骨膦抗去势雌鼠骨质疏松研究

切除８月龄雌性大鼠双侧卵巢后，皮下注射骨膦１２周，与单纯卵巢切除组（ＯＶＸ组）、假手术组（ｓｈａｍ组）及口服尼尔雌醇组（Ｅ３组）比较，用骨生物力学、骨密度测量、骨形态计量学等方法对骨膦的药效进行综合评价。结果表明，与ｓｈａｍ组比较，ＯＶＸ组骨灰重、骨干重、骨钙含量及骨密度、抗弯力、骨小梁体积密度、宽度均明显降低，而成骨细胞指数和破骨细胞指数、尿羟脯氨酸则明显增高。骨膦和Ｅ３对上述指标有显著改善作用。     

Evaluation of long-term sequential changes in bone mass and strength following withdrawal of incadronate disodium (YM175) in ovariectomized rats

We evaluated the long-term effects of withdrawal of a newer third-generation bisphosphonate, incadronate disodium (YM175), on both cancellous and cortical bone mass and strength in ovariectomized (OVX) rats. One hundred and sixty female SD rats at 13 weeks of age were randomized into four groups: sham-operated, OVX, and low- and high- YM (0.01 or 0.1 mg/kg s.c., three times a week after OVX). After 4 weeks of treatment with vehicle or incadronate disodium, rats from each group (n = 8) were killed at 0 (baseline), 3, 6, 9, and 12 months after the withdrawal of YM175. Histomorphometric studies of the proximal tibia revealed a dose-dependent decrease in OVX-induced bone turnover; cancellous bone volume was significantly higher in the YM groups compared with the OVX control group up to 6 months after withdrawal at low dose and up to 12 months after withdrawal at high dose. The low-dose group showed little effect on tibial diaphyseal cortical bone volume and width, while the high-dose group preserved both cortical parameters 12 months after withdrawal. Mechanical testing of femurs revealed that both metaphyseal and diaphyseal strengths were significantly higher at high dose compared with the OVX group until 12 months after withdrawal. These observations demonstrated that high-dose incadronate disodium preserved both cancellous and cortical bone mass and strength in OVX rats for 12 months after withdrawal of the agent. Received: July 7, 2000 / Accepted: October 3, 2000     

Temporal relationship between bone loss and increased bone turnover in ovariectomized rats

Summary To characterize osteopenic changes in ovariectomized (OVX) rats as a function of time, female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and killed at various times from 14–180 days postovariectomy. The proximal tibial metaphysis was processed undecalcified for quantitative bone histomorphometry. Osteopenia and increased indices of bone resorption and formation were detected in OVX rats as early as 14 days. Longitudinal bone growth was also significantly increased by ovariectomy at 14 days, but returned to control levels at all later times. In OVX rats, osteopenia became progressively more pronounced with time up to 100 days postovariectomy, after which trabecular bone volume appeared to stabilize at the markedly reduced level of 5%. Changes in osteoclast surface, osteoblast surface, and fluoro-chrome-based indices of bone formation in OVX rats followed a similar time course. The maximal increase in these parameters occurred during the first several months postovariectomy followed by a gradual decline toward control levels. Our results indicate that the initial rapid phase of bone loss in OVX rats is coincident with the maximal increase in bone turnover. At later times postovariectomy, bone loss and bone turnover both subside. These findings emphasize the close temporal association between the development of osteopenia and increased bone turnover in OVX rats.     

Rationale for the use of clodronate in osteoporosis

Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and in the hypercalcemia of malignancy. Because of their undoubted efficacy and relatively low toxicity, bisphosphonates are attractive candidates for the management of osteoporosis. Clodronate, one of the many bisphosphonates being tested in osteoporosis, may be given intravenously or by mouth. In contrast to etidronate, even high doses of clodronate do not impair the mineralization of bone, making it suitable for long-term use in osteoporosis. As do all the bisphosphonates tested thus far, clodronate appears to delay the rate of bone loss in osteoporosis. Long-term studies are relatively few, so that its steady-state effects on bone mass are not yet known. Most data suggest clodronate is capable at least of delaying the rate of bone loss, but several pilot studies with this agent suggest that increments of bone mass might be sustainable for several years. Clodronate is likely to decrease the frequency of osteoporotic fractures, but there is no evidence for this at present. Well-controlled, long-term prospective studies are needed.     

