Biomedical subjects

M D Grynpas

Publications and source records attributed to M D Grynpas.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effects of different estrogen and progestin regimens on the mechanical properties of rat femur.

The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat femoral cortical bone. Ninety-two 11-month-old female Sprague-Dawley rats were randomly divided into six groups and were treated for a duration of 6 months. Group-1 rats were intact controls, group-2 rats were ovariectomized controls, and groups 3-6 were ovariectomized and given continuous doses of estrogen with 5% estradiol 17B silicone-rubber implants. Groups 4, 5, and 6 were also given different doses of progestin (norethindrone): group 4 received a continuous dose of 3 micrograms per animal per day, group 5 received a cyclic dose of 6 micrograms per animal per day for 14 days of a 28-day cycle, and group 6 received an interrupted dose of 3 micrograms per animal per day for 3 days of a 6-day cycle. Femurs from each group were mechanically tested. Bending stiffness was measured by nondestructive three-point bending tests and maximum torque capacity, by destructive torsion tests. Geometrical properties and apparent density of cortical bone were also measured. The significant differences were: the increases in elastic modulus (measured from the three-point bending stiffness) of group 5 (cyclic norethindrone) compared with those of group 2 (ovariectomized controls) and group 3 (estrogen only); the increases in the size represented by the moment of inertia, the moment of the area, and medial-lateral width of group 2 compared with those of group 5; and the increases in apparent density and decreases in moment of inertia of group 6 (interrupted norethindrone) compared with those of group 2. Cyclic or interrupted treatment of progestin along with continuous treatment of estrogen after ovariectomy likely improves material properties of cortical bone, increases its density, and reduces the size of the bone compared with ovariectomized rats.

Animals↗

PubMed1997

Supraphysiologic levels of testosterone affect cancellous and cortical bone in the young female cynomolgus monkey.

The goal of this study was to evaluate the effects of chronically-elevated male levels of the potent androgen testosterone on the quality and quantity of both cancellous and cortical bone in a young (mean age 8.0 years), nonhuman female primate model (M. fascicularis). Thirteen intact female monkeys received continuous testosterone supplementation via subcutaneous implants over a 24-month period. A group of 16 untreated, intact, age-matched female monkeys served as controls. At sacrifice, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone, respectively, and compared to 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 the 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. A nonsignificant shift in the mineralization profile of the vertebrae was observed whereas there was a significant shift in the mineralization profile towards more dense bone in the treated femora as compared with controls (P < 0.05). There was no difference in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a trend towards an increase in cancellous bone area (B.Ar.) in the testosterone-treated vertebrae (P = 0.08) as compared with controls. The architecture of the cancellous bone remained nonsignificantly different between the treatment and control groups as evaluated by image analysis. There was a decrease in osteoid perimeter (P = 0.05) in the experimental group as compared with controls. There was a significant decrease in eroded perimeter measurements in the experimental group as compared with controls (P < 0.03). Although there was a trend towards an increase in cancellous bone area, mineralization was not significantly different in the vertebrae of testosterone-treated female monkeys, indicating that the newly-formed bone tissue became relatively normally mineralized over the two-year period. An increase in bone area, with indices of an overall decreased remodelling pattern as compared with controls, suggests that cancellous bone in the young, nonhuman female primate had been receptive to supraphysiologic levels of testosterone supplementation over the two-year period. There was a trend for an increase in cortical bone area and width with an increased periosteal perimeter in the testosterone-treated group as compare with controls. There was an increase in intracortical remodelling activity with a significant increase in percent porosity (P < 0.05), osteonal bone (P < 0.05), and mean wall width (P < 0.05) in the testosterone-treated group. In conclusion, the cancellous bone from female monkeys appeared to respond to the antiresorptive stimulus of male levels of testosterone with significantly diminished turnover parameters in this compartment. In contrast, the cortical bone compartment responded by displaying significant intracortical remodelling over a two-year period.

Animals↗

PubMed1997

Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits.

We hypothesized that fluoride partly acts by changing the levels of circulating calcium-regulating hormones and skeletal growth factors. The effects of oral fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The rabbits were divided into two study groups, one control and the other receiving about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of fluoride dosing, all rabbits were euthanized and bone and blood samples were taken for analyses. Fluoride treatment increased serum and bone fluoride levels by over an order of magnitude (P < 0.001), but did not affect body weight or the following serum biochemical variables: urea, creatinine, phosphorus, total protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal fluorosis or osteomalacia was observed histologically, nor did fluoride affect serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40% (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial ash weight by 10% (P < 0.05). However, the increases in bone mass and bone formation were not reflected in improved bone strength. Fluoride decreased bone strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in fluoride-treated bones (P < 0.001), and there was a negative association between crystal width and fracture stress of the femur (P < 0.02). In conclusion, fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1 was increased by fluoride and was associated with increased bone turnover, but was not correlated with bone formation markers. High-dose fluoride treatment did not improve, but decreased, bone strength in rabbits, even in the absence of impaired mineralization.

Acid Phosphatase↗

PubMed1997

Pamidronate content and turnover in sternum, vertebral body, and iliac bones of dogs.

Therapeutic efficacy of bisphosphonates depends on how much drug is present in bone. Therefore, it is important to measure the amount of bone bisphosphonate in toxicological and pharmacological studies. We analyzed pamidronate content of bone samples from two previously published long-term dose studies. In the first study, mature beagle dogs were given oral pamidronate at doses of 0, 2.5, 12.5 and 25 mg/kg per day for 1 year. The dogs in the second study received the same dosages for 1 year followed by 1 year without drug. In both studies, the amount of pamidronate measured was dependent upon dose in bone samples of ilium, sternum, and vertebral body. After 1 year of treatment, vertebral bone had more pamidronate than sternum or iliac bone on a permilligram basis. After 2 years, there was significantly less pamidronate in the vertebral body, sternum, and ilium than there had been at 1 year. The fall in pamidronate content was largest in vertebral body and least in the ilium. The higher uptake of pamidronate by the vertebral body during the 1 year study, and its greater loss of pamidronate after a year without drug treatment, would reflect the higher turnover of trabecular bone in the vertebral body vs. cortical bone in the ilium. The percent difference in bone pamidronate content between the 1 and 2 year dogs varied with dose. The largest percent loss occurred in the intermediate-dose group. These data suggest that, after 1 year without the drug, bone turnover rates in dogs treated with the highest dose of pamidronate were lower than at the intermediate dose. Thus, the time required for bone turnover rates to return to pretreatment levels is probably dose-dependent.

Animals↗

PubMed1996

Bone quantity and quality in past populations.

BACKGROUND: The study of osteoporosis in past populations offers valuable insight into the patterns and prevalence of the disease in both the past and in the present. METHODS AND RESULTS: A review is made of different paleopathological studies better to understand bone loss in past populations and to examine the contribution such studies can make to our knowledge of osteoporosis in modern populations. The review includes studies of bone mass in past populations from different geographic regions. Nutritionally based hypotheses, traditionally used to explain bone loss in past populations, are reviewed and assessed against the current clinical and epidemiological findings. In general, the various studies have revealed different degrees of low bone mass in past populations; however, the pattern of bone loss and fragility seen in age-related and postmenopausal osteoporosis today is not evident in the past. Bone loss in earlier populations is often found in both sexes, whereas significant bone loss in females occurs often among the young-age categories. In addition, a prevalence of osteoporotic fracture is absent. CONCLUSIONS: We suggest that, despite influences that may have reduced bone mass in past populations, a protection of bone quality may have occurred, reducing the likelihood of bone fragility and fracture typically seen in modern osteoporotics. It seems evident that, although reduced bone mass may be prevalent in past history, clinically recognized osteoporosis is not.

Bone Density↗

PubMed1996

Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect.

