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1.
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
2.
This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM
and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of
eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl
(SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP),
urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal
bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia,
as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution
mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the
SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats
compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4
animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted
than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status.
The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX
rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density.
Received: 20 May 1999 / Accepted: 4 February 2000 相似文献
3.
Calcitonin Provides Complete Protection Against Cancellous Bone Loss in the Femoral Neck of Ovariectomized Rats 总被引:2,自引:0,他引:2
Calcitonin (CT) has been found to partially prevent cancellous bone loss in the proximal tibia of ovariectomized (OVX) rats.
The current study was designed to determine whether CT has similar bone protective effects in the femoral neck, a skeletal
site with a slower rate of bone loss after ovariectomy than the proximal tibia. Female Sprague Dawley rats were sham-operated
or ovariectomized at 3 months of age. Groups of OVX rats were injected s.c. with vehicle or CT at a dose of 16 U/kg body weight
on alternate days for 30, 60, or 90 days. Sham-operated control rats were treated with vehicle alone on alternate days. The
proximal femur from each rat was processed undecalcified for quantitative bone histomorphometry. Cancellous bone volume in
the femoral neck of vehicle-treated OVX rats was significantly less than that of vehicle-treated control rats at all time
points. This cancellous osteopenia induced by ovariectomy was associated with increased indices of bone turnover such as osteoclast
surface, osteoblast surface, and bone formation rate (tissue level, total surface referent). In contrast, cancellous bone
volume in the femoral neck of CT-treated OVX rats was nearly identical of that of vehicle-treated control rats throughout
the study. In addition, CT treatment of OVX rats decreased all indices of bone turnover to near the level of vehicle-treated
control rats. The results indicate that CT treatment depresses bone turnover and provides complete protection against moderate
cancellous osteopenia in the femoral neck of OVX rats. Since previous studies have shown that CT only partially protects against
more pronounced cancellous bone loss in the proximal tibia of OVX rats, our findings suggest that CT has a greater bone protective
effect at a skeletal site with a slower rate of cancellous bone loss (femoral neck) than at a skeletal site with a rapid rate
of cancellous bone loss (proximal tibia).
Received: 21 August 1996 / Accepted: 10 December 1996 相似文献
4.
E. Jódar Gimeno M. Muñoz-Torres F. Escobar-Jiménez M. Quesada Charneco J. D. Luna del Castillo N. Oleà 《Calcified tissue international》1997,61(5):370-376
Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing
osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients.
We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 ± 16 years). Bone mineral density (BMD) was
measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2–L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group
B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical
variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of
bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age
and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater
levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin,
tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted
for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic
hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with
lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between
BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation
of hyperthyroid bone disease.
Received: 5 May 1997 / Accepted: 5 June 1997 相似文献
5.
P. Geusens S. Boonen J. Nijs Y. Jiang G. Lowet R. Van Auderkercke C. Huyghe F. Caulin J. M. Very J. Dequeker G. Van der Perre 《Calcified tissue international》1996,59(4):315-320
The aim of this study was to evaluate the effect of intermittent calcitonin on femoral bone quality in adult ewes from the
time of ovariectomy. Six months after the start of the experiment, bone density measurements and mechanical testing (torsion
and resonant frequency analysis of the diaphysis and compression of an excised trabecular bone cylinder from the femoral neck)
were performed in sham-control and ovariectomized (OVX) ewes treated with placebo or salmon calcitonin (50 or 100 units, 3
times/week). Crystallinity of bone was evaluated by measuring X-ray diffraction line broadening. After OVX, a nonsignificant
bone loss was found at all measured sites in the femur (−3 to −9%) together with a decreased biomechanical competence in the
trabecular bone (compressive strain −28%, P < 0.05). Treatment with salmon calcitonin, 50 or 100 IU subcutaneously three times a week from the time of ovariectomy, resulted
in a significant dose-dependent preservation of bone strength in the trabecular bone of the femoral neck compared with OVX.
