Effects of tibolone on bone quality in ovariectomized monkeys

OBJECTIVE: The purpose of this report is to examine the effects of two doses of tibolone on bone quality (bone biomarkers, bone density, and bone strength) in ovariectomized cynomolgus monkeys fed high-fat diets. DESIGN: Ovariectomized cynomolgus monkeys were randomized into one of five treatment groups: placebo-treated control, tibolone (0.2 mg/kg/day), tibolone (0.05 mg/kg/day), conjugated equine estrogens (Premarin, 0.042 mg/kg/day), and conjugated equine estrogens plus medroxyprogesterone acetate (0.042 and 0.167 mg/kg/day, respectively). Bone quality was assessed by determining bone strength and density in vertebrae and femora collected after 24 months of treatment. RESULTS: Monkeys treated for 24 months with tibolone had increased bone mineral density in the distal femur and improved biomechanical properties in the midshaft femur compared with placebo-treated ovariectomized monkeys, as did monkeys treated with conjugated equine estrogens with or without medroxyprogesterone acetate. No treatment effects were seen in lumbar vertebra bone density or strength. There was no significant difference between tibolone and estrogen on biomechanical properties of the femur. CONCLUSION: These data show that tibolone is comparable to conjugated equine estrogens with or without medroxyprogesterone acetate in decreasing bone turnover and increasing bone strength in ovariectomized monkeys.     

Effects of lasofoxifene on bone in surgically postmenopausal cynomolgus monkeys

OBJECTIVE: The purpose of this study was to evaluate the effects on bone of two doses of the selective estrogen receptor modulator lasofoxifene in surgically postmenopausal cynomolgus monkeys for 24 months. The primary endpoint of this study was biomechanical testing of animals treated for 2 years. DESIGN: The design of the study was a five-group (sham-ovariectomy, ovariectomy, conjugated [0.02 mg/kg], and two doses of lasofoxifene [1.0 and 5.0 mg/kg]), parallel arm design, with the treatments lasting for 24 months. Bone biomarker and estradiol data were collected at baseline and 3, 6, 12, 18, and 24 months after surgery. Vertebral bone mineral density was determined at baseline and every 6 months after ovariectomy. Hip bone density was determined at baseline and 12 and 24 months postovariectomy. Iliac bone biopsies were collected at 7 months, and the second lumbar vertebra and left femur were collected at 24 months after initiation of treatment for histomorphometric examination. The third lumbar vertebra and right femur were tested for mechanical strength after 24 months of treatment. RESULTS: Lasofoxifene and conjugated estrogens prevented ovariectomy-induced increases in serum alkaline phosphatase and CrossLaps and resulted in increased vertebral (all three treatments) and hip (conjugated estrogens and high-dose lasofoxifene only) bone mineral density, although both doses of lasofoxifene exceeded the doses projected to be used in women. In the 7-month iliac biopsy specimens, both doses of lasofoxifene reduced bone turnover rates. These histomorphometric changes were not present in either the vertebral or femoral compartments measured after 24 months of treatment. Lasofoxifene-treated animals did not differ from ovariectomized controls in mechanical strength testing of either the third lumbar vertebra or right femur. CONCLUSIONS: Lasofoxifene prevented ovariectomy-induced increased bone turnover and loss of bone mineral density without having a detrimental effect on bone strength.     

辛伐他汀干预卵巢切除大鼠骨密度和生物力学性能的变化

BACKGROUND: Osteoporosis and its complications severely threaten the elder’s health. Simvastatin, widely accepted as a lipid-lowering drug, is reported to potentially promote bone formation, but it is in debate when orally administered, and there is no evidence to support whether this is due to the region difference. OBJECTIVE: To investigate the effect of orally administered simvastatin on bone mass and biomechanical properties of the femur and vertebrae in osteopenia rats induced by ovariectomy (OVX). METHODS: Twenty-four 6-month-old female Sprague-Dawley rats were subjected to OVX+orally administered saline vehicle (OVX group, n=8), OVX+orally administered simvastatin (5 mg/kg/d; intervention group, n=8) or sham surgery (sham group, n=8). After 8 weeks of treatment, all rats were sacrificed and the level of procollagen type I N-terminal propeptide in blood serum was assessed by ELISA. Bone mineral density was determined in the L5 vertebra and left femur using dual-energy X-rays. Furthermore, the biomechanical properties of the L4 vertebra and right femur, including maximum load and elastic modulus, were detected by compression testing and three-point bending test, respectively. RESULTS AND CONCLUSION: The serum level of procollagen type I N-terminal propeptide in the sham group was significantly lower than that in the other two groups. OVX rats showed significantly lower bone mineral density in both the L5 vertebra and left femur than sham rats (P < 0.05). Rats in the intervention group showed higher bone mineral density than those in the OVX group, with statistically significant difference in the L5 vertebra (P < 0.05), but insignificant difference in the femur. Maximum load and elastic modulus of the L4 vertebra in the OVX group were significantly lower than those in the sham and intervention group. Markedly lower elastic modulus of the femur was found in the OVX group than the sham and intervention groups. These findings demonstrate that simvastatin treatment can partially prevent bone loss in OVX rats with more notable effect on the vertebrae than the femur, and for this model, the vertebra is superior to the femur used in biomechanical test. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized mice

