雌激素对骨折愈合过程中骨形态发生蛋白4 mRNA表达的影响

目的：探讨骨折愈合过程中雌激素对骨形态发生蛋白4(bone morphogenetic protein-4，BMP—4)基因表达的影响，了解BMP—4在骨折愈合过程中的作用。方法：180只雌性SD大鼠随机分成4组。OVXE1组为卵巢切除后1d开始雌激素替代治疗；OVXE2组为骨折后雌激素替代组；OVX组为雌激素缺乏组；SO组为正常对照组。所有动物在一侧胫骨中段造成骨折模型；各组动物分别在骨折后1、2、3、4、5、6、7、14、28d处死取材；标本制成石蜡切片，用地高辛标记的BMP-4 cDNA探针进行原位核酸分子杂交；实验结果经计算机图像处理系统分析并作统计学处理。结果：各组动物骨折后1—3d，骨折周围血肿及组织内BMP—4 cRMA检测为阳性，从第4d开始为阴性。OVX组的BMP—4 mRNA表达较任何一组都明显增多(P＜0．05)；SO组及OVXE1组最少。结论：BMP—4主要在骨折愈合早期起作用。雌激素对BMP-4基因的表达有抑制作用，将BMP—4基因的表达控制在一定程度内可能是雌激素调节骨折愈合的一种方式。     

卵巢去势对骨折愈合超微结构和BMP-4基因表达的影响

目的:探索雌激素对骨折愈合超微结构和骨形态发生蛋白-4(BMP-4)基因的定位分布的影响.方法:选用健康SD大鼠,随机分为卵巢切除(OVX)组和假手术对照(S)组.制成胫骨骨折愈合模型并分别于骨折后不同时间点处死取材.通过电镜观察超微结构变化;采用原位杂交方法研究卵巢去势对BMP-4基因表达影响.结果:(1)OVX组在骨痂形态及成骨细胞和破骨细胞活性与S组比较有明显差异;(2)骨折后1～3d BMP-4m RNA表达强度:S组＜OVX组.结论:雌激素缺乏时,骨转换加快,从而BMP-4表达增多.雌激素在骨折愈合过程中起重要作用.     

Early period of fracture healing in ovariectomized rats

Objective. To evaluate the effect of osteoporosis on fracture healing through observing the hlstomorphological changes, bone mineral density of callus and expression and distribution of transforming growth factor beta 1 (TGF-β1 ), basic fibroblast growth factor (bFGF)and bone morphogenetic protein.2 (BMP-2) in ovariectomized rats. Methods. Sixty female Sprague-Dawley rats ( aged 12 weeks and weighing 235 g on average ) were randomly divided into an ovariectomized (OVX) group (n =30) anda sham-operated (SO) group ( n = 30). Ovariectomy was performed in the OVX rats and same incision was made in the SO rats. Three months later, fracture of femoral shaft was made on all the rats. Then they were killed at different time points. Callus formation was observed with histological and imethods. Results: A reduction in callus and bone mineral density in the healing femur and a decrease of osteoblasts expressing TGF-β1 near the bone trabecula were observed in the OVX rats 3-4 weeks after fracture.Histomorphological analysis revealed a higher content of soft callus in the OVX rats than that in the SO rats.Immunohistochemistry results showed that no remarkable difference in expression and distribution of BMP-2 and bFGF between the OVX and SO groups was found. Conclusions: Osteoporosis influences the quantity and quality of callus during the early period of fracture healing. The effect of osteoporosis on fracture healing has no relationship with the expression of BMP-2 or bFGF. The decreased expression of TGF-I31 in osteoblasts may cause a decrease in quality of facture healing after osteoporosis.     

Relationship among bone mineral density, collagen composition, and biomechanical properties of callus in the healing of osteoporotic fracture

Objective： To study the change and relationship among bone mineral density （BMD）, collagen composition and biomechanical properties of the callus in the healing process of osteoporotic fracture. Methods： The osteoporotic rat model and fracture model were established through bilateral ovariectomy （OV＇X） and osteotomy of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats were randomly divided into OVX group and sham group. With the samples of blood and callus, roentgenoraphic and histological observation were performed for the assessment of the healing progress of the fracture, and the serum concentration of TRAP-5b, proportion of type I collagen, BMD and biomechanical properties of the callus were measured. Results： The OVX group experienced a significant delay of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX group was much higher than that in the sham group after the operation （P 〈 0.05）, but the difference at the same time point after fracture was smaller than that before fracture （P 〈 0.05）. The BMD of the callus in both groups reached the peak value at the 6 th week after fracture while the proportion of the type I collagen and the biomechanical strength reached the peak at the 8th week. Conclusions. The deficiency of estrogen after the ovariectomy could induce the up-regulation of the osteoclasts activities, whereas the potency of further activation after fracture was depressed. Although the synthesis of collagen together with its mineralization determines the biomechanical properties of new bone, the accumulation of collagen could be assessed as an index in the prediction of biomechanical strength of bones independent of the bone mineral deposition.     

卵巢切除对大鼠关节内骨折后软骨愈合的影响

目的探讨骨质疏松对大鼠关节内骨折后软骨愈合的影响。方法16只4.5月龄的雌性SD大鼠分为两组,实验组行双侧卵巢切除,对照组施行假手术。10周后,经手术制造右胫骨平台内髁劈裂骨折,克氏针交叉内固定。术后大鼠自由活动,6周后全部处死,标本行大体和组织学观察。结果所有标本骨折均愈合。实验组胫骨平台内侧关节软骨多不平整伴轻度塌陷,软骨裂隙依稀可辨,色泽稍暗;对照组内侧关节软骨多平整光滑,软骨裂隙消失。HE染色光镜观察发现,实验组关节软骨裂隙处可见较多纤维组织,透明样软骨呈岛状散在分布于关节表面;对照组多为透明样软骨,细胞排列较规则,但未见明显分层及潮线。结论卵巢切除导致大鼠骨质疏松,延缓了关节内骨折后软骨愈合的进程,且软骨愈合质量较差。     

Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats

Summary

Fractures in post-menopausal osteoporosis cause significant morbidity; however, animal models for post-menopausal fracture healing lack the effect of ageing. Therefore, we developed a model using aged animals with chronic oestrogen deficiency, which demonstrates inferior fracture repair (decreased healing histologically, bone mineral density and content and strength). This novel model may help develop molecular strategies for osteoporotic fracture repair.

Introduction

The femur is susceptible to damage by both systemic conditions such as osteoporosis and locally by traumatic injury. The capacity for fracture repair decreases with age, while the risk of fracture increases. As studies of osteoporotic fracture healing in rats traditionally use a period of 3 months or less of oestrogen deficiency prior to fracturing, we aimed to establish a osteoporosis model in rats with chronic oestrogen deficiency by 12 months to better mimic human female osteoporosis.

Methods

Seventy female Sprague–Dawley rats (10 weeks old) were ovariectomised or sham operated and housed for 12 months. The right femur was fractured by way of an open osteotomy and fixed with an intramedullary Kirschner wire. Animals were sacrificed at 1, 3 and 6 weeks for radiography, dual-energy X-ray absorptiometry, tensile testing and histology.

Results

Bone mineral density and bone mineral content were lower by 60 and 63 %, respectively, (p?<?0.05) in the bilaterally ovariectomized (OVX) groups than those in the sham groups at 6 weeks in the right fractured femurs. Maximum breaking force of the OVX group was lower than that of the sham group, with the greatest difference seen at 6 weeks following osteotomy. Histologically, the OVX groups demonstrated a delay in cellular differentiation within the fracture callus and the presence of bone resorption. The sham animals had a superior histological healing pattern with an Allen score of 4 at 6 weeks compared to a score of 1 for the OVX groups (p?<?0.01).