No adverse effects of calcitonin were observed on bone crystal composition as assessed by diffractiometry. We conclude that
in adult ewes intermittent calcitonin treatment from the time of OVX was associated with a significant preservation of cancellous
bone strength and strain in trabecular bone of the femoral neck, without affecting crystalline properties of bone.
Received: 20 October 1995 / Accepted: 19 February 1996 相似文献
6.
X. Li M. Takahashi K. Kushida S. Koyama H. Hoshino K. Kawana K. Horiuchi T. Inoue 《Calcified tissue international》1996,59(4):271-276
The effects of tamoxifen (TAM) treatment on bone metabolism and skeletal growth were studied in sexually mature intact or
ovariectomized (OVX) rats. Experiment 1 was designed to observe the effects of TAM on bone metabolism and skeletal growth
in intact rats and included two groups: (1) intact plus vehicle and (2) intact plus TAM. Experiment 2 was designed to investigate
the effects of TAM on OVX rats and included the other two groups: (3) OVX plus vehicle and (4) OVX plus TAM. Serum calcium
osteocalcin and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured serially before and after TAM treatment
for 6 weeks in order to monitor bone turnover. Bone mineral density (BMD) and bone mineral content (BMC) of excised right
femora and lumbar vertebrae were determined by dual energy X-ray absorptiometry (DXA). To examine the effect of TAM on skeletal
growth, the conventional parameters of femora and the histology of right tibiae were also measured. TAM did not induce significant
change in the biochemical markers in intact rats during the 6-week experiment. Bone mass and skeletal growth were not changed
by TAM treatment in intact rats. However, TAM treatment reduced the increase in serum osteocalcin and urinary pyridinium cross-links
from 1 week to 6 weeks postovariectomy in the OVX rats. TAM inhibited the skeletal growth in OVX rats, because TAM treatment
shortened femoral length and decreased the cell number in the growth plate in OVX rats in this study. Our findings indicate
that TAM exerts an effect of estrogen agonist on bone metabolism and skeletal growth in OVX rats, however, it does not affect
them in intact rats.
Received: 1 September 1995 / Accepted: 20 February 1996 相似文献
7.
8.
Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites. 相似文献
9.
Mori H Tanaka M Kayasuga R Masuda T Ochi Y Yamada H Kishikawa K Ito M Nakamura T 《BONE》2008,43(5):840-848
This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control animals were significantly reduced compared to the sham animals. Minodronic acid prevented these reductions in bone strength at 0.15 mg/kg. There was significant correlation between BMD and bone strength, suggesting that the increase in bone strength was associated with the increase in BMD produced by minodronic acid. In micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved trabecular architecture, converting rod structures into plate structures, and preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In conclusion, similar to patients with postmenopausal osteoporosis, reduction in bone strength of lumbar vertebral bodies and femoral neck was clearly demonstrated in OVX cynomolgus monkeys. Minodronic acid prevented these reductions at a once-daily oral administration. Also, minodronic acid prevented OVX-induced changes in bone turnover, bone mass and bone microarchitecture. Long-term minodronic acid treatment was well tolerated and no adverse effects could be detected. These results suggest that minodronic acid may be a clinically useful drug for osteoporosis. 相似文献
10.
It is well established that estrogen deficiency at menopause results in increased bone turnover, which is reflected in increased
concentrations of markers of bone formation and bone resorption in serum and urine. Since serum 17β-estradiol concentrations
vary markedly throughout the menstrual cycle, one would expect to see changes in bone turnover as well. Studies in humans
have not yielded consistent results, perhaps because of differences in diet and activity throughout the test period. Therefore,
we examined changes in bone biomarkers throughout the menstrual cycle in cynomolgus macaques. Seven intact female cynomolgus
macaques (Macaca fascicularis) were evaluated. Vaginal swabs for menstrual blood were performed 3 times/week to determine the stage of the reproductive
cycle. Blood and urine were collected at weekly or biweekly intervals for a total of eight samples per monkey for analysis
of serum 17β-estradiol, progesterone, parathyroid hormone (PTH), osteocalcin, bone-specific alkaline phosphatase (BSAP), and
urinary CrossLaps™. Cycle lengths were determined, and collection days were adjusted to a standardized length of 28 days for
all monkeys. Values for bone biomakers were evaluated as % mean for each monkey cycle. By fitting the data to a sine wave
(cosinor analysis), serum osteocalcin, BSAP, and urinary CrossLaps demonstrated significant cycles with peaks at days 2.6,
7.3, and 27.8, respectively. Serum osteocalcin and urinary CrossLaps were inversely correlated to serum 17β-estradiol. Urinary
CrossLaps were significantly lower in the week just prior to and during ovulation when estradiol was elevated. No rhythm was
detected in serum PTH. A peak in bone resorption when serum 17β-estradiol is at its nadir is consistent with the hypothesis
that estrogen decreases bone turnover.
Received: 19 March 1999 / Accepted: 30 September 1999 相似文献
11.
Bone Density, Vitamin D Status, and Disordered Bone Remodeling in End-Stage Chronic Liver Disease 总被引:4,自引:0,他引:4
Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine
the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical
markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured
at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed
using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present
in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and
hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation
(osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27
(85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that
increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed
to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives
to bone biopsy in evaluating hepatic osteodystrophy.
Received: 11 September 1997 / Accepted: 22 September 1998 相似文献
12.
《BONE》2014
This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis. 相似文献
13.
S. Castañeda L. Carmona I. Carvajal R. Arranz A. Díaz A. García-Vadillo 《Calcified tissue international》1997,60(4):343-347
Osteoporosis is a common disease among patients undergoing transplantation. Its prevalence and complications have been well
described in solid organ recipients, especially kidney, liver, and heart. However, studies in bone marrow transplantation
(BMT) are scarce. Among the mechanisms invoked in the pathogenesis of BMT osteoporosis are the baseline disease, the use of
immunosuppressive drugs and, more remarkably, secondary hypogonadism. We present a study of 27 women who underwent BMT, all
of them suffering ovarian failure. We studied different biochemical markers of bone formation/resorption and also evaluated
the presence of osteopenia/osteoporosis by dual energy X-ray absorptiometry (DXA) of the lumbar spine. Osteopenia was observed
in nine patients (33%) and osteoporosis in another five (18%), according to the World Health Organization criteria. We also
detected a subgroup showing elevation of several bone turnover biochemical markers, indicating high osseous remodeling. A
remarkable increase in urine hydroxyproline/creatinine was detected in 95% of cases, although an explanation is lacking. We
outline a reasonable therapeutic approach for osteoporosis in BMT emphasizing the need to monitor these patients after transplantation.
Received: 11 January 1996 / Accepted: 25 October 1996 相似文献
14.
Ovariectomy-Induced Bone Loss Can be Affected by Different Intensities of Treadmill Running Exercise in Rats 总被引:2,自引:0,他引:2
Fifty-six Sprague-Dawley rats were either ovariectomized (OVX, n= 24), sham-operated (Sham, n= 24), or sacrificed (n= 8) at the beginning of the experiment to serve as a baseline group. The OVX and Sham groups were further randomly divided
into control (CTRL), slow running (R10), and faster running (R18) groups. R10 and R18 groups ran for 2 × 30 min/day for 8
weeks at speeds of 10 m/min and 18 m/min, respectively. Exercise did not affect the mechanical or histomorphometric parameters
of bone in the sham-operated rats. There was no effect of exercise on body weight gain in the OVX-R10 group, but in OVX-R18
it decreased the gain of body weight. In the OVX–CTRL group the maximal load and energy absorption of the femoral neck were
16.7% (P < 0.001) and 30.0% (P < 0.001) lower than in the Sham–CTRL group, respectively. In OVX animals, slow running had a positive effect on the maximal
load of the femoral neck (86.5 N) when compared with OVX–CTRL rats (77.1 N, P < 0.07). 51.7% of the trabecular bone was lost in the distal femur as a result of OVX and exercise reduced this loss to 30.2%
(R10) and 39.9% (R18). Ovariectomy increased the bone formation rate (BFR) and the mineral apposition rate (MAR) on the periosteum
of the femoral shaft. Exercise decreased the periosteal BFR and MAR in OVX rats, but increased it at the endosteum. Osteoclast
numbers in the femoral metaphysis were increased after OVX and running exercise inhibited this effect significantly. The maximal
bending load of the humerus increased after OVX by 12.1% (P < 0.05). Exercise enhanced this effect, the slow running being more effective. These results suggest that bone in OVX rats
is either more sensitive to exercise than in sham-operated rats or that the higher body weight with slow running induces optimal
loading and strengthens the bones.
Received: 2 May 1996 / Accepted: 15 October 1996 相似文献
15.
Mechanical Stimulation in the Form of Vibration Prevents Postmenopausal Bone Loss in Ovariectomized Rats 总被引:11,自引:0,他引:11
J. Flieger Th. Karachalios L. Khaldi P. Raptou G. Lyritis 《Calcified tissue international》1998,63(6):510-514
Physical exercise is recommended for the prevention and treatment of osteoporosis. However, its exact role and effectiveness
in adulthood is unclear. While vigorous exercise of long duration enhances bone density, few adult individuals comply with
such training programs. The present study evaluates the influence of nonphysiological mechanical stimulation, in the form
of low intensity vibration (frequency: 50 Hz, acceleration: 2 g, 30 min/day for 5 days/week), on the prevention of bone loss
in an animal model of postmenopausal osteoporosis. In the ovariectomised groups of rats a statistically significant (p < 0.05)
decrease of bone density (femur and tibia) was recorded at 5 weeks postovariectomy. This effect was maintained for the 12
week duration of the study. Vibration prevented early bone loss after ovariectomy. Vibrated ovariectomised rats showed statistically
significantly higher (p < 0.05) BMD values compared to those of their ovariectomised controls at 5 weeks. Vibration did not
influence the bone density of the SHAM-operated rats. Although vibration increased ultimate strength (fracture load of the
rat femur) in the ovariectomised rats, this finding was not statistically significant. Our data indicate that this method
of safe and easily applicable vibration, in the form of a vibrating platform, is effective in preventing early postovariectomy
bone loss in an animal model.
Received: 16 April 1997 / Accepted: 8 April 1998 相似文献
16.
Prevention of Corticosteroid-Induced Osteoporosis with Alendronate in Sarcoid Patients 总被引:10,自引:0,他引:10
S. Gonnelli P. Rottoli C. Cepollaro C. Pondrelli V. Cappiello M. Vagliasindi C. Gennari 《Calcified tissue international》1997,61(5):382-385
Prolonged corticosteroid administration, as often required in the treatment of sarcoidosis, increases the risk of osteoporosis
and fracture. The aim of the present study was to evaluate the usefulness of alendronate, a third generation bisphosphonate,
in preventing corticosteroid-induced osteoporosis. Forty-three consecutive, previously untreated, sarcoid patients (17 men
and 26 premenopausal women) were included in the study: 13 needed no treatment and served as controls (Group 1) and 30 needed
glucocorticoids (prednisone) and were randomly selected to also receive either placebo (n = 15, Group 2) or alendronate 5
mg/day (n = 15, Group 3). Bone mineral density (BMD) at the ultradistal radius by dual photon absorptiometry (Osteograph 1000,
NIM, Verona, Italy) and biochemical markers of bone turnover were measured at baseline and after 6 and 12 months of glucocorticoid
therapy. No significant difference was found between Groups 2 and 3 in the mean cumulative dose of prednisone (4945 ± 1956
mg and 5110 ± 2013 mg, respectively). At the end of the study period, BMD increased by 0.8% in the alendronate-treated group;
in the placebo-treated group, BMD decreased by 4.5%. The difference between groups was significant (P < 0.01, ANOVA). A significant decrease in markers of bone formation was found in all patients treated with prednisone (Groups
2 and 3), independently of alendronate. Alendronate, however, counteracted the increase in markers of bone resorption induced
by glucocorticoid therapy. Our data suggest that alendronate is effective in preventing glucocorticoid-induced bone loss in
sarcoid patients. Further studies on alendronate use in steroid-induced osteoporosis are needed.