降钙素对卵巢切除大鼠骨转换的影响

尽管降钙素已在临床用于防治骨质疏松症，但其对骨转换的影响并未阐明，为此本实验以骨组织形态计量学为手段，观察了降钙素对卵巢切除大鼠小梁骨体积和骨转换的影响。实验分三组：卵巢切除后用降钙素组、卵巢切除后用生理盐水组和假手术组。取胫骨干骺端作不脱钙骨切片，行骨组织计量学测定。结果表明，与假手术组相比，卵巢切除后用生理盐水组其小梁骨体积明显下降，破骨细胞表面积、成骨细胞表面积、类骨质表面积、矿化表面积、矿化沉积率和骨形成率均明显升高。相反，卵巢切除后用降钙素组其小梁骨体积恢复正常，骨转换指标也接近假手术组。说明降钙素不仅抑制卵巢切除大鼠骨吸收，而且抑制其骨形成，使骨转换降低，从而预防卵巢切除大鼠骨丢失。     

Effect of weight manipulation on bone loss due to ovariectomy and the protective effects of estrogen in the rat

Summary While characterizing the effects of estrogen on an ovariectomized (OVX) rat model of bone loss, we examined several weight-matching regimens e.g.,ad libitum (feed bins continually full), weight matched (rate of weight gain for OVX and Sham-OVX groups was equalized), and weight restricted (weight gain rates for all groups were equalized to that of estrogen-treated OVX rats) for possible effects. Bone loss following ovariectomy is primarily the result of an increase in bone resorption and is extremely sensitive to the effects of estrogens. Thus, in all of our analyses, treatment with 170-estradiol served as a positive control for the prevention of bone loss. Each weight-matching study had three groups: control (Sham-OVX), OVX, and OVX + 170 estradiol (0.1 mg/kg/day), and lasted for either 2, 4, or 6 weeks. Throughout the study, each Sprague Dawley rat was weighed every other day, and following sacrifice, a femur was removed for bone mineral density (BMD) analysis at the distal metaphysis by single photon absorptiometry. Following 2 weeks of dietary modifications, no significant differences were detected in BMD among thead lib or weight matched groups. However, an estradiol-preventable reduction in BMD in restricted OVX rats was detected at 2 weeks postovariectomy. Additionally, OVX rats in all three dietary regimens displayed an estrogen-preventable reduction in proximal femur BMD at 4 and 6 weeks postovariectomy. These results indicate that a 4-week rat ovariectomized model of bone loss, under conditions of ad libitum feeding, shows great potential for pharmacologic manipulation.     

骨宝液在去卵巢大鼠骨质疏松症中抑制骨转换作用的实验研究

目的：探讨骨宝液对去卵巢大鼠骨质疏松症中抑制骨转换作用。方法：60只大鼠去卵巢诱导骨质疏松症，随机分为正常对照组、模型组、尼尔雌醇组、骨宝液低、中、高剂量组。正常对照组、模型组以0．9％生理盐水每天10ml／kg，尼尔雌醇组以尼尔雌醇每2周1mg／kg，其他三组每天分别以骨宝液5、10、15ml／kg的剂量灌胃给药3个月后，以比色法测定其血清钙（s-Ca）、骨碱性磷酸酶（b-AKP）和血清抗酒石酸酸性磷酸酶（s-TRAP）的活性，竞争放射免疫法测定血清中骨钙素（s-BGP）的含量；双能x线骨密度仪（DEXA）测定股骨及腰椎的骨密度；三点弯曲试验法测定骨生物力学；扫描电镜进行骨小梁形态计量学分析。结果：骨宝液组与其他组比较，s-TRAP水平降低，腰椎骨密度增加，股骨抗弯抗拉能力改善，骨小梁形态改善，骨小梁平均宽度（MTT）与骨小梁面积百分比（TS％）显著增加。结论：骨宝液对去卵巢大鼠骨质疏松症具有防治作用，其机制可能与抑制骨转换有关。     

