摘要:

AbstractRenal transplant patients exhibit increased rates of trabecular bone fractures, probably due to glucocorticoid‐induced osteopenia, which is known to occur within 6 months after kidney grafting. This mineral loss at a mostly trabecular site (lumbar spine) contrasts with a gain at the radius, which consists mainly of cortical bone. However, the early effects of kidney transplantation on the other parts of the human skeleton and the time course of these changes during the first 5 months after transplantation remain unknown. Therefore, 34 kidney transplant recipients were prospectively followed immediately after kidney grafting (12 ± 1 days, mean ± SEM, and then on a monthly basis up to 152 ± 3 days) and compared with 34 normal healthy volunteers matched for age, sex, and body mass index. Bone mineral measurements of whole body (n= 34), lumbar spine (n= 32), and upper femur (n= 23) were performed using dual‐energy x‐ray absorptiometry (Hologic QDR 1000W). At time of transplantation, lumbar bone mineral density (BMD) and BMD of the upper femur were lower (p<0.01) in female but not male patients compared with controls. Lumbar BMD decreased by 1.6 ± 0.2% per month in both sexes (p<0.01), whereas BMD of upper femur further decreased in males (p<0.01) but only tended to decrease in females. At time of transplantation, whole‐body bone area (BA), bone mineral content (BMC), and BMD were decreased by about 8, 15, and 9%, respectively, in patients compared with controls (p<0.01). Compartmental analysis revealed similar reductions in BMD and BMC at trunk, head, and limbs, whereas BA was reduced only at limbs (p<0.01). During the 152 ± 3 days of observation, BMC and BMD of limbs remained essentially unchanged, whereas BA of limbs increased (p<0.01) and BA, BMC, and BMD of trunk and head decreased (p<0.01). In conclusion, within 5 months after successful kidney transplantation resulting in good renal function, about 41 g bone mineral is lost, mostly due to losses in the trabecular bone compartment (i.e., about 10%). Longitudinal trials to prevent trabecular bone loss during the phase of terminal renal failure and during the first half‐year following transplantation are urgently needed to develop rational and effective therapeutic strategies in patients on dialysis and kidney trans

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090102

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

年代:1994

数据来源: WILEY

摘要:

AbstractIt has been proposed that Paget's disease of bone is caused by the infection of bone cells with one or several paramyxoviruses. In this study we used the polymerase chain reaction (PCR), which allows the detection of very low levels of a target nucleic acid sequence, to study cultures of pagetic bone cells and samples of pagetic bone. Oligonucleotide primers were designed to flank a sequence of the nucleocapsid genome of measles virus and canine distemper virus (CDV). Within this fragment there were contrasting restriction endonuclease sites specific to measles or CDV that allowed identification of the original template. We were unable to detect paramyxovirus RNA in four strains of human bone cells outgrown from pagetic bone and one strain derived from an uninvolved site of a patient with Paget's disease. Furthermore, paramyxovirus sequences were not detected in cDNA prepared from six samples of pagetic bone biopsies. The work presented here further questions the role of measles and CDV in the abnormal remodeling observed in Paget's disease.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090103

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe use of stereoscopic scanning electron microscopy to analyze quantitatively the topography of excavations made by osteoclasts in slices of devitalized cortical bone was evaluated. Using this innovative technique, the need mechanically to tilt the specimen stage to gather three‐dimensional information is obviated by instead tilting the electron beam both to produce real‐time stereo pairs and to gather measurement data. Based on the comparison of two images of microscopic areas, cross‐correlation is used to determine the image shift between the features in the stereo pair. This information is then used dynamically to correct the height of the tilt axis and lens focus in a feedback loop, generating a quantitative measurement of height difference. With this approach, relative heights of individual points, line profiles, area topography maps, and three‐dimensional reconstructions of excavations were obtained rapidly and at high resolution. This approach combines the advantage in topographic data acquisition of confocal microscopy with the advantages of the increased resolution and focal depth of scanning electron microscopy (SEM). The technique should facilitate not only the topographic analysis of osteoclastic excavations in bone slices at high resolution but also the three‐dimensional analysis of the structure of bo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090104

