摘要:

AbstractAdministration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low‐dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR‐106 cells. When the osteoblasts were preincubated with bPTH‐(1–34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone‐free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. [NIe8, NIe18, Tyr34]bPTH‐(3–34)amide significantly impaired the desensitization process by PTH‐(1–34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 μM), prostaglandin E, (50 μM), or prostaglandin E2(50 μM) for 2 h. Binding experiments with [125I]PLP‐(1–36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH‐(1–34) but not by cAMP generation itself. It is not primarily dependent on protein synthesis or on activation of adenylate cyclase. A decrease in receptor affinity is important in the process of desensitization. Desensitization of parathyroid hormone receptors is potentiated and recovery impaired by monensin, an inhibitor of internalization and recycling, showing that both processes are important in the

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051202

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

年代:1990

数据来源: WILEY

摘要:

AbstractPrimary cultures of embryonic chick osteoblasts consist of a heterogeneous cell population. Patch clamp measurements were done on 1‐ to 5‐day‐old osteoblasts, osteocytes, fibroblastlike cells, and cells that could not be classified on morphologic criteria. The measurements showed the omnipresence of depolarization‐activated high‐conductance channels in cell‐attached patches. The whole‐cell experiments showed an outward rectifying conductance activating at positive membrane potentials. Channels underlying the latter conductance were found to be K+conducting in outside‐out membrane patches. The activation potential of the outward rectifying K+conductance shifted to negative membrane potentials upon increasing the intracellular Ca2+concentration within the range of 10−8–10−3.2M. The same happened with the activation potential of the K+channels found in outside‐out patches. Finally, inside‐out patch experiments directly demonstrated the dependency of the activation potential of K+channels on Ca2+ions. Thus the identity and main characteristics of Ca2+‐activated K+channels expressed by the various cell types present in chick osteoblast cultures have now been established. Decreased input resistances were found in cells of cultures more than 2 days old. This is consistent with the establishment of electrical coupling between the cells. Functions in which Ca2+‐activated K+channels co

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051203

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

年代:1990

数据来源: WILEY

摘要:

AbstractProlonged high‐dose corticosteroid therapy is known to result in an increased risk of osteoporotic fracture. Reductions in bone density have been demonstrated at the distal radius and lumbar spine in patients receiving corticosteroids; however there have been few studies of bone density in the hip (the most important site of osteoporotic fracture) in this context. To examine the effect of corticosteroids on the hip we measured bone mineral density (BMD) by dual‐photon absorptiometry at three sites in the proximal femur as well as the lumbar spine in 32 patients aged 18–77 years who had been treated with corticosteroids (mean daily prednisone dose 12.7 mg) for up to 23 years. BMD was compared with the expected values using age regressions in normal subjects. BMD was significantly reduced in the femoral neck, Ward's triangle, and the trochanteric region (p<0.001 all sites). In the lumbar spine BMD was also significantly reduced (p<0.001). We also measured BMD serially in 29 patients receiving corticosteroids. BMD measurements were made in 12 patients who had already been treated with long‐term corticosteroids at the time of first BMD measurement (chronic group) and from the commencement of corticosteroid therapy in 17 patients (acute group). The mean (± SEM) change in BMD (g/cm2per year) in the lumbar spine and femoral neck were 0.006 ± 0.006 and –0.021 ± 0.007, respectively, for the chronic group and –0.02 ± 0.005 and –0.039 ± 0.006 for the acute group. The rate of bone loss from the lumbar spine was significantly greater in the acute than the chronic group (p<0.01), and a similar trend was seen in the femoral neck (p= 0.07). These data suggest that bone loss with corticosteroids is most rapid soon after starting treatment and occurs to a similar extent from the proximal femur to the lumbar spine. The bone loss at the femoral neck suggests an increased risk of fracture at that site, particularly in older subjects on long‐term co

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051204

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

年代:1990

数据来源: WILEY

摘要:

AbstractOsteoclasts may or may not be directly related to monocytes and macrophages, but it is well established that these cell types share a number of features in common.(1)In the present study we sought to extend this comparison by assessing lysozyme synthesis in osteoclasts, an enzyme known to be produced and secreted in large amounts by monocytes and macrophages.(2,3)Our data show that freshly isolated chicken osteoclasts and osteoclasts in situ contain an abundant amount of lysozyme and correspondingly high steady‐state levels of the enzyme's messenger RNA. Marrow macrophages, at various stages of in vitro maturation, also possess lysozyme mRNA but in amounts approximately two to four times lower than osteoclasts. These observations reaffirm the monocyte‐macrophage nature of the osteoclast but raise questions about the function of the lysozyme in this cell. At present, the role of the lysozyme in osteoclast activity remains unexplai

