摘要:

AbstractBone mineral density (BMD) is under strong genetic control. Polymorphisms at the vitamin D receptor (VDR) gene have been recently suggested to account for up to 75% of this genetic effect. We analyzed these polymorphisms, i.e., that ofBsmI,TaqI, andApaI restriction enzymes by PCR of the DNA in 189 healthy premenopausal women aged 31 to 57 years. For theBsmI polymorphism they were 17% BB homozygotes, 51% Bb heterozygotes, and 32% bb homozygotes, genotype frequencies that are very similar to those previously reported in other Caucasian populations of north European ancestry. Women in the three genotypes for any of the three polymorphisms were matched for age and did not differ in body weight, height, physical activity, nor smoking habits. We found no relationship between the genotype for any of the three polymorphisms nor bone formation and resorption rate assessed by five specific biochemical markers of bone turnover nor with BMD measured at the spine, proximal femur, forearm, and whole body by dual‐energy X‐ray absorptiometry (DXA). We concluded that these polymorphisms are not predictive of bone turnover nor BMD in a sample of healthy premenopausal women drawn from the French populat

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100902

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

年代:1995

数据来源: WILEY

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100903

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

年代:1995

数据来源: WILEY

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100904

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe effects of anesthetics on serum parathyroid hormone (PTH) concentrations were determined by a new homologous two‐site immunoradiometric assay for rat PTH. Serum PTH concentrations (mean ± SE) from ether‐anesthetized rats (14.7 ± 1.5 pg/ml,n= 22) were not significantly different from those of decapitated unanesthetized female rats (13.0 ± 1.8 pg/ml,n= 21). Serum PTH concentrations in pg/ml (n= 4–14) for other anesthetics tested were: ketamine, 12.5 ± 1.1; Na pentobarbital, 23.3 ± 2.4; methoxyflurane (inhalation), 42.2 ± 6.8; and xylazine combined with ketamine, 51.4 ± 11.3 pg/ml. The latter two concentrations were significantly (p<0.001) higher than the values for all other anesthetics and decapitation. Elevation of serum PTH induced by pentobarbital or ketamine + xylazine increased with time under anesthesia. Neither serum Ca2+concentrations nor pH differed among any of the groups. We conclude that anesthesia induced by pentobarbital, methoxyflurane, or ketamine + xylazine in rats leads to a marked elevation of serum PTH levels that appears to be related to the duration of anesthesia and not due to any measurable fall i

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100905

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe separate and combined effects of weight‐bearing exercise and hormone replacement therapy (HRT) on bone mineral density (BMD) were studied in 32 women, 60 to 72 years of age. HRT consisted of continuous conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Exercise consisted of 2 months of low‐intensity exercise followed by 9 months of more vigorous weight‐bearing exercise ˜45 minutes/day, ≥3 days/week, at 65–85% of maximal heart rate. Lumbar spine and proximal femur BMD were significantly increased in response to exercise and to HRT, and total body BMD was significantly increased in response to HRT; neither exercise nor HRT had an effect on wrist BMD. The combination of exercise + HRT resulted in increased BMD at all sites except the wrist, with effects being additive for the lumbar spine and Ward's triangle and synergistic for the total body. Based on reductions in serum osteocalcin levels, it appears that increases in BMD in response to HRT and exercise + HRT were due to decreased bone turnover. The lack of change in serum osteocalcin and IGF‐I in response to exercise alone suggests that increases in BMD were due to decreased bone resorption and not increased formation. Results indicate that weight‐bearing exercise + HRT may be effective in preventing and/or treating osteoporosis. It is likely that the additive effects of weight‐bearing exercise and HRT on bone mineral accretion, coupled with other adaptations to the exercise (i.e., increased strength and functional capacity), could effectively reduce the incidence of falls and osteop

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100906

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

年代:1995

数据来源: WILEY

摘要:

AbstractA randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [P] = 8) consuming 1.3–2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, ≤2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual‐energy X‐ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25‐hydroxyvitamin D (25[OH]D), 1,25‐dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B‐ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation –4.3% (P) (p<0.04) and –6.3% (Ca) (p<0.01) at the lumbar spine (L2–L4) and 5.7% gains of the ultradistal (UD) radius (Ca) (p<0.04); lactation to postweaning, –6% to –11% at all sites of the radius and ulna (Ca, P) (p<0.04) +3% at L2–L4 (Ca) (p<0.03); baseline to postweaning, (UD) radius –5.2% (P) (p<0.03), UD radius + ulna –6% to –8% (Ca, P) (p<0.04) but no significant loss of L2–L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%,p<0.001), osteocalcin (+25%,p<0.01), TRAP (+11%,p<0.005) as was PRL (+81%,p<0.001). Indicators of calcium metabolism were higher postweaning than lactation for PTH (+40%,p<0.01) and 25(OH)D (+45%,p<0.02) but not for 1,25(OH)2D. There were no differences between P or Ca for indices of calcium metabolism, bone turnover, or PRL. An increase in markers of bone turnover and a loss of BMD of the spine during lactation appears to be part of the physiological changes of lactation and not preventable by increasing calcium intake above the recommended dietary allowance (RDA). A return of BMD toward baseline of the spine but not the arm, was associated with an increase in PTH without an increase in 1,25(OH)2D postweaning. Loss of estrogen during lactation and a return postw

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100907

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

年代:1995

数据来源: WILEY

摘要:

AbstractIt has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin‐6 (IL‐6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3′‐triiodothyronine (T3) on bone resorption (45Ca release) and on the IL‐6 concentration in medium from cultured 19‐day‐old fetal rat limb bones. T3alone increased45Ca release significantly only at a fairly high concentration (10−6M) under the conditions used. T3alone, over a 10−11–10−6M concentration range, failed to elicit a detectable effect on the medium IL‐6 content. However, T3potentiated the stimulatory effect of interleukin‐1β (IL‐1β) on IL‐6 production in a dose‐dependent manner. T3, 10−8M, also significantly increased IL‐1β‐stimulated calcium release. Inhibition of IL‐1β with 1 μM interleukin‐1 receptor antagonist (IL‐Ira) abrogated the potentiating effects of T3on IL‐1β‐stimulated IL‐6 production and blocked the combined effect of T3and IL‐1β on45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL‐1β, as well as the combined effect of IL‐1β and T3on resorption and IL‐6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 μM prostaglandin E1(PGE1) significantly increased both the IL‐6 production and the calcium release. By potentiating the effect of IL‐1β, T3increased bone resorption at much lower concentrations. We therefore speculate that the enhancement of IL‐1β effects

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100908

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

年代:1995

数据来源: WILEY

摘要:

AbstractWhether renal phosphate wasting in X‐linked hypophosphatemia (XLH) results from an intrinsic renal or humoral defect remains controversial. In studies of the murine homolog of XLH, harboring the Simian Virus 40 (SV40) large T antigen, we obviated the influence of renal cell heterogeneity and impressed memory by comparing Na+‐phosphate cotransport in immortalized cells from the S1segment of the proximal tubule. Cells from SV40 transgenic normal andHypmice exhibit characteristics of differentiated proximal tubule cells including gluconeogenesis and alkaline phosphatase activity. Surprisingly, however, we found two distinct populations of cells from the S1proximal tubule of both normal andHypmice. In one, PTH treatment increases cAMP accumulation, while in the other both PTH and thyrocalcitonin enhance cAMP production. Kinetic parameters for Na+‐phosphate cotransport were similar in both subpopulations of cells from normal (Km, 0.29 ± 0.03 vs. 0.39 ± 0.04 mM; Vmax, 4.6 ± 0.6 vs. 5.2 ± 0.4 nmol/mg/5 minutes) andHypmice (0.33 ± 0.02 vs. 0.26 ± 0.04; 6.0 ± 0.7, 4.8 ± 0.6). More importantly, phosphate transport in S1cells of either subpopulation fromHypmice is no different than that of normals. These data indicate that renal proximal tubule cells fromHypmice have intrinsically normal phosphate transport and support the hypothesis that a humoral abnormality underlies renal phosphate w

