ISSN:0884-0431    

DOI:10.1002/jbmr.5650020102

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractA double‐blind randomized study of 29 patients with symptomatic Paget's disease was conducted comparing the clinical, biochemical, and histomorphometric responses to 3‐month treatment with placebo (10 patients), low‐dose disodium etidronate (EHDP) (5–7 mg/kg/day) (10 patients), and low‐dose EHDP plus 1α‐hydroxy‐vitamin D3(1αD3) 0.5 mcg daily (9 patients). In placebo‐treated patients no significant changes were observed in symptoms, biochemistry, or bone histomorphometry. Histologically apparent mineralization defects developed after 3 months of therapy in 90% of patients in the EHDP group, compared with 45% of patients in the EHDP/1αD3group. In 19% of the patients treated with active medication, the mineralization defects in pagetic bone were accompanied by histological evidence of continued osteoclastic resorption. The development of mineralization defects was not related to serum levels of vitamin D metabolites, alkaline phosphatase, or intestinal calcium absorption but did correlate with the occurrence of hyperphosphatemia during treatment, which was most marked in patients treated with EHDP alone. Although mineralization defects were less frequent in the EHDP/1αD3group, these patients also responded less well symptomatically, thus limiting the potential usefulness of this drug combination in Paget's disease. It is suggested that the diminished response in the EHDP/1αD3group and the lower frequency of mineralization defects may have been related to an alteration in the intestinal absorption of EHDP by the vitamin D metabolite.Of patients treated with EHDP alone, 90% had symptomatic and biochemical improvement, suggesting that this agent is generally an effective and safe treatment in Paget's disease. However, in view of the high incidence of mineralization defects, we would continue to advise caution in the use of EHDP where there is significant deformity of, or lytic lesions, in

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020103

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractWe report a study to test the feasibility of studying mineral density distributions in bone using the backscattered electron signal in scanning electron microscopy. Samples were human sixth ribs ranging in age from 8 weeks to 59 years, embedded in polymethylmethacrylate (PMMA), cut, polished, and carbon coated. The proportions of pixels falling in a uniform set of gray level slices of the BSE signal were determined using a microcomputer‐based image analysis system interfaced directly to the SEM. The amount of high‐density bone gradually increased with age at the expense of low‐density bone, and there was an associated compression of the range of the mineral density distribution. Age‐related differences were noted between the density distributions in the outer and inner rib cortices. The distribution in the inner cortex in neonates was influenced by the inclusion of densely mineralized endochondral bone and cartilage trabeculae formed at the growth cartilage zone. In adults it appeared that greater bone turnover occurred in the outer cortex, perhaps reflecting a differential mechanical loading across the rib. The technique enabled rapid, unbiased discrimination between the bone of neonates, children, and

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020104

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractAutologous growth‐promoting activity has been shown to be secreted by bone organ cultures. To identify the cellular source of these growth factors, we have studied the activity present in cell extracts prepared from isolated bone cells released early or late from mouse calvariae following collagenase digestion. Previous studies have established that early released cell populations reside on the bone surface and consist of a heterogeneous mixture of cells that are less osteoblastic than late released cells. We find that soluble extracts of the latter cells contain more growth‐promoting activity/mg of cellular protein than those of the former. By this criterion late released cells appear to be the major source of endogenous growth factors. On the other hand, upon exposure to bone cell‐derived cell extracts, early released cells express a greater‐fold increase in [3H]‐thymidine incorporation into acid insoluble radioactivity than late released osteoblasts because of the high basal mitogenic activity of the latter which may be related to their production of autologous growth factor. These data suggest that both early and later released cells may be major targets for bone growth factors producedin situby late released os

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020105

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractA transforming growth factor of the beta class (TGF‐β), defined by its ability to induce normal rat kidney cells (NRK, clone 49F) to form anchorage‐independent large colonies in soft agar in the obligate presence of epidermal growth factor, has been prepared from culture medium conditioned by fetal rat calvariae. This activity was purified by acetic acid extraction, gel permeation chromatography, and two reversed‐phase HPLC (rpHPLC) steps. Bone culture derived‐TGFβ‐like activity was soluble in 1.0Macetic acid, eluted from Sephadex G‐75 at relative molecular mass (Mr) 25,000, from μBondapak C18 rpHPLC at 63 ± 5% methanol in 0.1Macetic acid, and from μBondapak CN rpHPLC at 36 ± 2%n‐propanol in 0.1% trifluoroacetic acid. Based on specific activity estimations at each stage of purification, TGFβ‐like activity was purified 2500‐fold with a 14% recovery, and 1 I of conditioned medium yielded 1–2 μg of factor. Silver‐stained polyacrylamide gels of this material after CN μBondapak rpHPLC revealed a p

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020106

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractThree bioassays are widely employed for the measurement of PTH‐like adenylate cyclase‐stimulating factors (ACSFs) drived from tumors associated with humoral hypercalcemia of malignancy. These include renal cortical adenylate cyclase (RAC) assays, rat osteosarcoma (ROS) adenylate cyclase assays, and fetal bone resorption (FBR) assays. A previous study has suggested that the potency of one human tumor‐derived ACSF, expressed in PTH equivalents, was 30‐fold higher in the ROS assay than in the RAC assay, but no study has directly compared all three bioassays using a single PTH standard and a single ACSF preparation.We compared one partially purified ACSF preparation to a single lot of bPTH 1–34 in all three bioassays. The results indicate that the relative potency of this ACSF as compared to the PTH standard varied with the assay employed, with the ROS assay yielding a specific activity estimate 47.5‐fold higher than the RAC, and the FBR 6.7‐fold higher than the RAC but 7.1‐fold lower than the ROS.These findings support the possibility that distinct subpopulations of PTH receptors exist on different PTH target tissues. Further, they underscore the importance of bioassay choice when estimating the specific activity of tumor‐derived

