利塞膦酸钠和阿仑膦酸钠治疗对股骨粗隆下侧皮质骨密度变化的影响对比研究

目的回顾性评估利塞膦酸钠和阿仑膦酸钠治疗对股骨粗隆下侧皮质(subtrochanteric lateral cortex,STLC)骨密度(bone mineral density,BMD)变化的影响。方法共有168例受试者,使用双能X线骨密度仪(dual energy X-ray absorptiometry,DXA)对其BMD进行2～4年间隔随访,纳入本次回顾性研究,分为3组:46例未服用任何抗骨质疏松药物(对照组),69例使用阿仑膦酸钠(阿仑膦酸钠组),53例使用利塞膦酸盐(利塞膦酸盐组)。通过在骨皮质上绘制矩形感兴趣区,在每位患者的STLC和转子下内侧皮质(subtrochanteric medial cortex,STMC)中测量BMD。通过使用协方差模型控制来分析STLC中BMD的百分比变化,以控制年龄、体质量指数、STMC百分比变化、髋轴长度、DXA检查之间的时间间隔的5个独立变量。结果对照组、阿仑膦酸盐组和利塞膦酸盐组BMD的最小均数±标准差分别为1.47±1.51、2.24±1.27和6.98±1.23。与对照组(调整后的P=0.010)或阿仑膦酸盐组(调整后的P=0.011)相比,利塞膦酸盐组的STLC显示出更高的BMD百分比变化。结论利塞膦酸盐组中STLC的BMD变化百分比大于阿仑膦酸盐组和对照组。     

Clinical trial of risedronate in Japanese volunteers: a study on the effects of timing of dosing on absorption

Because of its chemical structure, risedronate was thought to form a complex with divalent cations, e.g., Ca²⁺, and to be likely to show changes in the efficiency of absorbance from the gastrointestinal tract according to the presence of food. Therefore, we conducted a crossover study using healthy Japanese adults to examine the effects of food intake on absorption after the oral administration of risedronate and to choose the best timing of regimen for risedronate. Using single doses of 5mg risedronate, the following four dose times were investigated: (a) in the morning under a fasting condition without breakfast; (b) 30min before breakfast; (c) 30min after breakfast; and (d) 3h after breakfast. The results showed that the C_max and AUC_0–24 of the plasma risedronate concentrations and its cumulative urinary excretions decreased in the following order: fasting without breakfast 30min before breakfast 3h after breakfast 30min after breakfast. In other words, it was demonstrated that the absorption of risedronate decreases due to the effects of food. Several adverse events, whose causality with risedronate was unknown or possibly related, were observed, including headaches, diarrhea, increased CK-BB, and an increased urinary ₂-microglobulin excretion rate, but none of these events was clinically significant, and none differed in frequency or severity from the events after a single oral administration. In consideration of the optimal practical timings required to administer risedronate for Japanese patients, therefore, it was found that ingesting the drug immediately after waking up in the morning, when the stomach is empty, was optimal, and that it was necessary to refrain from eating and drinking for at least 30min after drug ingestion. Therefore, we determined that the optimal time for risedronate to be administered in Japanese patients is 30min before breakfast.     

Enhancement of osteogenesis post‐splenectomy does not attenuate bone loss in ovariectomized rats

The roles of different immune cell populations and cytokines in bone metabolism have been extensively investigated. However, the influence of whole immune organ removal on osteopathology remains unknown. In the current study, we investigated the effects of splenectomy on bone metabolism and microarchitecture in rats with or without concurrent ovariectomy. Ovariectomized (OVX) rats were used as osteoporosis model. Sixty 12‐week‐old female rats were randomized into 4 groups (n = 15): sham, splenectomized (SP), ovariectomized, as well as ovariectomized and splenectomized (OVX + SP). Bone microarchitecture was assessed by micro CT analysis at 4 week and 12 week post‐operation, respectively. Bone pathology and metabolism were evaluated via immunohistochemical staining. The serum levels of alkaline phosphatase (ALP), tumor necrosis factor‐alpha (TNF‐α), tartrate‐resistant acid phosphatase 5b (Tracp5b), and C‐terminal telopeptide (CTx) were analyzed at 4 and 12 weeks post‐operation. Removal of the spleen led to alterations in the homeostasis of bone metabolism and increased bone formation in rats. In this study, our findings indicate that the spleen is involved in skeletal metabolism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1356–1363, 2015.     

Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies

The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1mg to 2.5, 5, 10, or 20mg. Subsequently, risedronate was given by multiple administration, 5mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary ₂-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20mg or as a multiple administration of up to 5mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C_max, after the administration of risedronate at 1, 2.5, 5, 10, and 20mg, increased dose dependently, and the T_max, t_1/2, and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5mg risedronate to the United Kingdom study population.     

Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized Rats

Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re‐established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re‐establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen‐deficiency osteoporosis. Two hundred ten, 6‐mo‐old female Sprague‐Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle‐treated controls (CON; 0.3 ml sterile water), ALN (2.4 μg/kg), low‐dose RIS (RIS low; 1.2 μg/kg), and high‐dose RIS (RIS high; 2.4 μg/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L₄ vertebrae) bone. DXA and mechanical testing was performed on the L₅ vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug‐treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate‐treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re‐established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN‐treated animals but not in RIS‐treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug‐treated animals through 16 wk after withdrawal.     

Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats

The effect of dietary vitamin K₂ (menaquinone-7) on bone loss in ovariectomized (OVX) rats was investigated. OVX rats were freely given experimental diets containing menaquinone-4 (MK-4; 12 mg/100 g diet) or menaquinone-7 (MK-7; 18.1 mg/100 g diet) for 24 days; MK-4 and MK-7 were equal in molar concentrations. This feeding caused a remarkable increase of MK-4 and MK-7 concentrations in the serum and femur of OVX rats. OVX-induced decrease in the femoral dry weight and femoral calcium content was prevented by the feeding of dietary MK-4 or NK-7. In separate experiments, OVX rats were freely given experimental diets containing the fermented soybean (natto; including 9.4 μg MK-7/100 g diet) without or with added MK-7 (37.6 μg/100 g diet) for 77 days. Feeding produced a significant elevation of MK-4 and MK-7 concentrations in the serum of OVX rats. In this case, a significant increase in the femoral MK-4 content was observed but MK-7 was not detected in the femoral tissues. OVX-induced decreases in the femoral dry weight and femoral calcium content were significantly prevented by the feeding of diets containing natto with MK-7 added (37.6 μg/100 g diets). This study demonstrates that the intake of dietary MK-7 has a preventive effect on bone loss caused by OVX. This effect may be partly caused by MK-4, which is formed by degradation of MK-7. Received: July 23, 1998 / Accepted: Sept. 28, 1998     

黄芪多糖治疗对去卵巢诱导骨质疏松大鼠骨密度、骨量和骨代谢的影响

目的探索黄芪多糖对去卵巢大鼠骨量和骨代谢以及BMP-2/Smads信号通路的影响。方法30只雌性SD大鼠进行去卵巢手术或假手术。正常饲养12周后被分为黄芪多糖组(ASNT组)、对照组(CON组)和去卵巢组(OVX组),其中黄芪多糖组每天给予400 mg/kg黄芪多糖治疗。通过骨密度、骨代谢指标、Micro-CT以及WB检测评估ASNT对骨质疏松症大鼠骨量、骨代谢以及BMP-2/Smads信号通路的影响。结果经过12周治疗,ASNT组大鼠骨密度较OVX组显著增加(P<0.05);ASNT治疗12周可以降低血清ALP和OC水平,增加血钙含量,增加股骨骨密度。经过12周治疗,ASNT组大鼠骨体积分数(BV/TV)、表面积体积分数(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)较OVX组显著增加;而骨小梁间隙(Tb.Sp)较OVX组显著降低,差异比较有统计学意义(P<0.05)。WB结果表明OVX大鼠骨组织的BMP-2/Smsds信号通路受到抑制;ASNT可以通过上调BMP-2、p-Smad1和p-Smad5的表达显著激活BMP-2/Smsds信号通路传导。结论研究表明ASNT对去卵巢大鼠骨密度和骨量具有保护作用,可能和激活BMP-2/Smads信号通路有关。     

Prolonged intake of fermented soybean (natto) diets containing vitamin K2 (menaquinone-7) prevents bone loss in ovariectomized rats

The effect of the prolonged intake of dietary vitamin K₂ (menaquinone-7, MK-7) on bone loss in ovariectomized (OVX) rats was investigated. OVX rats were freely given experimental diets containing the fermented soybean (natto; including 9.4 μg MK-7/100 g diet) without or with supplemental MK-7 (containing 14.1 or 18.8 μg of MK-7 as total per 100 g diet) for 150 days. Feeding produced a significant elevation of MK-7 concentration in the serum of OVX rats. In this case, the femoral MK-4 content was significantly increased, but MK-7 was not detected in the femoral tissues, indicating degradation of MK-7. Serum γ-carboxylated osteocalcin concentration was significantly decreased by OVX. This decrease was significantly prevented by the feeding of the natto diets with supplemental MK-7 (18.8 μg/l00 g diets). OVX caused a significant decrease in femoral dry weight, femoral calcium content, and mineral density. These decreases were significantly prevented by feeding with diets containing natto with MK-7 (total, 18.8 μg/100 g diets). This study demonstrates that the prolonged intake of natto dietary including MK-7 has a preventive effect on bone loss induced by OVX. Dietary MK-7 may be useful in the prevention of osteoporosis. Received: June 18, 1999 / Accepted: Sept. 3, 1999     

