摘要:

AbstractWe compared the procollagen synthetic properties of MG‐63 osteosarcoma cells with those of cultured human skin fibroblasts. In both cells, the expressions of type I and III procollagens are largely dependent on the constant presence of ascorbate and coordinately decreased by the neutral polymer dextran T‐40. The amino‐terminal propeptides of pro‐α1and pro‐α2chains of type I procollagen are phosphorylated and those of the pro‐α1and pN‐α1chains of type III procollagen both phosphorylated and sulfated, there being no difference in net charge in the propeptides between these cell types. The major differences between MG‐63 and normal fibroblasts are the exceptionally high relative synthesis of type III procollagen by MG‐63 cells, up to about 40% of the total of types I and III (6% in cultured skin fibroblasts), and the inability of ascorbate‐supplemented MG‐63 cells to deposit collagens into an insoluble pericellular matrix. A longer dextran treatment shifts up to one‐fourth of the proline‐labeled extracellular macromolecules into the matrix fraction within 4 days (in control 4%). Despite processing of the procollagens to the respective collagens in the matrix, neither control matrices nor those induced by dextran induced increased production of alkaline phosphatase. In cultures up to 4 days postconfluence the proportion of type III collagen produced tended to increase over that in early confluent cultures. With respect to collagen production, the MG‐63 cell line is not a representative of the osteoblast lineage but rather resembles a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080602

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

年代:1993

数据来源: WILEY

摘要:

AbstractAdjuvant polyarthritis (AP) in rats is known to result in extensive bone loss. This study investigates the mechanisms responsible for the early trabecular osteopenia evaluated at a single point in time — 2 weeks after adjuvant injection—in the hindpaw of female Lewis rats using biochemical and histomorphometric methods. At this early point in time, the inflammation was generalized (inflammatory score, 20; albumin/globulin, —80% versus control). Histomorphometric analysis of the noninjected femur showed that the trabecular bone volume was significantly decreased (‐28% versus control) in both proximal and distal parts, and the femur growth rate was unaffected. The trabecular osteopenia was associated with a 90% decrease in osteoid surface and a concomitant thinning (‐19%) of the trabeculae. Both the double‐fluorescence‐labeled surface and the osteoblast surface were also markedly decreased (‐75%). In addition, the mineral apposition rate was reduced (‐50%) and the bone formation rate was decreased by as much as 90%. The trabecular bone volume was decreased in relation with the extent of double‐fluorescence labeling (r= 0.38,p= 0.03) and bone formation rate (r= 0.42,p= 0.01), suggesting that the generalized osteopenia resulted from the reduced bone formation. This was associated with a 26% reduction in plasma osteocalcin. Neither the osteoclast surface nor the number of osteoclasts was consistently affected. However, urinary hydroxyproline was increased by 100–200%, which likely reflected the cartilage and bone destruction at the site of injection. The present data show that the early extensive osteopenia observed 2 weeks after AP induction in rats results from defective bone formation with unchanged bone resorption. The role of cytokines in such an inhibitory effect on bone formation rem

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080603

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

年代:1993

数据来源: WILEY

摘要:

AbstractBone mineral density (BMD) and risk factors for osteoporosis were assessed in 348 apparently healthy women over 70 years of age (mean 82.3 years). BMD was measured at both hips and the dominant distal radius. With stepwise multiple regression the best determinants of BMD, selected from anthropometric measurements, age, and years since menopause, were body weight and years since menopause (R2between 0.07 and 0.20,p<0.001). Risk and protective factors for osteoporosis were analyzed as indicator variables by multiple regression and corrected for confounding by age, years since menopause, and body weight. Significantly lower BMD at the hip was found in participants with impaired mobility (‐5%) and users of loop diuretics (‐5%). Use of thiazide(like) diuretics did not influence BMD significantly at any site. Users of oral corticosteroids had a significantly lower BMD at the hip and the distal radius (range ‐9.1 to ‐24.3%). Participants with a history of Colles' fracture (n= 56) had a significantly lower BMD at the other radius (‐12.9%). The mean calcium intake from dairy products was high (mean 921 mg/day), only 11% having an intake below 500 mg. A relation of calcium intake with BMD could not be detected at any measurement site. We conclude that BMD cannot be adequately predicted in elderly women. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility, and use of loop diuretics and oral corticosteroids. Calcium intake was not a risk factor in this study, but the number of individuals on a low calcium intake

