摘要:

AbstractA group of 75 healthy women nearing menopause were entered into a longitudinal study of bone mass and bone cell function. All were at least 46 years, were still menstruating, and had premenopausal levels of follicle stimulating hormone (FSH) and estradiol (E2). Bone density measurements of the spine (dual‐photon absorptiometry, DPA) and total‐body (DPA) and forearm (single‐photon absorptiometry, SPA) were made at 6 month intervals along with measurements of FSH and E2over an average of 2.04 + 0.45 years. The annual rate of change in bone mass was determined for each individual by regressing the bone mass measurement at each site at the time of observation. The slopes were pooled, and the percentage annual change was calculated as the mean slope divided by the initial mean bone mass value. The mean rates of change in bone mass were calculated with and without weighting by length of observation. No meaningful differences in the results were seen in the weighted values compared to the unweighted values, and none of the sites showed a slope significantly different from zero. Demonstrated reproducibility and sample size provided sufficient power to detect annual weighted rates of change of 0.81% for spine BMC, 0.69% for spine BMD, 1.31% for forearm BMC, 1.55% for forearm BMC/BW, and 1.09% for total body bone mineral. We conclude that if changes in bone mineral are occurring in women at this age, they are substantially less than 1%/ year for spine and not much more for the forearm or total ske

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070802

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

年代:1992

数据来源: WILEY

摘要:

AbstractDiaphyseal bone from normal Sprague‐Dawley rats was delipidated in chloroform‐methanol and demineralized in 0.6 N HCl at 4°C. The bones were then implanted for 7–28 days into rats made rachitic by a low‐phosphate, vitamin D‐deficient diet (VDP−) for 3 weeks. Bones from VDP−and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP−hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP−hosts. Treatment of VDP−hosts with either 1α‐hydroxyvitamin D3or 24,25‐dihydroxyvitamin D3did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25‐(OH)2D3administered alone or in combination with 1α‐OHD3significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP−hosts or those treated only with 1α‐OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D‐treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D‐treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP−hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP−rat hosts to respond to osteoinductive factor(s). This impaired response appea

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070803

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe hypothesize that the mechanisms governing bone formation and remodeling involve the assembly of some of the components of the extracellular matrix into supramolecular complexes. We have examined the associations of osteopontin (OPN) with other proteins isolated from demineralized rat long bones. Three ligand binding techniques were used to demonstrate the formation of complexes between osteopontin and osteocalcin (OCN). Using gel overlay assays, the binding between soluble125I‐OPN and OCN immobilized in acrylamide gels was visualized. Competition for125I‐OPN‐OCN complexes was demonstrated when unlabeled OCN‐enriched bone extract was included in gel overlay solutions. Also, gel overlay assays showed125I‐OCN binding to OPN. Saturable binding was shown in solid‐phase filter binding assays, which yielded an equilibrium binding constant of moderately high affinity (∼ 10−8M). Specificity of OPN‐OCN complex formation was confirmed by measuring binding in the presence of unlabeled OPN and OCN versus a bone‐localized serum protein, α2HS‐glycoprotein. Finally, the formation of soluble complexes were demonstrated in a modified Hummel‐Dreyer gel filtration assay. These results indicate that OPN and OCN form complexes in vitro. The possible functions of OPN‐OCN complexes in osteoclast recruitment an

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070804

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

年代:1992

数据来源: WILEY

摘要:

AbstractParathyroid hormone‐related protein (PTHrP) is a potent bone‐resorbing protein that frequently mediates the humoral hypercalcemia of malignancy syndrome. Since prostaglandins may mediate the bone‐resorptive action of certain hormones, we examined the effect of PTHrP on prostaglandin E2(PGE2) secretion by human osteoblast‐like cells. There was low‐level basal secretion of PGE2by Saos‐2 cells (8.1 + 0.6 pg/ml). Using four different preparations of PTHrP, it was observed that with increasing peptide length, from 36 to 141 amino acids, a significant increase in efficacy for PGE2release was seen in these cells. All forms of PTHrP were agonists for PGE2release, with effects seen at concentrations as low as 10−12M in 48 h conditioned media. The amino terminus of the molecule appeared critical for this effect since the truncated derivative PTHrP‐(7–34) did not induce significant PGE2secretion. However, the influence of peptide length could not be explained by differential activation of adenylate cyclase since [Tyr26]PTHrP‐(1–36)amide was equipotent to the longest peptide preparation, PTHrP‐(1–141), in stimulating cyclic AMP accumulation in the Saos‐2 cells. In contrast, PTHrP‐(1–141) was significantly more effective than [Tyr35]PTHrP‐(1–36)‐amide in inducing a rise in cytosolic calcium. Further, this effect was noted at concentrations lower than those that caused significant cyclic AMP accumulation in the Saos‐2 cells. PTHrP‐(1–141) induced the release of PGE2from primary human bone cell cultures to levels entirely comparable to those seen in the Saos‐2 cells. PTHrP‐(1–141) also induced PGE2release by cultured fetal rat long bones at 72 h. We conclude that the carboxy‐terminal region of PTHrP has important effects on cellular signal transduction pathways and on

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070805

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

年代:1992

数据来源: WILEY

摘要:

AbstractSince osteoporosis develops in most postmenopausal women and is probably the most important single factor in the pathogenesis of osteoporotic fractures of the spine, hip, and wrist (and at other sites), methods suitable for mass screening should be developed. In this study of 97 women aged 24–79, measurements of the lumbar spine mineral content by dual‐photon absorptiometry (DPA) were compared with the summed combined cortical thickness measurements from radiographs of the radius and metacarpal II (MR). There was good correlation between the two methods (r= 0.90). The correlation of age with MR was higher than with DPA. The correlation of years postmenopause was significant with MR but not with DPA. Taking the ‐2 SD level of the premenopausal means to be previously established vertebral fracture thresholds, 24% of the DPA measurements, but no MR measurements in patients with vertebral compressions, were above the fracture threshold. Since MR measurement requires taking only two small plain radiographs using ordinary x‐ray equipment, it is concluded that this less expensive method is better suited to screening for osteoporotic vertebral fracture risk in postmenopausal women t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070806

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

年代:1992

数据来源: WILEY

摘要:

AbstractIt is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to ‐70°C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by ≥ 1 lamella of osteoid and ≥ 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (xstatistic, range 0.71–1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which>3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP‐positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP‐positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level). At the tissue level, the line of regression of AP‐positive O.Pm on M.Pm (calculated either as label 2 extent or conventionally as dL + 1/2sL extent) was not significantly different from the line of identity. The presence of osteoblastic AP activity in biopsies from normal and osteoporotic patients distinguishes osteoid currently contributing to bone formation and should be useful for the study of bone formation in unlabeled bone samples from such individuals. Further studies are necessary to establish the broader applicability of this technique, particularly when a mineralization defect is involved, as i

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070807

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28–68 years) and 23 women (26–68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age‐matched subjects, 17 men and 7 women. Two‐dimensional indices of cancellous structure–node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)–were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age‐related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two‐dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architectur

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070808

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

年代:1992

数据来源: WILEY

摘要:

AbstractExtracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age‐matched cultures were investigated by steady‐state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age‐matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the α1(I) and/or α2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age‐matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal de

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070809

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

年代:1992

数据来源: WILEY

摘要:

AbstractOxygen‐derived free radicals are produced by osteoclasts. Oxygen radical formation occurs at the osteoclast/bone surface interface. This location next to bone implies that oxygen radicals, including but not limited to superoxide, are needed for bone resorption. Compounds that scavenge superoxide are being developed as pharmaceutical agents to inhibit the damaging effects of oxygen radical formation on tissues. One such scavenger is the Desferal‐manganese complex (DMnC). DMnC reduced the amount of formazan staining produced by the interaction of oxygen radicals with nitroblue tetrazolium (NBT) in both individual mouse calvarial osteoclasts in tissue explants and isolated osteoclasts. As a result of the reduced concentrations of oxygen radicals, DMnC inhibited bone resorption by calvarial explants and isolated osteoclasts. Superoxide dismutase (SOD) inhibited NBT reduction and bone resorption by isolated osteoclasts but to a lesser degree than DMnC. Inhibition of bone resorption in the isolated osteoclast system increased in parallel to the concentration of DMnC in cultures. Desferal without Mn had no effect on bone resorption by isolated osteoclasts. These results support the hypothesis that osteoclasts produce oxygen radicals as part of the process of bone resorpt

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070810

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

年代:1992

数据来源: WILEY

摘要:

AbstractRecent studies have provided evidence that cells of the immune system and their associated cytokines function in the regulation of bone turnover. The incisors absent (ia) osteopetrotic rat represents a model in which a defect in the immune system and bone resorption can be studied. Osteopetrosis in theiarat is characterized by a generalized excess accumulation of bone as a result of reduced bone resorption by defective osteoclasts that lack a ruffled border and the ability to exocytose their osteolytic enzymes. Previous attempts to identify associated defects in theiaimmune system have proven unsuccessful;iarats demonstrate normal delayed hypersensitivity, mitogenic activity, and macrophage function. Inasmuch as the skeletal manifestations of theiamutation may be the result of a defect in exocytosis, related defects may be evident in immune cells utilizing exocytosis of granules or enzymes for their cytolytic function. Natural killer (NK) cells function by such a mechanism. Therefore, these studies were undertaken to evaluate the natural immune system iniarats. NK activity assessed by51Cr release assays was significantly reduced iniaanimals compared to normal littermates. Mononuclear cells isolated from the peripheral blood ofiarats revealed a significantly greater percentage of large granular lymphocytes than normal littermates. Comparison of NK cell phenotypes using two phenotypic parameters for NK cells (OX8+, OX 19−cells and 3.2.3+cells) revealed that the mononuclear isolates of spleen and peripheral blood of mutant animals had significantly greater percentages of OX8+, OX 19−and 3.2.3+cells than normal controls. Levels of BLT esterase (BLTE), a serine protease associated with the cytolytic mechanism of NK cells, were found to be greater in unsortediamononuclear cells than in normal cells but were equivalent in normal and mutant 3.2.3+cells isolated by fluorescence‐activated cell sorting. BLTE activity was enhanced but equal in normal and mutant 3.2.3+cells stimulated with IL‐2. The 3.2.3+NK isolates demonstrated equal lytic activity iniaand normals, but when normal or mutant 3.2.3−cells (non‐NK cells) were added to the 3.2.3+iacells the lytic activity was significantly reduced. 3.2.3−cells had no effect on the activity of 3.2.3+normal cells. The results indicate that 3.2.3+mutant NK cells have normal lytic activity and BLTE activity and can respond to IL‐2. The NK cells in the mutant are suppressed by a non‐NK mononuclear cell, resulting in the lytic defect. A known suppressor of NK cells, prostaglandin, does not appear to be responsible for the NK defect in this mutant, because indomethacin, an inhibitor of prostaglandin synthesis, did not c

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070811

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

年代:1992

数据来源: WILEY