摘要:

AbstractABSTRACT: The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age + SD, 66 + 6 years) and in 32 carefully selected normal postmenopausal women (64 + 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P<0.05) at the cellular level and by 67% (P<0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P<0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P<0.001) was probably exacerbated by a 45% increase (P<0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1%/year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050402

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:

AbstractTheophylline has been shown to induce the hepatic microsomal enzyme system. These same enzymes increase the metabolism of vitamin D and 25‐hydroxyvitamin D when induced by chronic barbiturate or phenytoin administration. To assess the long‐term effects of theophylline on vitamin D and calcium metabolism, young rats were treated for 4 weeks with constant subcutaneous theophylline infusions. Theophylline‐treated animals had a significantly increased urinary calcium excretion (p<0.0001), a significantly decreased total body calcium per gram body weight (p<0.05), and significantly decreased serum 25‐hydroxyvitamin D concentrations (p<0.002) when compared to control animals. These alterations in the concentration of 25‐hydroxyvitamin D may impair the ability to increase 1,25‐dihydroxyvitamin D‐dependent intestinal calcium absorption to compensate for excessive urinary calcium losses. These data suggest that theophylline promotes skeletal calcium loss, and its use may be a risk factor for the development of osteope

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050403

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 report here the use of a cloned cDNA for the avian calbindin‐D28K(28 kD, vitamin D‐dependent calcium binding protein, CaBP) to investigate the expression of the chick calbindin gene in the kidney. All three calbindin‐D28KmRNA species (2000, 2600, and 3100 nucleotide transcripts) were present in the kidney tissue of chronically vitamin D‐deficient (‐D) chicks; this basal constitutive level of expression was, however, enhanced by administration of the vitamin D3metabolite, 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] in both a time‐ and dose‐dependent manner. D‐deficient chick renal calbindin‐D28Kprotein levels (measured by ELISA) were maximally (twofold) stimulated by 6.5 nmole per animal of 1,25‐(OH)2D3when measured 48 h later; a concomitant level of augmentation of calbindin‐D28KmRNA accumulation was also observed at this time. Time course experiments showed that enhanced renal calbindin‐D28KmRNA accumulation (in −D chicks) was significantly stimulated as early as 8 h and were maximal 12 h after a single pharmacologic dose of 1,25‐(OH)2D3; this elevated level of gene expression was maintained for at least 72 h.Renal calbindin‐D28Kprotein levels (constitutively expressed in the −D chick) were significantly stimulated (twofold) as early as 12 h following the single dose of steroid hormone; the level of calbindin‐D28Kalso remained elevated for a minimum of 72 h. Collectively, these data indicate that 1,25‐(OH)2D3acts upon the renal calbindin‐D28Kgene in a manner similar to that operable in the intestine. However, significant differences exist in the responses of these two tissues, and other (tissue‐specific) vitamin D‐independent factors also seem to regulate the exp

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050404

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:

AbstractCalbindin‐D28Kis a member of a superfamily of calcium binding proteins that share a common avidity for the divalent calcium ion. The ambient concentration of calcium in the blood circulation is thought to orchestrate the release of parathyroid hormone and calcitonin and to govern the activity of renal 1‐hydroxylase and thereby synthesis of 1,25‐dihydroxyvitamin D3. We report here the results of experiments designed to assess the possible contribution of dietary calcium status upon calbindin‐D28Kgene expression in the intestine of vitamin D‐deficient chicks. The actions of 1,25‐dihydroxy vitamin D3[1,25‐(OH)2D3] and dietary calcium intake upon intestinal calbindin‐D28Kand calbindin‐D28KmRNA were monitored by ELISA and dot‐blot hybridization analyses, respectively. Vitamin D3‐deficient chicks were fed either a calcium‐supplemented diet (3% w/w) or a diet containing low calcium (0.4% w/w). These dietary manipulations evoked a highly significant change in serum calcium status. However, the levels of calbindin‐D28Kprotein and its corresponding mRNA were unaffected. Administration of 1,25‐(OH)2D3(1‐16 nmol per animal) to both “normocalcemic” and hypocalcemic vitamin D‐deficient chicks resulted in an equivalent stimulation of duodenal calbindin‐D28Kaccumulation of calbindin‐D28KmRNA. Intestinal calbindin‐D28Kwas stimulated 20‐ to 28‐fold (above control levels) by 6‐8 nmol 1,25‐(OH)2D3in both dietary treatment groups when measured 48 h after the single injection. Hence, despite the existence of a relatively large difference in serum calcium levels, the molecular actions of 1,25‐(OH)2D3in the vitamin D‐deficient animal are apparently well insulated from serum calcium chemistry. These observations support the notion that, in the absence of vitamin D3, the calcium ion per se

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050405

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:

AbstractPrimary bone cell cultures were derived from human bone explants. Cellular activity was characterized by the alkaline phosphatase (AP) activity, osteocalcin, and type I and III collagen secretions in the supernatant. The determination of bone cell activity was performed in three different wells. No significant difference was noted between wells: the coefficient of variation was 8.0 + 2.9% for AP activity, 18.3 + 1.9% for osteocalcin secretion, and 22.5 + 14.3% for collagen. The AP activity and osteocalcin secretion significantly decreased with the number of passages: they were the highest after the first passage. Between each subject, the coefficient of variation was 85% for AP activity and osteocalcin secretion and 63 and 57% for type I and III collagen secretion, respectively. The AP activity did not differ with the age or sex of the donor. In contrast, osteocalcin secretion was significantly lower in females than in males. In males, osteocalcin significantly decreased with the age of the donor (r= −0.61;p<0.05). Cellular activity did not depend on the site of the biopsy. When bone explants from one donor were cultured in two different petri dishes, the activity of cells was similar in both dishes, except in one case. Primary cell cultures derived from human bone explants are the only model providing untransformed osteoblastlike cells of human origin. Because of the experimental conditions, some factors may have influenced the cellular activity and they must be taken into account to validate further in vitro studie

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050406

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:

AbstractLack of adequate data concerning the effect of age on biochemical variables relating to bone and mineral metabolism hampers research on age‐related bone loss in women. Furthermore, to detect disease and to monitor therapy, clinical laboratories require reference values derived from an appropriate population sample. Therefore, we determined the age‐specific distribution of values for serum concentrations of calcium, inorganic phosphorus, alkaline phosphatase, bone Gla protein, and parathyroid hormone; for creatinine clearance; for fasting urinary calcium:creatinine ratio; and for 24 h urinary excretion of calcium, hydroxyproline, and cyclic AMP in a population‐based sample of 301 white women. From this sample, a healthy subgroup of 181 women was identified by medical record review. Age‐related effects were seen in all variables except serum calcium and phosphorus. Moreover, substantial differences between the population sample and the healthy subgroup were noted in values for creatinine clearance, serum alkaline phosphatase, and 24 h urinary calcium excretion. These observations may prove useful for assessment of normality in other populations of aging whit

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050407

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:

AbstractBinding of125I‐labeled rat (r) PTH‐(1‐34) to ROS 17/2.8 osteoblastic bone cells and to membranes from these cells was examined. Competitive binding inhibition experiments were performed using unlabeled rPTH‐(1‐34) with particular emphasis on concentrations of peptide below 1 nM. In intact cells, binding of labeled rPTH‐(l‐34) was highly specific, and inhibition of binding by unlabeled ligand suggested the presence of two classes of binding sites, one with high affinity and low capacity (KD= 40 pM, approximately 20% of total binding sites) and the other with lower affinity and high capacity (KD= 2 nM, approximately 80% of the sites). Membranes prepared from ROS cells also exhibited a pattern of binding from competitive inhibition curves consistent with two distinct binding sites (KD= 30 pM and 6 nM). In intact ROS cells, cellular cAMP levels increased over the range of 10−11‐10−9M rPTH‐(l‐34) with an ED50intermediate between the twoKDvalues (0.25 nM). These data suggest that osteoblastic bone cells possess two distinct classes of membrane receptors for PTH. Since theKDof the higher affinity site more closely approximates circulating concentrations of PTH, binding to this site may hav

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050408

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:

AbstractThe calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast‐feeding for 6 months (Lac) and in 40 age‐matched controls (Con) using fasting urine and blood biochemistry and forearm single‐photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women.During lactationthe significant findings were (1) a selective reduction (7.1%,P<0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 + 0.12 μmol/liter GF (mean + SEM), Con 1.19 + 0.04,P<0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 + 2.5 IU/liter, Con 53.5 + 2.7,P<0.001, and serum osteocalcin, Lac 14.0 + 0.7 μg/liter, Con 7.3 + 0.4,P<0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pibut not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25‐hydroxy‐ and 1,25‐dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine. In 25 of these Lac women restudied at one or more of the times 2, 4, or 6 monthsafter weaning, the findings were (1) an early (2 months) normalization of bone resorption and renal Pihandling with continuing increased bone formation and renal Ca conservation, associated with the onset of increased intact PTH levels; and (2) a recovery, within 4‐6 months in ultradistal BMD associated with normalization of bone formation but with persisting renal Ca conservation and elevated intact PTH levels. We conclude that in established adult human lactation there is increased bone turnover with an accompanying loss of trabecular bone, despite renal conservation of Ca and Pi. After weaning, the deficit in trabecular bone is made up during a period of imbalance between a normal bone resorption rate and an elevated bone formation rate. The moderately elevated PTH after weaning may play a role in the recovery of bone mass by maintaining renal Ca conservation and by an anabolic

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050409

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:

AbstractSeasonal variation in physical activity, back extensor muscle strength (BES), and bone mineral density (BMD) of the lumbar spine was studied in 65 healthy postmenopausal women. Physical activity score (PAS) was assessed with an ordinal scale (0‐18); this score and the BES were obtained monthly for 2 years (25 readings). BMD values were obtained semiannually (5 readings). A periodic (cosine) regression model was fit to each subject's PAS and BES data to obtain individual estimates of the annual peak daydand the average annual range due to seasonality. There was a strong (P<0.001) seasonal pattern in physical activity; August 3 was the average peak day, and the seasonal range was 2.0 PAS units. There was modest (P= 0.047) seasonality in BES; June 6 was the estimated peak day, and the seasonal range was 8.22 pounds (about 7% of the mean). BMD averaged 0.015 g/cm2higher in August through November than February through May (P= 0.002), and the highest monthly average BMD was in August. This seasonal range of 1.4% is larger than the average annual decline with age in BMD observed in longitudinal studies of postmenopausal women. The results of this study have important implications for the planning of longitudinal studies involving changes in physical activity or bone mass in geographic areas with diverse season

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050410

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:

AbstractIn maintenance dialysis patients, low‐turnover osteomalacia and aplastic bone disease are generally attributed to aluminum toxicity. Both groups of patients have a relative deficiency of PTH. The reason for the development of osteomalacia versus aplastic bone disease is unclear. The present study was performed to evaluate whether parathyroidectomy (PTX) modifies the effect of aluminum administration on bone histology in renal failure. Seven groups of pair‐fed rats were studied: normals (N); renal failure (RF); RF + PTX; PTX; RF + aluminum (AL); RF + PTX + AL; and PTX + AL. Aluminum was administered intraperitoneally 5 days/week for 6 weeks. All groups were sacrificed at 6 weeks. Renal failure increased the serum calcium in both the parathyroid intact (RF versus N, 11 + 0.1 versus 10 + 0.3 mg/dl,X+ SEM,P<0.05) and calcium‐supplemented PTX groups (PTX + RF versus PTX, 9.7 + 0.2 versus 9.2 + 0.2 mg/dl,P<0.05). After PTX, aluminum administration increased the serum calcium (PTX + AL versus PTX, 9.8 + 0.3 versus 9.2 + 0.2,P<0.05, and PTX + RF + AL versus PTX + RF, 10.8 + 0.1 versus 9.7 + 0.2 mg/dl,P<0.05). In rats with renal failure receiving aluminum, PTX decreased osteoid volume and surface but not osteoid thickness. Rats receiving aluminum did not mineralize bone. Additionally, in PTX rats receiving aluminum, renal failure per se increased osteoblast surface, osteoid surface, osteoid volume, and osteoclast number. In conclusion, (1) aluminum administration in the absence of PTH produced a bone disease that resembled aplastic bone disease, (2) both renal failure and aluminum administration independently increased the serum calcium concentration, and (3) in aluminum‐loaded rats, the presence of renal failure independent of PTH resulted in an increase in cellular activity and osteoid dep

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050411

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