Low doses of strontium and fluoride were shown to increase bone formation and trabecular bone density in rodents. To assess whether strontium or fluoride affect the quality of the mineral at doses known to increase bone density, we have determined the effects of low doses of strontium and fluoride on bone formation and bone mineral characteristics in rats. Adult rats were given strontium alone (0.20%), fluoride alone (1 mg/kg per day), or the combined treatment for 8 weeks. Strontium levels in serum and femur were similar in groups treated with strontium alone or in combination, being about 5% of calcium levels. Biochemical and neutron activation analyses in femur showed that calcium and magnesium contents did not differ in the four group of rats, suggesting that strontium was incorporated in the apatite lattice of the bone minerals in the strontium-treated rats. The mineralized bone volume was significantly increased by 17% in the strontium-treated group, by 20% in the fluoride-treated group, and by 19% in rats given with the combined treatment. This was associated with increased osteoid surface, osteoblast surface, and double tetracycline labeled surfaces in the strontium-treated and fluoride-treated groups, showing that the number of bone forming sites was increased. However, the mineral apposition rate, the osteoid thickness, and the mineralization lag time were similar in controls and treated groups, reflecting the lack of deleterious effects of low doses of strontium and fluoride on bone mineralization. The density fractionation analysis measured in the femur also showed that neither strontium, nor fluoride at the low doses used, significantly altered the mineralization profile. The results indicate that treatment with low doses of strontium or fluoride increase the number of bone forming sites and vertebral bone volume in rats, but does not have detectable adverse effects on the mineral profile, bone mineral chemistry or bone matrix mineralization.

Analysis of Variance↗

PubMed1995

The effect of different hormone replacement therapy regimens on the mechanical properties of rat vertebrae.

The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat lumbar vertebrae. Ninety-two Sprague-Dawley rats (11 months old) were divided into six groups for treatment. The first group was an intact control, the second group (OVX) was ovariectomized only, and the third group (estrogen-only) was ovariectomized and received continuous estrogen through a 17 beta-estradiol implant. The remaining groups were ovariectomized and received estrogen and progestin (norethindrone, NET) therapy; 3 micrograms of NET was injected daily (estrogen plus continuous NET), or 6 micrograms of NET was injected for 14 consecutive days of a 28-day cycle (estrogen plus cyclic NET), or for 3 consecutive days of a 6-day cycle (estrogen plus interrupted NET). The animals were sacrificed after 6 months, and the vertebrae were dissected out. The vertebral processes of the fourth lumbar vertebrae were removed, and the density of the vertebral bodies was determined. They were then subjected to compression testing. We found that all three estrogen/progestin regimens maintain bone density and all mechanical properties at a level indistinguishable from the control. However, the cyclic and continuous NET treatment results were, with the exception of density, also indistinguishable from those of the ovariectomized group. The estrogen plus interrupted NET group on the other hand, has a significantly greater compressive modulus and density than the ovariectomized group. In conclusion, with respect to the ovariectomized group, the estrogen plus interrupted NET treatment resulted in a superior density and compressive modulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Lumbar vertebral density and mechanical properties in aged ovariectomized rats treated with estrogen and norethindrone or norgestimate.

OBJECTIVE: This study was designed to investigate the effects of estrogen alone or combined with two different progestins, norethindrone or norgestimate, on bone density and compressive mechanical properties in an aged rat model. STUDY DESIGN: Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control (group 1) and the ovariectomized (group 2) and the first of the ovariectomized plus estrogen (group 3) groups were injected subcutaneously daily for 6 months with corn oil (vehicle). Two other groups of rats with estrogen capsules received daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5 micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted progestin). The effects of these various treatments on bone mineral content and bone mineral density in the vertebrae were measured by dual energy x-ray absorptiometry. The L4 vertebral bodies were also tested to failure in compression. RESULTS: The ovariectomized rats receiving corn oil alone had the lowest bone mineral density compared with intact controls. Estrogen treatment alone resulted in a lower bone mineral density than in the intact controls. In contrast, both interrupted progestin regimens resulted in vertebral bone mass index at the same level as the intact controls. Compression tests revealed that ovariectomized controls also had the lowest modulus of elasticity of all groups. However, unlike bone mineral density, estrogen alone resulted in mechanical properties similar to intact controls, whereas the vertebrae in both interrupted progestin groups had variable mechanical properties compared with the ovariectomized and intact control groups. CONCLUSIONS: We conclude that in this experimental model hormone replacement therapy with estrogen and an androgenic (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone mineral density and mechanical properties. In addition, both interrupted progestin regimens had a better effect than estrogen alone on vertebral bone density.

Absorptiometry, Photon↗

PubMed1995

The effects of androgens on the mechanical properties of primate bone.