荣骨颗粒对去卵巢大鼠骨质疏松症治疗作用的实验研究

目的 探索补肾中药“荣骨颗粒”治疗骨质疏松症的作用机理。方法 摘除大鼠双侧卵巢，正常喂养3个月后造成骨质疏松大鼠模型，按大、中、小剂量分组并灌服荣骨颗粒，对照组分别灌服己烯雌酚和中药骨疏康。3个月后处死所有大鼠，眼球取血，测定血清骨钙素(BGP)、碱性磷酸酶(ALP)、白介素1(IL-1)、白介素6(IL-6)、雌二醇(E2)。结果 荣骨颗粒能使血清BGP、ALP、IL-1、IL-6含量降低，使血清E2水平升高。结论 该药对骨质疏松症之骨吸收．骨形成偶联具有一定的调节作用；能够抑制IL-1、IL-6的分泌，具有促进雌激素分泌效应或类雌激素样作用。本实验从激素和细胞因子层面初步阐述了荣骨颗粒治疗骨质疏松症的作用机理。     

去卵巢后大鼠不同部位的骨组织计量学与骨密度研究

目的 观察大鼠去除卵巢后不同部位骨的骨组织计量学参数与骨密度以及两之间的相关性。方法 分别进行卵巢去除和伪手术，56d时处死大鼠，取离体胫骨，股骨测量骨密度与组织学参数%Tb.Ar,Tb.Th,Tb.N。结果 OVX后5d时，股骨远端和胫胫骨近端大部分骨组织计量学参数下降；全股骨和股骨远端1/3处骨密度降低；股骨部分骨组织计量学参数与骨密度测量值之间存在正相关性且差异有显性。结论 切除大鼠卵巢56d时，大鼠骨组织计量学参数下降显，骨密度测量以股骨较为敏感，骨组织计量学与骨密度测量值之间的相关性以股骨明显。     

Effect of vitamin K2 on lumbar vertebral bone: histomorphometric analyses in experimental osteoporotic rats

The in-vivo effect of vitamin K₂ on bone metabolism was investigated by histochemical and morphometric methods, using an animal model of osteoporosis. Eighteen female Wistar rats were divided into three groups. Rats in group A had sham ovariectomies, group B were ovariectomized, and group C were ovariectomized and received vitamin K₂, at 10 mg/kg per day, injected subcutanously. The lumbar vertebral bones were evaluated 8 weeks after the operation by a modified tetrachrome method after decalcification. Mineralized bone areas, osteoid, and deficectively mineralized bone areas in group B were markedly decreased compared with findings in group A, but these features in group C were not severely decreased. There was no significant difference in total bone areas and total bone volumes among the three groups. Accordingly, it appeared that vitamin K₂ had an effect in reducing mineralized bone loss after the ovariectomy. In conclusion, vitamin K₂ is thought to be beneficial for the properties of bone microarchitecture in the condition of osteoporosis. Received: September 14, 2000 / Accepted: June 11, 2001     

