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PubMed1980

The effects of nandrolone decanoate on rarefying bone tissue.

The effects of nandrolone decanoate on rarefying bone tissue were studied with the aid of microradiography and fluorescence microscopy in tetracycline-labelled preparations of the rabbit calcaneus and the long bones of old dogs. Osteoporosis was induced in the rabbit calcaneus by resecting of the Achilles tendon. In 20 of the 24 rabbits treated with nandrolone decanoate, the osteoporosis observed was less severe than in 8 untreated controls. Furthermore, in comparison with the controls, the signs of active osteogenesis in the treated groups increased systematically. In the old dogs, nandrolone decanoate caused a new opposition, identified by tetracycline labelling, to appear at the periphery of the medullary cavity. All the observations suggest that nandrolone decanoate has a favourable effect on osteogenetic phenomena and probably an inhibitory action on bone resorption. Consequently, nandrolone decanoate is capable of preventing or, at least, of partially correcting losses of bone mass.

Animals↗

PubMed2004

Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease.

BACKGROUND: Accumulating data emphasize the gender specificity of key components of the atherosclerotic process and the importance of gonadal steroids on the human vasculature. Steroid receptors, including the androgen receptor (AR) and estrogen receptors (ERs) alpha and beta are expressed in key vascular tissues, including endothelial cells and vascular smooth muscle cells. However, the relative abundance and importance of these receptors in the coronary artery are not well defined, particularly in men. We therefore examined AR, ER alpha, and ER beta expression as a function of key components of atherosclerosis, namely plaque and calcium area, in male human coronary arteries. METHODS: Coronary arteries were obtained at autopsy from 24 men without known coronary artery disease. Coronary calcification was measured by contact microradiography, and atherosclerotic plaque area was quantified histologically. Coronary artery cross-sections were immunostained for AR, ER alpha, and ER beta and then measured semiquantitatively in each arterial wall layer (intima, adventitia, and media). RESULTS: AR, ER beta, and ER alpha were expressed in all artery wall layers but most avidly in the media (P < 0.001). ER beta exceeded ER alpha expression (P < 0.0005). AR expression in the media correlated negatively with plaque area (P = 0.006, R = -0.55), whereas intimal ER beta expression correlated positively with plaque area (P = 0.012, R = 0.50). CONCLUSIONS: We conclude that both AR and ER beta are important in relatively early coronary atherosclerosis, but inversely so, because decreasing AR and increasing ER beta expression correlate with more extensive atherosclerosis. ER beta seems to be the predominate ER in coronary arteries harvested from men without known coronary artery disease. Interventional studies are required to assess the functional significance of these observations.

Aged↗

PubMed2006

Intimal estrogen receptor (ER)beta, but not ERalpha expression, is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women.

BACKGROUND: Controversy exists over the association of estrogen and cardiovascular disease. Estrogen receptors (ERs) alpha and beta are expressed in the endothelial cells and vascular smooth muscle cells (VSMCs) of many arteries, but the relative importance of ERalpha or ERbeta in mediating the vascular response to estrogens is not well defined, particularly in humans. We have shown previously that postmenopausal women receiving hormone therapy (HT) had lower mean coronary artery calcium, plaque area, and calcium-to-plaque ratio compared with untreated women. In this study, we examined coronary artery ERalpha and ERbeta expression in pre- and postmenopausal women as a function of plaque area, calcium area, calcium-to-plaque ratio, and estrogen status. METHODS: Coronary arteries were obtained at autopsy from a total of 55 women: nine premenopausal women, 13 postmenopausal women on HT and 33 untreated postmenopausal women (non-HT). Coronary calcification was quantified by contact microradiography, and atherosclerotic plaque area was measured histologically. Coronary artery cross-sections were immunostained for ERalpha and ERbeta, and the amount of receptors was estimated semiquantitatively in each arterial wall layer (intima, adventitia, and media). Double immunofluorescence was used to colocalize ERalpha and ERbeta with smooth muscle actin, a marker of VSMCs. RESULTS: ERbeta and ERalpha were expressed in all artery wall layers, but most avidly in the media (P = 0.001), and colocalized with VSMCs. ERbeta expression exceeded ERalpha expression in all wall layers (P < 0.001) and was adjacent to areas of calcium deposition. ERbeta expression in the intimal layer correlated with calcium content, plaque area, and calcium-to-plaque ratio (all P < 0.01) and tended to be greater in non-HT than in HT women (P = 0.06). ERalpha expression did not vary significantly among groups, nor did it correlate with calcium content, plaque area or calcium-to-plaque ratio. Expression of ERalpha but not ERbeta declined with age (P < 0.01) in HT women only. Age had no effect on ERalpha or ERbeta expression in non-HT or premenopausal women. CONCLUSIONS: ERbeta is the predominant ER in human coronary arteries and correlates with coronary calcification, a marker of severe atherosclerosis. Increased ERbeta expression is linked to advanced atherosclerosis and calcification independent of age or hormone status. Future pharmacogenetic studies that target this receptor are needed to confirm causality.

