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1.
A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats. 总被引:1,自引:0,他引:1
Hua Zhu Ke D Todd Crawford Hong Qi Hollis A Simmons Thomas A Owen Vishwas M Paralkar Mei Li Bihong Lu William A Grasser Kimberly O Cameron Bruce A Lefker Paul DaSilva-Jardine Dennis O Scott Qing Zhang Xiao Yan Tian Webster Ss Jee Thomas A Brown David D Thompson 《Journal of bone and mineral research》2006,21(4):565-575
CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia. INTRODUCTION: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia. MATERIALS AND METHODS: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined. RESULTS: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls. CONCLUSIONS: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces. 相似文献
2.
Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats 总被引:1,自引:0,他引:1
S. Williams A. Wakisaka Q.Q. Zeng J. Barnes G. Martin W.J. Wechter C.T. Liang 《BONE》1996,19(6):637-644
In the current study, we examined the effects of minocycline, on the osteopenia of ovariectomized aged rats. Old female rats were randomly divided into five groups: sham, ovariectomized control and ovariectomized treated with minocycline, 17β-estradiol, or both agents. Bone samples were collected 8 wk after the treatment. Ovariectomy reduced bone mineral density of the whole femur and at the condylar, distal metaphyseal and head-neck-trochanter regions 10%–19% and the loss of bone density was prevented by treatment with minocycline or 17β-estradiol. Histomorphometric analysis of distal femur showed ovariectomy reduced the trabecular bone area, the trabecular bone number, trabecular bone thickness and increased the trabecular bone separation. The microanatomic structure of trabecular bone also showed that the number of nodes, node to node, cortical to node, node to free end was reduced by ovariectomy. Treatment with minocycline attenuated the effect of ovariectomy on trabecular bone in aged animals. In contrast, cortical bone was not affected by ovariectomy or minocycline treatment. The effect of minocycline on bone turnover was also examined. Minocycline increased osteoid surface, mineralizing surface, mineral apposition rate, bone formation rate and reduced eroded surface. We have therefore concluded that the modest increase in bone mineral density and the improvement in the trabecular bone status noted in minocycline treated ovariectomized aged rats is likely due to an increase in bone formation coupled with a decrease in bone resorption. 相似文献
3.
Hua Zhu Ke Hong Qi D Todd Crawford Hollis A Simmons Gang Xu Mei Li Lori Plum Margaret Clagett-Dame Hector F DeLuca David D Thompson Thomas A Brown 《Journal of bone and mineral research》2005,20(10):1742-1755
An orally active, highly potent analog of 1alpha,25-dihydroxyvitamin D3, 2MD, restores trabecular and cortical bone mass and strength by stimulating periosteal bone formation and decreasing trabecular bone resorption in OVX rats with established osteopenia. INTRODUCTION: The purposes of this study were to determine the effects of long-term treatment with 2-methylene-19-nor-(20S)-1alpha,25(OH)2D3 (2MD) on restoring bone mass and bone strength in ovariectomized (OVX) rats with established osteopenia and 2MD effects on bone formation and bone resorption on trabecular and cortical bone surfaces. MATERIALS AND METHODS: Sprague-Dawley female rats were sham-operated (sham) or OVX at 4 months of age. Beginning at 8 weeks after OVX, OVX rats were orally dosed with 2MD at 0.5, 1, 2.5, 5, or 10 ng/kg/day for 16 weeks. Serum calcium was measured at 6, 13, and 16 weeks after treatment, and bone mass and structure, bone formation, bone resorption, and bone strength were determined at the end of the study. RESULTS: Serum calcium did not change significantly with 2MD at 0.5 or 1 ng/kg/day, whereas it significantly increased at 2.5, 5, or 10 ng/kg/day. 2MD significantly and dose-dependently increased total body BMD, total BMC, and stiffness of femoral shaft (FS), maximal load and stiffness of femoral neck, and toughness of the fifth lumbar vertebral body (L5) at all doses compared with OVX controls. In 2MD-treated OVX rats, there was a dose-dependent increase in total BMD and total BMC of the distal femoral metaphysis (DFM), trabecular bone volume of L3, ultimate strength and stiffness of L5, and maximal load of FS compared with OVX controls at dosages>or=1 ng/kg/day. At dosages>2.5 ng/kg/day, most of the bone mass and bone strength related parameters were significantly higher in 2MD-treated OVX rats compared with sham controls. Bone histomorphometric analysis of L3 showed dose-dependent decreases in osteoclast number and osteoclast surface on trabecular bone surface and a dose-dependent increase in periosteal bone formation associated with 2MD treatment. CONCLUSIONS: 2MD not only restored both trabecular and cortical bone mass but also added bone to the osteopenic OVX rats beyond that of sham controls by stimulating bone formation on the periosteal surface and decreasing bone resorption on the trabecular surface. 2MD increased bone mass and strength at doses that did not induced hypercalcemia. 相似文献
4.
Summary Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats. 相似文献
5.
The present study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone histomorphometry and bone strength in ovariectomized (OVX) rats. Female F344/DuCrj rats, aged 14 weeks, were OVX or sham operated. After 3 months, the OVX rats showed an increase in bone turnover, and a decrease in bone mass and bone strength. Minodronic acid was administered orally once a day for 12 months at doses of 0, 0.006, 0.03 and 0.15 mg/kg from 3 months after OVX. Minodronic acid dose-dependently inhibited the decrease in BMD of lumbar vertebrae and femur. In the femur, treatment with 0.15 mg/kg minodronic acid increased the BMD of distal and mid sites to sham levels. Minodronic acid dose-dependently suppressed OVX-induced increase in urinary deoxypyridinoline, a bone resorption marker, after a month of treatment and these effects were maintained for 12 months of treatment. Minodronic acid also decreased serum osteocalcin, a bone formation marker. In bone histomorphometric analysis after 12 months of treatment, OVX rats showed an increase in bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (MS/BS and BFR/BV) at lumbar vertebral bodies. Minodronic acid suppressed the OVX-induced increase in bone turnover at tissue level. Trabecular bone volume, trabecular thickness and trabecular number of lumbar vertebral bodies were decreased after OVX. Minodronic acid increased these structural indices, indicating that it prevented the deterioration in trabecular architecture. In a mechanical test at 12 months of treatment, ultimate load of lumbar vertebral bodies and mid femur in the OVX-control group was decreased compared to the sham group. Minodronic acid prevented the reduction in bone strength at both sites. In particular, in the mid femur, treatment with 0.03 and 0.15 mg/kg minodronic acid increased bone strength to sham levels or greater. In conclusion, minodronic acid suppressed increased bone turnover, plus prevented the decrease in BMD, deterioration of bone microarchitecture and reduction in bone strength in OVX rats with established osteopenia. These results suggest that minodronic acid may be clinically useful for treatment of osteoporosis. 相似文献
6.
R. K. Fuchs M. R. Allen K. W. Condon S. Reinwald L. M. Miller D. McClenathan B. Keck R. J. Phipps D. B. Burr 《Osteoporosis international》2008,19(9):1331-1341
INTRODUCTION: Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium. METHODS: Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed. RESULTS: SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca. CONCLUSION: These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats. 相似文献
7.
Vertebral deformity in chinese men: prevalence, risk factors, bone mineral density, and body composition measurements 总被引:6,自引:0,他引:6
Lau EM Chan YH Chan M Woo J Griffith J Chan HH Leung PC 《Calcified tissue international》2000,66(1):47-52
The present study was performed to evaluate possible interactions between estrogen and progesterone on peak cancellous bone
mass. Ovariectomized (OVX) growing rats were treated with 17β-estradiol (4.8 μg/day), progesterone (4.8 mg/day), a combination
of the two sex steroids, or with vehicle for 14 days beginning 7 days after OVX. The tibiae were removed for histomorphometric
analysis of the proximal metaphysis. OVX and growth each resulted in net resorption of cancellous bone at a sampling site
adjusted for longitudinal bone growth. Estradiol and progesterone treatment each antagonized bone loss by inhibiting the decrease
in trabecular number. Estradiol increased but progesterone had no effect on trabecular thickness. Progesterone did not influence
either osteoclast number or the resorption of the pretreatment fluorochrome label. Estradiol reduced osteoclast number and
inhibited label resorption, the latter change being accentuated by combination treatment. Estradiol reduced and progesterone
enhanced the mineral apposition and bone formation rates. The results indicate that estradiol and progesterone have independent
activities on cancellous bone turnover during growth. Whereas estradiol reduced bone turnover, progesterone had a stimulatory
effect on bone formation. These findings suggest that progesterone has a role in establishing and maintaining peak cancellous
bone volume during growth.
Received: 28 June 1999 / Accepted: 11 January 2000 相似文献
8.