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe binding sites and chronologic localization of elcatonin (eCT) in osteoclasts were examined by autoradiography using [125I]elcatonin (125I‐eCT). In addition to the structural changes induced by calcitonin (CT) reported so far, changes were also observed in the structure of Golgi apparatus. These changes continued until 48–72 h after incubation with eCT. Developed silver grains of125I‐eCT were localized into multinucleated osteoclasts and mononuclear cells that were ultrastructurally defined as “preosteoclasts.” The silver grains located on plasma membranes of those cells and were then internalized; they accumulated, especially in the Golgi apparatus, and remained for 48–72 h. A few silver grains were also detected in lysosomes and small vesicles. The decrease in the number of silver grains in the Golgi apparatus accompanied the recovery of osteoclast structures – Golgi apparatus and then ruffled borders. These findings suggest that (1) CT especially inhibits the sorting function of Golgi apparatus in osteoclasts, resulting in prolonged retention of CT in this organelle. (2) The CT in Golgi apparatus may keep its activity and cause the prolonged effect of CT on osteoc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090105

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

年代:1994

数据来源: WILEY

摘要:

AbstractCD44 is a transmembrane glycoprotein with cell‐cell and cell‐matrix adhesion functions that is expressed by a wide variety of cell types and has a number of known biologic functions. Because of its ability to bind matrix macromolecules, such as fibronectin, collagen, and hyaluronate, we investigated the possibility that it is expressed by the cells of bone, the matrix receptors of which are largely unknown. Immunohistochemical study of a variety of sources of human bone was carried out using a panel of six well‐characterized anti‐CD44 monoclonal antibodies. Osteocytes strongly expressed CD44, whereas osteoblasts and lining cells were negative. Osteoclasts and periosteal cells also expressed CD44, although not as strongly as osteocytes. These patterns of staining were observed with all six antibodies. These results demonstrate that acquisition of CD44 immunoreactivity is a sensitive marker of osteocytic differentiation and raise the possibility that CD44 acts as a cell matrix receptor

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090106

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

年代:1994

数据来源: WILEY

摘要:

AbstractMost previous literature on muscle strength and bone density examined the association between specific muscle groups and adjacent bones. This study examined the association of grip strength with bone density at distant sites, such as the spine and hip, as well as at the wrist and radius. Subjects were 649 postmenopausal women aged 65 years and older. Bone mineral density was measured at the ultradistal wrist and midshaft radius in the nondominant arm using single‐photon absorptiometry and at the lumbar spine and hip using dual‐energy x‐ray absorptiometry. Grip strength was measured in both the dominant and nondominant hands using a dynamometer. Overweight women had significantly stronger grip strength in both hands (p<0.01 for dominant hand,p<0.05 for nondominant hand grip strengths). Exercisers had significantly stronger grip strength in the nondominant hand than nonexercisers (p<0.05). Women reporting arthritis had significantly weaker grip strength in both hands than women not reporting arthritis (p<0.001). There were no significant differences in grip strength by estrogen use, cigarette smoking, or thiazide use. Regression analyses adjusted for age, obesity, exercise, cigarette smoking, thiazide use, arthritis, years postmenopausal, and estrogen use indicated significant positive associations between grip strength and bone density at all sites. Regression analyses stratified by exercise indicated that only women who exercised had significant associations of grip strength with bone mineral density (allp<0.05). In this cohort of older women, grip strength was an independent indicator of general bone density. These results are compatible with the thesis that grip strength is a marker for overall fragility and general health and for the adequacy of skeletal loading exe