Feral adult female cynomolgus monkeys were divided into three groups and treated for two years: (1) normal controls; (2) weak androgenic treatment (androstenedione+estrone); and (3) strong androgenic treatment (testosterone). The tibiae and the trabecular bone of femoral head from each group were tested mechanically. There were no significant changes in the elastic modulus and shear modulus of the tibiae, measured by three point bending and torsion tests, among the three groups. Significant increases in energy absorption capacity (+45% for testosterone) and maximum shear stress (+19.4% for androstenedione and +39% for testosterone) of the tibiae, measured by torsion tests, and the cortical bone density (+5.5% for androstenedione and +8.7% for testosterone), were observed. Testosterone treatment significantly increased torsional rigidity (+23%) and bending stiffness (+15%) of the tibiae while androstenedione did not change any of these structural properties. The results of compression tests of the trabecular bone samples indicated significant increases in their elastic modulus after androstenedione (+88%) or testosterone (+107%) treatment. The maximum compressive stress of the testosterone treated samples was significantly higher than those of both normal (+28%) and androstenedione treated groups (+26%). The trabecular bone density increased after both androgenic treatments. This increase was significant for the testosterone treated group (+8.6%). We conclude that in the young cynomolgus monkey, long-term androgenic treatment significantly improves some of the mechanical properties of both cortical and trabecular bones, increases bone density, and the stronger the androgen, likely, the more pronounced is the effect.

Androstenedione↗

PubMed1995

The effect of pamidronate in a new model of immobilization in the dog.

Bone loss resulting from immobilization or disuse has been shown in humans following paralysis or bedrest. We have developed a new model of immobilization in the dog which is reversible and we have studied the effect of pamidronate (APD) in this model. Twelve mature beagle dogs were fitted with specially designed mesh jackets. These jackets were used to bind the left forelimb against the body of the dog, thereby preventing weight bearing on that limb. The experimental group (n = 6) was treated with an I.V. dose of 0.45 mumol/kg/day APD (pamidronate) for 7 days followed by 3 weeks without treatment. This cycle was repeated 3 times for a total of 12 weeks. The control group (n = 6) followed the same pattern, but received only saline injections. At the end of the experiment, the dogs were sacrificed and the humeri and radii cleaned of soft tissues. Mineralization profiles, which determine the distribution of mineralization densities of the cortical and trabecular bone were obtained and the main fractions were analyzed chemically. Static histomorphometric parameters were determined on 5 microns undecalcified sections from the distal humerus and on 50 microns section of the humeral shaft. Three point bending and torsional testing were performed on the radius. Immobilization induces hypomineralization in cortical and cancellous bone but is prevented by APD treatment in cancellous. Immobilization in this model induces osteopenia and increases turnover in cancellous bone. These effects are counteracted by APD. Finally, cortical bone density and stiffness are reduced by immobilization but this is prevented by APD treatment. This experiment shows that the mature dog model is useful to study the immobilization-induced increase of bone turnover and concomitant decrease in bone density, stiffness and mineralization. It also shows that these effects of immobilization can be prevented by treatment with the bisphosphonate pamidronate.

Animals↗

PubMed1995

Stone formation in genetic hypercalciuric rats.

Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% calcium diet for 18 weeks, measured urine supersaturation every two weeks, and examined the urinary tract of 1/3 of the rats for the presence of stones every six weeks. Any stones formed were studied by SEM, X-ray and electron diffraction and X-ray microanalysis. Over the entire study UCa was increased in the GH compared to Ctl, resulting in greater supersaturation with respect to calcium hydrogen phosphate (CaHPO4) at all times and calcium oxalate (CaOx) at most times. There was a progressive increase in the incidence of stone formation in GH rats with one of five rats having stones at six weeks, three of five with stones at 12 weeks and five of five with stones at 18 weeks. There were no stones formed in Ctl rats. SEM reveals discrete stones and not nephrocalcinosis. X-ray and electron diffraction and X-ray microanalysis reveal the stones to be poorly crystalline apatite which is a solid phase of calcium and phosphate. Compared to Ctl, in the GH rats the saturation ratio for CaHPO4 increased proportionally more than that for CaOx, perhaps explaining why the rats formed apatite and not oxalate stones. This is the first description of an animal model of spontaneous nephrolithiasis.

Animals↗

PubMed1995

The effect of three hormone replacement regimens on bone density in the aged ovariectomized rat.