Jeroen Aerssens Remy Van Audekercke Piet Geusens Lodewijk P. C. Schot Amin Abdel-Hamid Osman Jan Dequeker 《Calcified tissue international》1993,53(4):269-277
Summary Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or Stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on Serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the Start of the experiment) were Studied for 6 months. The results were compared with those obtained in agematched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of Serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were Significantly reduced.Treatment of OVX rats with 1 mg ND/14 days resulted in a Significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and Strength, and bone IGF-I content, and a decrease in Serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVX to the level of the intact controls.These results indicate that ND acts as an antiresorptive drug and as a bone formation Stimulating drug. Furthermore, the increased bone mass and bone mineral density is associated with improved bone Strength and stiffness and the presence of an increased amount of IGF-I. IGF-I is a growth factor considered to play a role in the maintenance of normal skeletal balance by a paracrine or autocrine mechanism. 相似文献
9.
Temporal relationship between bone loss and increased bone turnover in ovariectomized rats 总被引:24,自引:0,他引:24
Summary To characterize osteopenic changes in ovariectomized (OVX) rats as a function of time, female Sprague Dawley rats (240 g body
weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and killed at various times from 14–180 days
postovariectomy. The proximal tibial metaphysis was processed undecalcified for quantitative bone histomorphometry. Osteopenia
and increased indices of bone resorption and formation were detected in OVX rats as early as 14 days. Longitudinal bone growth
was also significantly increased by ovariectomy at 14 days, but returned to control levels at all later times. In OVX rats,
osteopenia became progressively more pronounced with time up to 100 days postovariectomy, after which trabecular bone volume
appeared to stabilize at the markedly reduced level of 5%. Changes in osteoclast surface, osteoblast surface, and fluoro-chrome-based
indices of bone formation in OVX rats followed a similar time course. The maximal increase in these parameters occurred during
the first several months postovariectomy followed by a gradual decline toward control levels. Our results indicate that the
initial rapid phase of bone loss in OVX rats is coincident with the maximal increase in bone turnover. At later times postovariectomy,
bone loss and bone turnover both subside. These findings emphasize the close temporal association between the development
of osteopenia and increased bone turnover in OVX rats. 相似文献
10.
Additional Weight Bearing during Exercise and Estrogen in the Rat: The Effect on Bone Mass, Turnover, and Structure 总被引:6,自引:0,他引:6
Tromp AM Bravenboer N Tanck E Oostlander A Holzmann PJ Kostense PJ Roos JC Burger EH Huiskes R Lips P 《Calcified tissue international》2006,79(6):404-415
Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites. 相似文献
11.
Fox J Miller MA Newman MK Metcalfe AF Turner CH Recker RR Smith SY 《Calcified tissue international》2006,79(4):262-272
Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton
of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used
densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose
PTH (15 or 30 μg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone
strength were reduced substantially in control OVX rats. The 15 μg/kg dose of PTH restored BMD to levels similar to those
in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain
from 6 to 12 months. The 30 μg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total
volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing
trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 μg/kg
dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation,
and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased
bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal
cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through
increased bone turnover and enhanced formation of both trabecular and cortical bone. 相似文献
12.
John Fox Michael A Miller Michael K Newman Charles H Turner Robert R Recker Susan Y Smith 《Journal of bone and mineral research》2007,22(2):260-273
Histomorphometric studies of treatments for osteoporosis in humans are restricted to iliac crest biopsies. We studied the effects of PTH(1-84) treatment at the lumbar spine of skeletally mature ovariectomized rhesus monkeys. PTH increased bone turnover, rapidly normalized BMD, and increased vertebral compressive strength. PTH increased trabecular bone volume primarily by increasing trabecular number by markedly increasing intratrabecular tunneling. INTRODUCTION: Histomorphometric studies of the anabolic properties of PTH(1-84) (PTH) and related peptides in human bone are restricted to iliac crest biopsies. The ovariectomized (OVX) monkey is an accepted model of human postmenopausal bone loss and was used to study the effects of PTH treatment at clinically relevant skeletal sites. MATERIALS AND METHODS: Skeletally mature rhesus monkeys were OVX or sham-operated and, after a bone depletion period of 9 months, treated daily for 16 months with PTH (5, 10, or 25 microg/kg). Markers of bone formation (serum osteocalcin) and resorption (urine N-telopeptide [NTX]) and lumbar spine BMD were measured throughout the study. Trabecular architecture and vertebral biomechanical properties were quantified at 16 months. RESULTS: PTH treatment induced dose-dependent increases in bone turnover but did not increase serum calcium. Osteocalcin was significantly increased above OVX controls by 1 month. NTX was significantly elevated at 1 month with the highest dose, but not until 12 months with the 5 and 10 microg/kg doses. Lumbar spine BMD was 5% lower in OVX than in sham animals when treatment was started. All PTH doses increased BMD rapidly, with sham levels restored by 3-7 months with 10 and 25 microg/kg and by 16 months with 5 microg/kg. PTH treatment increased trabecular bone volume (BV/TV), primarily by increasing trabecular number, and dose-dependently increased bone formation rate (BFR) solely by increasing mineralizing surface. The largest effects on BV/TV and yield load occurred with the 10 microg/kg dose. The highest dose reduced trabecular thickness by markedly increasing intratrabecular tunneling. CONCLUSIONS: PTH treatment of OVX rhesus monkeys increased bone turnover and increased BV/TV, BMD, and strength at the lumbar spine. All PTH doses were safe, but the 10 microg/kg dose was generally optimal, possibly because the highest dose resulted in too marked a stimulation of bone remodeling. 相似文献
13.
Calomme M Geusens P Demeester N Behets GJ D'Haese P Sindambiwe JB Van Hoof V Vanden Berghe D 《Calcified tissue international》2006,78(4):227-232
Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have
a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss
in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks
(OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher
compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion,
which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA
supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC
in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal
region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased
by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat
model. 相似文献
14.
目的探讨硬化蛋白抗体和跑台运动对老龄去势大鼠骨重建的影响。方法 8月龄雌性Wistar大鼠,按体质量随机分层分为5组:Sham组(假手术组)、OVX组(去卵巢组)、OVX+E组(去卵巢+运动组)、OVX+S组(去卵巢+硬化蛋白抗体组)、OVX+E+S组(去卵巢+运动+硬化蛋白抗体组)。在14w后取材进行相关指标测试。结果 1单纯性的运动锻炼能降低脂肪量,增加骨小梁数目,减少骨吸收标记物NTx水平,防止老龄去势大鼠全身、股骨骨密度发生下降。2单纯性的硬化蛋白抗体治疗能增加骨形成标志物OC,提高去势大鼠的皮质孔隙率、皮质骨体积和皮质骨厚度,提高骨密度。3运动与硬化蛋白抗体交互作用时,可以降低脂肪量,提高骨密度和皮质骨参数,增加骨量和骨强度,提高OC水平、降低NTx水平。结论适度的跑台运动可以防止老龄去势大鼠骨量丢失,改善去势大鼠骨健康。硬化蛋白抗体疗法可以增加皮质骨骨量和骨强度,预防去势大鼠绝经后对骨代谢的不良影响。硬化蛋白和运动表现出良好的协同作用,对老龄去势大鼠骨重建具有积极的作用。 相似文献
15.
H. Rico M. Gómez M. Revilla J. González-Riola C. Seco E. R. Hernández L. F. Villa J. J. Gervás 《Calcified tissue international》1999,65(4):272-275
The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action
involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 ± 20 g).
A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of
life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and
a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats
were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height
were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral
density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA).
Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm−1), trabecular thickness (Tb-Th μm), and trabecular separation (Tb-Sp μm) were measured in the femurs by histomorphometric
study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass
(P < 0.0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX
rats (P < 0.0001).
Received: 1 June 1998 / Accepted: 17 February 1999 相似文献
16.
目的 探讨抗骨质疏松新药XW630对去势大鼠骨组织力学性能及骨小梁结构参数的影响。方法 3月龄SD雌性大鼠36只,随机分为Sham组、OVX组、OVX+CFT组和OVX+XW630组,每组3只。取左侧股骨作三点弯曲力学强度测试,左侧胫骨作骨小梁结构参数测定。结果 整个观察期内,OVX组股骨三点弯曲强度呈下降趋势,与Saham组存在显性差异(P<0.01),两个治疗组骨强度则呈上升趋势,与OVX组存在显性差异(P<0.05或P<0.01)。胫骨骨小梁结构参数测定结果显示,OVX组骨形成参数(Vx、Tb.Th、Tb.N)逐渐下降,而骨吸收参数(Tb.Sp)逐渐增加,呈骨量丢失状态,而两个治疗组骨形成参数逐渐增加,骨吸收参数逐渐下降,与OVX组之间存在显性差异(P<0.05和P<0.01)。两个治疗组同期各项测定结果无显性差异(P>0.05)。结论 XW630能有效地促进去势大鼠骨组织的成骨和预防骨质疏松性骨折的发生,显示出良好的应用前景。 相似文献
17.
McManus JF Davey RA Maclean HE Doust EA Chiu WS Sims NA Bouxsein ML Glatt V Zajac JD Danks JA 《BONE》2008,42(6):1164-1174
Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1-34) sharing only 53% identity with hPTH(1-34). Here we demonstrate the in vivo actions of fPth1(1-34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 microg-1,000 microg/kg body weight (b.w.), (30fPth1-1,000fPth1)] or hPTH [30 microg-100 microg/kg b.w. (30hPTH-100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 microg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1-34), we have clearly established the efficacy of fPth1 (1-34) as an anabolic bone agent. 相似文献
18.