Conclusions

Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.     

雌激素对实验性骨质疏松症骨折愈合的影响

目的 研究不同剂量的雌激素对卵巢除后发生骨质疏检习股骨骨折愈合的影响。方法 成年ｂａｌｂ／ｃ小鼠卵巢除后３个月开始制作右股骨中段闭合骨折模型,同一天开始皮下注射高低两种剂量雌激素,小鼠于折骨后５、１０、１５、２０、３０天分批处死,采用Ｘ射线、骨痂称重、骨痂中钙盐沉积率测定、组织学检查、血清生化检测等方法研究雌激素对骨折愈合的影响,并和卵巢除组、假手术对照组进行比较。结果 卵巢除组骨痂较小,     

葛根素对去卵巢大鼠骨质疏松性骨折骨痂血管形成的影响

目的探讨葛根素对骨质疏松性骨折骨痂血管形成的影响及对骨折愈合的作用。方法60只雌性SD大鼠分为3组:假手术组、去势组、葛根素组,20只/组,去卵巢大鼠骨质疏松性骨折动物。观察评估骨折愈合情况,检测血清BMP-2和VEGF浓度,观察骨痂形态结构变化,检测骨痂BMP-2和VEGF表达。结果去势组较假手术组骨折愈合评分、血清BMP-2和VEGF浓度、骨痂BMP-2和VEGF表达、微血管数均显著降低(P<0.05),葛根素组较去势组上述指标均显著增高(P<0.05)。去势组骨痂组织可见少量骨小梁,生长稀疏,排列紊乱,大量纤维软骨细胞等纤维组织,成骨细胞及新生小血管少见;葛根素组骨痂可见较多骨小梁,生长较旺盛,排列有序,可见较多成熟的骨细胞,新生微小血管较多。结论葛根素通过介导去卵巢大鼠骨质疏松性骨折骨痂BMP-2和VEGF表达,促进骨痂血管形成,改善骨组织形态学,加快骨折愈合。     

Low intensity pulsed ultrasound enhances fracture healing in both ovariectomy‐induced osteoporotic and age‐matched normal bones

Low intensity pulsed ultrasound (LIPUS) was proven to enhance fracture healing effectively. Similar effect of LIPUS on accelerating the osteoporotic fracture healing was therefore hypothesized. The normal and osteoporotic fracture healings under this non‐invasive biophysical intervention of LIPUS were compared and investigated. Closed femoral fracture procedures were performed on 120 Sprague–Dawley rats, in which 60 of them were ovariectomized (OVX). The rats were randomly assigned into four groups: sham OVX with treatment (Sham‐T), sham OVX control (Sham‐C), OVX with treatment (OVX‐T) and OXV control (OVX‐C). LIPUS treatment was 20 min a day, 5 days a week for durations of 2, 4, or 8 weeks. Results from weekly radiography, histomorphometry, micro‐computed tomography and mechanical test showed both the treatment groups were with better healing responses than their control groups. Moreover, between the normal and the osteoporotic treatment groups, a significantly higher (p = 0.015) callus width (week 4), higher ratio of increment in bone volume to tissue volume ratio value (7.4% more), faster response of endochondral ossification and a higher stiffness measurement were observed in the osteoporotic treatment group. These comparable results on healing responses imply that LIPUS can be applied clinically to enhance both normal and osteoporotic fracture healing. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:129–136, 2012     

Postsurgical administration of estradiol benzoate decreases tensile strength of healing skin wounds in ovariectomized rats

