstrate mineral density-associated changes in protein composition that reflect a rapid maturation of mineral crystals in embryonic porcine bones.

Animals↗

PubMed2000

Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice.

The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very different femoral peak bone densities and may serve as models for studying the genetic regulation of bone mass. Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitecture of the proximal femur, femoral midshaft, and lumbar vertebrae were evaluated in three dimensions using microcomputed tomography (microCT) with an isotropic voxel size of 17 microm. Mineralization of the distal femur was determined using quantitative back-scatter electron (BSE) imaging. MicroCT images suggested that C3H mice had thicker femoral and vertebral cortices compared with B6. The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and greater trochanter. The trabecular number (Tb.N) in the C3H vertebral bodies was about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs. 5.1(-1) +/- 0.2 mm(-1); p < 0.0001). The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs. 27.4 +/- 0.5N, p < 0.0001). In contrast, strengths of the lumbar vertebra were not significantly different between inbred strains (p = 0.5), presumably because the thicker cortices were combined with inferior trabecular structure in the vertebrae of C3H mice. These results indicate that C3H mice benefit from alleles that enhance femoral strength but paradoxically are deficient in trabecular bone structure in the lumbar vertebrae.

Animals↗

PubMed2000

Structure, composition, and maturation of newly deposited calcium-phosphate crystals in chicken osteoblast cell cultures.

Characterization of the very early calcium phosphate (CaP) crystals deposited in bone or in osteoblast cell cultures has been hampered by the overwhelming presence of organic matrix components and cells that obscure spectral analyses. We have overcome this problem using isolated protein-free crystals and have obtained new data including 31P nuclear magnetic resonance (NMR) spectra for the first time from mineral crystals deposited during osteoblast calcification in culture. Crystals were isolated from cultures at two time points: (a) at first calcium accumulation (day 8-10) and (b) after 60 days of culture, to assess maturational changes. The analyses show that the chemical composition overall and short range order of the early and mature crystals are characteristic of the apatite crystals found in young embryonic chick bone in vivo. No mineral phase other than apatite was detected by any of the methods used. 31P NMR spectroscopy identified the HPO4 groups as those present in bone apatite. Similar to bone apatites, no OH groups were detected by Fourier transform infrared (FTIR) spectroscopy. The temporal maturational changes in composition and structure of the mineral phase were difficult to assess because of the continuous deposition of crystals throughout culturing. The pathway of the maturational changes observed were similar to those occurring in chick bone in vivo and synthetic apatite crystals in vitro although to a much smaller extent.

Animals↗

PubMed2000

Differential effects of ovariectomy on the mechanical properties of cortical and cancellous bone in rat femora and vertebrae.

The purpose of this study was to evaluate the effects of ovariectomy on the mechanical properties of bone in the aged Sprague-Dawley rat model of osteoporosis. Eight female rats were sacrificed at the start of the study, at the age of four months. Twenty-four remaining rats were then bilaterally ovariectomized (OVX), and another twenty-four served as controls. Eight rats from each group were sacrificed at five, ten or fifteen weeks. The mean density of L1 vertebral bodies from OVX rats was lower than in their control counterparts, as was the compressive modulus, the ultimate compressive stress and the toughness. The second lumbar vertebra from each rat was cored to remove the bulk of the cancellous bone and tested in compression to failure. Ovariectomy did not affect the mechanical properties of the cored vertebrae, suggesting that the mechanically relevant changes take place in the cancellous bone. The gravimetric density and bone mineral density (measured by dual-energy x-ray absorptiometry) of whole femora were lower in OVX rats than control rats. However, the gravimetric density of the cortical bone was unchanged, and when femora were tested to fracture in three-point bending, the mechanical properties of the midshaft were found to be unaffected. This study suggests some limitations to the mature ovariectomized rat model of osteoporosis: mechanically significant loss of cancellous bone occurs in vertebrae much more rapidly than suggested by other studies. Further, there is little evidence of mechanically important bone loss in cortical bone within four months of ovariectomy.

Animals↗

PubMed2000

Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency.

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6 deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflamed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1alpha-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resorption) associated with vitamin B6 deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.

Animals↗

PubMed1999

The effect of fluoride treatment on bone mineral in rabbits.

Fluoride therapy has been used clinically for many years, but its use remains controversial and many basic questions remain unanswered. Accordingly, this study returns to an animal model to study the effects of high doses of fluoride on bone mineral in rabbits. Twelve rabbits, aged 3(1/2) months at the start of the study, received drinking water fluoridated at 100 ppm while their 12 control counterparts drank distilled water. All rabbits were sacrificed after 6 months. Fluoride was readily incorporated into femoral cortical bone (7473 +/- 966 ppm F versus 1228 +/- 57 ppm in controls; P < 0.00005). Fluoride therapy led to increased mineralization, as measured by density fractionation (P < 0.0005 for the distributions). The bone mineral itself was altered, with a significant increase in the width of crystals (66.2 +/- 2.0 A versus 61.2 +/- 0.9 A; P < 0.01). The microhardness of both cortical and cancellous bone in the femoral head of fluoride-treated rabbits was greater than that in the controls (P < 0.05). The phosphate, calcium, and carbonate contents in the bone was the same in both groups. Finally, fluoride administration did not affect the architecture or connectivity of cancellous bone in the femoral head. Previously published data [1] indicated that the mechanical properties of bone were adversely affected; this suggests that the effect of high doses of fluoride on the strength and stiffness of bone may be mediated by its effect on bone mineral.