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080604

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe effects of 17β‐estradiol (E2) and treadmill exercise on tibial bone mass, tibial uptake of45Ca, and proximal tibia osteoblast and osteoclast cell number were determined in adult ovariectomized rats. Female rats aged 10 months were ovariectomized and divided into five groups: (1) sham‐operated; (2) ovariectomized; (3) ovariectomized, given 10 μg E2biweekly; (4) ovariectomized, trained to exercise on a treadmill daily; and (5) ovariectomized, given E2and exercised. E2and/or exercise interventions were started 2 months following surgery and continued for 4 months. The calcium content of the tibial metaphysis and diaphysis and the proximal cancellous bone (BV/TV) were lower in the ovariectomized than in the sham‐operated controls 6 months after ovariectomy. This lower bone content was associated with a greater bone uptake of45Ca and a greater number of osteoblasts and osteoclasts in the proximal tibia compared to the control rats. The meta‐physeal calcium content was higher and the45Ca uptake and osteoblast and osteoclast number were lower in the E2‐treated rats than in the nontreated rats. In the exercised group, higher diaphyseal calcium content and proximal cancellous bone were associated with lower bone resorption parameters without a significant effect on bone formation. This study demonstrates that E2primarily influences tibial cancellous bone of the ovariectomized rat and a positive adaptation to exercise occurs in both cancellous and cortical bone. Under estrogen deficiency, E2replacement suppresses increased bone formation and resorption; exercise suppresses mainly bone resorption. The effects of E2replacement and exercise training are independent a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080605

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

年代:1993

数据来源: WILEY

摘要:

AbstractTo establish a comprehensive model for peripheral phalangeal bone loss, bone mass was studied in 1984 and 1989 using quantitative microdensitometry (QMD) in a total of 330 healthy women (age range 43–78.7 years). Bone mass and changes in bone mass were analyzed in relation to age and menopausal status. Ideal and nonideal populations were distinguished to assess the effect of diseases and medication. Both groups showed a decrease in bone mass, which proved to be more dependent on menopausal status than on age. A substantial loss started in the ideal group in the early postmenopausal period and in the nonideal group in the premenopausal period. Because the nonideal group started to lose bone at an earlier stage, the lifetime risk for osteoporosis is higher than in the ideal grou

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080606

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn research settings, longitudinal measurements of bone mineral density have become an integral part of the assessment of patients with metabolic skeletal disorders. To adequately utilize longitudinal measures, confidence in the long‐term precision of the measurement technique must be very high. Dual‐energy x‐ray absorptiometry (DXA) has become commonly utilized in this context, and to better understand its long‐term precision and to develop quality assurance protocols for its use, we examined the performance of eight DXA machines over a 3 year period. Anthropomorphic spine phantoms were measured frequently on each machine during the period of observation, and precision was estimated from the consistency of these determinations. Overall precision was excellent (mean longitudinal coefficient of variation, 0.4%). Nevertheless, by using a series of objective quality control criteria, small alterations in the performance of each machine were identified (mean number of changes, 4.6 in 3 years; mean magnitude, 0.0039 g/cm2, or 0.4%). The cumulative effects of those changes were sufficient to cause a significant (albeit minor) change in the regression slopes (phantom mineral density versus time) of most machines. The same quality control rules were also used to quantitate the magnitude of change and to adjust retrospectively machine performance during the period of observation, such that alterations were minimal and regression slopes were not significantly different from zero. Although the precision of DXA is excellent, alterations in machine function must be anticipated during longitudinal use. The development of quality control protocols provides the means to detect change objectively and to adjust for alterations in performance during the course of longitudinal eval

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080607

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe studied the influence of circulating parathyroid hormone‐related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. We also examined the changes in circulating PTHrP levels during the normalization of serum Ca to determine if part of the increase in PTHrP concentrations is not secondary to hypercalcemia itself, as suggested by some in vitro data. We sequentially measured in 45 hypercalcemic cancer patients treated by pamidronate the circulating concentrations of PTHrP (by an amino‐terminal RIA; normal values<9 pmol/liter), Ca, Ca2+, Pi, intact PTH, and the fasting urinary excretion of Ca (Ca/Cr) and cyclic AMP (cAMP). Mean ± SEM baseline PTHrP levels were 9.5 ± 1.3, with a median (range) value of 6.0 (<3.4–43) pmol/liter. PTHrP levels were elevated in 18 of 45 patients, more often in epidermoid than in glandular carcinomas (P<0.05), and they were significantly (P<0.05) correlated with the concentrations of Pi(r= ‐0.46), Ca/Cr (r= ‐0.31), and urinary cAMP (r= 0.47). Mean pretreatment Ca levels were not significantly different between patients with elevated and patients with normal PTHrP levels, 13.3 ± 0.4 versus 12.9 ± 0.4 mg/dl, but the concentrations became significantly different (P<0.005) 4 days after therapy, 10.2 ± 0.3 versus 9.2 ± 0.1 mg/dl, respectively. The fall in fasting urinary Ca excretion was significantly (P<0.05 from day 4 to day 14) lower in patients with elevated baseline PTHrP levels: for example, Δ (day 4 ‐ day 0), 0.31 ± 0.11 in patients with elevated PTHrP levels versus 0.64 ± 0.08 mg Ca per mg Cr in patients with normal PTHrP levels. In agreement with a lesser effect on serum Ca, intact PTH levels did not increase significantly in patients with elevated PTHrP levels, in contrast with a clear‐cut recovery of PTH secretion in the other group. Last, PTHrP levels did not change significantly after bisphosphonate therapy: for example, at the day of the nadir of Ca, the levels were 8.2 ± 1.2 (6.4,<3.4–28) pmol/liter. In summary, our data suggest that circulating PTHrP concentrations do not change during correction of tumor‐induced hypercalcemia but significantly influence the response to bisphosphonate therapy. Elevated PTHrP concentrations in hypercalcemic cancer patients thus constitute a primary phenomen