Received: 30 September 1996 / Accepted: 30 April 1997 相似文献
17.
Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. In this study, we investigated
the bone-sparing effects of oral 1α,24R,25-trihydroxyvitamin D3 (1,24,25(OH)3D3) in a wide dose range in aged OVX rats. Fifty-three female Fischer-344 rats (6 months old, 170 g BW) were either ovariectomized
or sham-operated (SHAM). Eight rats served as baseline controls. Groups of OVX rats (n= 7–8 each) received vehicle alone or graded oral doses of 1,24,25(OH)3D3 (0.05, 0.1, 0.2, and 0.3 μg/kg BW/day), starting five days after surgery. Urine and blood samples were collected one, two,
three, and four months after surgery. Serum samples were analyzed for total calcium and alkaline phosphatase. Calcium, hydroxyproline,
and collagen crosslinks (HPLC) were determined in urine. After fluorochrome double labeling, the rats were sacrificed four
months postsurgery and the first lumbar vertebrae and the proximal tibiae were processed undecalcified for bone histomorphometry.
Ovariectomy induced a 28% and a 69% reduction in vertebral and tibial cancellous bone area, respectively. Osteopenia in OVX
rats was associated with increased histomorphometric and biochemical indices of bone turnover. The administration of 1,24,25(OH)3D3 to OVX rats dose-dependently increased vertebral and tibial cancellous bone mass, serum calcium, and urinary calcium excretion,
and reduced histomorphometric and biochemical indices of bone resorption. 1,24,25(OH)3D3 at doses of 0.2 and 0.3 μg/kg/day produced strong anabolic effects, especially on vertebral cancellous bone in OVX rats,
and increased mineral apposition rate and wall width of completed remodeling units relative to vehicle-treated OVX rats. Even
at high doses, 1,24,25(OH)3D3 did not impair bone mineralization. We conclude that oral administration of 1,24,25(OH)3D3 can effectively prevent estrogen depletion-induced cancellous bone osteopenia in the aged OVX rat model. The therapeutic
window for 1,24,25(OH)3D3 in OVX rats, however, is also narrow, comparable to that for calcitriol.
Received: 29 March 1996 / Accepted: 23 September 1996 相似文献
18.
Rico H Gallego-Lago JL Hernández ER Villa LF Sanchez-Atrio A Seco C Gérvas JJ 《Calcified tissue international》2000,66(1):53-55
The effect of silicon (Si) supplement on preventing bone mass loss induced by ovariectomy (OVX) in rats was investigated.
Three groups of 15, 100-day-old female Wistar rats each, with a mean initial weight of ∼260 g per animal, were selected for
the present study. One of the experimental group consisting of 15 OVX rats was fed a diet supplemented with 500 mg of Si per
kg of feed (Si + OVX). The other two groups consisting of 15 OVX and 15 sham-OVX rats did not receive these supplements. Morphometric
(weight and length) and densitometric studies with dual-energy X-ray absorptiometry were performed on the whole femur and
5th lumbar vertebra of each animal 30 days after the experiment. The Si + OVX rats did not show a loss of bone mass induced
by OVX at axial level (5th lumbar vertebra) or periphery (femur). Nonetheless, a significant increase (ANOVA with Bonferroni/Dunn
post hocs test) of longitudinal development of the femur (P < 0.0001) was patent. These results, obtained through the measurements of axial and peripheral bones, warrant closer scrutiny
in connection with the Si inhibitory effect on bone mass loss as well as the stimulatory effect on bone formation. Both actions,
namely, inhibition of resorption and stimulation of formation, infer that Si may have a potential therapeutic application
in the treatment of involutive osteoporosis.