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020107

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractAmino‐hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease.Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 ± 26 U/I (x̄ ± SEM) to 103 ± 10 U/I after 6 months (nl<120 U/I).Urinary excretion of hydroxyproline decreased immediately and became normal (nl<2.3 μmol/IGF) as a mean at day 5 (from 4.6 ± 0.4 μmol/IGF to 2.1 ± 0.3 μmol/IGF). Thereafter it remained within the normal range (2.0 ± 0.2 μmol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020108

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractOsteoclasts freshly isolated from embryonic chicks have been examined for calcitonin receptors using radio‐iodine‐labeled salmon calcitonin. Calcitonin binding to chick osteoclasts could not be shown by either autoradiography or biochemical binding studies. Furthermore, calcitonin did not stimulate cyclic AMP production. By contrast, rat osteoclasts have abundant calcitonin receptors, and a sensitive cyclic AMP response to calcitonin has been shown previously. It is concluded that chick osteoclasts do not possess calcitonin receptors, a finding which could explain the lack of calcitonin responsiveness observed in other avian osteoclast culture syst

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020109

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effects of ethanol on bone and mineral metabolism were investigated in 3 groups of male rats. The first group received ethanol administered as 36% of caloric content in a liquid diet for 3 weeks. A second group of pair‐fed animals was given the same liquid diet, except that sucrose was substituted isocalorically for ethanol. A third group of rats was fed standard laboratory chow. The ethanol‐treated rats gained significantly less weight than laboratory chow‐fed controls but gained the same weight as the pair‐fed animals. Ethanol‐treated rats had a modest but significant decrease in mean serum calcium compared to pair‐fed controls (10.3 ± 0.1 vs. 10.6 ± 0.1 mg/dl,p<.001). Mean serum phosphate, 25‐hydroxyvitamin D, 1,25‐dihydroxyvitamin D and immunoreactive parathyroid hormone were the same in the 3 groups. The ethanol‐treated animals showed significant decreases in mean tibial length (1.88 ± 0.01 vs. 1.98 ± 0.02 cm,p<.01), mean endosteal bone formation rate (0.0006 ± 0.0001 vs. 0.0026 ± 0.0003 mm3/day,p<.001) and mean periosteal bone formation rate (0.022 ± 0.001 vs. 0.026 ± 0.001 mm3/day,p<.01) compared to the pair‐fed controls. The ethanol‐treated rats demonstrated significant decreases in mean periosteal mineralization rate (7.5 ± 0.3 vs. 10.3 ± 0.6 μm/day,p<.01) and mean periosteal apposition rate (8.5 ± 0.5 vs. 11.0 ± 0.8 μm/day,p<.05) and a significant increase in mean periosteal osteoid thickness (15.5 ± 1.4 vs. 10.4 ± 0.8 μm,p<.01) compared to pair‐fed controls. The laboratory chow‐fed controls had higher mean endosteal bone formation rate (0.0040 ± 0.0004 mm3/day,p<.01), mean periosteal bone formation rate (0.034 ± 0.001 mm3/day,p<.01), mean periosteal mineralization rate (12.5 ± 0.7 μm/day,p<.01) and mean periosteal apposition rate (13.0 ± 0.7 μm/day,p<.01) than the pair‐fed control animals. The results are interpreted to mean that in the rat ethanol alters mineral homeostasis and diminishes formation of bone matrix and mineralization of osseous tissue. These effects cannot be accounted for by alterations in the metabolism of vitamin D. Further, caloric restriction and inhibition of growth themselves diminish formation o

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020110

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractX‐linked hypophosphatemic (Hyp) mice are a model for human sex‐linked vitamin D‐resistant rickets. We have reported intestinal malabsorption of calcium in youngHypmice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2vitamin D3, this hormone was continually infused via osmotic minipumps into 4‐week‐old normal andHypmice at 0,17, 50 or 150 ng/kg/day. After 3 days,45Ca and inorganic32P were administered by gavage, and the mice were sacrificed on the fifth day. TheHypmice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both45Ca and32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D‐dependent calcium‐binding protein (calbindin‐D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of45Ca and32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal andHypmice and was found to be lower in 4‐week‐oldHypmice than in 4‐week‐old normal mice (113 ± 10 pM(n= 18) vs. 67 ± 10 (n= 20), normal vs.Hyp, p<.01), but unchanged at 13 weeks of age (77 ± 13 (n= 13) vs. 70 ± 15 (n= 15), NS). This observed difference in plasma 1,25(OH)2D between normal andHypmice at 4 weeks of age was sufficient to explain the observed normal‐to‐Hypdifferences in intestinal absorption of45Ca and duodenal and renal CaBP. It also explained 72 ± 18% of the observed difference in32P absorption. We conclude thatHypmouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4‐week‐oldHypmice causes intestinal ma

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020111

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY