ISSN:0884-0431    

DOI:10.1002/jbmr.5650050202

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 have examined circulating concentrations of a parathyroid hormone‐like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino‐terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concentrations were found in 2 of 39 control subjects. In 2 patients with breast cancer plasma PLP declined concomitantly with a reduction in tumor burden. Adenocarcinoma of the breast and squamous cell carcinomas were most frequently associated with high plasma PLP levels although a variety of histologic types were represented. The presence of metastases on bone scans did not correlate with either the severity of hypercalcemia or the extent of PLP elevation. Increased concentrations of plasma PLP were also observed in 4 of 20 patients with primary hyperparathyroidism and in 5 of 16 patients with chronic renal failure and secondary hyperparathyroidism. Gel filtration analysis of immunoreactive PLP in plasma from 2 hypercalcemic breast cancer patients revealed heterogeneity, with, in each case, both large (greater than 15 kD) and small (6–) KD) molecular weight amino‐terminal moieties. The results document the presence of PLP in the circulation of patients with cancer and are consistent with a pathogenetic role for PLP in the hypercalcemia of malignancy irrespective of whether skeletal metastases have occurred. PLP may also contribute to the skeletal and/or renal manifestations of hyperparathyroi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050203

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:

AbstractParietal bones from 2‐week‐old rats were dissected free from the sutural regions, dura mater, and periosteum, leaving the surface covered with osteoblasts and some osteoclasts. Prostaglandin (PG) production by these “stripped” bones under basal conditions and after exposure to parathyroid hormone (PTH) was measured by radioimmunoassay of the culture medium (minimum essential medium with or without added 10% heat‐inactivated fetal calf serum). Cultured specimens were examined by scanning electron microscopy for changes in osteoblast length, orientation, ruffling, and overlap. As demonstrated previously, PTH caused the osteoblasts to elongate, align, and show fewer ruffles compared to controls. PTH increased PG synthesis by the stripped bones. Indomethacin inhibited PG formation but did not affect the osteoblast shape change. PGE2, indomethacin, or both drugs together had no discernible effect on any morphologic features. These findings indicate that PGE2does not change osteoblast shape and that the cell shape change with PTH is not mediated by endogenous pr

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050204

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:

AbstractMeasurements by scanning electron microscopy (SEM) of femoral hemisections confirmed and amplified results by single‐photon absorptiometry that had shown a marked increase in lactation osteopenia in rats fed a low‐calcium diet (LCD, 0.04% Ca) as compared with a medium‐(adequate) calcium diet (ACD, 0.4% Ca). SEM of bones from rats at the end of lactation on either diet showed a large loss of trabecular bone, increased porosity of endosteal surfaces, and cortical thinning. These changes were much more striking in LCD rats than in ACD rats. Backscattered electron imaging of cross sections of the femora revealed marked cortical thinning at midshaft after lactation, especially in rats on the LCD; this method also showed a marked increase in newly formed, less dense diaphyseal bone on the endosteal surface when dietary calcium had been made available to the LCD rats after lactation ceased. Unlike the rats fed the ACD after lactation, the rats continued on the LCD for the first 3 weeks postlactation failed to recover bone mineral, even though there was a marked decrease in resorbing surfaces of the femora as revealed by morphologic examination. When the diet was changed from the LCD to the ACD for the second 3 weeks postlactation (weeks 4–6), the bone mineral increased substantially. Overall, these results demonstrate the marked loss of bone during lactation, especially severe in rats fed a low‐calcium diet, and the rapid postlactational recovery of bone when adequate dietary calcium was made available, even if the recovery had been delayed for the first 3 weeks by feeding a diet very low

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050205

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:

AbstractMouse osteoblasts contain and secrete insulinlike growth factor I (IGF‐I), which can be measured by radioimmunoassay after separation from endogenous IGF‐I binding activity. Our studies indicate that IGF‐I is produced by all bone cell populations prepared by sequential digestion of mouse calvaria with collagenase and protease. Furthermore, relatively small amounts of IGF‐I are cell associated, and IGF‐I is recovered primarily in the cell medium after 24 h of culture. Basal IGF‐I secretion is also density dependent, and secretion per cell is approximately 20‐fold higher when cultures are inoculated at 0.125 versus 1.0 × 105cells per cm2.Growth hormone increased the secretion of IGF‐I only in cells released in the earlier stages of digestion. These growth hormone‐responsive populations were previously shown to differ from late released cells in that they show a lower expression of the osteoblastic phenotype, harbor more EGF receptors per cell, and have a higher proliferative response to low doses of exogenous IGF‐I and EGF.These data reaffirm the presence of different subclasses of bone cells in populations obtained by sequential digestion of bone and suggest that growth hormone stimulates IGF‐I secretion