Received: 15 February 1999 / Accepted: 25 June 1999 相似文献
19.
A recombinant human parathyroid hormone, rhPTH-(1-84), which is currently in Phase II clinical trial, and hPTH-(1-31)NH2 (Ostabolin) are promising anabolic agents for treating osteoporosis because they can stimulate cortical and trabecular bone
growth in osteopenic, ovariectomized (OVX) rats and in osteoporotic, postmenopausal women when injected subcutaneously and
intermittently at low doses. We have now found that, despite their different sizes and signaling properties (rhPTH-(1-84)
stimulates adenylyl cyclase and phospholipase C; hPTH-(1-31)NH2 only stimulates adenylyl cyclase), they are equally osteogenic in OVX rats. Thus daily subcutaneous injections of 0.6 nmol/100
g of body weight of rhPTH-(1-84) or hPTH-(1-31)NH2 into 3-month-old OVX rats for 6 weeks starting 2 weeks after OVX equally reduced the otherwise large OVX-triggered loss of
femoral trabecular bone. Daily subcutaneous injections of 0.4 or 0.8 nmol/100 g of body weight of the two agents for 6 weeks
also equally increased the mean thickness of the remaining femoral trabeculae in 3-month-old and 1-year-old OVX rats to 20
to 80% above the value in normal animals when started 9 weeks after ovariectomy.
Received: 22 December 1995 / Accepted: 20 March 1996 相似文献
20.
Effect of Estrogen Deficiency on Cancellous and Cortical Bone Structure and Strength of the Femoral Neck in Rats 总被引:5,自引:0,他引:5
Eighty mature Sprague-Dawley rats were weight matched before ovariectomy (Ovx) or Sham surgery (Sham). Sham rats had free
access to food and water throughout the experiment, whereas Ovx rats were kept on the pair-fed diet. Rats were euthanized
at 4, 8, and 12 weeks after surgery, and had received fluorochrome bone markers at 9 and 2 days prior to euthanasia. In addition
10 rats were euthanized at the time of surgery serving as baseline controls. All rats were also scanned for body composition
and bone mineral parameters by DEXA before surgery and euthanasia. Left proximal femurs (femoral necks) were used for bone
histomorphometry, whereas right femurs were used for in vitro DEXA measurements and mechanical testing. Despite pair-feeding, ovariectomized rats had increased body weights and fat body
mass, whereas the percent lean body mass steadily declined throughout the experiment. Mineral density of the whole femur and
femoral neck was significantly higher in the Sham rats relative to Ovx animals. Ovariectomy reduced trabecular number and
thickness, and increased trabecular separation and bone marrow space at the femoral midneck location. The structure of the
remaining trabeculae was dramatically changed toward simpler struts as revealed by nodal analyses. Cortical thickness in Ovx
rats was reduced because of the high endocortical resorption, which, in addition to cancellous bone resorption, resulted in
fewer endocortico-trabecular connections. Femoral necks obtained from ovariectomized rats had reduced strength and were less
stiff relative to controls. Because of the enormous clinical significance of the proximal femur for osteoporosis in humans,
and the opportunity for studying bone BMD, mass, structure, and strength at the same skeletal location, the femoral neck appears
superior to other skeletal sites routinely used for bone histomorphometry or mechanical testing in the Ovx rat model.
Received: 25 September 1996 / Accepted: 24 March 1997 相似文献