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080608

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

年代:1993

数据来源: WILEY

摘要:

AbstractBone loss with aging may at least in part be due to inadequate bone formation. In this study, we examined whether the proliferation of osteoblast‐like cells in vitro in response to local and systemic factors might be attenuated with age. A total of 36 cultures of osteoblast‐like cells were obtained from outgrowths of human trabecular bone. Parathyroid hormone, growth hormone, calcitonin, transforming growth factor β, insulinlike growth factor I, and platelet‐derived growth factor BB dose dependently increased DNA synthesis in all cultures. Increases in DNA synthesis with each of these factors were significantly negatively correlated with donor age in cultures obtained from the iliac crest bone of 50‐ to 70‐year‐old women. Cells from 61‐ to 70‐year‐old donors required approximately 10‐fold higher concentrations of growth factors and hormones to yield comparable increases in DNA synthesis than cells from 51‐ to 60‐year‐old donors. A significant negative correlation between age and mitogenic responsiveness to platelet‐derived growth factor and growth hormone, but not toward the other factors, was also observed in cultures from the femoral head trabecular bone of 60‐ to 90‐year‐old women. Our findings suggest that bone loss with aging may be partially due to a decreased capacity of osteoblasts to proliferate in response to systemic or lo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080609

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn anteroposterior (AP) bone mineral density (BMD) measurements of the lumbar spine (LS), the presence of ribs is used to identify vertebra T12. Similarly, in lateral LS‐BMD measurements, the position of the iliac crest is used to identify the lumbar vertebrae. The aim of this study was to determine the impact of variations in spinal segmentation and iliac crest position on BMD measurements. In 375 women (ages 50–85 years) radiographs were taken of the thoracic and lumbar spine, as well as AP measurement of LS‐BMD, by dual‐energy x‐ray absorptiometry (DXA). In 121 subjects lateral decubitus LS‐BMD was also measured. Anomalous spinal segmentation was found in 16.5%, and L1 would have been incorrectly identified on the AP‐DXA image in 13%. The change in BMC and BMD between adjacent vertebrae was greater in the upper than the lower lumbar spine. Misidentification of L1 for T12 resulted in underestimation of the bone mineral content in grams (BMC) of L1 by a mean of 11.5 ± 14.4% (SD; range ‐33.5 to 33.5%). For the usual region of interest, L2–4, the BMC (g) was underestimated by 8.4 ± 8.7% (range ‐1.5 to 29.2%), with the BMD (g/cm2) underestimated by 3.6 ± 4.8% (range ‐5.4 to 11.6%). The position of the iliac crest on the lateral decubitus DXA scans would have led to misidentification of either L2 or L4 for L3 in 15 cases (12%). This resulted in the BMD of L3 being underestimated by 2.7 ± 19.4% (range ‐ 242.4 to 34.6%). We conclude that (1) anatomic variations in spinal segmentation are common; (2) the impact of mididentification of vertebra L1 on the AP scan is considerable if only one lumbar vertebra is studied but small if a larger area is analyzed and expressed as g/cm2; and (3) misidentification of L3 in the lateral projection can result in a large error in the BMD measurement of L3, although the mean error in terms of a population is small. Thus the impact of misidentification of lumbar vertebrae does not result in important overall changes when studying groups of subjects but on an individual basis could lead to incorr

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080610

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe found that the cytoplasmic concentration of calcium (Cai) of MC3T3‐E1 osteoblasts was influenced by the type of pH buffer we used in the perfusing medium, suggesting that intracellular pH (pHi) might influence Cai. To study this effect, the Caiand pHiwere monitored as we applied various experimental conditions known to change pHi. Exposure to NH4Cl caused a transient increase in both pHiand Caiwithout a change in extracellular pH (pHo). Decreasing pHoand pHiby lowering the bicarbonate concentration of the medium decreased Cai, and increasing pHiby the removal of 5% CO2increased Cai. Clamping pHito known values with 10 μM nigericin, a potassium proton ionophore, also influenced Cai: acid pHilowered Cai, whereas alkaline pHiincreased it. The rise in Caiappears to be very sensitive to the extracellular concentration of calcium, suggesting the existence of a pH‐sensitive calcium influx mechanism. We conclude that physiologic changes in pH could modulate Caiby controlling the influx of calcium ions and could change the time course of the Caitransient associated with hormonal activa

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080611

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

年代:1993

数据来源: WILEY