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1.
T Hirano D B Burr C H Turner M Sato R L Cain J M Hock 《Journal of bone and mineral research》1999,14(4):536-545
Intermittent administration of parathyroid hormone (PTH) has an anabolic effect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim of this study was to determine the effects of biosynthetic human PTH(1-34) on the histology and mechanical properties of cortical bone in rabbits, which exhibit Haversian remodeling. Mature New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 micrograms/kg/day or 40 micrograms/kg/day for 140 days. Body weight in rabbits treated with PTH did not change significantly over the experimental period. Serum calcium and phosphate were within the normal range, but a 1 mg/ml increase in serum calcium was observed in rabbits given the higher dose of PTH. Histomorphometry of cortical bone in the midshaft of the tibia showed significant increases in periosteal and endocortical bone formation in these rabbits. Intracortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, stiffness, and work to failure of the midshaft of the femur of rabbits given the 40 micrograms dose of PTH were significantly greater than those in the control group, whereas elastic modulus was significantly lower than that in the rabbits given the 10 micrograms dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption without increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied by concurrent increases in bone at the periosteal and endocortical surfaces. The combination of these phenomena resulted in an enhancement of the ultimate stress, stiffness, and work to failure of the femur. 相似文献
2.
D B Burr T Hirano C H Turner C Hotchkiss R Brommage J M Hock 《Journal of bone and mineral research》2001,16(1):157-165
Cortical porosity in patients with hyperparathyroidism has raised the concern that intermittent parathyroid hormone (PTH) given to treat osteoporotic patients may weaken cortical bone by increasing its porosity. We hypothesized that treatment of ovariectomized (OVX) cynomolgus monkeys for up to 18 months with recombinant human PTH(1-34) [hPTH(1-34)] LY333334 would significantly increase porosity in the midshaft of the humerus but would not have a significant effect on the strength or stiffness of the humerus. We also hypothesized that withdrawal of PTH for 6 months after a 12-month treatment period would return porosity to control OVX values. OVX female cynomolgus monkeys were given once daily subcutaneous (sc) injections of recombinant hPTH(1-34) LY333334 at 1.0 microg/kg (PTH1), 5.0 microg/kg (PTH5), or 0.1 ml/kg per day of phosphate-buffered saline (OVX). Sham OVX animals (sham) were also given vehicle. After 12 months, PTH treatment was withdrawn from half of the monkeys in each treatment group (PTH1-W and PTH5-W), and they were treated for the remaining 6 months with vehicle. Double calcein labels were given before death at 18 months. After death, static and dynamic histomorphometric measurements were made intracortically and on periosteal and endocortical surfaces of sections from the middiaphysis of the left humerus. Bone mechanical properties were measured in the right humeral middiaphysis. PTH dose dependently increased intracortical porosity. However, the increased porosity did not have a significant detrimental effect on the mechanical properties of the bone. Most porosity was concentrated near the endocortical surface where its mechanical effect is small. In PTH5 monkeys, cortical area (Ct.Ar) and cortical thickness (Ct.Th) increased because of a significantly increased endocortical mineralizing surface. After withdrawal of treatment, porosity in PTH1-W animals declined to sham values, but porosity in PTH5-W animals remained significantly elevated compared with OVX and sham. We conclude that intermittently administered PTH(1-34) increases intracortical porosity in a dose-dependent manner but does not reduce the strength or stiffness of cortical bone. 相似文献
3.