OBJECTIVE: The effects of estrogen and selective estrogen receptor modulators (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed the manner and mechanism by which estrogen and raloxifene affect homeostatic pathways in ovariectomized mice after acute arterial injury. DESIGN: Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured. RESULTS: Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively. CONCLUSIONS: Ovariectomy amplifies thrombosis. We found that 4 months of treatment with both estradiol and raloxifene attenuates intravascular thrombosis. The antithrombotic effect was accompanied by increased expression of cyclooxygenase-2 and suppression of platelet surface adhesion.     

辛伐他汀对去卵巢骨质疏松大鼠股骨生物力学的影响

目的研究辛伐他汀(Simvastatin,SIM)对去卵巢(OVX)骨质疏松大鼠股骨生物力学性能的影响。方法48只3月龄雌性SD大鼠,随机分成3组,假手术(SHAM)组、OVX组和OVX+SIM组,每组8只。适应性喂养一周后进行手术。术后8周开始给药,OVX+SIM组给予SIM 5mg.kg-1·d-1,其余两组用等量生理盐水灌服。用药后第4周每组随机处死半数大鼠,12周后处死剩余大鼠,取股骨进行三点弯曲试验,检测股骨最大载荷、弹性载荷、最大桡度、弹性桡度、弯曲刚度系数、弯曲韧度系数等生物力学性能。结果(1)用药4周,最大载荷:SHAM组较OVX组明显增加(P<0.05);弹性载荷:OVX+SIM组较OVX组明显降低(P<0.05);最大桡度:SHAM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组较OVX组明显增加(P<0.01)。(2)用药12周,最大载荷:OVX+SIM组、SHAM组较OVX组明显增加(P<0.05,P<0.01);弹性载荷:OVX+SIM组较OVX组明显增加(P<0.05);弯曲韧度系数:OVX+SIM组、SHAM组较OVX组明显降低(P<0.05,P<0.01)。(3)用药12周较4周,OVX+SIM组最大载荷、弹性载简明显增加(P<0.01),OVX组弯曲韧度系数明显增加(P<0.01)。结论SIM能促进去势大鼠骨的再建,改变骨的空间微结构和骨组织有机成分和无机成分的比例及结合,随时间的延长能提高股骨的强度。     

Estradiol,but not raloxifene,improves aspects of spatial working memory in aged ovariectomized rhesus monkeys

Estrogen replacement therapy (ERT) alleviates many postmenopausal symptoms but whether it also benefits cognitive function remains controversial. Further, since estrogen increases the risk of breast and uterine cancers, a new class of compounds, called selective estrogen receptor modulators (SERMs) is being considered as possible alternative to ERT. The SERM raloxifene is particularly interesting because, like estrogen, it improves lipid metabolism and reduces bone loss, without adverse effects on the breast or uterus. Little is known, however, about its effect upon cognitive function.We used a rhesus monkey model of human menopause to examine the effects of ERT and raloxifene on cognitive function. We tested 5 aged females (21-24 years old) ovariectomized long-term (10-16 years) on a battery of age-sensitive tasks, including the Delayed Response (DR), the Delayed Non-Matching-to-Sample-10 min (DNMS-10 min) and the spatial-Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week on each task for 9 consecutive months, while undergoing treatments with placebo, ethinyl estradiol (EE(2)), and raloxifene in alternating 28-days blocks. EE(2) transiently enhanced the working memory component of the spatial-DRST, but did not affect performance on the other tasks of the battery. Raloxifene had no effect on cognitive performance. These findings indicate that estradiol is able to enhance some aspects of spatial working memory in aged monkeys despite many years of estrogenic deprivation. Further, they suggest that raloxifene does not affect cognitive function after long-term ovarian hormone deprivation.     

