摘要:

AbstractBlack‐white differences in calcium metabolism are sought because they may reveal why blacks have higher bone mass than whites. Comparative studies of calcium absorption in blacks and whites are not available. In this study, we compare fractional calcium retention, an index of calcium absorption, and calcium regulating hormone levels in black and white women on a high‐calcium diet and after adaptation to a low‐calcium diet. A total of 30 healthy women (15 black and 15 white) had measurements of fractional47Ca retention and calcium regulating hormone levels after 8 weeks on a 2000 mg calcium diet and, subsequently, after 1, 2, 4, and 8 weeks on a 300 mg calcium diet. By 2 weeks after the diet change, fractional47Ca retention, parathyroid hormone (PTH), and 1,25‐dihydroxyvitamin D [1,25‐(OH)2D] had reached a plateau at higher levels, urine calcium at a low level, and serum calcium at the same level (repeated‐measures ANOVA). Fractional47Ca retention, serum calcium, and PTH were similar on both diets in blacks and whites. Blacks had higher levels of 1,25‐(OH)2D on both diets (e.g., 125.1 ± 53.5 SD versus 73.4 ± 19.0 pmol/liter,P= 0.003 on low‐calcium diet) and a greater increase in 1,25‐(OH)2D after the diet change (33.9 ± 30.1 SD versus 11.8 ± 17.9 pmol/liter,P= 0.021). Serum phosphorus was lower in blacks throughout. For hormone levels and fractional calcium retention to stabilize after a diet change, 2 weeks was needed. Similar levels of fractional retention in black and white women despite higher levels of 1,25‐(OH)2D in blacks suggest that blacks may have a gut resistance to th

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080702

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r= 0.49,p<0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone‐forming patients devoid of RTA or CDS, half of whom had “idiopathic” hypocitraturia. The 18 stone‐forming patients without RTA or CDS received potassium citrate (30–60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r= 0.62,p<0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080703

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

年代:1993

数据来源: WILEY

摘要:

AbstractDual‐energy x‐ray absorptiometry (DEXA) is now an established method of measuring bone mineral density (BMD) in humans. We have applied the technique to measuring BMD in the rat. The short‐term precision of the technique was assessed by calculating the BMD coefficient of variation at the rat spine (1.20%), total femur (0.52%), proximal femur (1.16%), midfemur (1.00%), distal femur (0.96%), and proximal tibia (2.2%). The long‐term precision of femoral measurements in rat cadavers over a 4 week period was 0.72% for the total femur and 1.2% for the distal femur. The accuracy of the technique was assessed by comparing DEXA‐measured bone mineral content (BMC) in vitro and in vivo with ashed BMC. Results indicated a highly significant positive correlation between in vitro DEXA measurements and ash BMC (r= 0.99) and between in vivo DEXA measurements and ash BMC (r= 0.89). The ability of the technique to detect bone loss was assessed at the femoral site by comparing the BMD of ovariectomized (OVX) and sham‐operated rats at baseline and at a 1 month follow‐up. There was no significant difference in BMD between the groups at baseline. However, at 1 month follow‐up the OVX group showed a significant (p<0.001) decline in BMD at the distal femur (‐8.6%) and in the total femur (‐4.8%) compared with sham‐operated rats. A comparison of retired breeder female rats with age‐matched nulliparous rats indicated that the BMD of retired breeder rats was significantly lower than that of virgin females at all femoral sites (p<0.01). The results suggest that the DEXA technique has the precision and accuracy necessary to study changes in rat BMD. Furthermore, the technique can be used quickly and noninvasively to detect a bone loss following ovariectomy in the rat, and the distal femur may be an optimal site for det

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080704

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

年代:1993

数据来源: WILEY

摘要:

AbstractAndrogens have important effects on bone in vivo, possibly by direct activation of the androgen receptors in osteoblasts. To test this hypothesis, calcium homeostasis, bone mass, and bone turnover were evaluated in mature (4‐month‐old) androgen‐resistant (testicular feminized, TFM) male rats. Data were compared with data from both female and male littermates of the same age and strain. Compared to normal males, TFM had similar serum testosterone, twofold higher estradiol and estrone, and sixfold higher androstenedione concentrations. Compared to normal females, TFM rats showed lower estradiol but also elevated concentrations of androstenedione and estrone. Despite similar free 1,25‐(OH)2D3concentrations, both TFM and male rats maintained higher serum calcium and phosphate concentrations than their female littermates. Serum IGF‐I concentrations in TFM rats were decreased compared to male rats (‐12%) or female rats (‐27%). Serum osteocalcin concentrations, however, were twofold higher in TFM rats than in females but not significantly different from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous bone density of the femur and cancellous bone volume of the proximal metaphysis of the tibia, however, were not significantly different between groups. The ash weight of the tibia was also not significantly different, and the ash weight of the four distal lumbar vertebrae ranged between male and female values. Bone mechanical properties as measured by torsional strength and energy absorption of the femur were lower in TFM than in females but not different from males. Osteoblast surfaces, osteoid, and osteoclast surfaces in the proximal tibial metaphysis of TFM rats were in the female range and lower than in males. Bone formation and mineral apposition rates measured at the same site were intermediate between male and female rates. Bone formation rates were significantly higher in male than in female rats. We conclude that the absence of functional androgen receptors results in a decrease in radial and longitudinal bone growth and in a decrease in serum IGF‐I concentrations. TFM rats, however, have a cancellous bone volume and density similar to those of their normal male and female littermates. Bone turnover at the cancellous level is not increased compared to normal males. Cancellous bone volume in androgen resistance, in contrast to androgen deficiency, is probably maintained by a modest increase in serum estrogen

