摘要:

AbstractAltogether 733 postmenopausal women were interviewed with regard to their age at menopause. Subsequent fragility fractures over an 11 year period were recorded. Fragility fractures had occurred in 212 women. These women had an earlier menopause, but the deviation from the nonfracture group was significant only in those who were<70 years at the beginning of the fracture catchment period. Women 50–69 years of age, in the lowest quartile of menopausal age, sustained 50% more fragility fractures than those in the highest quartile. In older women menopausal age does not predict fragility fractures. Women<70 with an early menopause had a significantly lower initial bone mas

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060502

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

年代:1991

数据来源: WILEY

摘要:

AbstractSuppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid‐induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25‐(OH)2D3or prednisone. However, the two steroids have opposing effects: 1,25‐(OH)2D3increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25‐(OH)2D3can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 μg 1,25‐(OH)2D3and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 μg 1,25‐(OH)2D3+ placebo in a crossover study. Seven normal subjects aged 23–36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25‐(OH)2D3serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p<0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p<0.01). The course of serum OC after administration of 1,25‐(OH)2D3+ prednisone almost paralleled the course after placebo. We conclude that 1,25‐(OH)2D3and prednisone have opposin

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060503

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

年代:1991

数据来源: WILEY

摘要:

AbstractRecordings of fura‐2 fluorescence from single osteoblastic MC3T3‐E1 cells showed that bradykinin (BK, 1 μM) induced a rapid increase in cytoplasmic free Ca2+(Cai2+, from 114 + 13 to 239 + 17 nM, mean + SEM). Following this initial transient (<1 minute) increase there was a second slow increase in Cai2+(from 117 + 11 to 151 + 12 nM). Incubation in buffer with no Ca2+did not affect the first rapid BK‐induced increase in Cai2+but eliminated the second slow increase. Addition of indomethacin or hydrocortisone to the incubation buffer did not inhibit the effect of BK on Cai2+. BK caused a dose‐dependent initial rapid increase in Cai2+with threshold at 1 nM and a maximal effect (241 + 30% of basal Cai2+concentration) at 0.1 μM. The B1 BK receptor agonist des‐Arg9‐BK (1 μM) caused only a small increase in Cai2+in MC3T3‐E1 cells (from 101 + 20 to 140 + 4 nM). BK dose and time dependently stimulated the formation of inositol phosphates in MC3T3‐E1 cells with EC50at 2.4 nM and a significant increase in inositol trisphosphate already seen after 15 s. The Ca2+ionophore ionomycin induced a rapid increase in Cai2+and prostaglandin E2(PGE2) formation in MC3T3‐E1 cells. Forskolin (10–30 μM) increased cyclic AMP accumulation but did not affect Cai2+or PGE2formation. Depletion of extracellular Ca2+significantly reduced (but did not abolish) BK‐induced PGE2formation. The initial action of BK on Cai2+is probably due to an inositol‐(1,4,5)‐trisphosphate‐mediated rapid release of Ca2+from intracellular stores in osteoblasts and is followed by an influx of extracellular Ca2+. The effect is due to B2 BK receptor occupancy and is not secondary to the prostaglandin synthesis. The BK‐induced breakdown of phosphatidylinositol‐(4,5)‐bisphosphate with a subsequent increase in Cai2+may be involved in BK‐induced

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060504

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

年代:1991

数据来源: WILEY

摘要:

AbstractTo determine the extent to which the effects of cortisol on collagen synthesis in 21 day fetal rat calvariae are linked to its effects on cell replication, calvariae were cultured for 24–72 h with 0.1 and 1 μM cortisol in the presence or absence of 1 mM hydroxyurea (HU) or 30 μM aphidicolin (APC), inhibitors of DNA synthesis. The incorporation of [3H]proline into collagenase‐digestible protein (CDP) and [3H]thymidine into DNA were measured during the last 2 h of culture. At 24 h HU and APC decreased thymidine incorporation by>90%, and this remained low for the duration of culture. In contrast, cortisol reduced thymidine incorporation by only 44% at 72 h. Although cortisol caused a 24 h stimulatory effect and a 48 and 72 h inhibitory effect on CDP labeling and the percentage of collagen being synthesized (PCS), HU, and APC had no effect on basal CDP labeling or PCS over the 72 h culture period. Cortisol caused parallel alterations in the steady‐state levels of α‐1(I) procollagen mRNA, suggesting that its effects occur at the pretranslational level. At 24 h HU and APC did not prevent the stimulatory effect of cortisol on CDP labeling and PCS. At 48 h the inhibitory effects of cortisol on CDP labeling and PCS were observed in the presence of APC but not in the presence of HU. At 72 h the inhibitory effects of cortisol on CDP labeling and PCS were still observed in the presence of HU and APC. The inhibitory effect of cortisol on CDP labeling was only partially reversed 48 h after removing cortisol from calvariae treated with hormone for 48 h. These data show that DNA synthesis inhibitors by themselves do not mimic the effects of cortisol on collagen synthesis nor do they prevent the early stimulation and the late inhibition of collagen synthesis by cortisol. Thus we conclude that the long‐term inhibitory effect of cortisol on collagen synthesis in calvariae is largely independent of cell replication. The component of collagen synthesis that is reversible may represent the direct inhibitory effect of cortisol on differentiated osteoblasts. The nonreversible component of inhibition may be due to a more permanent effect of cortisol on cell populations within the calvariae. One possibility is that cortisol inhibits differentiation of osteoprogenitor cells to the osteoblast lineage leading to decreased osteoblast number and a subsequent inhibition of collage

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060505

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

年代:1991

数据来源: WILEY

摘要:

AbstractSerum parathyroid hormone (PTH) and low‐normal serum phosphorus (P) concentrations have well‐known trophic effects on renal 1‐hydroxylase. A role for serum ionized calcium (Ca2+) in the day‐to‐day regulation of 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] has not been identified in normal humans. The associations between serum Ca2+, PTH, P, and plasma 1,25‐(OH)2D3were evaluated in a cross‐sectional study of 275 healthy postmenopausal women. Partial correlations of Ca2+, PTH, and P (each controlled for the other two) with 1,25‐(OH)2D3were sought within quintiles of Ca2+At low‐normal concentrations (1.32 mmol/liter, quintile 5) Ca2+attenuated the positive associations of both PTH and low‐normal P with 1,25‐(OH)2D3. In quintile 5 Ca2+, PTH, and P together accounted for none of the variability in 1,25‐(OH)2D3(R2= 0.03,p= 0.671). Women with Ca2+below 1.32 mmol/liter were next examined by quintile of P. As expected, at low‐normal concentrations (<1.03 mmol/liter, quintile 1) P was significantly correlated with 1,25‐(OH)2D3(rp= ‐0.32,p= 0.047). The association between PTH and 1,25‐(OH)2D3was statistically significant only at midnormal concentrations of P (rp= 0.52,p= 0.001, quintile 3). We conclude that Ca2+, along with PTH and P, is associated with the plasma concentration of

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060506

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe evaluated fecal calcium density (mass of calcium per g dry weight of feces) as a measure of compliance with a prescribed calcium intake regimen using 4 day fecal pools collected on a metabolic research unit from subjects ingesting measured, constant intakes. Fecal calcium density was highly correlated with intake (r= 0.897,P<0.001). Intake estimates based on fecal calcium density exhibited a standard error of the mean equal to 3.76 mmol calcium. Since a typical calcium supplement table contains 12.5 mmol calcium, the measurement of fecal calcium density is sensitive enough to detect regular omission of one or more pills daily. Applicability of this approach to convenience samples of feces was evaluated in 15 individuals by testing homogeneity of fecal calcium density values on up to six different 3–9 g portions (wet weight) of each volunteer's fecal sample. The within‐sample coefficient of variation was 9.5% for all subsamples and 7.3% for samples from individuals with intakes above 25 mmol calcium per day. Thus feces are reasonably homogeneous in regard to calcium density. Accordingly, reasonably small fecal collections should suffice for its measurem

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060507

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

年代:1991

数据来源: WILEY

摘要:

AbstractHigh concentrations of inorganic phosphate (Pi) are known to inhibit bone resorption, although the mechanism(s) underlying this effect is unclear. To investigate whether Pican inhibit the formation of osteoclasts we studied the effects of changes in Piconcentration between 1 and 4 mM on osteoclast‐like cell formation in 1 week cultures of mouse bone marrow. Osteoclast‐like cells were identified by multinuclearity, positive staining for tartrate‐resistant acid phosphatase (TRAP), and contraction in response to calcitonin. Increasing concentrations of Piinhibited formation of these cells in a dose‐dependent manner. To study effects of Pion the bone‐resorbing activity of mature osteoclasts we isolated osteoclasts from calcium‐deficient egg‐laying hens or rat pups and incubated them on sperm whale dentine slices. High Piconcentrations markedly reduced both the number of resorption pits formed per dentine slice and the mean area of each pit in both avian and mammalian systems. These data indicate that high concentrations of Piact on bone directly, both to inhibit generation of new osteoclasts from their precursor cells and to inhibit bone resorption by mature osteoclasts. These effects of extracellular Piconcentration may play an important modulatory role on bone turnover in vivo and have potential importance in several disease states in which Pimetabolism

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060508

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe effects of TGF‐β1on osteoclastic resorption of fetal mouse calvaria and long bones at various stages of development was studied in organ culture. In resorbing calvariae and long bones with an established marrow cavity TGF‐β1(4–10 ng/ml) had a stimulating effect on45Ca release that was partially inhibited by indomethacin. In primitive long bones, however, which were explanted before osteoclast invasion and excavation of a marrow cavity had started, TGF‐β1(1–4 ng/ml) inhibited45Ca release by an indomethacin‐insensitive mechanism.Histomorphometry of long bones after staining for tartrate‐resistant acid phosphatase (TRAP) revealed that TGF‐β1treatment inhibited the migration of TRAP‐positive cells from periosteum to developing marrow cavity and inhibited cell fusion. However, the formation of (mononuclear) TRAP‐positive cells in the periosteum‐perichondrium was strongly enhanced.These data suggest that TGF‐β1modulates various steps in the cascade of osteoclast development, recruitment, and activation in different ways, involving both prostaglandin‐mediated and prostaglandin‐independent pathways. Therefore the net effect of exogenous TGF‐β1on osteoclastic resorption in bone organ cultures depends on the relative prevalence of osteoclast progenitors, precursors, and mature os

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060509

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe NH2‐terminal cleavage peptide of procalcitonin (N‐proCT) recently was reported to be a bone cell mitogen (Burns DM et al., Proc Natl Acad Sci USA 86:9519–9523, 1989). We have investigated the effect of N‐proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N‐proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 μM did not significantly increase [3H]thymidine uptake (means ranged from ‐19% to 38% of control, no significant differences) in hOB cells (6–10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor β (3 ng/ml), bovine insulin (300 μg/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus our data do not support the hypothesis that N‐proCT is a potent mitogen for normal

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060510

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

年代:1991

数据来源: WILEY

摘要:

AbstractThis epidemiologic study of Paget's disease of bone used data from 788 cases and 387 spouse controls to investigate the following: (1) the extent to which this disorder aggregates in families; (2) the cumulative incidence of the disease in first‐degree relatives of patients throughout life; and (3) the influence of age at diagnosis (<55 versus 55+ years) and presence of bone deformity in the case on risk of Paget's disease in relatives.A positive family history in parents or siblings was reported by 12.3% of cases and 2.1% of controls. The rate of Paget's disease was approximately seven times as high in relatives of cases as in relatives of controls, and this increased rate did not differ according to gender of case or control or gender of relatives. Cumulative incidence of Paget's disease to age 90 was much higher in relatives of cases (8.9 + 1.0% SEM) than in relatives of controls (1.8 + 0.9% SEM). Among relatives of cases, cumulative risk was highest when the case had both early age at diagnosis and bone deformity (20.7 + 3.6% SEM) compared with risk when the case had early age at diagnosis but not bone deformity (10.8 + 3.2% SEM), bone deformity but not early age at diagnosis (5.8 + 1.3% SEM), or neither bone deformity nor early age at diagnosis (3.6 + 0.8% SEM). Risk in siblings of cases was higher when a parent was affected (22.1 + 8.0% SEM) than when both parents were unaffected (6.7 + 1.1% SEM).These findings suggest that first‐degree relatives of patients with Paget's disease have increased risk of developing the disorder, especially if the affected relatives have early age at diagnosis or deforming bone dise

ISSN:0884-0431    

DOI:10.1002/jbmr.5650060511

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

年代:1991

数据来源: WILEY