甲状旁腺素和二膦酸盐对骨密度和骨生物力学的影响

目的:研究应用甲状旁腺素和阿仑膦酸钠对激素性骨质疏松兔骨密度和生物力学的影响。方法:采用成年新西兰大白兔,随机分为对照组、激素模型组、甲状旁腺素和阿仑膦酸钠治疗组,9周后取股骨和腰椎行超声骨密度测量,再行股骨扭转、三点弯曲和腰椎压缩试验。结果:激素模型组的宽频超声衰减(BUA)、超声传导速度(SOS)值和骨生物力学参数较对照组有非常明显减少,甲状旁腺素和阿仑膦酸钠治疗组的BUA、SOS值和骨生物力学参数较激素模型组明显增加。结论:序贯应用甲状旁腺素和阿仑膦酸钠可以减少激素性兔骨量的丢失,预防骨质疏松的发生。     

磁场对去卵巢大鼠骨密度、骨强度和骨代谢的影响

本文研究了旋转恒定磁场对去卵巢大鼠骨密度，骨强度和骨代谢的影响。结果表明磁场处理30分钟且加钙组的骨密度，能量吸收，弹性能量吸收，最大载荷，最大桡度和弹性桡度等指标均显著高于去卵巢组，分别增加3.5%,15.4%,12.4%,7.6%,5.8%,11.9%t 5.2%。其碱性磷酸酶，血磷，血钙等指标也比去卵巢组分别高71％，108％，156％。实验还检测了暴磁1个月及停止暴磁后1到2个月，大鼠骨密度和骨矿含量的变化，结果表明磁场处理存在着窗口效应和滞后效应。     

康力龙对类固醇性大鼠骨质疏松骨密度和生物力学的影响

目的　从生物力学和骨矿含量测定角度研究康力龙对类固醇性大鼠骨代谢的影响。方法　采用 3月龄雄性SD大鼠 2 8只 ,随机分为基础对照组、年龄对照组、激素模型组和康力龙预防组。后两组给醋酸泼尼松 4 5mg·kg-1,ig ,2次 /周 ;预防组还给康力龙 0 5mg·kg-1·d-1,ig。 3个月后取股骨和第 5腰椎行骨密度测定 ,再行扭转、3点弯曲和压缩试验。结果　与年龄对照组比较 ,激素模型组股骨和第 5腰椎的总骨密度减少了 14 6 4 % (P <0 0 1) ;股骨干在 3点弯曲试验时所承受的载荷减少了17 1% (P <0 0 5 ) ;其余的力学参数都出现减少的趋势。与激素模型组比较 ,康力龙预防组股骨和第 5腰椎的总骨密度有所增加 ;股骨扭转角度明显增加 72 5 % (P <0 0 5 ) ,其余的力学参数都出现增加的趋势。结论　长期使用糖皮生激素 (GC) ,会使大鼠皮质骨和松质骨的骨密度和力学性能下降 ,从而易致骨折 ;应用康力龙则能阻止GC所致骨量丢失 ,还能增加其力学性能。     

人甲状旁腺激素相关蛋白（1-34）对去卵巢大鼠骨密度和骨生物力学性能的影响

目的：观察人甲状旁腺激素相关蛋白氨基端肽(PTHrP 1-34)对去卵巢的骨质疏松大鼠骨密度(BMD)和骨生物力学性能的影响。 方法： 80只4月龄Wistar健康雌性大鼠，其中60只行双侧卵巢摘除术，20只做假手术，6周后各处死10只证实骨质疏松造模成功。剩余50只骨质疏松模型鼠随机分为5个治疗组，每组10只，其它10只假手术组作对照。PTHrP治疗组（PTHrP 20组， PTHrP 40组， PTHrP 80组）分别用20、40、80 μg/kg剂量，每日皮下注射1次PTHrP 1-34；雌二醇治疗组（E2组）用苯甲酸雌二醇40 μg/kg, 每3 d注射1次；安慰剂组及假手术对照组分别用生理盐水，每3 d注射1次。治疗3个月后，测定并比较股骨、腰椎BMD、骨生物力学参数及血清钙、磷、碱性磷酸酶（ALP）水平。结果： 双侧卵巢摘除6周后，大鼠腰椎BMD及腰椎压缩最大载荷明显低于假手术组(P<0.05)。3个月治疗后，PTHrP 40组和PTHrP 80组大鼠股骨、腰椎BMD及骨生物力学性能明显高于安慰剂组，与雌二醇治疗组无显著差异，腰椎BMD明显高于PTHrP 20组（P<0.05）； PTHrP 40组与PTHrP 80组无明显差异。结论： 每日每公斤体重皮下注射40和80 μg PTHrP 1-34对去卵巢骨质疏松大鼠有明显治疗作用。     