Age Factors↗

PubMed1999

Effects of recombinant amelogenin on hydroxyapatite formation in vitro.

To determine the role of amelogenin in the mineralization of dental enamel, the effects of the recombinant mouse amelogenin rM179 on in vitro hydroxyapatite formation have been studied. In a steady-state agarose gel assay for hydroxyapatite nucleation, rM179 lacked significant activity at concentrations up to 300 microgram/ml. In an autotitration assay for inhibition of de novo hydroxyapatite formation, rM179 had no significant activity at concentrations up to 30 microgram/ml. Using selected-area dark-field electron microscopy, it was shown that rM179, at concentrations up to 30 microgram/ml, did not significantly affect the length of hydroxyapatite crystals formed in steady-state agarose gels. These findings suggest that amelogenins do not possess the specific crystal-modulating properties characteristic of certain acidic mineralized tissue proteins proteins.

Amelogenin↗

PubMed1999

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats.

BACKGROUND: Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. METHODS: To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. RESULTS: Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. CONCLUSION: Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.

Animals↗

PubMed1999

Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis.

OBJECTIVE: To test the hypothesis that bisphosphonate treatment has a chondroprotective effect in the carrageenan model of inflammatory arthritis (IA). METHODS: Experimental IA was induced in rabbits by intraarticular injections of carrageenan. One group also received subcutaneous injections of zoledronate, a new bisphosphonate. After 4 weeks, the joints were harvested. Articular cartilage degradation and the degree of synovitis were assessed by light microscope using qualitative grading scores. Articular cartilage and subchondral and cancellous bone were evaluated histomorphometrically. Bone microhardness was measured. RESULTS: Carrageenan injected knees showed changes of inflammatory arthritis with cartilage erosion. Zoledronate treatment partially protected the articular cartilage from degradation. This effect was unlikely due to an antiinflammatory effect of the drug as the carrageenan induced synovitis was unaffected by zoledronate treatment. The treatment preserved subchondral bone thickness and cancellous bone volume and prevented focal breaks in the osteochondral barrier. The subchondral bone hardness was also maintained. CONCLUSION: Zoledronate had a partial effect in a rabbit model of inflammatory arthritis. The chondroprotection may be due to the prevention of bone resorption. By maintaining an intact subchondral bone, normal joint loading may have been maintained and contact between the bone marrow and the articular cartilage averted.

Animals↗

PubMed1998

Static and dynamic finite element analyses of an idealized structural model of vertebral trabecular bone.

An idealized three-dimensional finite element model of a rodlike trabecular bone structure was developed to study its static and dynamic responses under compressive loading, considering the effects of bone marrow and apparent density. Static analysis of the model predicted hydraulic stiffening of trabecular bone due to the presence of bone marrow. The predicted power equation relating trabecular bone apparent elastic modulus to its apparent density was in good agreement with those of the reported experimental investigations. The ratio of the maximum stress in the trabecular bone tissue to its apparent stress had a high value, decreasing with increasing bone apparent density. Frequency analyses of the model predicted higher natural frequencies for the bone without marrow than those for the bone with marrow. Adding a mass relatively large compared to that of bone rendered a single-degree-of-freedom response. In this case, the resonant frequency was higher for the bone with marrow than that for the bone without marrow. The predicted vibrational measurement of apparent modulus was in good agreement with that of the static measurement, suggesting vibrational testing as a method for nondestructive measurement of trabecular bone elastic moduli.

Bone Density↗

PubMed1998

Analysis of compositional bone density data using log ratio transformations.

In skeletal research, one of the techniques available to measure bone mineralization produces compositional data, which consist of vectors of ordered proportions of bone sample in prespecified density intervals. We investigated the value of two multivariate data transformations, the cumulative log ratio and the continuation log ratio, in the analysis of an experimental study of the dose-response effect of a drug treatment on bone mineralization. Based on a comparison of alternative approaches to the analysis of compositional bone mineralization data in the application and in a simulation study, we recommend the use of the average of the cumulative log ratios over all the density intervals to detect change in the density distribution. We also recommend the use of one of the continuation log ratios when a specific density interval of interest can be specified a priori.

Animals↗

PubMed1998

Vanadium and diabetes.

We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-term effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanadium compounds. One of these, bismaltolato-oxovanadium IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadium is a phosphatase inhibitor and that vanadium can activate serine/threonine kinases distal to the insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.

Animals↗