Skeletal alterations in hypophysectomized rats: II. A histomorphometric study on tibial cortical bone

Background: Pituitary hormones play an important role in bone growth, modeling, and remodeling. The purpose of this study is to examine the effect of hypophysectomy (HX) on tibial cortical bone with histomorphometry. Methods: Forty-Five female Sprague-Dawiey rats, at 3 months of age, were hypophysectomized or served as intact controls. They were sacrificed at 0, 2, and 5 weeks after the surgery. Cortical bone histomorphometry was performed on double-fluorescent-labeled 30-mcm-thick sections of the tibial shaft. Results: The dry weight and density of tibial diaphysis and the cortical bone area of the tibial shaft in the HX rats were significantly lower (P<0.05) than that of the age-matched intact rats, but did not differ between the HX and basal control rats. The dynamic data show that the bone formation parameters (labeled surface, mineral apposition rate, and bone formation rate) were profoundly decreased (P<0.01) on both the periosteal and endocortical surfaces in the HX rats as compared with the age-matched intact rats at the 2 and 5 weeks. However, the decrease in the labeled surface was much less on the endocortical envelope than on the periosteal envelope in the HX rats. Although no significant change was detected in the medullar size between the HX and age-matched intact rats, the eroded surface on the endocortical surface was greater (P<0.05) in the HX rats than in the intact rats at either time point. Conclusions: Hypophysectomy-suppressed, radial growth-dependent bone gain without a bone loss in the tibial shaft of the young rat. This is associated with decreased modeling-dependent bone formation. A greater eroded surface on the endosteum did not affect the marrow size at 5 weeks after hypophysectomy. © 1995 Wiley-Liss, Inc.     

Adaptation of cancellous bone to aging and immobilization in growing rats

Two-and-half month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 μm sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area refent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats.© Willey-Liss, Inc.     

增龄及去睾丸大鼠的骨形态计量学研究

目的探讨4月龄雄性大鼠增龄及去睾丸后不同部位骨量的变化,了解两者对成熟期大鼠骨代谢的影响。方法30只4月龄SD雄性大鼠,随机分为基础对照组、年龄对照组和去睾丸组,同等条件下饲养90d。90d后取胫骨上段、腰椎和胫骨中段行不脱钙制片进行骨形态计量学观察。结果年龄对照组(7月龄)与基础对照组(4月龄)比较,胫骨上段骨形成和骨吸收都下降(骨小梁面积百分率减少28.6%);腰椎骨形成和骨吸收有下降趋势。去睾丸组与年龄对照组比较,胫骨上段骨量进一步丢失(骨小梁面积百分率减少57.1%);腰椎骨量也下降,表现为骨形成下降,骨吸收增加;胫骨中段皮质骨外膜的骨形成动态参数如矿化沉积率、骨形成率下降(P﹤0.05),内膜骨形成和吸收均有增加趋势。结论4月龄大鼠增龄及去睾丸90d均能引起大鼠骨量丢失。胫骨上段出现较早和更严重,腰椎和胫骨中段皮质骨丢失表现滞后。去睾丸后的大鼠主要表现为松质骨的骨量在增龄基础上进一步丢失。     

Iron lactate-induced osteopenia in male Sprague-Dawley rats.

Osteopenia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 2 or 4 weeks. Blood chemistry, urinalysis, and bone histomorphometry of the proximal tibial metaphysis were performed. Urinary pyridinoline and deoxypyridinoline and the osteoclast number per bone surface were selected for the measurement of dynamic resorption. The osteoclast surface, eroded surface, and osteoblast surface increased at both ends of the exposure periods, and bone resorption and formation both increased. The bone volume, trabecular thickness, and trabecular number decreased, and the secondary spongiosa of proximal metaphysis showed a marked bone loss. However, no mineralization defect was observed. At the end of the 2-week exposure period, biomarkers of osteoclasts and osteoblasts had increased the most, and the osteoblast surface, osteoclast surface, and osteoclast number per bone surface increased with prolonged exposure. The pathological changes of the bone lesion in iron lactate-overloaded rats were similar to those in rats of the osteoporotic model, because they consisted of changes reflecting the increase of bone resorption and formation without an osteomalacic change. However, the decline of serum parathyroid hormone (PTH) levels was different from that of the osteoporosis model rat. We concluded iron-induced bone lesions probably differ from those of low turnover bone diseases.     