去势大鼠骨形态计量学、生物性能变化

目的 通过观察大鼠血清学、骨形态计量学测定、骨生物性能等方法研究去卵巢大鼠骨变化.方法 采用7-12月龄SD雌性大鼠30只,随机分为对照组、模型组和尼尔雌醇组.模型组和尼尔雌醇组大鼠切除双侧卵巢进行造模.尼尔雌醇组大鼠造模后45天开始灌服尼尔雌醇,连续90天;对照组和模型组大鼠手术后第45天开始灌服去离子水,连续90天.所有大鼠给药第80、87天时两次ip四环素20mg/kg进行骨荧光标记.实验结束时,取出大鼠股骨及第四腰椎骨进行股骨形态计量学测定、股骨骨密度测量、股骨三点弯曲实验及椎骨压缩实验,同时测定血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(StrACP)水平.结果 大鼠去双侧卵巢后,股骨骨密度、骨最大载荷、最大应力、弹性模量、刚度水平和骨小梁体积显著性提高;椎体压缩性能、股骨形态计量学、股骨弯曲性能有明显改变;而雌激素对以上变化有不同程度改善作用.结论 骨组织形态、骨生物性能是评价骨质疏松模型或药物疗效的重要指标;发生骨质疏松时,骨组织形态学变化先于骨生物性能变化.     

Effects of alfacalcidol on muscle strength, muscle fatigue, and bone mineral density in normal and ovariectomized rats

Vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall prevention are still unclear. The purpose of this study was to investigate the effects of alfacalcidol [1α(OH)D(3)] on muscle strength, muscle fatigue, and bone mineral density (BMD) in ovariectomized rats. Seven-month-old female Wistar rats were orally administered 1α(OH)D(3) or its vehicle everyday for 4 weeks after ovariectomy (OVX) or sham operation. Calf muscle strength and fatigue were evaluated by electrical stimulation of the sciatic nerve under general anesthesia. 1α(OH)D(3) administration significantly increased the maximum muscle strength in the sham-operated (P < 0.01) and the OVX (P < 0.01) groups compared to their respective control groups. However, 1α(OH)D(3) administration did not significantly affect muscle fatigue in these groups. The BMD of the femur in the 1α(OH)D(3)-treated OVX group was significantly higher than that in the vehicle-treated OVX group (P = 0.04). These results suggested that 1α(OH)D(3) increases muscle strength but does not affect muscle fatigue in this rat model. The effectiveness of activated vitamin D in preventing bone fractures may be partly owing to its effect on muscle strength in addition to its known effect on bone metabolism.     

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.     

不同剂量糖皮质激素对大鼠骨密度和生物力学性能的影响

目的通过双能X射线骨密度仪(dual energy X-ray absorptiometry,DXA)、骨生物力学测试及骨组织计量学等方法研究不同剂量糖皮质激素摄入对正常3月龄大鼠骨骼的影响。方法 31只SPF级3月龄SD雌性大鼠,随机分为正常对照组、地塞米松(Dex)1、2.5、5 mg/kg组,每周尾静脉注射给药2次,共8周,对照组给予生理盐水对照。给药结束后,离体股骨和第3腰椎通过DXA进行骨矿含量(bone mineral content,BMC)、骨矿密度(bone mineral density,BMD)测定,全股骨和第5腰椎分别进行三点弯曲和压缩力学实验,并通过骨组织病理切片观察胫骨近端骨小梁的显微结构并定量分析。结果与正常组相比,所有激素组大鼠体重均明显降低,腰椎BMC、BMD及最大压缩载荷均未明显下降,全股骨BMC均有所降低,但只有Dex 1 mg组全股骨和股骨远端、近端BMD降低;Dex 1 mg组三点弯曲实验断裂载荷、最大载荷和弹性载荷都明显降低,而Dex 2.5 mg、Dex 5 mg组只有弹性载荷仍低于正常对照组。激素组骨小梁有空间密度分布不均现象,骨代谢处于低转换。结论应用糖皮质激素8周对3月龄大鼠骨骼的不利影响股骨较腰椎明显,股骨骨量丢失,力学性能下降,两者均无剂量依赖性。更高剂量Dex并没有增加骨量丢失和力学性能改变。力学性能特别是弹性载荷下降以及骨小梁密度分布不均,提示糖皮质激素更多的是引起骨质量下降。临床上应用糖皮质激素时,应使用多种方法评价其对骨骼的副作用。     