槲皮素对去卵巢大鼠骨量丢失的保护作用

目的探讨槲皮素在去卵巢大鼠骨质疏松防治中的作用及其可能的作用机理。方法60只3月龄健康雌性Wistar大鼠被分为6组:假手术组(S组);模型对照组(OVX组);低剂量槲皮素(50mgkg·d)、中剂量槲皮素(100mgkg·d)和高剂量槲皮素(200mgkg·d)组(分别称L、M、H组);尼尔雌醇(1.5mgkg·w)组(E组)。术后第2d开始每天灌胃给药,S和OVX组则灌胃生理盐水。3个月后处死大鼠,留取血清测定碱性磷酸酶(ALP)、酸性磷酸酶(ACP)活性和雌二醇(E2)水平;分离子宫测定其重量;分离右股骨测定其生物力学性能;分离左股骨测定其骨密度。结果槲皮素对大鼠体重、子宫重量、ALP活性和E2均无明显影响,能抑制ACP活性,提高大鼠股骨骨密度,对其生物力学性能无明显影响,其作用与尼尔雌醇相似。结论槲皮素能预防去卵巢大鼠骨质疏松的发生,在体内无明显促进子宫增长的活性,其可能通过抑制骨吸收起作用,而对成骨代谢无明显影响,有望用于临床防治绝经后骨质疏松症。     

Effects of two non-endurance exercise protocols on established bone loss in ovariectomized adult rats

Summary The effects of non-endurance exercise on bone properties were evaluated in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The studies were started 3 months postsurgery, after bone mass was decreased in OVX rats. The sham and OVX rats were either kept sedentary (SED) or were trained to run with one of two protocols: 12 m/minute, 50 minutes/day, 4 days/week (low intensity, frequent, EX-1); or 21 m/minute, 40 minutes/day, 1 day/week (moderate intensity, infrequent, EX-2). A group of seven rats evaluated at the beginning of the study served as baseline control. The bone mineral was assessed by the ash weight of the left femur, tibia, and 4th lumbar vertebra. Biomechanical (strength, deformation, stress, strain, and stiffness) and morphometric (length, cortical and medullary area, moment of inertia) properties were evaluated for the right femur. There was a significantly lower bone mineral and mechanical properties in OVX-SED (n=7) than in SH-SED (n=10) rats. The OVX-EX-1 (n=6) rats had higher ash content of femur and tibia than OVX-SED rats, but the change was significant only for tibia. The EX-2 had no effect on the ash content, but femur stress was higher in OVX-EX-2 (n=8) than in OVX-SED rats. The femur yield force and deformation were improved in OVX rats with both exercise protocols, whereas the vertebra ash weight, femur strain, modulus of elasticity, length, cortical area, and moment of inertia were not changed. Non-endurance exercise did not affect bone properties in either SH-EX-1 (n=7) or SH-EX-2 (n=8) groups. We conclude that non-endurance exercise has beneficial effects on established osteopenia in ovariectomized rats.     

Differences of bone mass and bone structure in osteopenic rat models caused by spinal cord injury and ovariectomy

Summary Both spinal cord injury and ovariectomy can result in ostepenia in rats. SCI induces more deterioration of cortical geometric structure and trabecular microstructure in the proximal tibial metaphysis than OVX. The proximal tibial metaphysis microstructure significantly correlates with its biomechanical properties. Introduction The purpose of the present study was to compare the effects of spinal cord injury (SCI) and ovariectomy (OVX) on bone gain in young female rats. Methods Thirty young female Sprague-Dawley rats were randomized into three groups: age-matched intact control (CON), OVX and SCI. The tibiae were assessed for DXA and micro-CT analysis, biomechanical testing, the upper tibial epiphyseal plate height, and blood samples for biochemical analysis. Results SCI rats showed lower aBMD in the proximal tibiae as compared with OVX rats. Cortical geometric structural parameters of the tibial midshaft in SCI rats were significantly lower than OVX rats. SCI or OVX induced significant changes in all trabecular microstructural parameters in the proximal tibial metaphysis. The trabecular separation (Tb.Sp) and structure mode index (SMI) in SCI rats were significantly higher than in OVX rats. BV/TV explained 84% of the variation of ultimate load of the proximal tibial metaphysis. There was no difference of the upper tibial epiphyseal plate height between SCI and OVX rats. Serum NTX level in SCI rats was significantly higher than in OVX rats. Conclusions SCI induces more deterioration of cortical bone geometric structure and trabecular microstructure in the proximal tibial metaphysis than OVX.     

Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys

Levormeloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), has been evaluated for its effects on bone in cynomolgus monkeys (Macaca fascicularis). Adult female monkeys were imported from Indonesia and randomized into six groups of 25-28 animals each (n = 158). Animals in one group were sham ovariectomized (sham) and received vehicle. Animals in the remaining five groups were ovariectomized and received either vehicle (ovx); 17beta-estradiol at 0.016 mg/kg (est); or levormeloxifene at 0.5 (L1), 1 (L2), or 5 (L3) mg/kg. Lumbar spine and whole body bone mass were measured by dual-energy X-ray absorptiometry (DXA) pretreatment and at 6 and 12 months following the initiation of treatment. Bone mass at the femoral neck was measured by peripheral quantitative computed tomography (pQCT) at 0 and 12 months. Serum markers of bone turnover, including bone-specific alkaline phosphatase (BSAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary collagen C-terminal extension peptides (CrossLaps), were measured at 0, 6, and 12 months. Ovariectomy resulted in an increase in these markers; the increase was prevented by estradiol or levormeloxifene. Estradiol or levormeloxifene inhibited loss of lumbar spine bone mineral density (BMD) following ovariectomy compared with untreated monkeys (ovx -5.0%; sham -0.4%; est +0.2%; L1 -3.6%, L2 -2.0%, L3 -2.5%). Estradiol, but not levormeloxifene, prevented loss of BMD at the femoral neck (ovx -7.4%; sham -3.1%; est -3.6%; L1 -8.0%, L2 -6.5%, L3 -7.8%), and whole body bone mineral content (BMC) (ovx -7.6%; sham -1.9%, est -2.9%; L1 -6.2%, L2 -6.1%, L3 -6.7%). Bone loss at each site was correlated with bone turnover as measured by serum and urine biomarkers. There was no dose effect of levormeloxifene.     

去势后雌性大鼠体内成骨细胞活性变化的实验研究

目的了解去势后不同时相雌性大鼠体内成骨细胞功能的变化特点,分析其机理。方法6个月龄清洁级健康雌性SD大鼠40只,随机均分为去卵巢组和假手术组,实验时间为4个月。分别于2、16周时每组各处死10只大鼠,取L4和血清,检测骨源性碱性磷酸酶(BALP)、骨钙素(BGP);透视电镜观察成骨细胞的分泌功能和电镜下的形态学变化。结果去势组大鼠体内BGP、BALP水平2周时皆升高,16周时与对照组差异无显著性意义。透视电镜下观察2周时成骨细胞功能活跃,16周时功能趋于静止。结论雌激素减少时,大鼠体内的成骨细胞可出现短暂的功能活跃,而后发生的成骨功能低下是导致骨质疏松症的一个因素。     

Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 ± 1.5 years (x ± SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 ± 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 ± 0.22 vs. −0.12 ± 0.25, +0.03 ± 0.19 vs. −0.54 ± 0.24, and +0.08 ± 0.14 vs. −0.02 ± 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 ± 0.04 vs. 0.40 ± 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (−2.1 ± 1.1 vs. +7.0 ± 3.3 μg/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 ± 2.5% vs. −0.3 ± 1.4%, and +8.1 ± 4.7 vs. −0.9 ±1.7, after 10.3 ± 0.4 and 17.3 ± 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.     