低钙饮食对雄性大鼠松质骨和密质骨影响的比较

目的　比较低钙饮食对大鼠胫骨上段松质骨和胫骨中段密质骨的影响。方法　实验用 3月龄SD雄性大鼠 2 0只 ,随机分为正常年龄对照组 (control)、极低钙组 (VLCD)、低钙组 (LDC)。Control组饲养正常饲料 ,VLCD组饲养 0 0 1%含钙饲料 ,LCD组饲养 0 3%含钙饲料。 3个月后取各组大鼠左侧胫骨近心端和中段 ,行不脱钙骨制片 ,进行骨组织形态计量学测量。结果　松质骨 :与对照组相比 ,VLCD组和LCD组的大鼠骨量减少 ,骨小粱面积百分率 (%Tb .Ar)分别减少 5 7% (P <0 0 1)和4 0 % (P <0 0 5 ) ,骨结构参数变差 ,代表骨形成指标荧光周长百分数 (L .Pm % )、矿化沉积率 (MAR)、骨形成率 (BFR/BV)有增加的趋势。VLCD组骨吸收参数骨小粱周长破骨细胞数量 (N .OC/Tb .Pm)有显著增加 ,呈现骨高转化的改变。密质骨 :与对照组相比 ,VLCD组和LCD组的骨量有减少的趋势 ,骨外膜面代表骨形成的参数增加 ,骨内膜代表骨形成的参数变化不大 ,骨内膜骨吸收增加。结论　低钙饮食使骨量减少 ,但不同的部位有不同的骨丢失速度     

Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: A comparative histomorphometric study on the cancellous bone formed before,during, and after treatment

To study the anti-resorptive effects of zoledronate and pamidronate on growing long bones we have performed a histomorphometric analysis of the three regions of the proximal tibial cancellous bone of bone formed before, during, and after drug treatment. Male rats (190–220 g) were treated subcutaneously for 10 days with zoledronate (0.028–2.8 μg/kg) or pamidronate (3.7–370 μg/kg) and sacrificed 5 days later. To delineate the three regions of cancellous bone, and for dynamic bone histomorphometry, calcein and demeclocycline were injected at various times. Both bisphosphonates caused a dose-dependent suppression of cancellous bone turnover and resorption to produce an increase in cancellous bone, but zoledronate was 100 times more potent than pamidronate. The increase in the bone amount and connectivity was more pronounced in the bone formed during treatment where transient bone resorption and normal bone formation led to a positive bone balance. In the bone formed before treatment, inhibition of bone resorption associated with reduced bone formation produced a net gain in amount of bone. Although both bone regions showed a positive bone balance, more bone accumulated in the bone formed during treatment probably because its trabecular bone surface was three times greater. In the primary spongiosa formed after treatment, a moderate increase in the bone amount and connectivity was observed only at the highest dose of both bisphosphonates. The bone formed before, during, and after treatment with bisphosphonates responds differently due to differences in bone architecture, rates of modeling and remodeling, and period of drug exposure. Anat. Rec. 249:458–468, 1997. © 1997 Wiley-Liss, Inc.     

Adaptation of cancellous bone to aging and immobilization in growing rats.

Two-and-half-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 microns sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats.     