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051205

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe effect of glucocorticoids on bone resorption was examined in a serum‐free mineralizing organ culture system derived from 20 day fetal rat parietal bones. Bone resorption was assessed by prelabeling the fetal rats in utero with45Ca and determining the daily release of45Ca into the medium of cultured bones. During the first 24 h of treatment a transient stimulation of bone resorption was found; 4.5 ± 0.3% of the total45Ca was released into the medium with 1 nM corticosterone and 4.1 ± 0.2% with 10 nM corticosterone compared to 2.9 ± 0.2% in control bones. Treatment with 1 and 10 nM dexamethasone for 24 h also showed an increase in45Ca release compared to control bones. During the same time period45Ca release was 6.9 ± 1.4% with 10 nM parathyroid hormone. At later time points 100 and 1000 nM corticosterone inhibited45Ca release, but 1 and 10 nM corticosterone values were similar to controls. At 24 h the number of osteoclasts per mm2tissue in bone lacunae was significantly elevated with 1–100 nM corticosterone and 10 nM parathyroid hormone compared to control bones. In control bones 0.10 ± 0.05 osteoclasts per mm2of tissue were found, but 0.59 ± 0.21 osteoclasts per mm2were seen with 10 nM corticosterone and 1.50 ± 0.34 with 10 nM parathyroid hormone. An additional assay of bone resorption, the release of lysosomal β‐glucuronidase into the medium was also elevated in glucocorticoid and parathyroid hormone‐treated cultures. During 0–24 h, the medium from 10 nM parathyroid hormone‐treated bones contained elevated levels of β‐glucuronidase activity, 7.5 ± 0.7 versus 6.0 ± 0.4 μg/ml in the control bones and, during 24–48 h, 10.5 ± 0.8 versus 7.7 ± 0.6 μg/ml of phenolphthalein in the controls. With 10 nM corticosterone there was a significant increase of 10.0 ± 0.5 μg/ml released at 24–48 h, but high concentrations of glucocorticoids decreased β‐glucuronidase release. We conclude that corticosterone can cause a transient increase in bone resorption by increasing o

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051206

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

年代:1990

数据来源: WILEY

摘要:

AbstractDisodium pamidronate (APD) is a potent inhibitor of bone resorption, with less risk of defective mineralization than earlier bisphosphonates. We assessed the response to six spaced low‐dose intravenous infusions of APD given at intervals of approximately 6 weeks followed by weekly infusions if bone turnover remained abnormal. Three groups of 10 patients were studied, each group receiving infusions of 15, 30, or 45 mg. Hydroxyproline excretion fell by 62% and alkaline phosphatase was reduced by 72%, with no difference between the dose levels. A total of 21 patients (70%) achieved normal levels of bone turnover, indicating that low‐dose infusions of APD are a safe and effective treatment for Paget's dise

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051207

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 μm thick sections of the bodies of the second lumbar vertebrae from six men (aged 21–58 years) and seven women (aged 25–58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer‐assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellou

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051208

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

年代:1990

数据来源: WILEY

摘要:

AbstractIt has previously been reported that low extracellular pH stimulates the excavation of resorption lacunae by rodent osteoclasts in vitro. Using avian bone cells in a similar in vitro assay we have demonstrated that osteoclast activity is optimal at pH 7.20–7.40 and is inhibited at extremes of pH (7.60). Over the first 24 h of incubation at low pH there may be an increase in osteoclastic resorption but to a lesser extent than that reported for rodent cells. However, after 24–30 h in culture there is little or no further increase in bone resorption, presumably due to a cytotoxic effect of low pH acting either on the osteoclast directly or via nonosteoclastic bone cells. In contrast to a previous report, in which preincubation of wafers for 24 h had no effect on bone resorption, we found that preincubation of bone substrates at pH 6.50 for longer periods enhances subsequent resorption at pH 7

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051209

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

年代:1990

数据来源: WILEY

摘要:

AbstractIndirect evidence suggests a causative role for intraperitoneal free fatty acids (FFA) in hypocalcemia associated with pancreatitis. We examined the effects of intraperitoneal injection of four naturally occurring FFAs on serum calcium in rats. Two saturated FFAs, stearate and palmitate, induced little or no hypocalcemia. Two unsaturated FFAs, oleate and linoleate, caused dramatic hypocalcemia in treated versus control rats (6.3 ± 1.4 and 5.3 ± 0.7 mg/dI, respectively, versus 10.1 ± 0.6). Dose‐response studies demonstrated that minute quantities of oleate (100 μl per 250 g rat) caused marked hypocalcemia (7.2 ± 0.3 mg/dI). Treated versus control rats also revealed a decrease in ionized calcium (3.15 ± 0.2 versus 5.6 ± 0.05 mg/dI) and magnesium (1.4 ± 0.15 versus 2.0 ± 0.10), an appropriate increase in PTH levels (1670 ± 451 versus 396 ± 235 pg/ml), and a fall in calcitonin levels (70.4 ± 21.3 versus 47.5 ± 16.4 pg/ml) but no change in albumin or phosphate levels. In vitro, theKspof calcium dioleate was shown to be 5.3 × 10‐−8m3/liter3; thus under physiologic conditions 100 μl oleate binds 7.2 mg calcium, or approximately twice the total ECF ionized calcium in the rat.The amounts of intraperitoneal FFA that can easily be achieved in pancreatitis complex pathophysiologically significant amounts of calcium and may lead to

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051210

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe describe a young woman who acquired a painful, diffuse osteosclerosis of the cervical, thoracic, and lumbar spine, pelvis, and long bones of the legs as an adult. Bone densitometry showed a large increase in apparent bone density. Skeletal radiographs demonstrated progressive endosteal and periosteal thickening of the cortices. A bone scan showed increased uptake of radiolabel. The serum total alkaline phosphatase and 1,25‐(OH)2D3levels were substantially elevated and the immunoreactive PTH was mildly elevated. Bone biopsy showed increased bone turnover, especially on endocortical and intracortical surfaces, but the structural indices were normal. By 4 years after presentation the bone pain had remitted and the serum alkaline phosphatase, 1,25‐(OH)2D3, and PTH were normal. No cause for the occurrence of osteosclerosis in this patient could be fo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051211

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

年代:1990

数据来源: WILEY