目的 了解孕激素对去势雌性大鼠骨密度及骨形态计量作用。方法 5 0只 6月龄Wistar雌性大鼠随机分为 5组 :假手术组和卵巢切除组、卵巢切除后分别加安宫黄体酮 2mg组、安宫黄体酮 2 0mg组和倍美力组。手术后 7d喂药 ,用药后 3个月处死。测定各组大鼠子宫湿重、全身及股骨骨密度并取大鼠椎骨、胫骨组织切片进行形态计量分析。结果 两组孕激素组子宫湿重与卵巢切除组相同 ,均显著低于假手术组与倍美力组 (P <0 0 0 1)。假手术、雌、孕激素组全身骨密度测定均大于卵巢切除组 (P <0 0 5 )。各组股骨骨密度无显著差异。组织切片观察显示 ,假手术与倍美力组骨小梁粗壮、饱满、结构完整 ;卵巢切除组则纤细、断裂、完整性差。孕激素组骨小梁结构优于卵巢切除组但不及假手术及倍美力组。计量分析显示孕激素组椎骨骨小梁面积明显大于卵巢切除组(P <0 0 5 ) ,但低于倍美力组 (P <0 0 5 )。胫骨骨小梁面积与卵巢切除组相仿 ,均明显低于假手术和倍美力组 (P <0 0 5 )。孕激素 2mg与 2 0mg组间无明显差异。结论 两种剂量的安宫黄体酮对卵巢切除大鼠骨质疏松均有一定防治作用 ,但从骨组织形态计量分析 ,其作用较弱 ,与结合雌激素相比 ,尚不足以维持骨量 相似文献
19.
Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy. 总被引:1,自引:0,他引:1
Y Kasukawa N Miyakoshi E Itoi T Tsuchida Y Tamura T Kudo K Suzuki A Seki K Sato 《Journal of orthopaedic research》2004,22(3):457-464
The purpose of this study was to determine whether h-PTH (1-34) treatment would recover cancellous bone connectivity and bone strength in ovariectomized (OVX) or ovariectomized and sciatic-neurectomized (OVX+NX) rats. Seven-month-old female Wistar rats were treated with h-PTH or vehicle (6.0 microg/kg, six times a week, subcutaneously) for four weeks beginning 4, 8, or 12 weeks after OVX or OVX+NX. These were compared to age-matched baseline and sham-operated groups. Right tibiae were used for bone histomorphometry and node-strut analysis, and left tibiae were used for mechanical testing. The bone formation rates in the OVX and OVX+NX rats treated with h-PTH were significantly higher than those in their baseline controls. h-PTH treatment increased the node numbers and failure energies in the OVX rats, compared to their baseline controls, at all time points. However, in the OVX+NX rats, the effects of h-PTH treatment on the node number and failure energy were observed only at four weeks after surgery, but not at eight weeks or 12 weeks after surgery. These results suggest that the lowest limit, at which trabecular connectivity and bone strength are able to be restored by h-PTH, occurred between four and eight weeks in OVX+NX rats, but not in OVX rats. h-PTH cannot recover trabecular connectivity and bone strength in advanced osteopenia. 相似文献
20.
Rohanizadeh R LeGeros RZ Bohic S Pilet P Barbier A Daculsi G 《Calcified tissue international》2000,67(4):330-336
Bisphosphonates have been widely used in the treatment of human bone pathologies including osteoporosis. In this case, bisphosphonates
have been shown to reduce bone resorption, thereby increasing the mass and mechanical resistance of bone. Determining the
effects of these molecules on the properties of the bone apatite crystals could provide a better insight into the mechanism
of bisphosphonate/bone interaction. The aim of this study was to determine the ultrastructural effects of a third generation
bisphosphonate (tiludronate) on the morphology, size, distribution, chemical composition, and structure of apatite crystals
in bone (trabecular) in a rat osteoporotic model. Four groups of rats were studied: (1) sham operated, (2) untreated ovariectomized
(OVX), (3) OVX rats which received 35 mg/kg of tiludronate, (4) OVX rats which received 160 mg/kg of tiludronate. The rats
of groups 3 and 4 received tiludronate orally in 2 consecutive days every week for 1 year. Scanning electron microscopy (SEM),
high and low resolution transmission electron microscopy (TEM), and electron microprobe analysis (EDX) were used for the ultrastructural
characterization of the bone mineral. This study demonstrated that tiludronate slightly increased the width of bone apatite
crystals without changing any other crystal characteristics.
Received: 20 November 1999 / Accepted: 6 April 2000 相似文献