OBJECTIVE: To investigate the effects of estrogen (E) alone or with cyclic, continuous, or interrupted P regimens on bone density in an aged rat model. DESIGN: Randomized controlled trial. ANIMALS: Twenty 12-month-old female Sprague-Dawley rats were sham operated (intact control) and 100 were ovariectomized (OVX). INTERVENTION: Four groups of 20 OVX rats were implanted with silastic capsules containing 5% E2 (wt/wt) in cholesterol. All rats in the intact control (group 1), OVX (group 2), and the first of the OVX plus E groups (group 3) were injected subcutaneously daily for 6 months with corn oil (vehicle). Three other groups of rats with E capsules received daily injections of norethindrone in corn oil, according to the following dosage schedules: 6 micrograms norethindrone/rat per day for 2 of every 4 weeks (cyclic; group 4); 3 micrograms norethindrone/rat per day every day (continuous; group 5); or 3 micrograms norethindrone/rat per day for 3 of every 6 days (interrupted; group 6). MAIN OUTCOME MEASURES: Bone mineral content (BMC) and bone mineral density (BMD) in the femur and vertebrae were measured by dual-energy roentgenogram absorptiometry. RESULTS: The OVX rats (group 2) receiving corn oil alone had the lowest BMD. Intact controls (group 1), E plus cyclic P (group 4), and E and interrupted P (group 6) were all similar and had significantly greater bone density in the vertebrae than the OVX controls. In contrast, vertebral BMD with E alone (group 3) and continuous E and P (group 5) was not significantly different from the OVX group. Femur BMD was significantly lower in the OVX group compared with the other five groups, which did not differ significantly from each other. CONCLUSION: In this experimental model, compared with OVX controls, combined hormone replacement therapy with E and cyclic or interrupted P resulted in the best vertebral BMD whereas continuous E and P resulted in the worst BMD. In the femurs, E alone and E plus P had equal effects on BMD.

Adrenal Glands↗

PubMed1994

Cellular and matrix changes before and at the time of calcification in the growth plate studied in vitro: arrest of type X collagen synthesis and net loss of collagen when calcification is initiated.

To understand the growth, maturation, and regulation of growth plate chondrocytes, it is necessary to isolate the different chondrocytes into distinct subpopulations of maturational development. Five subpopulations (A-E) of bovine fetal growth plate chondrocytes were separated by discontinuous gradient centrifugation. Four subpopulations (B, C, D, and E, from low to high density) with good viability were cultured at high density in microwells for up to 30 days. They all established an extensive extracellular matrix composed of proteoglycan and collagen. The largest and last dense cells in subpopulation B were the first to synthesize (at days 5-6) type X collagen and to calcify this matrix. Matrix calcification (formation of hydroxyapatite in the presence of sodium beta-glycerophosphate) always followed the initiation of type X synthesis. All the other subpopulations synthesized type X collagen and calcified their extracellular matrix. Although these events occurred in the same order, they were delayed according to the order of increasing cell size. These observations indicate that these subpopulations represent different stages in cellular maturation that lead to expression of the hypertrophic phenotype. Once mineral formation was well established, there was an increase in the matrix content of the C-propeptide of type II collagen (which is known to bind to hydroxyapatite and accumulate in calcifying extracellular matrix). This was accompanied by a reduction in the total collagen content, which accompanied an abrupt reduction in type X collagen synthesis, whereas type II collagen synthesis was largely maintained. These reductions in collagen content and type II collagen synthesis were not observed in the absence of calcification (beta-glycerophosphate omitted from culture). This new culture system recreates many of the sequential cellular and extracellular changes exhibited in situ during the development of the physis and provides new information about cellular and extracellular matrix changes that occur before and at the time of calcification.

Absorptiometry, Photon↗

PubMed1994

Effects of intermittent administration of pamidronate on the mechanical properties of canine cortical and trabecular bone.

