摘要:

AbstractAlthough levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention of non‐biologically active PTH fragments by the aging kidney. In 102 normal women, aged 30 to 89 yr, serum iPTH increased with age by 58% (r= 0.33,p<0.001) with antiserum GP‐1M (which has midmolecule specificity) and 43% (r= 0.32,p<0.001) with antiserum CH‐12M (which may have whole molecule specificity); urinary cAMP/GFR excretion increased by 29% (r= 0.22,p<0.05). The results of these assays were validated by comparison with serum levels of biologically active PTH (BioPTH) in immunoextracts of serum followed by renal adenylate cyclase assay in a selected subgroup of 25 of the women. Serum BioPTH correlated with serum iPTH assessed by antiserum GP‐1M (r= 0.48,p<0.05) and antiserum CH‐12M (r= 0.48,p<0.05) but not with urinary cAMP. The data are consistent with an increase of parathyroid function with aging: clearly, we do not find decreased parathyroid function as would be expected if age‐related bone loss was not mediated, in p

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020502

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

年代:1987

数据来源: WILEY

摘要:

AbstractCirculating levels of parathyroid hormone (PTH) rise with age in normal men and women. To resolve the basis for this observation we measured iPTH in 137 normal men and women, age 23 to 85 years, using two antisera which responded to different portions of the PTH molecule. A midmoleeule assay (Mid‐PTH) employed antiserum NG‐5, which recognizes mid‐ and carboxy‐terminal portions of hPTH, whereas antiserum CK‐67, which recognizes determinants in the 1–34 hPTH sequence, was used to measure intact PTH (NH2‐PTH). Two‐hour fasting urine was collected for measurement of creatinine clearance and excretion indices of phosphorus and cyclic AMP. Serum was analyzed for 25‐hydroxyvitamin D (25‐OHD) in addition to iPTH. Mid‐PTH rose significantly with age in the 72 women (r= 0.38,p<0.001) and in the 65 men (r= 0.40,p<0.001). NH2‐PTH rose with age in women (r= 0.23,p<0.05), but a change in men was not significant (r= 0.19, n.s.). Cyclic AMP excretion rose significantly with age in both women (r= 0.42) and men (r= 0.41), whereas phosphorus excretion rose significantly in women only (r= 0.32,p<0.01). 25‐OHD levels were 27.5 ± 1.3 ng/ml for women and 26.1 ± 1.2 ng/ml for men. No change in 25‐OHD was observed with age in women, and a significant decrease in men was due entirely to extremely high values in three young subjects. Endogenous creatinine clearance decreased with age in women (r= ‐0.65,p<0.001) and men (r= ‐0.46,p<0.001). In women, creatinine clearance correlated significantly with Mid‐PTH (r= 0.21,p<0.05), but the relationship of Mid‐PTH to age remained significant when the effect of renal function was eliminated in the multiple regression. Creatinine clearance did not correlate significantly with NH2‐PTH. Fourteen women with the highest values of NH2‐PTH were compared with 12 women with the lowest NH2‐PTH levels for multiple indices of PTH action and bone turnover, including urinary excretion indices for calcium, phosphorus, cyclic AMP, and hydroxyproline, and serum alkaline phosphatase activity and 25‐OHD. In no case were significant differences observed between the two groups of elderly women. We conclude that increased iPTH with age in women reflects an increase in steady‐state levels of intact hormone. Although a similar phenomenon probably occurs in men, results from men in this study did not reach significance. Although it is considered likely that elevated PTH levels may contribute to age‐related bone loss, we found no correspondence of iPTH to several measures of PTH action and bone turnover. These results point out the need for a prospective evaluation of the relations

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020503

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of a preincubation period, in basic medium or in medium with inhibitors of prostaglandin biosynthesis, on the response to different stimulators of bone resorption has been studied in an organ culture system using calvarial bones from neonatal mice. Bone resorption was assessed either by the release of45Ca or by the release of3H from [3H]‐proline labeled bones. Preincubated bones were cultured for 18–24 hr in medium, with and without indomethacin, hydrocortisone, and dexamethasone, and then extensively washed before being transferred to culture medium containing different stimulators of bone resorption. Preincubation in medium containing indomethacin or corticosteroids resulted in an increased response to parathyroid hormone (PTH), prostaglandin E2(PGE2), 1‐alpha‐hydroxyvitamin‐D3and thrombin as compared to the response in bones which were exposed to the stimulants directly after dissection. Preincubation in basic medium did not enhance the subsequent response to PTH. By using a preincubation period in indomethacin, the dose‐response curves for the stimulatory effect of PTH and PGE2on mineral mobilization could be sensitized as compared to the curves obtained with fresh bones. Thus, the concentration of agonists causing 50% stimulation of45Ca release was decreased by a factor of 10. The threshold for actions of PTH and PGE2on45Ca release was 0.01–0.03 and 1–3 nmol/

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020504

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

年代:1987

数据来源: WILEY

摘要:

AbstractOsteoblast‐like cells isolated from fetal rat calvaria (RC) form three‐dimensional nodulesin vitrohaving the morphological and immunohistochemical characteristics of bone. When administered continually over 21 days of culture, EGF caused a dose‐related inhibition of nodule formation, as well as a reduction in the proportion of mineralized nodules, at concentrations between 10−12to 10−7M.The same conditions caused an increase in both cell proliferation and saturation density in the cultures, suggesting that decreased nodule formation was not the result of general cell toxicity. Inhibitory concentrations of EGF caused a reversible alteration in cell shape, although changes in protein synthesis were not detectable. Indomethacin (5 × 10−7M) did not affect either nodule formation or its inhibition by EGF. When cultures were pretreated for various time periods with 10−8MEGF followed by its removal and continued culture in supplemented medium for 21 days, the number of bone nodules formed with brief exposures to EGF (4 hr up to 48 hr) was increased compared to the numbers formed in supplemented medium alone, whereas exposures to EGF of 4 days or longer decreased the number of nodules formed. These data indicate that EGF can either increase or decrease the osteogenic potential of RC cellsin vitrodepending on the duration of exposure

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020505

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of a low calcium diet, mithramycin, or dichlorodimethylene bisphosphonate were evaluated in nude mice with humoral hypercalcemia of malignancy associated with the transplanted canine adenocarcinoma (CAC‐8). Low calcium (0.01%) diet significantly reduced serum calcium levels in hypercalcemic nude mice and reduced urine calcium excretion to control levels. Mithramycin (8 mg/kg) decreased serum calcium concentration and urine calcium excretion to the range of control non‐tumor‐bearing nude mice at day 5 after a single injection, but there was no change in the number of tartrate‐resistant acid phosphatase‐positive osteoclasts in lumbar vertebrae. Osteoclasts from CAC 8‐bearing nude mice after mithramycin administration were decreased in size, had small ruffled borders, and increased relative size of clear zones. Dichlorodimethylene bisphosphonate (Cl2MDP) (45 mg/kg) partially reduced serum calcium concentration of hypercalcemic tumor‐bearing nude mice, decreased urine calcium excretion to control levels, and markedly reduced the numbers of tartrate‐resistant acid phosphatase‐positive osteoclasts in lumbar vertebrae. Osteoclasts from Cl2MDP‐treated nude mice were smaller and had a reduced frequency of ruffled borders than saline‐treated hypercalcemic nude mice.In vitrobone resorption induced by CAC‐8 extract was significantly reduced by C12MDP and mithramycin. The results of these investigations suggest that the hypercalcemia and hypercalciuria associated with HHM in nude mice with CAC‐8 are the combined result of altered calcium homeostasis in the bone, kidney, and intestine. Chemotherapeutic agents that specifically affect only bone or feeding a low calcium diet alone may not completely ameliorate

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020506

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe influence of sex steroid hormones on plasma calcitonin levels in healthy subjects was studied in 15 males and 10 premenopausal (PREMF) and 12 postmenopausal females (PMF). A standardized ionized calcium stimulus was achieved by means of the calcium clamp technique, and a sensitive RIA was used to determine immunoreactive CT (iCT) in plasma. Plasma iCT levels increased in response to the calcium clamp with an initial peak at 15 or 30 min. The iCT levels then declined but remained at an elevated level for the rest of the 180‐min infusion period in all three groups. In males a positive correlation was found between the serum testosterone levels at 0 min and the estimates for initial iCT response, i.e., the change between 0 and 15 min (r= 0.80,n= 11,p<0.01), between 0 and 30 min (r= 0.56,n= 15,p<0.05) and between 0 and the maximum value (r= 0.68,n= 15,p<0.01). In the two female groups no such correlation was found. Serum 17 β‐estradiol or dehydroepiandrosterone sulfate concentrations were not correlated either to basal iCT levels or to the iCT response to the calcium clamp. PMF had lower levels of 17 β‐estradiol than PREMF (p<0.001), while the testosterone levels were similar. The iCT levels and response to the calcium clamp showed no significant difference in the two groups. The results indicate that sex difference in the plasma CT levels may be related to different testosterone levels. In addition, physiological levels of serum 17 β‐estradiol seem to bear no direct relation to basal or Ca‐stimulated iCT levels in pre‐ and postmeno

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020507

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

年代:1987

数据来源: WILEY

摘要:

Abstract19 nor, 10 keto, 25‐hydroxyvitamin D3(19/10–25OHD3) is a metabolite of 25‐OHD3producedin vitroby various phagocytes including normal human blood monocytes and transformed cell lines, U937 and HL‐60. We recently reported that 19/10–25OHD3induced differentiation of U937 cells. In these studies, 19/10–25OHD3alone produced no detectable effect on the growth rates, surface adherence, and oxidative metabolism of U937 and HL‐60 cells. When combined with lymphocyte‐conditioned medium (LCM), 19/10–25OHD3reduced proliferation, increased surface adherence and stimulated luminol‐dependent luminescence (LDL) of the U937 cells. In contrast, the combination of 19/10–25OHD3and LCM had no effect on the growth of HL‐60 cells but did increase the surface adherence and the expression of a complement receptor component. 19/10–25OHD3competed for tritium‐labeled 1,25(OH)2D3binding to receptors extracted from cultured human skin fibroblasts. This displacement capacity was 600 times weaker than that of unlabeled 1,25(OH)2D3. Incubation of human skin fibroblasts for 24 hr with 19/10–25OHD3induced 25OHD3‐24‐hydroxylase activity in the fibroblasts. The inductive potency of 19/10–25OHD3was 1/50 that of 1,25(OH)2D3. These results demonstrate bioactivity of 19/10–25OHD3in several systems. At least one of these responses, the induction of 25OHD3‐24‐hydroxylase, is a receptor‐mediated event. Some of the other responses may be independent of the cellular receptor for 1,25(OH)2D3. Interestingly, the potency of 19/10–25OHD3was highest in the receptor‐mediated response (1:50) and lower in the other parameters, ranging from 1: 100 to 1:600 compared to 1,25(OH)2D3. This range of bioactivity in phag

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020508

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

年代:1987

数据来源: WILEY

摘要:

AbstractA sensitive spectrophotometric assay for micromolar amounts of lanthanum in the presence of calcium and phosphate (as hydroxyapatite) was developed utilizing the change in absorption (at 652 nm) when the dye arsenazo III was complexed with lanthanum. Arsenazo III was used at a level of 25 μMand the solution pH was maintained at 3.1 with 0.2Msodium acetate. Lanthanum concentrations down to 0.5 μMcould be reliably assayed. Calcium ion did not complex well with arsenazo III at pH 3.1. With calcium present at 100 μMand lanthanum at 10 μM, the assay was 115 times more sensitive for lanthanum. The assay is simple, rapid, reproducible and, unlike the assay using radioactive lanthanum, can be performed at any t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020509

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

年代:1987

数据来源: WILEY

摘要:

AbstractWe measured iliac bone formation rates on all surfaces after double tetracycline labeling, serum levels of type 1 procollagen carboxy‐terminal extension peptide (pColl‐I‐C), and serum levels of total alkaline phosphatase activity (TAP) in four normal subjects and in 44 patients with various forms of metabolic bone disease. In three patients with enzymatic evidence of liver disease both biochemical serum markers were disproportionately raised. In a patient with idiopathic axial osteosclerosis serum pColl‐I‐C was selectively increased by more than ten‐fold. In the remaining 44 subjects pColl‐I‐C and TAP levels correlated significantly with each other (r= 0.70) and both showed the same directional changes and broadly similar correlations with iliac bone formation rate expressed in different ways. In general, pColl‐I‐C levels correlated better with cancellous bone formation rates and TAP levels with cortical bone formation rates. There was a modest improvement in prediction of bone formation rate with multiple regression using both markers. In 15 patients with typical uncomplicated postmenopausal osteoporosis, neither biochemical marker, singly or jointly, correlated significantly with any expression of bone formation rate. Disadvantages to the use of pColl‐I‐C as a marker include a significant contribution to the serum level from type 1 collagen biosynthesis in tissues other than bone, and (probably) variable metabolic clearance. For both biochemical markers the most consistently high correlations (r= 0.77–0.79) were found with total bone formation rate for the entire biopsy core volume, which is the best estimate available from a biopsy of formation rate at the bone organ level of organizationin vivo.The core volume as a referent also allows the amount of bone formed on cortical, endocortical, and cancellous surfaces to be compared. Measurement of serum pColl‐I‐C levels merits further study as a noninvasive index of bone metabolism. Differences between normal and abnormal subjects in the relationships between a variety of biochemical markers and a variety of histologic indices have the potential for providing insight into the

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020510

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

年代:1987

数据来源: WILEY

摘要:

AbstractTo investigate the biochemical effects of pulsed electromagnetic fields (PEMF) on bone in particular and on cell membrane‐associated activity in general, we have studied the modification by PEMF of cAMP metabolism in primary calvarial bone cells. We report that PEMF inhibited cAMP accumulation stimulated by bovine PTH(1–34) peptide. After a 1‐hr PEMF exposure, the cAMP response to PTH (2–7 min) was decreased in exposed cells to 48–70% (p<0.05) of the response of unexposed cells; furthermore, this inhibition disappeared after 10–20 min with PTH. This inhibition occurred at submaximal PTH doses (2.4–7.3 nM) and no effect was observed at maximal PTH doses (24 nM). Thus with PEMF, the dose response curve for PTH became 0.5 log unit less sensitive. PEMF did not affect the cAMP response to cholera toxin and forskolin. However, when submaximal doses of both forskolin (0.5–1.0 μM) and PTH (0.24–2.4 nM) were used, forskolin prevented inhibition of cAMP production by PEMF in the range of fields and stimulus epochs which normally inhibit cAMP production.It is proposed that PEMF inhibits PTH‐stimulated coupling of the adenylate cyclase system and that this inhibition does not affect the intrinsic activity of the G‐protein and

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020511

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

年代:1987

数据来源: WILEY