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050206

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 attempted to establish whether systemic changes in trabecular bone explain the development of stress fractures in the lower limbs during fluoride therapy for osteoporosis. To this end we compared transiliac bone biopsies obtained before treatment with those taken around the time of stress fractures after 14.3 ± 10.9 (SD) months of therapy in six patients (group A). Biopsies from a comparable group of six patients without stress fractures at the time of the second biopsy (after 11.9 ± 2.7 months of treatment) served for comparison (group B). The biopsies were processed undecalcified and examined by routine histomorphometry. The second biopsies did not show any significant improvement in mean bone volume or trabecular architecture. Although the second biopsies in group A had increased erosion surfaces (p<0.05) and greater osteoid volume (p<0.05), group B biopsies showed no difference in erosion surfaces but an increase in all osteoid parameters: osteoid volume (p<0.05), osteoid surface (p<0.05), and osteoid seam thickness (p<0.01). We reached the following conclusions: (1) the combination of increased erosion and replacement of removed bone by as yet unmineralized osteoid in the stress fracture group must have weakened bone and allowed the development of stress fractures. (2) Stress fracture patients may have mounted a less vigorous osteoblast response to fluoride than non‐stress fracture patients. Under these conditions microfractures are likely to heal poorly and propagate to develop into full stress fractures. (3) Renal failure is a contraindication to fluoride the

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050207

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:

AbstractA group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual‐photon absorptiometry and of the os calcis with single‐photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gammacarboxyglutamic acid (Gla). Subjects wer given a daily 500 mg supplement of elemental calcium.There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a pairedt‐test revealed a significant difference between the matched pairs in percentage change in lumbar BMD. The os calcis showed no significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated popu

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050208

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:

AbstractTumor‐associated hypercalcemia is due, in part, to enhanced osteoclastic bone resorption induced by soluble factors elaborated from malignant cells.rastransformation of NIH 3T3 cells results in a 50‐fold induction of cathepsin L mRNA and secretion of the corresponding protein. Since cathepsin L is an acid proteinase we asked whether conditioned medium from these cells would directly increase calcium release from bone in vitro. We tested conditioned medium obtained after 72 h culture of NIH 3T3rar‐transformed cells (DT) or nontransformed NIH 3T3 cells (3T3) and identical medium not exposed to cells (Ctl). Incubation of either live or dead neonatal mouse calvaria for 48 h in DT‐conditioned medium increased calcium release compared to bones incubated with 3T3 medium. In both states the increased calcium release with DT medium was blocked by 0.25 mM E‐64, a general cysteine proteinase inhibitor, and 1 μM Z‐Phe‐Ala‐CH2F, a specific inhibitor of cathepsin L activity. Thus, conditioned medium fromras‐transformed cells enhances calcium release in both live and dead bone. Since cathepsin L is the major protein secreted by these cells and the effect of DT‐conditioned medium is blocked by a specific inhibitor of cathepsin L, these studies suggest that this acid proteinase acts directly on bone mineral to enhanc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050209

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:

AbstractCalcitonin gene expression in the TT cell line can be regulated by phorbol esters, cAMP, glucocorticoids, and 1,25‐dihydroxyvitamin D3. To further study the regulation of this gene we have sequenced 1460 bases 5′ to the start of calcitonin gene transcription. This DNA sequence containscisconsensus elements for both phorbol ester‐ and cAMP‐responsive elements. To study the role of these elements, calcitonin 5′ flanking DNA was coupled to the human growth hormone gene as a reporter and transiently transfected into TT cells, a human thyroid C cell line. Treatment of transfected TT cells stimulated a two‐ to fivefold increase in reported gene product expression, confirming the existence of functional cAMP‐ and phorbol ester‐dependent enhancers within the calcitonin 5′

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050210

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:

AbstractPrevious studies have suggested that both plasma 24,25‐dihydroxyvitamin D [24,25‐(OH)2D] concentrations and renal 25‐hydroxyvitamin D‐24‐hydroxylase activity are increased in mice with X‐linked hypophosphatemia (Hypmice). However, because the plasma levels of 24,25‐(OH)2D seemed surprisingly high, we repeated these assays using two different techniques. Mass fragmentographic and radioreceptor assays were employed to compare the plasma concentrations of 25‐hydroxyvitamin D (25‐OHD) and 24,25‐(OH)2D in normal mice with those inHypmice. These assays yielded 24,25‐(OH)2D concentrations much lower than previously reported in mice (both normal andHyp).The concentrations of 25‐OHD3, and 24,25‐(OH)2D3, determined by mass fragmentography, were lower inHypmice than in controls [25‐OHD3, 9.7 ± 0.4 versus 14.6 ± 0.6 ng/ml,p<0.01; 24,25‐(OH)2D3, 7.1 ± 0.3 versus 10.4 ± 0.4 ng/ml,p<0.01]. Plasma 25‐OHD concentration was the main determinant of plasma 24,25‐(OH)2D, and the ratio of 25‐OHD3to 24,25‐(OH)2D3obtained from mass fragmentographic measurements did not differ between the two groups (1.40 ± 0.05 versus 1.36 ± 0.03 ng/ml, NS in normal andHypgroups, respectively). Separate measurement of plasma 25‐OHD, 24,25‐(OH)2D, and 25‐OHD3‐26,23‐lactone by radioreceptor assay showed no difference between either plasma 24,25‐(OH)2D, or the ratio of 25‐OHD concentration to 24,25‐(OH)2D concentration amongHypand control animals. In neither study was plasma phosphate concentration related to the 25‐OHD3: 24,25‐(OH)2D3ratio. We conclude that previous estimations of plasma 24,25‐(OH)2D3concentrations in mice were erroneously high and, further, that in fact t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050211

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