The mechanical properties of cortical and trabecular bones from beagles treated with the bisphosphonate pamidronate (administered intermittently 1 week every month for 3 months, at a dosage of 0.45 mumol/kg/day) were assessed. The mechanical properties of cortical bone were measured by four-point bending tests on femoral quadrants, in order to measure their elastic modulus and ultimate stress. The structural properties of whole tibias were measured in torsion to determine the torsional stiffness and failure torque. The elastic modulus and maximum compressive stress of the trabecular bone samples were measured by compression tests of trabecular cores. Intermittent treatment with pamidronate did not change the pattern of mechanical properties that occurs naturally around the femur or the torsional stiffness and failure torque of the tibias. By contrast, pamidronate did significantly increase the modulus of elasticity (by 19%) and maximum compressive stress (by 33%) of vertically aligned cylindrical trabecular specimens taken from the vertebrae of the beagles.

Animals↗

PubMed1994

Recovery from pamidronate (APD): a two-year study in the dog.

The goal of this study was to find out if bone can recover after long-term administration of bisphosphonate. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1 year (0.1% concentration) and the animals were allowed to recover for another year. At sacrifice, the os ilium was used to determine bone mineralization profile and, subsequently, each density fraction was analyzed chemically. The ribs were used to determine the lattice parameters and the size of the apatite crystals of bone. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and, subsequently, to determine bone mechanical properties using a 3-point bending technique. We found that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was indistinguishable from the controls. The lattice parameters and crystal size of bone apatite remained unchanged. The image analysis shows a dose-related increase in trabecular volume and thickness. The connectivity increased with dose but the anisotropy of bone remained unchanged. Both the elastic modulus and the maximum stress of bone remain unaffected by APD. We conclude that when dogs are treated with APD for 1 year, their bones can reestablish their physical-chemical characteristics (mineralization profile, chemistry, and crystal size/strain) after 1 year of recovery, provided that the treatment dose is 2.5 mg/kg/day. In addition, the mechanical properties of the bone remained unaffected and the gains in trabecular volume and thickness are maintained.

Animals↗

PubMed1994

Energy-dispersive X-ray microanalysis of the bone mineral content in human trabecular bone: a comparison with ICPES and neutron activation analysis.

To evaluate the accuracy of bone mineral composition determination by electron microprobe analysis (EDX) the measurements have been compared to instrumental neutron activation analysis (INAA) and chemical analysis (ICPES). Bone specimens from five femoral heads were used. The trabecular content of calcium (Ca) and phosphorus (P) was analyzed by the three different methods. The EDX method allows for a microstructural analysis of intact, methylmetacrylate-embedded, undecalcified bone and the measuring points can thus be distinctly identified centrally in each trabecula. The analysis yielded 25.8 +/- 0.7 wt % Ca and 10.5 +/- 0.1 wt % P, compared with 22.2 +/- 0.5 and 23.0 +/- 1.0 wt % Ca, and 9.83 +/- 0.21 and 10.02 +/- 0.44 wt % P for INAA and ICPES, respectively. The EDX analysis was calibrated by consecutive measurements of a hard, pressed tablet of hydroxyapatit of known content. The mean Ca content deviated with -0.38 wt % from the given content and P with -0.89 wt %. We could not verify any particular interference from the embedding procedure, however, it is possible that the relatively lower P content still may reflect this. The magnesium (Mg) concentration was 0.31 +/- 0.02 wt % by EDX and 0.26 +/- 0.02 wt % by INAA. The EDX analytical method provides a useful tool for simultaneous elemental quantification in bone. It has the advantage of permitting the use of regular bone biopsy material and thus allowing for a unique microstructural evaluation of the degree of mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Analysis of collagens solubilized from cartilage of normal and spontaneously osteoarthritic rhesus monkeys.

Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.

Animals↗

PubMed1994

Effect of pamidronate on the mechanical properties of canine bone.

Pamidronate (Aredia) has been used in the treatment of hypercalcemia of malignancy, in Paget's disease of bone, and in osteoporosis to prevent bone resorption. In a 3-month study, intermittent intravenous infusions of pamidronate in dogs did not change the mechanical properties of cortical bone, either in torsion or bending. However, such treatment increased the compressive stiffness and torsional strength of trabecular specimens taken from vertebrae. In a 1-year study, oral administration of pamidronate at various doses produced a linear increase in the elastic modulus of trabecular bone with the square root of the dose and no change in cortical bone. Finally, in a 2-year study (1 year on pamidronate followed by 1 year recovery), no differences were found in the mechanical properties of whole bone whatever dose was given.

Animals↗