Effects of FPL 55712, ETYA and aminophylline upon Ascaris-induced bronchoconstriction in cynomolgus monkeys

Dose-related impairment of pulmonary functions was induced in artificially respired, anesthetized cynomolgus monkeys by inhalation of aerosolized Ascaris antigen (AA) in ascending doses. The effects of pharmacologic agents were assessed by increases in threshold Ascaris dose (TAD). TAD were defined as the doses of AA needed for 20% increase in pulmonary resistance and 15% decrease in compliance. Inhaled FPL 55712, an SRS-A antagonist (1.24 mg through-the-valve dose; TTVD), and 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of lipoxygenase and cyclooxygenase (1.0 mg TTVD) resulted in significant increases in the geometric means of TAD for changes in compliance (p less than 0.01). The effects of both agents upon resistance were of borderline significance. Orally administered aminophylline (30 mg/kg) had no significant effect upon mean TAD for resistance or compliance. The activities of FPL 55712 and ETYA suggest that spasmogenic leukotrienes are involved in the pulmonary allergic reactions in cynomolgus monkeys.     

酒精摄入对小鼠不同骨骼形态学参数的影响

目的：通过骨组织形态计量学方法探讨和比较酒精摄人对小鼠松质骨和皮质骨形态学参数的影响。方法：清洁级昆明种小鼠30只随机分成3组，基础对照组，正常对照组（蒸馏水灌胃），酒精组给予50％（体积分数）乙醇，按4g&#183;kg^-1&#183;d^-1剂量灌胃，共60d，实验结束后取小鼠胫骨上段、中段经不脱钙骨切片进行骨组织形态计量学参数测量。结果：与正常组比较，酒精组松质骨的形态学参数骨小梁面积百分数（％Tb．Ar）明显降低（-66％，P〈0．05），骨形成率（BFR／TV）降低（-35％，P〈0．05）；皮质骨面积百分率（％Ct．Ar）降低（-7％，P〈0．05）及髓腔面积百分率增加（％Ma．Ar＋32％，P〈0．05），骨内膜骨形成率E—BFR／BS降低（-41％，P〈0．05）。结论：长期摄入酒精使小鼠皮质骨和松质骨骨量均下降，微观结构改变，骨质量下降。     

Comparison of effects of alendronate and raloxifene on lumbar bone mineral density, bone turnover, and lipid metabolism in elderly women with osteoporosis

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. SUBJECTS AND METHODS: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.     

Tibial implants: biomechanical and histomorphometric studies of hydroxyapatite-coated and uncoated stainless steel and titanium screws in long-term ovariectomized sheep.

This study was designed to evaluate osteointegration of HA-coated and uncoated titanium and stainless steel screws in the cortical bone of long-term (24 months) ovariectomized sheep (OVX group), in comparison with Sham-aged sheep (control group). The screws were tested biomechanically (extraction torque) and histomorphometrically (affinity index: Al) 12 weeks after their implantation in tibial diaphyses. Tibial cortical bone parameters showed significant differences between the groups, showing a reduction of the selected parameters in the OVX group. ANOVA showed significant effects for both material and ovariectomy factors on obtained extraction torque (material: F=159.26, p < 0.0005; ovariectomy: F=20.04, p < 0.0005) and Al data (material: F=8.04, p < 0.001; ovariectomy: F=7, 17, p < 0.05). In both groups the extraction torque for coated screws of both materials was significantly higher than for uncoated screws, and uncoated titanium had a better extraction torque than uncoated stainless steel. In the OVX group, the HA-coated stainless steel and titanium Al data were significantly higher than uncoated Al data. In conclusion, the biomechanical and histomorphological results obtained suggest employing HA-coated screws in the presence of osteopenic cortical bone.