骨形态计量学评价低钙对大鼠皮质骨的作用研究

目的 评价低钙饮食对大鼠皮质骨的影响。方法 3月龄SD普通级雄性大鼠40只，随机分为5组。第1、2组饲养1个月，分为正常对照组(1mol，ca1．0％)和极低钙组VLCD(1mol，Ca0．1％)，余下3组饲养3个月，分为正常对照组(3mol，Ca1．0％)、极低钙组VLCD(3mol，Ca0．1％)和低钙组LCD(3mol，Ca0．3％)。各组动物喂养包含对应钙含量的精制饲料，处死前进行双荧光标记。实验结束时，取左侧胫骨中段行骨形态计量学检测。结果 无论是低钙饮食1个月，还是3个月，无论是极度缺钙，还是仅有轻微的钙不足，胫骨中段横截面皮质骨始终未出现显著意义的变化，但骨内膜骨吸收有增加的趋势。结论 低钙对皮质骨作用不明显，这可能与机体在低钙状态下动用骨骼的次序或快慢有关。     

中药骨康对去卵巢大鼠腰椎骨形态计量学的影响

目的 探讨中药骨康对卵巢切除大鼠骨质疏松症的治疗作用。方法 选择6m龄SD大鼠48只。随机分为假手术模型组（Sham）、手术模型组（OVX）、尼尔雌醇组（E2）、中药骨康组。切除大鼠卵巢3m后。大鼠骨质疏松症模型制备成功，分别给予尼尔雌醇、中药骨康灌胃治疗，并与Sham组和OVX组对照。治疗3m后，体内双荧光标记，取第2腰椎包埋切片。全自动图像分析及松质骨骨形态计量学软件处理。观察中药对骨形态计量学参数的影响。结果 卵巢切除后大鼠骨小梁面积百分数（％Tb．Ar）下降35．84％，骨小梁数量（Tb．N）下降16．60％，骨小梁宽度（Tb．Th）下降25．79％，表明绝经后骨质疏松症动物模型成立。骨康治疗3个月后，与OVX组相比，Oc．N／mm^2下降42．80％，有显著性差异（P〈0．01）；％Tb．Ar、Tb．Th、Tb．N和MAR有上升趋势（P〉0．05）；15．Sp，％L．Pm、BFR／BS、BFR／TV和Oc．N／mm，BFR／BV有下降趋势（P〉0．05）。结论 中药骨康具有降低骨转换以及促进骨形成和抑制骨吸收的双重作用，说明中药骨康对骨质疏松有明显的治疗作用。     

Effects of salmon calcitonin on the bone loss induced by ovariectomy

Summary We present the results of a 12-month clinical study assessing the effects of synthetic salmon calcitonin (sCT) on a group of fertile white women who had undergone ovariectomy for uterine fibromatosis. The study was performed to verify whether CT can prevent the loss of bone mass and the changes in calcium-phosphorus metabolism associated with acute estrogen deficiency. The study consisted of an initial double-blind phase of 6 months, followed by a 6-month open period. Treated patients were given 100 MRC U of synthetic salmon CT injected i.m. in the morning, every other day, starting on the 7th day after the operation and continued for 12 months. Control patients received a placebo injection for the first 6 months; subsequently, they too were treated with sCT i.m. every other day for 6 months at the same dose as the 12 month-treated group. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radio nuclides, 241 Am and 125 I, with energies of about 60 and 30 KeV. Biochemical parameters of the calcium-phosphorus metabolism were also measured. After 12 months of study, no significant changes of BMC were observed in the 12 months sCT treated group, while control patients, treated 6 months after the ovariectomy, showed a significant decrease in BMC values. Total hydroxyproline/ creatinine (OHPr/Cr) ratio, which increased after ovariectomy, returned to normal after the first month of sCT administration in the continuously treated group whereas it remained high in the control group up to the 6th month of observation, declining thereafter in coincidence with sCT treatment. The behavior of Bone GLA-protein (BGP), like that of the nondializable OHPr/Cr ratio, was substantially similar in both treated and control groups for the entire period of observation. These results show that prophylactic administration of salmon CT in ovariectomized women prevent estrogen deficiency-induced bone loss, inhibiting skeletal resorption and allowing osteogenesis to occur normally.