BACKGROUND: The most effective method of increasing the level of estrogen in the wounds of post-menopausal women undergoing routine surgical procedures is by long-term preoperative administration. However, in the case of acute surgery or trauma, the most effective method of increasing the level of estrogen is administration immediately pre- or postsurgery. This study, therefore, was aimed at assessing the effect of postsurgical administration of estradiol benzoate on wound healing in ovariectomized (OVX) Sprague Dawley rats. MATERIALS AND METHODS: Three months prior to the wound healing experiment, 16 rats were anesthetized and underwent ovariectomy, while the other eight rats were sham operated. Two parallel full thickness skin incisions and two round full thickness skin excisions were performed on the dorsum of each rat. Dose of 10 microg/d of estradiol benzoate was administered to eight OVX rats for 6 d postoperatively, whereas the other animals received a placebo. After 6 d, all animals were sacrificed and samples removed for biomechanical and histological evaluation. RESULTS: The mean wound tensile strength of OVX estrogen treated rats (9.54 +/- 3.24 g/mm(2)) was significantly lower compared with vehicle-treated OVX animals (14.57 +/- 4.12 g/mm(2)) as well as with control rats subjected to sham-OVX surgery (11.71 +/- 3.33 g/mm(2)). Nevertheless, the histological evaluation in OVX estrogen treated rats showed a significantly increased process of neo-angiogenesis associated with slightly decreased collagen deposition. CONCLUSION: Our results indicate that the question of the clinical significance of this type of hormone replacement therapy remains open and requires further research.     

甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成的影响

目的探讨甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成及骨折愈合的影响。方法 75只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、阿仑膦酸钠组、联合用药组,每组15只,首先行双侧卵巢切除术,术后4周行右侧股骨干骨折髓内固定术,以构建大鼠骨质疏松性骨折动物模型。观察并评估骨折愈合,检测骨痂生物力学和骨密度(bone mineral density,BMD),检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和骨形成发生蛋白-2(bone morphogenetic protein-2,BMP-2)浓度,观察骨痂形态结构,检测骨痂VEGF表达。结果去势组较假手术组骨折愈合评分、骨痂生物力学强度、骨痂BMD、血清BMP-2和VEGF浓度、骨痂VEGF蛋白表达、骨痂微血管数均显著降低(P0.05),甲状旁腺素组、阿仑膦酸钠组、联合用药组较去势组上述指标均升高,其中以联合用药组升高最显著(P0.05)。结论甲状旁腺激素联合阿仑膦酸钠通过介导VEGF,上调BMP-2表达,促进骨质疏松性骨折大鼠骨痂血管形成,增加骨密度,改善生物力学强度及骨组织形态学,加快骨折愈合。     

密骨方对去卵巢大鼠骨折的影响

目的 采用卵巢切除法建立原发性骨质疏松及骨折动物模型,观察中药密骨方对去势大鼠骨痂组织的影响.方法 将90只雌性Wistar大鼠随机分为对照组(sham),模型组(OVX)与密骨方治疗组(MGF),模型组及治疗组行卵巢摘除术,同时3组大鼠均致其右侧股骨上1/3处骨折.MGF组按每日100mg/kg体重的剂量灌胃给药,Sham组和OVX组给予同体积的生理盐水,每日1次,疗程分别为2、4、6周,用SABC免疫组织化学方法检测骨折端转化生长因子(TGF-β1)的表达.结果 在骨折端MGF组软骨细胞的阳性表达率较高;TGF-β1的表达在时间的变化上呈显著升高趋势;第4、6周TGF-β1表达显著高于OVX组和Sham组.结论 密骨方对骨质疏松性骨折的愈合有一定的促进作用.     