去睾丸大鼠骨形态计量学的研究

目的：探讨4月龄雄性大鼠去睾丸后骨量的变化，重点比较松质骨和皮质骨骨代谢的变化。方法：20只4月龄SD雄性大鼠，随机分为假手术组（A组）和去睾丸组（B组），同等条件下饲养90d后，取腰椎和胫骨中段行不脱钙制片进行骨形态计量学观察。结果：去睾丸组与假手术组比较，前者腰椎松质骨吸收增加、骨形成下降（P〈0．05），出现明显骨质疏松；皮质骨外膜的骨形成动态参数如矿化沉积率、骨形成率下降（P〈0．05），内膜骨形成和吸收均有增加趋势。结论：去睾丸90d能使大鼠松质骨出现骨质疏松，皮质骨丢失不如松质骨显著。松质骨对去睾丸敏感性比皮质骨高。     

Adaptation of cancellous bone to aging and immobilization in the rat: a single photon absorptiometry and histomorphometry study

Nine-month-old female rats were double-labeled with bone markers and subjected to right hindlimb immobilization or served as control for 0, 2, 10, 18, or 26 weeks. The right limb was immobilized against the abdomen, thus unloading it, while the left limb was overloaded during ambulation. Single photon absorptiometry and cancellous bone histomorphometry were performed on dissected intact femur and 20-microns-thick undecalcified specimens of the proximal tibial metaphysis. In the unloaded limb, immobilization-induced muscle and cancellous bone loss occurred rapidly before 10 weeks and stabilized at 50% less bone mass after 18 weeks. Unloading caused a negative bone balance from a combination of elevated bone resorption and depressed bone formation. At 2, 10, and 18 weeks of immobilization, the ratios of bone resorption to bone formation surfaces were 1.6, 1.5, and 1.3, respectively; at 26 weeks, the ratio was 1. The bone loss was accompanied by poorer trabecular architecture (trabecular number decreased and trabecular separation increased), reaching the maximum at 18 weeks and stabilizing thereafter. These observations are in general agreement with Frost's postulate for mechanical effects on lamellar bone remodeling, and the findings on disuse osteoporosis in man. Therefore, the one-legged immobilization model can be useful in studies of the mechanisms of structural adaptation to mechanical usage.     

Short-term healing kinetics of cortical and cancellous bone osteopenia induced by unloading during the reloading period in young rats

 We investigated the short-term recuperation of bone mass during skeletal reloading after a period of unloading in young rats. One hind limb of 4-week-old rats was either unloaded irreversibly by sciatic neurectomy, or unloaded reversibly by external fixation. Other animals were sham-operated. After 9 days, the fixation-unloaded limbs were reloaded for 1–3 weeks and were compared with the hind limbs of age-matched unloaded (neurectomized) and sham-operated controls. Cortical and cancellous bone mass was measured using ashing and histomorphometry. Cortical bone mass (expressed as femoral dry and ash weight and tibial cortical bone area) was reduced in both unloaded groups and was accompanied by production of hypomineralized bone, as shown by a reduction in the percent ash of the dry weight. Cancellous bone mass (expressed as bone area and surface at the tibial metaphysis) was also reduced in both unloaded groups. Cortical bone mass deficit was greater in the fixation group than in the neurectomy group. Thereafter it increased in the neurectomy group despite a normal longitudinal growth rate, but returned to age-matched values in the reloaded group by 3 weeks. The changes in tibial cancellous bone mass were more pronounced but followed a similar pattern and normalized by 2 weeks. These data demonstrate that total unloading produced by external fixation causes a greater degree of bone mass deficit than partial unloading (produced by neurectomy); the rate of bone loss during unloading in the rat hind limb is more rapid than its recovery during reloading; and cancellous bone recuperates during the reloading phase faster than does cortical bone. Received: 11 February 1997 / Accepted: 28 May 1997     

骨形态计量学观察睾酮对雄性去势大鼠皮质骨的影响

目的通过骨形态计量方法观察雄激素替代疗法对去睾丸大鼠皮质骨代谢的影响。方法30只4月龄SD雄性大鼠,随机分成基础对照组(A组、实验开始时处死),年龄对照组(B组)、去睾丸组(C组)和去睾丸加睾丸酮组(D组),B组和C组生理盐水5ml·kg-1·d-1,D组甲基睾丸酮片1.8mg·kg-1·d-1,灌胃90d。实验结束,处死全部大鼠,取胫骨中段进行不脱钙骨制片,用计算机全自动图象分析系统进行骨组织形态计量学分析。结果去睾丸后皮质骨静态参数如截面总面积、髓腔面积等无明显变化,动态参数骨外膜骨形成降低(P<0.05),内膜骨形成和吸收均有增加趋势。睾酮则使去睾丸大鼠皮质骨的静态参数有增加趋势,促使骨外膜形成增加,减少内膜骨吸收(P<0.05),对内膜骨形成影响不大。结论睾酮补充治疗短期内能对抗去睾丸引起的大鼠皮质骨内外膜的代谢变化,维持正常的皮质骨结构。     

Iron lactate-induced osteomalacia in association with osteoblast dynamics

Osteomalacia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 13 weeks. The histopathology and histomorphometrical dynamics of osteoblasts under this condition were examined. Bone histomorphometry of the proximal tibial metaphysis revealed that the osteoblast surface, osteoid volume, osteoid surface and labeled surface ratio, which are the parameters of bone formation had increased. The blood chemistry revealed the greatest elevation in the osteocalcin level; however, the parathyroid hormone (PTH) secretion and inorganic phosphorus level were very low. From the serum biochemical, histopathological and histomorphometrical findings, the bone lesion in iron lactate-overloaded rats was considered to be similar to low turnover osteomalacia showing decreased trabeculae in secondary spongiosa and increased lamellar osteoid. Furthermore, an iron-positive reaction was detected at the interface between osteoid and mineralized bone. In the bone lesions induced by chronic iron overload, osteoblast recruitment exceeded that of mineralization or, alternatively, the iron within osteoblasts along the trabecular bone suppressed the remodeling and led to an increase in osteoid thickness.     

Comparison of osteopenic changes in cancellous bone induced by ovariectomy and/or immobilization in adult rats

Background: Ovariectomy (OVX) and immobilization (IMM) in rats are useful models of osteopenia, replicating some aspects of osteoporosis in humans. The purpose of this study was to compare changes in cancellous bone after OVX and/or IMM. Methods: Differences in cancellous bone were determined at 6 and 12 weeks after OVX or IMM. Comparisons were also made when rats were ovariectomized or immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized (IMM/OVX), respectively, for 6 more weeks. The femurs were used to determine bone mineral content (BMC) using single photon absorptiometry (SPA) and for scanning electron microscopy (SEM). Tibias were collected for microradiography, image analysis, and histomorphometry of metaphyseal cancellous bone. Results: Six and 12 weeks after OVX, there was less cancellous bone mass, compared with controls, as indicated by SPA, SEM, microradiography, image analyses, and histomorphometry. Bone was lost primarily from the central metaphyseal regions in the OVX animals, whereas the loss occurred throughout the metaphyses in the IMM animals. There were more rodlike bone spicules and fewer platelike trabecule in the OVX and IMM groups compared with controls. Differences in the structural aspects of the cancellous bone, including differences in the types of bone struts and marrow star volumes, indicated less trabecular connectivity and greater trabecular separation in the OVX and IMM animals, compared with controls. Endochondral growth indices in the IMM groups tended to be less, whereas the OVX groups tended to be greater than controls. Cancellous bone formation rates were generally greater in the OVX groups but less in the IMM groups compared with controls. Osteoclastic resorption surfaces were substantially elevated in the IMM and OVX groups, particularly the IMM groups. Changes reflecting OVX and IMM, independently, were apparent in the OVX/IMM and IMM/OVX groups and indices of osteopenia were different from controls, including less bone mass, trabecular connectivity, and greater trabecular separation, bone turnover rates, and osteoclastic surface. Conclusions: These results demonstrate differences in the osteopenic changes that occur in cancellous bone following OVX or IMM. The changes were generally more dramatic in the IMM than in the OVX animals. When OVX and IMM were applied in combination, the osteopenic changes are particularly severe, emphasizing the importance of mechanical usage even with a deficiency of gonadal hormones. © 1994 Wiley-Liss, Inc.     

Rapid determination of cancellous bone mineral loss in ovariectomized rats by a subtraction technique

We present a rapid technique for determining cancellous bone mineral changes in small experimental animals. We used the distal centimeter of the right femur from ovariectomized (OX) (N = 30) and shamovariectomized (ShOX) (N = 28) rats, aged 90 days at surgery and killed at times from 125-540 days postsurgery. We used dual photon absorptiometry to scan the segment three times: intact, after parasagittal splitting, and after removing all cancellous bone. We equated the difference between the second and third scans to cancellous bone mineral content (Cn.BMC). To validate this, we compared it with histomorphometrically determined bone volume (BV/TV) of the proximal tibial metaphysis of the same rat. Parasagittally splitting the segment removed no detectable mineral. OX rats had 40% less Cn.BMC than ShOX rats. However, OX rats had 80% lower BV/TV than ShOX rats. The subtraction technique not only makes a rapid, reasonable assessment of cancellous bone loss in OX rats but permits a smaller sample size than histomorphometry. The histomorphometric technique finds a greater difference between OX and ShOX rats because it examines a region where cancellous bone loss is more marked than does the scanning technique. The current technique measures bone of not only the central secondary spongiosa but also the juxtacortical region and the primary spongiosa, where OX-related differences are less prominent. The principles of this subtraction technique proved workable. However, for the future, we recommend a two-scan technique using a dual energy X-ray scanner. It is likely to take only 20-30 min per specimen to assess cancellous bone mineral.     

Analysis of the effects of growth hormone, exercise and food restriction on cancellous bone in different bone sites in middle-aged female rats

The aim of this study is to determine the effects of growth hormone (GH), exercise (EX), GH+EX and food restriction on cancellous bone in middle-aged female rats. Female F344 rats aged 13 months were divided into (1) age-matched controls; (2) GH treated (2.5 mg/kg. 5 day/week); (3) EX (voluntary wheel running); (4) GH+EX; and (5) food restricted (FR) (fed 60% of the ad libitum food intake). The animals were treated for 18 weeks, at the end of which they were sacrificed. Cancellous bone and cortical bone in the fourth lumbar vertebra, proximal tibial metaphysis (PTM), distal femoral metaphysis (DFM) and femoral neck (NF) were analyzed using peripheral quantitative computerized tomography (pQCT) densitometry. Growth hormone increased cancellous bone area, cancellous bone mineral content, cortical bone area and cortical bone mineral content in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly after GH treatment. Exercise increased the cancellous bone area in the vertebra, PTM and DFM. Cortical bone area and cortical bone mineral content increased after EX in the vertebra, PTM, DFM and NF. No significant change was seen in the tibial muscle wet weight after EX. Growth hormone+EX increased cancellous bone area in the vertebra PTM and DFM but had no effect in neck of the femur. Cancellous bone mineral content, cortical bone area and cortical bone mineral content increased with GH+EX in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly with GH+EX. Food restriction decreased cancellous bone area and cancellous bone mineral content in all the bones studied. The decrease was statistically significant only at the distal femoral metaphysis. The tibial muscle wet weight decreased when compared with the age-matched control, but this decrease was not statistically significant. We conclude that the effect of the dose of GH used and the levels of voluntary wheel running EX used increased cancellous bone in intact rats; the effect of GH is much greater and different bones respond with varying intensities. The effects of combined treatment of GH and EX on cancellous bone are not always significantly higher than those of GH alone. FR at the level studied has a mostly negative effect on cancellous bone.     

低蛋白饲料对雄性大鼠胫骨上段和腰椎的骨计量学研究

目的比较低蛋白饲料对大鼠胫骨上段和腰椎松质骨的影响。方法12只3月龄SD雄性大鼠,随机分成正常对照组、低蛋白组LPD(Pr8%)。实验90d时取胫骨上段和第五腰椎行不脱钙骨制片,骨组织形态计量学测量。结果与对照组比,LPD组胫骨上段骨小梁面积百分率(%Tb.Ar)减少(P<0.01),骨结构变差,骨转换率下降;而腰椎松质骨各项指标的变化均无统计学意义。结论低蛋白饲料诱导大鼠胫骨上段骨丢失,而对腰椎骨丢失无明显影响。     

Adaptation of cancellous bone to overloading in the adult rat: a single photon absorptiometry and histomorphometry study

Nine-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 2, 10, 18, and 26 weeks and were double-labeled with bone markers. The right limb was immobilized against the abdomen and considered unloaded, while the left limb was overloaded during ambulation. Single-photon absorptiometry was performed on intact femur; static and dynamic histomorphometry were performed on 20 microns thick undecalcified frontal sections of the proximal tibial metaphysis. Changes in the continuously overloaded limb was compared to that in both limbs of age-matched control animals. Single-photon absorptiometry detected increases of bone mineral density of +6%, +6%, and +5% in the proximal and +9%, +7%, and +10% in the distal femoral metaphyses after 10, 18, and 26 weeks of continuous overloading. Morphometrically, significant changes occurred in proximal tibial metaphyses compared to age-matched controls: trabecular area increased +41% and +45%, trabecular number increased +31% and +32%, and trabecular separation decreased -30% and -31% after 18 and 26 weeks of overloading. A significant increase in mineral apposition rate (+38%) was found only at 26 weeks of overloading. Insignificant decreases in both eroded and labeled bone surfaces occurred at all time periods. The histomorphometric changes indicated that increased cancellous bone mass was caused by an increase in bone formation activity (i.e., increases in mineral apposition and bone formation rates) and a decrease in remodeling space (i.e., decrease in bone eroded surface). These findings indicate that the adult skeleton can quickly adapt to the increased biomechanical needs by increasing its cancellous bone mass with an adequate structural pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats.

The effects of daily prostaglandin E2 (PGE2) treatment (on) and PGE2 treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/d for 60, 120, and 180 days, and the second group of rats were given PGE2 for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE2 treatment elevated cancellous bone mass of lumbar vertebral bodies 26-60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE2 treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near age-related controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE2-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE2 treatment than the fourth lumbar vertebral body.     

Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats

The effects of daily prostaglandin E₂ (PGE₂) treatment (on) and PGE₂ treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0,1,3, and 6 mg PGE₂ /kg/dfor 60, 120, and 180 days, and the second group of rats were given PGE₂ for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE₂ treatment elevated cancellous bone mass of lumbral vertebral bodies 26–60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE₂ treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near agerelated controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE₂-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE₂ treatment than the fourth lumbar vertebral body.© Willey-Liss, Inc.     

损毁弓状核对大鼠骨组织形态计量学的影响

目的： 研究损毁下丘脑弓状核对大鼠骨组织形态计量学的影响。 方法： SD大鼠于出生后第1、3、5、7、9 d皮下注射10％谷氨酸单钠(MSG)（4 g/kg BW），对照组同法注射等体积生理盐水，并设MSG毒性对照组，于70 d龄同法注射MSG，各组大鼠皆存活至160 d。用3％戊巴比妥钠腹腔麻醉，用4％多聚甲醛经左心室行全身灌注，取脑作下丘脑弓状核冠状面切片，HE染色。取右侧胫骨常规脱钙，石蜡包埋，矢状面连续切片，胶原特殊染色，用于显示骨小梁结构。HE染色用于破骨细胞计数。图像分析仪对弓状核正中隆起切面和骨组织进行照片和计量。用放免法测血清中GH（生长素）、E2（雌二醇）和T（睾酮）含量。 结果： MSG大鼠弓状核神经细胞数量显著减少，GH和E2、T水平明显降低，骨量显著减少，发生骨质疏松，NS组和MSG毒性对照组弓状核、GH、E2、T和骨组织无明显改变。 结论： ①MSG大鼠骨组织的改变不是MSG对垂体和骨组织的毒性作用所致；②下丘脑弓状核参与骨代谢的调控；③通过GH和性激素作用是ARC参与骨代谢调控的重要途径。