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100909

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

年代:1995

数据来源: WILEY

摘要:

AbstractThis experiment studied the effects of hypophysectomy (HX) and ovariectomy (OV) on cancellous bone in the proximal tibia and distal 5th lumbar vertebra by dynamic histomorphometry. Forty‐eight female Sprague‐Dawley rats, 3 months of age, were divided into age‐matched control, HX, OV, and HX + OV (HO) groups. Ten rats were sacrificed at 3 months of age as baseline controls, and the rest of the animals were sacrificed 5 weeks after the surgery. While the age‐matched controls and OV rats significantly increased in body weight compared with the baseline control rats, cancellous bone volumes in the proximal tibia and distal 5th lumbar vertebra increased in the age‐matched controls and decreased in the OV rats. In the HX and HO rats, body weight equaled baseline control values, and their cancellous bone volumes were decreased with a poorer trabecular architecture in both bone sites. In all HX, OV, and HO rats, uterine weight and serum estradiol were significantly decreased. OV significantly increased longitudinal bone growth and the tissue‐ and surface‐based bone formation and bone resorption parameters in both the proximal tibia and 5th lumbar vertebra (p<0.05). HX alone or HO significantly decreased longitudinal bone growth and the tissue‐based bone formation rate without significantly affecting surface‐based bone formation and bone resorption parameters when compared with the age‐matched controls. No significant differences were detected in any variable between the HX alone and HO rats. In this study, HX on OV rats decreased the longitudinal bone growth, cancellous bone turnover (tissuebased), and cancellous bone volume in the proximal tibia and distal 5th lumbar vertebra in young rats at 5 weeks after surgery. We suggest that the bone loss in the HO rats was due primarily to pituitary hormone deficiency and that the effect of ovarian hormone deficiency on cancellous bone is pituitar

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100910

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn studies of the regulation of parathyroid hormone (PTH) signal transduction, we observed that the peptide endothelin‐1 (ET) added prior to PTH greatly increased the calcium transients elicited by PTH in UMR‐106 osteosarcoma cells and mouse primary osteoblastic cells. Enhancement by ET also occurred in the presence of EGTA. The ETBreceptor‐specific agonist sarafotoxin 6c (S6c) likewise enhanced PTH‐induced Ca2+transients. Blocking the ETAreceptor‐mediated component of the ET signal with BQ123 failed to abolish enhancement of PTH responses by ET. The nonselective ETA/ETBreceptor antagonist PD 142893 blocked both ET and S6c‐induced enhancement of the PTH responses. Prostaglandin F1α(PGF1α) pretreatment also maximally potentiated PTH responses, whereas α‐thrombin, epidermal growth factor (EGF), or prostaglandin E1(PGE1) did not affect the PTH responses. Neither active phorbol ester nor forskolin mimicked the ET effect. The ET effect was not prevented by indomethacin, NG‐mono‐methylarginine, genistein, pertussis toxin, 4‐aminopyridine, tetraethylammonium chloride, okadaic acid, or long‐term treatment with phorbol‐12,13‐dibutyrate. ET pretreatment did not abolish the inhibition of PTH signals by PTH(3–34), although in ET‐pretreated cells the suppression of the PTH signal by PTH(3–34) was not as great. ET pretreatment did not enhance the cAMP response to PTH; rather, there was a significant inhibition of the cAMP response. Thus, the calcium signal elicited by PTH is selectively modulated by activation of the ETBreceptor. The effect of ET to enhance PTH‐stimulated calcium signaling appears to be independent of prostaglandins, nitric oxide, protein tyrosine kinase, protein kinase A, K+channel activation, or phor

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100911

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

年代:1995

数据来源: WILEY