骨吸收抑制剂对卵巢切除骨折大鼠脂类代谢及骨钙素的影响

目的 研究骨吸收抑制剂对卵巢切除大鼠脂类代谢及骨钙素的影响.方法 雌性SD大鼠共140只,随机分为5组,每组28只.3月龄时选取其中4组大鼠行双侧卵巢切除建立绝经后骨质疏松症模型(OVX组、OVX+ EE2组、OVX+ Rlx组、OVX+ Aln组),另一组行假手术(Sham组).OVX组及Sham组皮下注射生理盐水,余下3组分别注射阿仑膦酸钠(Aln)、雷洛昔芬(Rlx)、雌激素(EE2),每周注射5次.分别在卵巢切除术后4周、10周及20周测定大鼠血脂、骨钙素及相关生化指标.结果 OVX组与Sham组相比体重增加,总胆固醇升高,甘油三脂降低,差异有统计学意义.应用雌激素及雷洛昔芬可有效调节卵巢切除导致的脂代谢紊乱,表现为体重下降及总胆固醇水平降低,差异有统计学意义(P＜0.05).不同时期OVX组骨钙素水平高于Sham组,差异有统计学意义(P＜0.05),其中阿仑膦酸钠组血清骨钙素水平最低.随着时间推移,Sham组及OVX组骨钙素呈现先上升再下降趋势,而OVX+EE2组、OVX+ Rlx组及OVX+ Aln组骨钙素表现为持续降低.结论 骨吸收抑制剂能够降低骨钙素水平,从而降低卵巢切除导致的高骨转换率,防止骨量丢失.此外,雌激素及雷洛昔芬在预防骨丢失的基础上还能够有效调节卵巢切除引起的脂类代谢紊乱.     

麝香乌龙丸对卵巢切除大鼠股骨骨折愈合的实验研究

目的研究麝香乌龙丸对卵巢切除大鼠股骨干骨折愈合的作用。方法将30只雌性、12周龄Sprague-Dawley大鼠分成3组假手术组(Sham F V)、卵巢切除 骨折 生理盐水对照组(OVX F V)、卵巢切除 骨折 麝香乌龙丸给药组(OVX F M),每组10只大鼠。所有需制造骨折的大鼠均采用右股骨中段横行骨折,髓内针固定;麝香乌龙丸给药组采用大鼠灌胃给药(1.2g.kg-1.d-1),于术后4周杀死,取大鼠右侧股骨标本;分别进行CR摄片、组织形态学染色,并应用双能X线骨密度仪(DEXA)测量右股骨整体骨密度(tBMD)、远段骨密度(dBMD)和中段骨密度(mBMD)以及BMP-2免疫组化观察,并应用病理图像分析仪对BMP-2免疫组化进行光密度测定。结果麝香乌龙丸给药组与OVX F V比较,前者骨痂mBMD和BMP-2的表达显著增高,骨小梁增宽、排列较整齐,板层骨形成,软骨组织可见。结论麝香乌龙丸对OVX大鼠股骨骨折有明显促进骨折愈合的作用,并加快编织骨向板层骨的演变过程,这与BMP-2的表达有明显相关性。     

鲑鱼降钙素对骨质疏松大鼠骨折愈合的影响

目的　探讨鲑鱼降钙素 (密盖息 )对骨质疏松大鼠胫骨骨折愈合的影响。方法　Wis tar雌性大鼠卵巢摘除后 3个月开始制作左胫骨中段骨折模型 ,从术前 1周至术后 8周 ,连续每天皮下注射密盖息 2IU/kg。分别于术后 2 ,4,8周行X片检查和骨折处骨痂的组织学检查。 9周后检测腰椎和左侧胫骨中段的BMD、左胫骨扭转实验、腰椎体生物力学凹入实验。观察鲑鱼降钙对骨折愈合的影响 ,并和卵巢摘除组、雌激素注射组及假手术对照组进行比较。结果　密盖息组治疗 9周后BMD值明显升高 (P <0 0 5) ,骨折局部BMD明显高于治疗前 (P <0 0 5)。X片及组织学检查提示密盖息组比骨质疏松组的骨痂量多 ,愈合时间提前。密盖息组的凹入力和凹入应力明显高于骨质疏松组 (P <0 0 5) ,最大扭矩、剪切应力明显高于骨质疏松组 (P <0 0 5)。结论　鲑鱼降钙素能减少骨量丢失 ,促进矿化 ,加快骨痂的形成 ,促进骨折愈合 ,同时能提高骨生物力学特性和抗骨折能力     

Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats.