Sutada Lotinun Glenda L Evans James T Bronk Mark E Bolander Thomas J Wronski Erik L Ritman Russell T Turner 《Journal of bone and mineral research》2004,19(7):1165-1171
We examined the time course effects of continuous PTH on cortical bone and mechanical properties. PTH increased cortical bone turnover and induced intracortical porosity with no deleterious effect on bone strength. Withdrawal of PTH increased maximum torque to failure and stiffness with no change in energy absorbed. INTRODUCTION: The skeletal response of cortical bone to parathyroid hormone (PTH) is complex and species dependent. Intermittent administration of PTH to rats increases periosteal and endocortical bone formation but has no known effects on intracortical bone turnover. The effects of continuous PTH on cortical bone are not clearly established. MATERIALS AND METHODS: Eighty-four 6-month-old female Sprague-Dawley rats were divided into three control, six PTH, and two PTH withdrawal (WD) groups. They were subcutaneously implanted with osmotic pumps loaded with vehicle or 40 microg/kg BW/day human PTH(1-34) for 1, 3, 5, 7, 14, and 28 days. After 7 days, PTH was withdrawn from two groups of animals for 7 (7d-PTH/7d-WD) and 21 days (7d-PTH/21d-WD). Histomorphometry was performed on periosteal and endocortical surfaces of the tibial diaphysis in all groups. microCT of tibias and mechanical testing by torsion of femora were performed on 28d-PTH and 7d-PTH/21d-WD animals. RESULTS AND CONCLUSIONS: Continuous PTH increased periosteal and endocortical bone formation, endocortical osteoclast perimeter, and cortical porosity in a time-dependent manner, but did not change the mechanical properties of the femur, possibly because of addition of new bone onto periosteal and endocortical surfaces. Additionally, withdrawal of PTH restored normal cortical porosity and increased maximum torque to failure and stiffness. We conclude that continuous administration of PTH increased cortical porosity in rats without having a detrimental effect on bone mechanical properties. 相似文献
4.
This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of
PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old
rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62
μg/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks
(day 57-112) with either saline or bisphosphonate (risedronate 5 μg/kg twice a week). Two control groups were injected with
vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals
were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal
(35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the
femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced
endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry
defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased
by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal
of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical
strength and competence in these 2-year-old rats.
Received: 13 March 1997 / Accepted: 22 August 1997 相似文献
5.
The short-term effects of estrogen at a single high dose (4 mg/kg body weight/day for 14 days) were determined on tibiae
in the normal (noncastrate) growing male rat. In cortical periosteal bone, at a middiaphyseal site devoid of resorbing activity,
estrogen suppressed periosteal bone formation and apposition rates, resulting in a smaller cross-sectional area. In middiaphyseal
endocortical bone, estrogen had no effect on apposition and formation rates and, because medullary area was unchanged, probably
had no effect on endocortical bone resorption. In the proximal tibial metaphysis, estrogen greatly suppressed longitudinal
growth rate. In a site within the metaphysis adjusted for the effects of growth, cancellous mineral apposition was greatly
reduced by the hormone. Estrogen-treated rats retained more of a fluorochrome label deposited in cancellous bone at the beginning
of the study than vehicle-treated animals, indicating a reduced net bone loss. As a result of the lowered resorption induced
by estrogen, cancellous bone mass (area and perimeter) were both significantly higher in estrogen-treated rats. No evidence
was found for an anabolic action of the hormone in the male rat; indeed, estrogen reduced indices of bone formation.
Received: 31 December 1995 / Accepted: 3 May 1996 相似文献
6.
M. P. Akhter D. M. Cullen E. A. Pedersen D. B. Kimmel R. R. Recker 《Calcified tissue international》1998,63(5):442-449
We investigated the bone response to external loading in C57BL/6J and C3H/HeJ mice, both breeds with low and high bone density,
respectively. An in vivo tibial four-point bending device previously used for application of measured external loads in rats was adapted for mice.
It delivered a uniform medio-lateral bending moment to the region of the tibia located 1–5.5 mm proximal to the tibio-fibula
junction. The right legs of six C57BL/6J [low bone density (LBD)] and C3H/HeJ [high bone density (HBD)] mice were externally
loaded in the device for 36 cycles/day at 2 Hz, 6 days/week for 2 weeks at 9.3 ± 0.9 N force, inducing estimated lateral periosteal
surface compressive strains of 5121 ± 1128 με in C3H/HeJ (HBD) mice (n = 6), significantly higher than the estimated 3988
± 820 με in C57BL/6J mice (n = 6) (mean ± SD). In addition, C3H/HeJ HBD mice (n = 11) were externally sham (pad pressure or
no bending) loaded in the device for 36 cycles/day at 2 Hz, 3 days/week for 3 weeks at 9.3 ± 0.9 N force. Calcein injections
for bone labeling were given at the 10th and 3rd days before sacrifice. At the end of the experiment, all mice were killed
and both tibiae were removed, fixed, embedded, and cross-sectioned through the loaded region. Both tibiae were measured for
marrow area (Ma.Ar), cortical area (Ct.Ar), total area (Tt.Ar), cross-sectional moment of inertia (CSMI), and periosteal and
endocortical woven bone surface (Wo.B/BS), single-labeled surface (sLS), double-labeled surface (dLS), and total formation
surface (FS/BS). Differences in all variables due to breed and loading (both bending and sham-bending) were tested by two-way
analysis of variance (ANOVA) (P < 0.05). Ma.Ar, Tt.Ar, and CSMI were greater in C57BL/6J (LBD) than in C3H/HeJ (HBD) mice. Periosteal and endocortical woven
bone and formation surface were increased significantly more by loading (bending) in C57BL/6J than in C3H/HeJ mice. Periosteal
woven bone response due to sham-bending or sham-loading was significantly lower than due to bending loads in the C3H/HeJ mice.
We conclude that the bone response to external loading is greater in LBD mice than in HBD mice. The high bone density of C3H/HeJ
(HBD) mice is related to breed-specific factors other than the response to loading.
Received: 5 March 1997 / Accepted: 8 April 1998 相似文献
7.
E. A. Pedersen M. P. Akhter D. M. Cullen D. B. Kimmel R. R. Recker 《Calcified tissue international》1999,65(1):41-46
Bone, being sensitive to mechanical stimulus, adapts to mechanical loads in response to bending or deformation. Although
the signal/receptor mechanism for bone adaptation to deformation is still under investigation, the mechanical signal is related
to the amount of bone deformation or strain. Adaptation to changes in physical activity depends on both the magnitude of increase
in strain above average daily levels for maintaining current bone density and the Minimum Effective Strain (MES) for initiating
adaptive bone formation. Given the variation of peak bone density that exists in any human population, it is likely that variation
in levels for MES is, to a considerable degree, inherited and varies among animal species and breeds. This study showed a
dose-related periosteal response to loading in C3H/HeJ mice. The extent of active formation surface, the rate of periosteal
bone formation, and area of bone formation increased with increasing peak periosteal strain. In these mice, the loaded tibia
consistently showed lower endocortical formation surface and mineral apposition rate than the nonloaded bones at every load
level. Although periosteal expansion is the most efficient means of increasing moment of inertia in adaptation to bending,
a dose response increase in endocortical formation would have been predicted. Our characterization of the mouse bone formation
response to increasing bending loads will be useful in the design of experiments to study the tibial adaptive response to
known loads in different mouse breeds.
Received: 17 February 1998 / Accepted: 9 December 1998 相似文献
8.
Yumie Rhee Matthew R Allen Keith Condon Virginia Lezcano Ana C Ronda Carlo Galli Naomi Olivos Giovanni Passeri Charles A O'Brien Nicoletta Bivi Lilian I Plotkin Teresita Bellido 《Journal of bone and mineral research》2011,26(5):1035-1046
The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1‐caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1‐caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1‐caPTHR1 mice with mice lacking the Wnt coreceptor, LDL‐related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1‐Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1‐caPTHR1 mice. In addition, DMP1‐caPTHR1 lacking LRP5 or double transgenic DMP1‐caPTHR1;DMP1‐Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt‐independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research. 相似文献
9.
Y Ma W S Jee Z Yuan W Wei H Chen S Pun H Liang C Lin 《Journal of bone and mineral research》1999,14(3):439-448
Previous reports showed that bone mass and architecture only partially recovered by remobilization (RM) after immobilization (IM)-induced osteopenia, and that parathyroid hormone (PTH) had an anabolic effect on the skeleton. The aim of this study was to determine whether low doses of PTH could restore IM-induced cortical bone loss and whether a combination of PTH plus loading (RM) treatment would be more effective than the PTH in unloaded (IM) limbs. One hundred and sixty 6-month-old rats were divided into aging and IM groups. The right hindlimb of the rat was immobilized by elastic bandage for 18 weeks, and then groups of rats were either kept IM or RM and treated with 30 microgram or 80 microgram of hPTH(1-38)/kg/day for 2, 10, and 20 weeks. Fluorescent-labeled, undecalcified cross-sections of right tibial shafts were studied. We found that RM for 20 weeks after 18 weeks of IM only partially recovered IM-induced muscle weight loss and PTH had no effect on muscle weight in either IM or RM limbs; that RM for 20 weeks after 18 weeks of IM partially restored some minimal cortical width by stimulating periosteal and endocortical bone formation and decreasing endocortical resorption; that PTH treatment of IM limbs completely restored IM-induced cortical bone loss and added extra bone by stimulating bone formation indices on all bone surfaces and depressing bone resorption on endocortical surface; that PTH treatment of RM limbs produced similar anabolic effects as in IM limbs with 30 microgram/kg/day dose but the 80 microgram/kg/day dose-treated limbs had a higher periosteal bone formation rate, which created a larger cross-sectional area, more cortical bone area, and a thicker cortex than the same dose treated IM limbs; and that PTH 80 microgram/kg/day treatment produced more anabolic effect than the 30 microgram/kg/day in both IM and RM limbs. We concluded that reloading the hindlimb by RM after long-term IM could not recover the cortical bone mass. PTH at employed doses was able to completely restore IM-induced cortical bone loss, and this effect was independent of mechanical stimulation. However, when PTH was combined with mechanical loading (RM), a synergistic anabolic effect on periosteal bone formation occurred which increased the cross sectional area that can increase bone strength. 相似文献
10.
Cortical bone loss contributes substantially to the degradation of skeletal integrity associated with aging. However, animal models that closely mimic age-related alterations in cortical bone are limited. The objective of this study was to determine if aged rooster cortical bone demonstrates phenotypic alterations similar to those observed in aged human cortical bone (i.e., expansion of the endocortical and periosteal envelopes and elevated cortical porosity). When compared with young adult roosters, aged roosters demonstrated significant expansion of the endocortical (16%) and periosteal (10%) envelopes, resulting in significantly increased cross-sectional moments of inertia. In addition, aged rooster bone demonstrated significantly elevated cortical porosity (51%) and average area of porosity (83%). We conclude that rooster bone demonstrates age-related adaptations similar to those of humans at both tissue and cellular levels, and may therefore represent a relatively useful, inexpensive animal model for investigating the mechanisms of age-related bone loss. 相似文献
11.
The goal of this study was to evaluate the effects of chronically-elevated male levels of the potent androgen testosterone
on the quality and quantity of both cancellous and cortical bone in a young (mean age 8.0 years), nonhuman female primate
model (M. fascicularis). Thirteen intact female monkeys received continuous testosterone supplementation via subcutaneous implants over a 24-month
period. A group of 16 untreated, intact, age-matched female monkeys served as controls. At sacrifice, the lumbar vertebrae
and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone, respectively,
and compared to the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation
technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences
in %Ca, %P, Ca/P ratio, and mineral content (%Ca + %PO4) between the control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to
identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry
and image analysis. Cross sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical
parameters. A nonsignificant shift in the mineralization profile of the vertebrae was observed whereas there was a significant
shift in the mineralization profile towards more dense bone in the treated femora as compared with controls (P < 0.05). There was no difference in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray
diffraction. There was a trend towards an increase in cancellous bone area (B.Ar.) in the testosterone-treated vertebrae (P= 0.08) as compared with controls. The architecture of the cancellous bone remained nonsignificantly different between the
treatment and control groups as evaluated by image analysis. There was a decrease in osteoid perimeter (P= 0.05) in the experimental group as compared with controls. There was a significant decrease in eroded perimeter measurements
in the experimental group as compared with controls (P < 0.03). Although there was a trend towards an increase in cancellous bone area, mineralization was not significantly different
in the vertebrae of testosterone-treated female monkeys, indicating that the newly-formed bone tissue became relatively normally
mineralized over the two-year period. An increase in bone area, with indices of an overall decreased remodelling pattern as
compared with controls, suggests that cancellous bone in the young, nonhuman female primate had been receptive to supraphysiologic
levels of testosterone supplementation over the two-year period. There was a trend for an increase in cortical bone area and
width with an increased periosteal perimeter in the testosterone-treated group as compare with controls. There was an increase
in intracortical remodelling activity with a significant increase in percent porosity (P < 0.05), osteonal bone (P < 0.05), and mean wall width (P < 0.05) in the testosterone-treated group. In conclusion, the cancellous bone from female monkeys appeared to respond to
the antiresorptive stimulus of male levels of testosterone with significantly diminished turnover parameters in this compartment.
In contrast, the cortical bone compartment responded by displaying significant intracortical remodelling over a two-year period.
Received: 22 December 1995 / Accepted: 3 April 1996 相似文献
12.
《BONE》2014
Cortical bone, the dominant component of the human skeleton by volume, plays a key role in protecting bones from fracture. We analyzed the cortical bone effects of teriparatide treatment in postmenopausal women with osteoporosis who had previously received long-term alendronate (ALN) therapy or were treatment naïve (TN). Tetracycline-labeled paired iliac crest biopsies obtained from 29 ALN-pretreated and 16 TN women were evaluated for dynamic histomorphometric parameters of bone formation at the periosteal, endocortical and intracortical bone compartments, before and after 24 months of teriparatide treatment. At baseline, the frequency of specimens without any endocortical and periosteal tetracycline labeling, and the percentage of quiescent osteons, was higher in the ALN than the TN group. Endocortical and periosteal mineralizing surface (MS/BS%), periosteal bone formation rate (BFR/BS), mineral apposition rate (MAR) and the number of intracortical forming osteons were significantly lower in the ALN-pretreated patients than in the TN group. Following teriparatide treatment, the frequency of endocortical and periosteal unlabeled biopsies decreased; in the ALN-pretreated group the percentage of quiescent osteons decreased and, in contrast, forming and resorbing osteons were increased. Teriparatide treatment resulted in significant increases of MAR in the endocortical, and MS/BS% in the periosteal compartment in the ALN-pretreated group. Most indices of bone formation remained lower in the ALN-pretreated group compared with the TN group at study end. Endocortical wall width was increased in both ALN-pretreated and TN groups. Cortical porosity and cortical thickness were significantly increased in the ALN-pretreated group after teriparatide treatment. Our results suggest that 24 months of teriparatide treatment increases cortical bone formation and cortical turnover in patients who were either TN or had previous ALN therapy. 相似文献
13.
D. Maggio R. Pacifici A. Cherubini G. Simonelli M. Luchetti M. C. Aisa D. Cucinotta S. Adami U. Senin 《Calcified tissue international》1997,60(1):94-97
In order to evaluate in vivo the entity of endosteal and periosteal changes with age in the two sexes, and their relative contribution to age-related
cortical bone loss, we undertook a cross-sectional study on a population of normal Caucasian subjects. The group included
189 women and 107 men who were studied by photodensitometry and radiogrammetry of the second metacarpal bone, derived from
the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older (75 women and 59 men). Metacarpal bone mineral
density (BMD) correlated with age in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men. In the over
65 group, correlation was significant only in women, who underwent an acceleration in the rate of bone loss (1% per year).
Marrow cavity width (M), cortical index at the second metacarpal shaft (MI) and external width (W) all correlated with age
in both sexes, although generally better in the female than in the male sex. M almost doubled from the fourth to the ninth
decade in women and increased 50% in men. In the same age interval, MI showed an annual decrease of 0.49% in females and 0.33%
in males. In the over 65 group, cortical thinning rate was significant in women (0.39% per annum) but not in men (0.14% per
annum), whereas correlation of W was not significant in either sex. Finally, MI correlated with BMD in the whole study population
and in the over 65, with a female prevalence in correlation strength maintained throughout life. The following conclusions
can be derived for metacarpal aging: (1) an acceleration in cortical bone loss occurs in females after age 65; (2) age-related
growth in periosteal diameter, although significant in the whole population, is negligible in the elderly of both sexes; (3)
age-related cortical bone loss is generally more dependent on cortical thinning in women than in men.
Received: 1 November 1995 / Accepted: 23 May 1996 相似文献
14.
Glucocorticoids (GC) are used for the treatment of a wide spectrum of diseases because of their potent anti-inflammatory and immunosuppressive effects, and they are serious and common causes of secondary osteoporosis. Administration of intermittent parathyroid hormone (PTH) may induce formation of new bone and may counteract the bone loss induced by GC treatment. Effects of simultaneous PTH and GC treatment were investigated on bone biomechanics, static and dynamic histomorphometry, and bone metabolism. Twenty-seven-month-old female rats were divided randomly into the following groups: baseline, vehicle, PTH, GC, and PTH + GC. PTH (1-34) 25 mug/kg and GC (methylprednisolone) 2.5 mg/kg were injected subcutaneously each day for a treatment period of 8 weeks. The rats were labeled with fluorochromes 3 times during the experiment. Bone sections were studied by fluorescence microscopy. The PTH injections resulted in a 5-fold increase in cancellous bone volume. At the proximal tibia, PTH induced a pronounced formation of new cancellous bone which originated from the endocortical bone surfaces and from thin trabeculae. Formation and modeling of connections between trabeculae were observed. Similar but less pronounced structural changes were seen in the PTH + GC group. The compressive strength of the cancellous bone was increased by 6-fold in the PTH group compared with the vehicle group. GC partially inhibited the increase in compressive strength induced by PTH. Concerning cortical bone, PTH induced a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group. The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical competence after treatment with PTH + GC. 相似文献
15.
Treatment with parathyroid hormone 1-84 (PTH) or teriparatide increases osteonal remodeling and decreases bone mineral density (BMD) at cortical (Ct) bone sites but may also increase bone size. Decreases in BMD and increases in size exert opposing effects on bone strength. In adult ovariectomized (OVX) rhesus monkeys, we assessed the effects of daily PTH treatment (5, 10 or 25 microg/kg) for 16 months on BMD at the radial, tibial and femoral diaphyses, and on biomechanical properties (3-point bending) of radial cortical bone and the femoral diaphysis. PTH treatment did not affect areal BMD measured by dual-energy X-ray absorptiometry at the tibial diaphysis but caused a rapid, dose-related decrease at the distal radial diaphysis. Peripheral quantitative computed tomography at the radial and femoral diaphyses confirmed a significant PTH dose-related decrease in volumetric Ct.BMD caused primarily by increased cortical area. Significant increases in cortical thickness were the result of nonsignificant increases in periosteal length and decreases in endocortical length. Histomorphometry revealed increased endocortical bone formation at the tibial diaphysis and rib, higher Haversian remodeling at the rib and increased cortical porosity at the rib and tibia. Biomechanical testing at the femoral diaphysis showed that PTH treatment had no effect on peak load, but significantly decreased stiffness and increased work-to-failure (the energy required to break the bone). Similar changes occurred in radial cortical beams but only stiffness was changed significantly. Thus, PTH treatment of OVX rhesus monkeys decreased BMD and stiffness of cortical bone but did not affect peak load, likely because of increased bone size. However, PTH treatment increased the energy required to break the femur making it more resistant to fracture. 相似文献
16.
Clodronate Prevents Bone Loss in Aged Ovariectomized Rats 总被引:1,自引:1,他引:0
K. Kippo R. Hannuniemi L. Laurén Z. Peng P. Isaksson T. Virtamo T. Österman I. Pasanen R. Sellman H. K. Väänänen 《Calcified tissue international》1997,61(2):151-157
The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in
aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed
at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given
subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats
were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth
lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest
dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the
Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses
of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage
of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There
was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal
lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation
of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found.
Received: 28 August 1996 / Accepted: 5 March 1997 相似文献
17.
Iwamoto J Matsumoto H Takeda T Sato Y Liu X Yeh JK 《Calcified tissue international》2008,83(2):121-128
The purpose of the present study was to examine the effects of vitamin K(2) and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K(2), risedronate, or vitamin K(2) + risedronate. At the end of the 8-week experiment, classical bone histomorphometric analysis was performed, and the osteocyte lacunar system and porosity were evaluated on the cortical bone of the tibial diaphysis. GC administration decreased percent cortical bone area and increased percent marrow area as a result of decreased periosteal bone formation, and increased endocortical bone erosion, and increased cortical porosity. Vitamin K(2) prevented a reduction in periosteal bone formation but did not affect percent cortical bone and marrow areas. Risedronate prevented a reduction in periosteal bone formation and an increase in endocortical bone erosion, resulting in prevention of alterations in percent cortical bone and marrow areas. Both vitamin K(2) and risedronate increased osteocyte density and lacunar occupancy and prevented a GC-induced increase in cortical porosity. Vitamin K(2) and risedronate had additive effects on osteocyte density and lacunar occupancy and a synergistic effect on cortical porosity. The present study showed the efficacy of vitamin K(2) and risedronate for bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of GC-treated rats. 相似文献
18.
Sairanen S Kärkkäinen M Tähtelä R Laitinen K Mäkelä P Lamberg-Allardt C Välimäki MJ 《Calcified tissue international》2000,67(2):122-127
To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine
and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were
enrolled in the study. Eighteen started a 4-year supplementation with 0.5 μg of calcitriol daily and 37 served as controls.
Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol
group, but decreased by 1.6% in the control group (P= 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P= 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0.001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P= 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol
treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The
gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of
calcium and suppressed serum PTH levels.
Received: 8 January 1999 / Accepted: 29 February 2000 相似文献
19.
Horikoshi T Endo N Uchiyama T Tanizawa T Takahashi HE 《Calcified tissue international》1999,65(6):447-453
Peripheral quantitative computed tomography (pQCT) is able to evaluate trabecular and cortical bone separately, and to determine
geometric properties from cross-sectional images for noninvasive assessments of mechanical strength. In order to assess the
diagnostic value of pQCT of the femoral neck, 60 healthy women were examined with a new pQCT machine, XCT-3000 (Norland-Stratec,
Germany), which is suitable for direct measurement of the hip. The region of interest chosen was the center of the femoral
neck. pQCT of the distal radius and dual energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck were also
performed.
The study demonstrated that total bone mineral density (BMD) (femoral MD) and trabecular BMD (femoral-TBD) decreased with
advancing age. Percent cortical area showed a small but significant decrease with advancing age and % trabecular area increased
slightly. Both the endosteal perimeter and the periosteal perimeter were relatively constant with aging. Bone strength index
(BSI) and stress-strain index (SSI), which reflect the mechanical strength of bone, declined with advancing age, especially
after menopause. Femoral TBD correlated strongly with femoral neck BMD by DXA and L2-L4 BMD by DXA but femoral-CBD did not
correlate with femoral neck BMD by DXA. Volumetric BMD of the femoral neck and distal radius were closely correlated. It is
concluded that (1) cortical thinning occurs with aging by endocortical resorption and loss of femoral-TBD; (2) loss of femoral-CBD
occurred at a slower rate than radial CBD, perhaps due to the weight-bearing effect; (3) biomechanical parameters such as
the BSI and SSI may reflect increasing fragility of the femoral neck in pre- and postmenopausal women; (4) pQCT of the femoral
neck had diagnostic value at least equivalent to that of DXA or pQCT of the distal radius.
Received: 23 June 1998 / Accepted: 1 July 1999 相似文献
20.
Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia
Hiroshi Hagino Toru Okano Mohammed P. Akhter Makoto Enokida Ryota Teshima 《Journal of bone and mineral metabolism》2001,19(4):244-250
Cortical bone responses following administration of parathyroid hormone (PTH) were evaluated using a four-point bending
device to clarify the relationship between the effect of PTH and mechanical loading. Female Wistar rats, 36-months-old, were
used. Rats were randomized into three groups (n = 10/group), namely PTH-5 (5 μg PTH/kg body weight), PTH-30 (30 μg PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH
(1–34)) was injected subcutaneously three times/week for 3 weeks. Loads on the right tibia were applied in vivo at 29.1 ±
0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks using four-point bending. The administration of PTH and tibial mechanical
loading were performed on the same day. After calcein double labeling, rats were killed and tibial cross-sections were prepared
from the region with maximal bending at the central diaphysis. Histomorphometry was performed over the entire periosteal and
endocortical surfaces of the tibiae, dividing the periosteum into lateral and medial surfaces. The in vivo average peak tibial
strains (predicted) on the lateral periosteal surface were 1392.4, 1421.8 and 1384.7 μstrain in PTH-v, PTH-5 and PTH-30 groups,
respectively, showing no significant difference among the three groups. Significant loading-related increases in the bone
formation surface, mineral apposition rate, and bone formation rate were observed at the periosteal and endocortical surfaces.
Significant differences between PTH groups were also seen. Interaction between mechanical loading and PTH was significant
at both periosteal and endocortical surfaces. It is concluded that PTH has a synergistic effect on the cortical bone response
to mechanical loading.
Received: October 4, 2000 / Accepted: January 12, 2001 相似文献