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090107

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe thyroid calcitonin‐producing C cells possess vitamin D receptors and synthesize the vitamin D‐dependent calbindin D28K. The present study evaluates the possible direct or indirect influence of vitamin D on calcitonin secretion in the elderly. Serum calcitonin was measured before and after a short calcium infusion (1.5 mg/kg over 10 minutes) in nine normal young adults (30 ± 4 years, mean ± SEM) and eight elderly subjects (78 ± 4 years). The test was repeated 48 h after the last of three intravenous injections of calcitriol (2 μg) given every other day. Basal serum calcium did not change, but basal calcitonin of the elderly increased from 7 ± 1 to 10 ± 1 pg/ml (p<0.06), similar to basal values in young adults (11 ± 1 pg/ml). The increase in calcitonin after calcium infusion increased from 8 ± 1 to 14 ± 1 pg/ml (p<0.001) after calcitriol treatment and approached the increase in young adults (18 ± 3 pg/ml). These data demonstrate that calcitriol can improve and nearly normalize the impaired calcitonin secretion of the mildly vitamin D‐deficient elderly subjects without changes in serum calcium, whereas the inverse situation is observed for para

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090108

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

年代:1994

数据来源: WILEY

摘要:

AbstractCyclosporin A (CsA) administered to actively growing young rats produces a high‐turnover osteopenia. We investigated and compared the effect of CsA on the bone mineral metabolism in young rats with that of older rats, which have a lower rate of bone turnover. A group of 24 young (9 weeks) and 24 older (9 months) male Sprague‐Dawley rats were orally administered 15 mg/kg of CsA or placebo daily for 24 days. Rats were weighed and serum assayed serially for bone gla protein (BGP), parathyroid hormone, ionized calcium, blood urea nitrogen, creatinine, and 1,25‐dihydroxyvitamin D [1,25‐(OH)2D]. After sacrifice, histomorphometric analysis was performed on undecalcified proximal tibial metaphysis with double‐fluorescent labeling. Serum BGP levels were significantly elevated in both young and older rats administered CsA, and 1,25‐(OH)2D levels were significantly elevated in CsA‐treated young rats more than in older rats. Body weight was significantly reduced in CsA‐treated older rats. There were mild but significant alterations in renal function in both groups receiving CsA. In the most comprehensive examination to date of the effects of CsA on bone histomorphometry, both young (‐44%) and older rats (‐20%) lost significant amounts of trabecular bone compared to their respective controls. Bone loss in young rats was mainly due to a reduced number of trabeculae; older rats lost mainly trabecular thickness. Microanatomic nodal studies were consistent with these results. These data demonstrate that although cancellous bone loss induced by CsA is more marked in young rats, older rats with slower bone turnov

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090109

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe long‐term effect of intermittent low‐dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow‐up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6–36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p<0.05) outcome (1.8 ± 5.7%; mean ± SD) in the group treated with salmon calcitonin and calcium and a significant (p<0.01) loss (‐5.8 ± 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p<0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow‐up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopa

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090110

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe cytokine interleukin‐6 (IL‐6) is considered an important regulator of bone cell function and may play a central role in bone disease states characterized by increased bone remodeling, such as Paget's disease. Indeed, recent in vitro data suggest that IL‐6 may be an autocrine/paracrine factor for pagetic osteoclasts. However, its expression and role in vivo are not known. Using in situ hybridization we investigated the spatial localization of expression of IL‐6, IL‐6 receptor (IL‐6R), and the transcription factor (NF‐IL‐6) in pagetic bone. Our results show that osteoblasts in the normal remodeling bone of osteoarthritis (controls) and in Paget's disease express IL‐6, IL‐6R, and NF‐IL‐6 genes with higher levels of IL‐6 and IL‐6R mRNA in pagetic bone. Osteoclasts in both osteoarthritic and pagetic bone express IL‐6R mRNA and NF‐IL‐6, but only pagetic osteoclasts expressed IL‐6, suggesting that in Paget's disease IL‐6 can act as an autocrine factor on osteoclasts. These results provide evidence for a major role of the IL‐6 regulatory pathway in the phenotype of the pagetic osteoclasts and lead us to suggest a model linking possible paramyxovirus infection and IL

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090111

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

年代:1994

数据来源: WILEY