We investigated the effects of inhibitors of bone resorption (estrogen, raloxifene, and alendronate) on the processes of fracture repair in ovariectomized (OVX) rats. One hundred forty female Sprague-Dawley rats at 3 months of age were either OVX or sham-operated and divided into five groups: sham control, OVX control, estrogen (17alpha-ethynyl estradiol [EE2], 0.1 mg/kg), raloxifene (Rlx, 1.0 mg/kg), and alendronate (Aln, 0.01 mg/kg) groups. Treatment began immediately after the surgery. Four weeks postovariectomy, prefracture controls were killed and bilateral osteotomies were performed on the femoral midshafts and fixed with intramedullary wires. Treatment was continued and fracture calluses were excised at 6 weeks and 16 weeks postfracture for evaluation by X-ray radiography, quantitative computed tomography (QCT,) biomechanical testing, and histomorphometry. At 6 weeks postfracture, Aln and OVX had larger calluses than other groups. Sham and OVX had higher ultimate load than EE2 and Rlx, with Aln not different from either control. Aln calluses also contained more mineral (bone mineral content [BMC]) than all other groups. By 16 weeks postfracture, OVX calluses were smaller than at 6 weeks and the dimensions for Aln had not changed. Aln had higher BMC and ultimate load than OVX, EE2, and Rlx. EE2 and Rlx had similar biomechanical properties, which were similar to sham. Interestingly, OVX and Aln animals were heavier than other groups at all time points; therefore, ultimate load was normalized by body weight to show no significant differences in strength of the whole callus between groups at either 6 weeks or 16 weeks postfracture. However, Aln strongly suppressed remodeling of the callus, resulting in the highest content of woven bone, persistent visibility of the original fracture line, and lowest content of lamellar bone, compared with other groups. Therefore, the larger Aln callus appeared to be a remarkable, morphological adaptation to secure the fracture with inferior material. In conclusion, OVX-stimulated bone turnover resulted in the fastest progression of fracture repair that was most delayed with Aln treatment, consistent with marked suppression of bone resorption and formation activity. Estrogen and Rlx had similar effects that were generally similar to sham, indicating that mild suppression of bone turnover with these agents has insignificant effects on the progression of fracture repair.     

Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats

BACKGROUND: The question of whether fracture healing and mechanical properties of the callus are influenced by osteoporosis (OP) is still not settled. We therefore studied this issue in vitamin D-depleted ovariectomized (OVX) rats, an OP model previously shown to induce weakening of the femoral neck, and thus thought to be closer to the human condition than the classic OVX rat model. METHODS: 72 female Wistar rats were randomized into two groups: ovariectomy and vitamin D-deficient diet (Ovx-D group) or sham operation and normal rat chow (Sham group). After 12 weeks, a closed tibial midshaft fracture was performed on the right side and fixed with an intramedullary nail. Bone loss and callus formation were monitored with DXA; serum levels of estradiol and vitamin D3 were measured and histomorphometric analyses were performed. Mechanical properties of callus, tibia, femoral shaft, and femoral neck were examined in 3-point cantilever bending 6 weeks after fracture. RESULTS: The Ovx-D group showed reduced BMD in the spine and femoral neck, and reduced trabecular bone volume in the femoral head. There were no differences in BMD and mechanical properties of callus between the groups. Except for reduced stiffness of the right femoral neck in the Ovx-D group (p = 0.02), no differences in the mechanical strength of long bones were detected. INTERPRETATION: Our results suggest that the systemic effects of estrogen and vitamin D deficiency are not crucial for fracture healing or mechanical properties of the callus.     

Continuous parathyroid hormone and estrogen administration increases vertebral cancellous bone volume and cortical width in the estrogen-deficient rat.

