ISSN:0884-0431    

DOI:10.1002/jbmr.5650101002

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe first objective of this study was to design a hip protector that would effectively attenuate and shunt away from the greater trochanter the impact energies created in typical falls of the elderly. As the shock absorption material, the protector included the 12 mm‐thick Plastazote, which was found to be the most efficient energy‐absorbing material in our previous in vitro biomechanical tests. With an anatomically designed semiflexible outer shield of the protector (high density polyethylene), the impact surface was increased and the impact energy shunted away from the greater trochanter. In the second phase of the study, we determined the force attenuation capacity of this device in realistic (in vitro) falling conditions of the elderly. With the impact force of 6940 N used (a typical hip impact force measured in in vitro falling tests), the trochanteric soft tissue (25 mm‐thick polyethylene foam) attenuated the peak femoral impact force to 5590 N and the tested protector to 1040 N. In the second series of this experiment, the peak femoral impact force was set to be so high (13,130 N) that the protector, if effective, should prevent the hip fracture in almost all cases. The trochanteric soft tissue attenuated this peak impact force to 10,400 N and the tested protector to 1810 N. Thus, the force received by the proximal femur still remained clearly below 4170 N, the average force required to fracture in vitro the proximal femur of the elderly in a fall loading configuration. In conclusion, our test results suggest that an anatomically designed energy‐shunting and energy‐absorbing hip protector can provide an effective impact force attenuation in typical falling conditions of the elderly. However, the efficacy of the protector in the prevention of hip fractures can only be evaluated in randomized clinic

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101003

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

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious deletion studies using a series of COL1A1‐CAT fusion genes have indicated that the 625 bp region of the COL1A1 upstream promoter between ‐2295 and ‐1670 bp is required for high levels of expression in bone, tendon, and skin of transgenic mice. To further define the important sequences within this region, a new series of deletion constructs extending to ‐1997, ‐1794, ‐1763, and ‐1719 bp has been analyzed in transgenic mice. Transgene activity, determined by measuring CAT activity in tissue extracts of 6‐ to 8‐day‐old transgenic mouse calvariae, remains high for all the new deletion constructs and drops to undetectable levels in calvariae containing the ‐1670 bp construct. These results indicate that the 49 bp region of the COL1A1 promoter between ‐1719 and ‐1670 bp is required for high COL1A1 expression in bone. Although deletion of the same region caused a substantial reduction of promoter activity in tail tendon, the construct extending to ‐1670 bp is still expressed in this tissue. However, further deletion of the promoter to ‐944 bp abolished activity in tendon. Gel mobility shift studies identified a protein in calvarial nuclear extracts that is not found in tendon nuclear extracts, which binds within this 49 bp region. Our study has delineated sequences in the COL1A1 promoter required for expression of the COL1A1 gene in high type I collagen‐producing tissues, and suggests that differentciselements control expression of the

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101004

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe conventional approach to measuring structural parameters in trabecular bone rests on stereology from optical images, derived from sections of embedded bone. In order to provide data that are statistically representative of a sufficiently large volume, multiple sections need to be analyzed in each of the three orthogonal planes. In this work, an alternative technique is presented which is based on three‐dimensional (3D) volumetric proton nuclear magnetic resonance (NMR) microimaging. The method presented provides images from 9 × 9 × 4 mm3volumes of defatted bone specimens in 15–20 minutes scan time at isotropic resolution corresponding to (78 μm)3voxel size. Surface‐rendered images of bovine and human trabecular bone are shown and an algorithm was developed and implemented for determining the orientation and magnitude of the principal axes of the mean intercept lengt

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101005

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe two major processes of bone metabolism—bone formation and resorption—are regulated by cellular interactions. Osteoblasts and osteoclasts play a significant role in bone metabolism, which is known to be regulated by local soluble factors and systemic hormones. Although bone is a heterogeneous tissue comprised of osteogenic and hematopoietic cells, cellular adhesion of osteoblasts and its regulation remains to be understood. We first demonstrate that cellular adhesion by which osteoblasts communicate with opposing cells in bone milieu is involved in the osteoblast activation: (a) purified human osteoblasts obtained from osteoarthritis patients expressed particular adhesion molecules, ICAM‐1, VCAM‐1, and LFA‐3; (b) the osteoblasts adhered to T cells which were used as representative adhesive partners, since T cells possess all the receptors to these adhesion molecules; (c) mRNA transcription and secretion of IL‐1β and IL‐6 were induced in the osteoblasts by the cellular adhesion to T cells and they were reduced by interrupting the adhesion; (d) cross‐linking of ICAM‐1 and VCAM‐1 on the osteoblasts induced IL‐6 secretion from the osteoblasts. These results indicate that osteoblasts adhere to opposing cells through particular adhesion molecules on their surface and that the adhesion molecules on the osteoblasts not only function as glue with opposing partners but transduce activation signals that facilitate the production of bone‐resorbing cytokines. We propose that cellular adhesion of osteoblasts as well as soluble factors is significant for the regul

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101006

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

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1–34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three‐dimensional (3D) ex vivo in situ morphometry by X‐ray tomographic methods (XTM). Six‐month‐old retired Sprague‐Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post‐OVX, a prePTH‐treatment OVX group was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1‐34) at 4, 40, or 400 μg/kg of body weight (BW)/day and were sacrificed on day 84 post‐OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1‐34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p<0.05). The trabecular bone volume was equal to or greater than the Sham‐operated animals in both hPTH(1–34) 40 and 400 μg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the Sham‐operated group at day 84 post‐OVX and did not increase with any of the hPTH(1‐34) treatments. Intermittent hPTH(1‐34) treatment in osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabecule. Human PTH(1–34) did not re‐establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re‐establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101007

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

年代:1995

数据来源: WILEY

摘要:

AbstractBisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effects on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4‐ to 24‐fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar‐fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101008

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe studied bone mineral content (BMC), bone mineral density (BMD), cortical thickness/total width (CT/TW) ratio and cortical area/total area (CA/TA) ratio in boys with constitutional delay of puberty and the effect of short‐term testosterone treatment on bone mass. Seventeen boys (age 13.1‐15.8 years) who met the family history and the clinical criteria of constitutional delay of puberty were selected and enrolled in the study. All subjects were eating a diet assuring an adequate intake of calories and calcium. A subset of 8 boys (group A) was treated with testosterone depot (100 mg/month x 6 months) while 9 boys (group B) were not. At inclusion, BMC and BMD were reduced in the patients according to their chronological age (BMC ‐4.04 ± 1.34 standard deviation scores [SDS]; BMD ‐2.95 ± 0.56 SDS), statural age (BMC ‐1.75 ± 0.79 SDS; BMD ‐1.69 ± 0.78 SDS), and bone age (BMC ‐1.80 ± 0.65 SDS; BMD ‐1.86 ± 0.68 SDS). No significant differences between the groups were found (group A: BMC 0.480 ± 0.57 g/cm, BMD 0.488 ± 0.037 g/cm2, CT/TW ratio 0.43 ± 0.4, CA/TA ratio 0.68 ± 0.04; group B: BMC 0.476 ± 0.060,p= NS vs. group A; BMD 0.491 ± 0.036 g/cm2,p= NS vs. group A, CT/TW ratio 0.42 ± 0.05,p= NS vs. group A; CA/TA ratio 0.67 ± 0.06,p= NS vs. group A). At 12 months of follow‐up, BMC, BMD, CT/TW ratio, and CA/TA ratio significantly increased in group A (BMC 0.70 ± 0.13 g/cm, δ +41.1 ± 28.8%,p<0.003 vs. 0 month; BMD 0.617 ± 0.082 g/cm2, δ + 26.2 ± 13.6%,p<0.005 vs. 0 month; CT/TW ratio 0.52 ± 0.05, δ +20.59 ± 10.65%,p<0.001 vs. 0 month; CA/TA ratio 0.77 ± 0.05, δ +13.60 ± 6.65%,p<0.004 vs 0 month), but not in group B (BMC: 0.48 ± 0.05 g/cm; δ +5.1 ± 7.8%,p= NS vs. 0 month; BMD: 0.492 ± 0.037 g/cm2; δ + 0.54 ± 8.7%,p= NS vs. 0 month; CT/TW ratio 0.44 ± 0.04, δ +4.04 ± 6.75%,p= NS vs. 0 month; CA/TA ratio 0.68 ± 0.05, δ +2.39 ± 5.90%,p= NS vs. 0 month). We conclude that boys with constitutional delay of puberty have reduced BMC and BMD. The delay in statural and bone ages did not totally account for the decreased bone mass. Testosterone treatment for 6 months significantly increased BMC, BMD, CT/TW ratio, and CA/TA ratio in these patients, but definitive conclusions on the efficacy of the treatment in improving adult bone mass ca