Adult↗

PubMed1976

Effects of oral therapy with calcium and vitamin D in primary osteoporosis.

Eighteen patients (17 women and 1 man) with primary osteoporosis were divided into two groups of 9 patients each. Group A received 2.0 to 2.5 g of calcium and 400 units of vitamin D per day orally and was studied before and after short-term (3 to 4 months) treatment; group B received 1.5 to 2.0 g of calcium per day and 50,000 units of vitamin D twice weekly and was studied before, after short-term, and after long-term (1 year) treatment. In group A there was a decrease (P is less than 0.01) in bone-resorbing surfaces (microradiography of bone biopsy samples) after short-term treatment. In group B there was a decrease (P is less than 0.01) in bone-forming and bone-resorbing surfaces after both short-tern and long-term treatment. Fasting-state (morning) serum immunoreactive parathyroid hormone (iPTH) concentrations decreased after short-term treatment (combined data of groups A and B) and after long-term treatment (group B). We conclude that the principal effect of the oral calcium and vitamin D therapy in primary osteoporosis is to decrease bone turnover. The most probable mechanism for this effect on bone is a partial inhibition of PTH secretion.

Administration, Oral↗

PubMed1976

Effects of growth hormone in osteoporosis.

The effect of chronic administration of growth hormone (GH) to osteoporotic patients was studied using the techniques of total body neutron activation analysis, whole body counting, calcium tracer kinetics, photon absorptiometry, quantitative microradiography, and urinary hydroxyproline. Two dosage schedules were utilized for six months each: 2 units daily and 0.2 w3/4 units of GH daily (where W represents body weight expressed in kg). The lower dosage (2 units) did not produce any appreciable change in the indices studied. Following the higher dose, no evidence of any anabolic effect was apparent in most patients (i.e., no increase in total body levels of Ca, Na, K, P, or Cl). Increases were noted in the urinary calcium excretion rate and in the urinary hydroxyproline excretion. Bone mineral content decreased. The bone biopsies displayed an increase in bone formation and resorption surfaces in response to treatment, but these changes were not statistically significant. It may be concluded that under the conditions of this study, GH administration did not result in an increment in skeletal mass. Several side effects that are characteristic of acromegaly were observed, including hyperglycemia, hypertension, arthralgia, and the carpal tunnel syndrome. Because of the lack of demonstrated benefit and the associated complications of therapy, GH administration does not appear to be of value in the treatment of osteoporosis.

Bone and Bones↗

PubMed2002

Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women.

BACKGROUND: Coronary artery calcium, a radiographic marker for atherosclerosis and a predictor of coronary heart disease (CHD), is less extensive in women than in men of the same age. The role of estrogen in the pathogenesis of coronary artery calcification is unknown. We examined the association of estrogen status with extent of calcification and atherosclerotic plaque in coronary arteries of deceased women. METHODS: Coronary arteries were obtained at autopsy from 56 white women age 18--98 yr, 46 postmenopausal and 10 premenopausal. Exclusion criteria included patients with coronary stents, coronary artery bypass surgery, and medical-legal cases. Medical records were reviewed for demographics, CHD risk factors, menstrual status, and use of estrogen replacement therapy. Contact microradiography of coronary arteries assessed true calcium content and atherosclerotic plaque area was analyzed histologically. RESULTS: The coronary arteries from estrogen-treated postmenopausal women had lower mean coronary calcium content (P = 0.002), mean plaque area (P < 0.0001), and calcium-to-plaque area ratio (P = 0.004) than those from untreated menopausal women. Estrogen status, age, diabetes, and hypertension predicted calcium and plaque area by univariate analysis. After controlling for these CHD risk factors, estrogen status remained an independent predictor of both calcium (P = 0.014) and plaque area (P = 0.001) in all women. Mean calcium area (P < 0.05) but not plaque area (P = 0.44) was significantly greater in women treated with estrogen replacement therapy than in premenopausal women. Coronary calcium (P < 0.007) and plaque area (P < 0.03) varied significantly with age in untreated postmenopausal women, but not in the estrogen-treated or premenopausal women (P = 0.33). CONCLUSIONS: Estrogen status is associated with coronary calcium and plaque area independent of age and CHD risk factors. Estrogen may modulate the calcium content of atherosclerotic plaques, as well as plaque area and may slow the progression of atherosclerosis in women.

Adult↗

PubMed1992

[Effects of vanadyl sulfate on osteopenia in streptozotocin-induced diabetic (STZD) rats. Comparison with those of insulin].

The insulin mimetic effects of vanadium salts on glucose metabolism have been well-documented in STZD rats. In this study, the long-term effects of vanadyl sulfate (vanadium) on osteopenia in STZD rats were examined and compared with those of insulin. From 2 days after an intravenous injection of streptozotocin (30 mg/kg), the rats with hyperglycemia (> 300 mg/dl) received either vanadium (0, 0.02, 0.1 or 0.5 mg/ml) in drinking water or daily subcutaneous injections of insulin (0, 0.4 or 4.0 U/day) for 54 days. Their tibiae and femurs were examined by chemical analyses, by contact microradiography and by the method of double tetracycline labeling. Decreases in bone mass, bone density and in the rate of bone formation were observed in STZD rats. Development of these symptoms in the STZD rats with osteopenia was prevented by the administration of either vanadium or insulin in a dose-dependent fashion. The effects of vanadium at a dose of 0.5 mg/ml for preventing bone loss in STZD rats were similar to those of insulin at a dose of 4.0 U/day. These results indicate that vanadium has insulin mimetic effects on osteopenia in STZD rats.

Animals↗

PubMed1996

Histopathological findings on ulcerative lesions of carpal and tarsal joints in Japanese black cattle.

In order to determine the pathogenesis of ulcerative lesions of the articular cartilages in Japanese Black cattle, tissue samples of the ulcerative lesion, marginal portion of the ulcer, macroscopically normal portions and synovial membranes were histopathologically examined by light microscopy, scanning electron microscopy and contact microradiography. The results are summarized as follows: (1) In the ulcerative lesions, degeneration and complete destruction of articular cartilage and its replacement with a proliferation of myelogenic connective tissue were observed. (2) In macroscopically normal portions, fissures of the articular surface and changes of the trabecular pattern in subchondral bone were present. (3) In the marginal portions of the ulcerative lesions, evidences of the repair process such as connective tissue growth from subchondral bones and articular cartilages were seen. (4) In synovial membranes, no pathological findings were observed. And (5) among the above mentioned changes, no inflammatory findings were seen. In conclusion, the ulcerative lesions of bovine articular cartilage may be regarded as the early stage of osteochondrosis to osteoarthrosis since the findings such as noninflammatory destruction or degeneration and remodeling of the joints are characteristics of the latter.

Animals↗

PubMed1998

Local disappearance of epiphyseal growth plates in rats with hypervitaminosis A.

Epiphyseal growth plates of proximal tibiae in rats with high doses of vitamin A (V-A) were observed. Of 4 groups, each consisting of 5 rats, three groups were given V-A at doses, IU/100 g by body weight/day, of 50,000, 100,000, and 150,000, respectively. The other group rats were given no V-A (control). Rats were administered V-A for the 5 days from 4 weeks after birth and sacrificed at 12 weeks after birth. Three rats of the 150,000 IU group died during the period of observation. The decalcified sections were stained with hematoxylin-eosin or toluidine blue. In the ground sections, microradiography, backscattered electron imaging, and energy-dispersive X-ray microanalysis were performed. These observations suggest that the local disappearance of epiphyseal growth plates under high doses of V-A goes in the order of the increased doses through the process of (1) calcified cartilage areae appearing in the resting cell zone, (2) some of the calcified areae extending in the growth plate towards the diaphysial side, (3) bone tissue replacing the calcified areae, and (4) the local disappearing of the growth plate. Such a local disappearance may be formed in the stressed proximal regions of tibiae.

Animals↗

PubMed2003

Effects of a macrolide antibiotic on enamel formation in rat incisors--primary lesion of ameloblast at the transition stage.

A novel macrolide antibiotic was administered orally to 5-week-old Jcl:Wistar rats at a dose of 5,000 mg/kg/day for 5 weeks, and then a half of animals were maintained without any treatment for 10 weeks. A white discolored lesion with horizontal stripes developed on the surface of the upper and lower incisors after dosing for 4 weeks, and these macroscopical incisal lesions disappeared with the eruption in 4 weeks after stop of administration. Histopathologically, increase in number of karyopycnosis of ameloblast at the transitional stage, vacuolar degeneration of ameloblast and cystic change in the maturation stage, and impaired iron pigment secretion at the pigmentation stage were observed. Microradiography, calcio-traumatic zones, which means hypocalcification, were observed on the superficial layer of enamel. These results suggest that the primary lesion induced by a novel macrolide antibiotic is the increased karyopycnosis of ameloblast at the transitional stage, and followed by later stage.

Ameloblasts↗

PubMed1988

Radiography and histology of a threaded acetabular implant. One case studied at two years.

Threaded acetabular components are widely used in cementless total hip replacement, despite a poor understanding of the nature of the bone-implant interface. We have examined one case in which the threaded titanium ring appeared to be well incorporated with no discernible radiolucency. Microradiography and histology surprisingly showed that the threads were entirely encapsulated in fibrous tissue. This raises doubt about the relevance of plain radiography to the analysis of the acetabular interface.

Acetabulum↗

PubMed1997

Temporal changes of mRNA expression of matrix proteins and parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor in bone development.

Expression of parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor is one of the osteoblastic phenotypes; however, it has not been clear whether this phenotype expression is a marker of immature or mature osteoblasts. We examined the temporal expression pattern of PTH/PTHrP receptor in bone development in vivo and in vitro compared with the expression of other osteoblastic phenotypes: osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), alkaline phosphatase (ALP), and mineralization. Total RNA was extracted from rat calvariae, and cell culture of rat bone marrow at different developmental stages and then Northern blot hybridization were performed. Mineralization was detected with contact microradiography (CMR) in calvaria or with Alizarin Red S staining in bone marrow cell culture. Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation. Notably, PTH/PTHrP receptor was expressed at an early developmental stage (prenatal day 14 in calvaria, day 5 in culture) when mineralized tissue was not formed and other osteoblastic phenotypes were scarcely detected. Further study in cell culture revealed that the fold increase in cyclic adenosine monophosphate (cAMP) in response to PTH was elevated with the advance in the culture stage. These results indicate that mRNA expression of PTH/PTHrP receptor could be the early differentiation marker in osteoblastic lineage and that the levels of cAMP production in response to PTH represent the stage of osteoblastic differentiation.

Alkaline Phosphatase↗

PubMed1999

Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats.

This study was designed to test whether bisphosphonates disturb the process of fracture healing. Female Sprague-Dawley rats were injected with either two doses of bisphosphonate (incadronate) (10 microg/kg and 100 microg/kg) or vehicle three times a week for 2 weeks. Right femora were then fractured and fixed with intramedullary wires. Incadronate treatment was stopped in pretreatment groups (P-10 and P-100 groups), while the treatment was continued in continuous treatment groups (C-10 and C-100 groups). Animals were sacrificed at 6 and 16 weeks after surgery. Soft X-ray of all fractured femora was taken. After mechanical testing, fractured femora were stained in Villanueva bone stain and embedded in methyl methacrylate. Cross-sections near fracture line were analyzed by microradiography and histomorphometry. Radiographic study showed that bony callus was present in all the fractures and incadronate treatment led to a larger callus, especially in C-100 group at both 6 and 16 weeks. Histologic study showed that the process of fracture healing in pretreatment groups was delayed at 6 weeks, but reached control level thereafter and showed same characteristics as in control at 16 weeks. Woven bony callus could still be seen in continuous treatment groups at 16 weeks. Mechanical study indicated that the ultimate load of C-100 group was slightly higher than the other treatment groups and control. The results suggest that pretreatment with incadronate did not affect fracture healing at 16 weeks after fracture. However, continuous incadronate treatment could lead to larger callus, but it delayed remodeling process during fracture healing, especially with high-dose treatment.

Animals↗

PubMed2003

Optical path-length spectroscopy of incipient caries lesions in relation to quantitative light-induced fluorescence and lesion characteristics.

A basic understanding of the light-scattering processes that take place inside the dental tissue (either sound or carious) is obtained both with measurements of the photon path-length distribution of light inside such media and with Monte Carlo simulations. Furthermore, the following is investigated: the correlations between different momenta of the photon path-length distribution of light inside caries lesions, the fluorescence loss determined with quantitative light-induced fluorescence, and/or the demineralization and depth of caries lesions determined with transversal microradiography. It is concluded that (i) the light paths inside both carious and sound enamel are considerably influenced by the refractive-index contrast at the tooth surface; (ii) contrary to a previous hypothesis, the fluorescence loss is larger in lesions in which the average photon path length is longer; (iii) very good correlations are obtained between the optical characteristics and the physical parameters of lesions when the optical measurements are performed such that there is high refractive contrast at the tooth surface.

Dental Caries↗

PubMed1979

Effect of 1 alpha-hydroxyvitamin D3 in rats with experimental renal osteodystrophy.

A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) were studied. Male Wistar rats weighing 180 g were 5/6 nephrectomized and fed a normal diet (Ca and P : 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism. Treatment with 0.25 micrograms/kg/day p.o. of 1 alpha-OH-D3 for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1 alpha-OH-D3 appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseases.

Animals↗

PubMed1990

The fine structure and formation of hypermineralized petrodentine in the tooth plate of extant lungfish (Lepidosiren paradoxa and protopterus sp.).

Histological features of the tooth plate of lungfish were investigated by light and electron microscopy and contact microradiography with primary reference to the fine structure and formation of petrodentine, one of the principal constituents of the tooth plates. Petrodentine is a highly mineralized tissue noticeably analogous to that of enameloid, and is deposited intermittently in a proximal direction by the sole participation of mesenchymal petroblasts. The petroblasts appear very likely to have prominent biphasic functions of secreting the petrodentine matrix and of eliminating the matrix by resorption. The petrodentine thus may be capable of attaining hypermineralization with the participation mesenchymal cells alone. Mineral crystals constituting the petrodentine are large, hexagonal or similar but irregularly shaped columns. Initially these crystals appeared extremely thin, with curled ones frequently noted. The petrodentine of lungfish tooth plates is considered to be structurally distinct from the pleromin (Kosmin) of holocephalian tooth plates because of the difference between their constituent crystals.

Animals↗

PubMed2000

Time-related changes of developing enamel crystals after exposure to the tissue fluid in vivo: analysis of a subcutaneously implanted rat incisor.

To investigate the effects of tissue fluid on the growth of enamel crystals, upper and lower incisors extracted from 3-week-old Wistar rats were removed of the enamel organ, implanted subcutaneously in the dorsal portion of animals from the same litter, and harvested at 72 h or 1 week after implantation. The grafts were chemically fixed with surrounding tissues and prepared for light and electron microscopy, X-ray microanalysis, or for the immunohistochemistry of amelogenin. Mineralization of implanted enamel layers was examined by contact X-ray microradiography. The immunoreactivities for 25 kD amelogenin in immature enamel decreased sequentially, starting from the surface to the deeper layers; by 1 week after implantation, no positive reactivities remained in the entire enamel layers at the stages of matrix formation and early maturation. In accordance with the loss of enamel proteins, immature enamel gained mineral density until it attained higher radio opacity than that of the adjacent dentin by 1 week. In contrast, the radio opacity of the full thickness of the enamel at early maturation remained low except for a superficial thin layer. Electron microscopy revealed no sign of growth of original enamel crystals, but showed heavy precipitation of electron-dense fine granules of calcium phosphate in all layers of the secretory enamel and the superficial layer of enamel at early maturation, which showed high radio opacity. The Ca/P ratio and electron diffraction patterns of the granular materials precipitated between intrinsic enamel crystals indicated the property of hydroxy apatite or octacalcium phosphate though a characteristic ribbon-like profile of enamel crystals was lacking. These data indicate that the enamel organ blocks exogenous mineral precipitates in growing enamel during the stage of matrix formation and plays an essential regulatory role for fine enamel crystallites to grow into large hexagonal crystals.

Amelogenin↗

PubMed1989

[A study of secondary caries in cast restored teeth].

The purpose of this study was to investigate the state of the natural secondary caries and in vitro artificial secondary caries, associated with cast restorations cemented with zinc phosphate cement, histopathologically. For this study, the method of making and staining ground serial sections of teeth with cemented cast restorations was established. The material consisted of 50 extracted human permanent teeth with cemented cast restorations, and 12 human premolar teeth with in vitro secondary caries produced by the acid-gelatin system (pH 4.0). These specimens were embedded in MMA resin and then they were sliced to serial thin sections. Each section was etched by 0.1 N HCl, and stained with methylene blue fuchsin, and then observed with optical microscope, microradiography, and SEM. The result were as follows: 1. When the margin of restoration was set on dentine (cementum), the typical shape of natural secondary caries was found out. 2. The rate of natural secondary caries in case of margin set on dentine was about four times as many as the rate in case of margin set on enamel. 3. The shape of artificial secondary caries was very similar to the shape of natural secondary caries. 4. The resistance to secondary caries in case of the margin set on enamel was higher than the resistance in case of the margin set on dentine.

Crowns↗