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080705

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

年代:1993

数据来源: WILEY

摘要:

AbstractIt was recently shown that interleukin‐6 (IL‐6) is produced by bone and bone marrow‐derived stromal cells and that it plays an important role in osteoclast development. Here we examined whether parathyroid hormone (PTH), calcitonin (CT), or the calcitonin gene‐related peptide (CGRP) influence IL‐6 production by two murine bone marrow‐derived stromal cell lines: the preadipocyte‐like stromal cell line +/+ LDA11 and the fibroendothelial stromal cell line MBA 13.2. We found that CGRP (but not PTH or CT) exerted a dose‐dependent increase in cAMP and IL‐6 production in the +/+ LDA11 cells. In addition, CGRP had an inhibiting effect on the proliferation of this stromal cell line. CGRP, however, did not affect cAMP or IL‐6 in the rat osteogenic sarcoma cell line UMR‐106‐06, which exhibits CT receptors, whereas CT stimulated both cAMP and IL‐6 by the UMR‐106‐01 cells. In contrast to the specificity of the IL‐6 response of the +/+ LDA11 cells to CGRP, IL‐6 production by the MBA 13.2 stromal cells was stimulated by PTH whereas CGRP or CT had no effect. These data suggest that bone marrow‐derived stromal cells express receptors for either CGRP or PTH in a phenotype‐specific manner and that, acting via these receptors, CGRP and PTH stimulate IL‐6 production by stromal cells. In addition, the evidence for specific receptors for the neuropeptide CGRP in bone marrow stromal cells and an effect of CGRP on IL‐6 raises the possibility for a role of cytokines in a putative in

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080706

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

年代:1993

数据来源: WILEY

摘要:

AbstractA population survey was performed to estimate the prevalence of vertebral fractures in women aged 45–69 and to determine their relationship to bone density and symptoms. Subjects were 1035 women aged 45–69 (mean 55.4 years, response rate 77%) from the age‐sex register of a large 11,000‐person general practice in Chingford, London. Thoracic and lumbar spine x‐rays were read by a semiautomated quantitative method. Vertebral fractures were diagnosed using a variety of morphometric methods, including a new method we recently developed and the published methods of Melton and Eastell. These methods all detect abnormal ratios between anterior, central, or posterior vertebral height and between observed posterior vertebral height and values predicted from the posterior height of adjacent vertebrae. Bone mineral density (BMD) of lumbar spine L1–4 and neck of femur was measured by dual‐energy x‐ray absorptiometry (DXA). Using our method, 147, 14.2% (95% CI 12.0–16.2%) of the 1035 women, had minor fractures (at least two vertebral ratios 2–2.99 SD below the mean) and 20, 1.9% (95% CI 1.2–3.0%) of the total, had severe fractures (at least two ratios more than 3 SD below the mean). In the 147 women with minor fractures, bone density of the spine was not significantly lower than in the other 868 women, and reported back pain or loss of height was no more common. Women with multiple minor fractures did have lower bone density, by 0.4 SD. In the 20 women with severe fracture, bone density was significantly lower, by 0.6 SD. Loss of height was more common, but back pain was not. Using the method of Melton the prevalence of deformity was 10.2% and, for the Eastell 3 and 4 SD method, 9.7 and 1.3%, respectively, which is similar to published data from the Rochester population. Minor vertebral deformities are common in postmenopausal women, but they are not usually associated with pain, loss of height, or (unless multiple) reduced bone density. This suggests that they may not be of clinical or pathologic importance. Severe deformities associated with low bone density are rare in U.K. wome

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080707

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

年代:1993

数据来源: WILEY

摘要:

AbstractProteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) β affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF‐β1and L‐ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast‐like MC3T3‐E1 cells. TGF‐β1stimulated the synthesis of proteoglycans in MC3T3‐E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF‐β1and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF‐β1also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF‐β1influenced the synthesis of a heparan sulfate proteoglycan only slightly. L‐ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L‐ascorbate was added to the culture along with TGF‐β1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 ± 1.0 to 41.0 ± 0.5%. These data demonstrate that TGF‐β1markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L‐ascorbate, and that the effects of TGF‐β1and L‐ascorbate are additive. Because L‐ascorbate is required for the synthesis of collagen, the effect of L‐ascorbate on the distribution of decorin appears

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080708

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe recently found that 17β‐estradiol (E2) not only suppresses bone resorption but also stimulates bone formation in the cancellous bone of female rats. This raises the possibility that E2treatment might restore the bone lost after ovariectomy in the rat. To test this, 13‐week‐old rats were ovariectomized (ox). After a further 13 weeks the animals were injected with E2(4 mg or 40 μg/kg daily), human calcitonin (hCT) (3 IU/kg daily), (3‐amino‐1‐hydroxypropylidene)‐1‐bisphosphonate (AHPrBP) (0.3 mg/kg twice per week), or a combination of E2with hCT or AHPrBP, for 8 weeks. The bone volume at the tibial metaphysis of ox animals was approximately 40% of that of sham‐operated controls at the end of the experiment. Although the bone volume of ox rats treated with E2and/or hCT or AHPrBP was slightly higher than that of untreated ox rats, the increase was not significant. Neither E2alone nor a combination of E2with hCT or AHPrBP was associated with a higher bone volume than hCT or AHPrBP alone, suggesting no effect of E2beyond that of inhibition of bone resorption. Histodynamic indices of bone formation were increased in untreated ox rats compared to controls but suppressed in E2‐treated, hCT‐treated, and AHPrBP‐treated animals. These results emphasize the similar responses of rat and human bone, both of which not only show bone loss with estrogen deficiency, preventable by estrogen administration, but also show an inability of estrogen to restore bone lost as a resu

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080709

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis study describes the detailed characterization of four murine chondrogenic cell lines (wT2‐1, wT2–7, wT2–8, and wT2–9) that were isolated from a cartilage tumor induced by the protooncogene c‐fosin chimeric mice. All cell lines are clonal and display a fibroblastic morphology with a doubling time of 1–2 days. Northern blot analysis demonstrated that in addition to expressing high levels of exogenous c‐fos, all clones express varying levels of the cartilage marker gene type II collagen in addition to type I collagen. The clones also expressed high levels of the AP‐1 genes c‐junandfra‐1. The doubling times of these clones did not change over a period of 14 months in culture. Most importantly, however, expression of type II collagen was maintained in all cell lines for 8 months in culture, and two cell lines maintained type II collagen expression when analyzed after 14 months. Interestingly, type I collagen expression was lost after long‐term culture. Following injection into syngeneic and nude mice, all cell lines formed tumors containing areas with the morphologic appearance of hyaline cartilage, indicating that these cell lines are chondrogenic. Thus, these stable murine chondrogenic cell lines provide a useful tool for studying the transcriptional control of cartilage‐specific gene expression, as well as the growth contro

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080710

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

年代:1993

数据来源: WILEY

摘要:

AbstractMalignancy‐associated hypercalcemia is mainly caused by excessive production of parathyroid hormone‐related protein (PTHrP) by the tumor. Using anti‐PTHrP‐(1–34) monoclonal murine antibody (anti‐PTHrP MoAb), we studied whether repeated injection of the homologous antibody would continuously decrease the serum calcium concentration in hypercalcemic nude mice bearing transplanted human PTHrP‐producing tumors, leading to prolongation of their survival time. Daily SC injections of anti‐PTHrP MoAb decreased the serum calcium concentration almost to within the normal range in nude mice bearing transplanted human PTHrP‐producing tumors (T3M‐1, EC‐GI, PC‐3, and FA‐6) but not in a nude mouse bearing a transplanted parathyroid carcinoma. The antibody did not affect FA‐6 tumor growth either in vitro or in vivo. Pancreatic carcinoma cells (FA‐6), which caused the most severe hypercalcemia, were inoculated into 6‐week‐old nude mice. When severe hypercalcemia (˜19 mg/dl) had developed, daily SC injection of anti‐PTHrP MoAb was started. Within 18 days of this time point, all untreated tumor‐bearing mice (n= 10) died of hypercalcemia and cachexia, whereas all the treated mice (n= 10) showed an increase in body weight and survived for at least 25 days. Histologic examination of the treated mice revealed a marked decrease in osteoclastic bone resorption, without toxicologic findings in the kidney and liver. These results suggest that passive immunization against PTHrP can continuously ameliorate the hypercalcemia and markedly prolong the survival time of severely hypercalcemic, tumor‐bearing mice. If a human monoclonal antibody against PTHrP‐(1–34) could be developed, then passive immunization would be potentially one of the most effective therapies for patients with malignancy‐associated hype

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080711

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

年代:1993

数据来源: WILEY