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101009

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

年代:1995

数据来源: WILEY

摘要:

AbstractA marrow stromal osteogenic cell line (MBA‐15) was used to create monoclonal antibodies (MoAbs). In this study, we describe a series of MoAbs for mouse marrow stroma (MMS) (MMS‐25/17, MMS‐85/12, MMS‐302/40, and MMS‐319/4) that recognized antigens expressed by stromal cells including osteoblastic cells. The MoAbs were screened against various cell and tissue types. MMS‐85/12 was positive in detecting an antigen that was highly abundant in osteoblastic cells and primary adherent bone marrow cultures (BMC) but was negative for the marrow adipocytes copartner. The MMS‐85/12 MoAb is an IgGl immunoglobulin. The immunohistochemical staining pattern is suggestive of the antigen being associated with the osteoblasts' plasma membrane and with the extracellular matrix constituent secreted by these cells. Western blotting and immunoprecipitation indicated that the antigen that was recognized by MMS‐85/12 apparently had a molecular

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101010

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

年代:1995

数据来源: WILEY

摘要:

AbstractWhen bone mineral content (BMC) is measured by dual X‐ray absorptiometry (DXA), the X‐ray beam is attenuated by bone and soft tissue. Since the component of the attenuation caused by the soft tissue overlying bone cannot be measured, the attenuation caused by soft tissue adjacent to bone is measured and is used in the calculation of BMC. The assumption underlying this approach is that the amount and composition of this adjacent soft tissue is the same as overlying bone. The aim of this study was to examine the validity of this assumption by determining whether fat distribution over and adjacent to bone differ and whether this introduces accuracy errors in the measurement of BMC by postero‐anterior (PA) and lateral scanning. BMC (posterior processes plus vertebral body, g) of the third lumbar vertebra was 17.3 ± 0.7 by PA and 17.0 ± 0.7 by lateral scanning in 27 premenopausal women (p= NS), but 2.7 g or 20% higher by PA than lateral scanning in 27 postmenopausal women (14.4 ± 0.7, 11.7 ± 0.5,p<0.01). Thus, the respective diminutions across age by PA scanning was about half that by lateral scanning (16.8 ± 3.9%, 31.2 ± 3.0%,p<0.01). Percent fat in the soft tissue baseline (lateral to bone, ST‐lat) used to derive BMC by PA scanning, was higher than in the soft tissue baseline (anterior to bone, ST‐ant) used to derive BMC by lateral scanning by 2.6 ± 0.7% in premenopausal women and 7.5 ± 1.0% in postmenopausal women (bothp<0.01). After adjusting for these differences in percent fat, BMC by PA and lateral scanning no longer differed. Fat content (cm2) measured by quantitative computed tomography (QCT) in an additional 46 women, was higher in the soft tissue baseline (ST‐lat) than anterior to bone in the 18 premenopausal (30.7 ± 4.2, 24.3 ± 3.5,p<0.01) and the 28 postmenopausal women (41.6 ± 3.7, 34.1 ± 3.5,p<0.01). Fat content in the soft tissue baseline region (ST‐ant) was higher than on either side of bone in premenopausal women (31.3 ± 5.7, 26.5 ± 4.2,p<0.05) but less than on either side of bone in postmenopausal women (44.7 ± 4.3, 50.6 ± 5.1,p<0.05). In summary, the differing composition of soft tissue anterior 6and lateral to bone calls to question the validity of the assumption of tissue homogeneity needed for accurate measurement of BMC by DXA. In the elderly, BMC may be too high by PA scanning, resulting in a reduced cross‐sectional diminution with age. Thus accuracy errors due to fat inhomogeneity compound those caused by osteophytes and suggests caution is needed in making inferences regarding the magnitude of age‐related bone loss determine

ISSN:0884-0431    

DOI:10.1002/jbmr.5650101011

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

年代:1995

数据来源: WILEY