Generally, it is believed that intermittent administration of parathyroid hormone (PTH) has an anabolic effect on the skeleton, whereas continuous administration is catabolic. However, there is evidence that continuous exposure to PTH may have an anabolic effect, for example, in patients with mild primary hyperparathyroidism (PHPT). The possibility of delivering PTH continuously may have important implications for the treatment of osteoporosis. Furthermore, estrogen treatment may be useful in the medical management of PHPT. Therefore, we examined the skeletal effects of continuous administration of PTH, with or without estrogen, in the estrogen-deficient rat with established osteopenia. Forty 7-month-old SD rats were divided into four ovariectomy (OVX) groups and one sham-operated group. Eight weeks post-OVX, three groups received subcutaneous implants of Alzet mini pumps loaded with PTH(1-34) (30 microg/kg per day), 17beta-estradiol (10 microg/kg per day) pellet, or both PTH and 17beta-estradiol separately for 4 weeks. OVX and sham control groups were given the mini pumps loaded with vehicle. Two doses of calcein (10 mg/kg) were given subcutaneously to all rats 2 days and 8 days before death. Histomorphometry was performed on cancellous and cortical bone of the fourth lumbar vertebra. At 3 months, post-OVX rats displayed bone loss with high bone turnover. Estrogen reversed OVX-mediated high turnover without restoring cancellous bone volume (BV/TV). PTH infusion further increased bone turnover and partially restored BV/TV. However, PTH infusion increased cortical porosity. Estrogen inhibited PTH-mediated cancellous bone resorption and substantially increased BV/TV above sham control. The combined treatment was associated with a significant increase in peritrabecular fibrosis and woven bone formation. The combined treatment of PTH infusion and estrogen replacement enhanced cortical width but estrogen did not prevent the PTH-induced cortical tunneling. We conclude that continuous administration of PTH and estrogen increases cortical porosity but has substantial beneficial effects on vertebral cancellous bone volume and cortical width in OVX rats.     

The development of femoral osteopenia in ovariectomized rats is not reduced by high intensity treadmill training: A mechanical and densitometric study

The effect of treadmill running on the development of osteopenia was investigated in adult ovariectomized (OVX) rats compared with sedentary OVX and sedentary sham-operated rats. The rats were 3 months old with a mean weight of 214 g. OVX rats were fed a low calcium diet (0.01%), and the sham rats received the normal diet (1.1% calcium). The training consisted of treadmill running at a speed of 27 m/minute for 1 hour 5 out of 7 days during a period of 8^1/2 weeks. The weight gain was higher in the sedentary OVX (108 g) than in the training OVX (62 g) and sham-operated rats (61 g) (P<0.001). Comparing the two OVX groups, training had no significant effects on the development of femoral osteopenia as assessed by mechanical testing of the femoral shaft and neck, and by bone mass measurements by dual energy X-ray absorptiometry (DXA) or by ashing. Comparing all three groups bone mineral content (BMC) and bone mineral density (BMD) were reduced by more than 40% in both the OVX groups compared with the sham-operated rats (P<0.001). Ash weight and calcium content were reduced by approximately 40% in both OVX groups. Femoral volume and length were 10% higher in the sedentary OVX animals compared with the trained (P<0.05), indicating that the training had had a negative effect on the growth changes induced by ovariectomy. The fracture strength of the femoral shaft was reduced by 26% and 22% in the trained and sedentary OVX rats, respectively compared with the sham-operated group (P<0.001). The fracture strength of the femoral neck was reduced by 18% and 15% but due to one very weak neck in the sham group, this difference was not significant. The accuracy of BMC measured by DXA was high when compared with calcium content (r=0.98, P<0.001) and ash weight (r=0.96, P<0.001). DXA underestimated the BMC of the femur by 27% as compared with ash weight. BMC was also highly correlated to fracture strength of the shaft (r=0.85, P<0.001), but not to fracture strength of the neck. This study shows that high intensity training had no positive effect on the development of osteopenia in rats, and we have also validated and found DXA to be a precise and useful tool for experimental studies on osteoporosis in the rat.