Trabecular bone score in patients with liver transplants after 1 year of risedronate treatment

The aim of this study was to analyse the effect of risedronate on Trabecular Bone Score in liver transplant patients with low bone mass, during 1‐year follow‐up. In this retrospective cohort study, trabecular bone score (TBS) was calculated from dual X‐ray absorptiometry images of the lumbar spine (LS), collected from a prospective randomized open‐label 1‐year trial performed in liver recipient patients. A total of 89 patients with osteopenia or osteoporosis were randomized to receive RIS plus calcium and vitamin D3 or calcium and vitamin D3. TBS was low in both groups at baseline, 6 and 12 months. Baseline TBS at the LS showed degraded microarchitecture in 22.8% of patients, partially degraded in 40.3%, and normal values in 36.8% of the patients. After 1 year of treatment, no difference in TBS was observed between both groups. No correlations were found between bone mineral density (BMD) and TBS values at any follow‐up time point. No relationship was found between BMD, TBS or immunosuppressive drugs with incidental fracture. No significant effect in TBS was observed in liver transplant patients treated with RIS or calcium and vitamin D3 after 1 year of follow‐up. In these patients, the clinical usefulness of this new tool should be established.     

人工虎骨粉对去卵巢大鼠骨组织中Sirt1/Runx2信号通路的影响

目的探讨人工虎骨粉对去卵巢大鼠骨组织中Sirt1/Runx2信号通路的影响。方法选取40只成年雌性SD大鼠,建立去卵巢大鼠模型,切除卵巢2周后分成人工虎骨粉组与去卵巢组,人工虎骨粉组给予灌胃人工虎骨粉0. 24 g/(kg·d),去卵巢组给予灌胃等效剂量的生理盐水。另取20只成年雌性SD大鼠作为假手术组,仅切除卵巢周围脂肪组织,不切除双侧卵巢,切除卵巢周围脂肪组织2周后给予灌胃等效剂量的生理盐水。连续给药12周后,进行股骨骨密度、骨代谢、骨生物力学、股骨组织学与Western Blot检测。结果与假手术组比较,去卵巢组股骨骨密度、最大载荷、断裂载荷、最大应力、弹性模量及股骨组织Sirt1、Runx2、Foxo1、Foxo3a蛋白表达降低,骨钙素、抗酒石酸酸性磷酸酶、血钙、血磷及碱性磷酸酶浓度升高,股骨组织呈现骨质疏松病理改变;与去卵巢组比较,人工虎骨粉组股骨密度、最大载荷、断裂载荷、最大应力、弹性模量及股骨组织Sirt1、Runx2、Foxo1、Foxo3a蛋白表达升高,骨钙素、抗酒石酸酸性磷酸酶、血钙、血磷及碱性磷酸酶浓度均降低,骨质疏松病理改变显著改善。结论人工虎骨粉可能通过调节Sirt1/Runx2信号通路来发挥抗骨质疏松作用。     

Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single‐center study

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D₃ 800 IU/day (n = 45) or calcium and vitamin D₃ at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum β‐CrossLaps (β‐CTX) and procollagen type 1 amino‐terminal peptide (P1NP) and fracture rate. Spine X‐rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum β‐CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.     

缺氧诱导因子抑制剂对去卵巢大鼠骨质疏松症治疗效果的研究

目的研究缺氧诱导因子抑制剂对卵巢切除(ovariectomized,OVX)雌性Sprague-Dawley大鼠的治疗效果,比较缺氧诱导因子抑制剂对骨密度的影响。方法在大鼠卵巢切除12周后,使用缺氧诱导因子抑制剂进行治疗。治疗8周后,在实验结束时将大鼠进行安乐死处理,获取大鼠血清、股骨和胫骨。通过生物力学测试,Micro-CT扫描和血清生化分析进行评估。结果与未给药的OVX大鼠相比,缺氧诱导因子抑制剂的全身给药显著降低了骨代谢指标Ⅰ型前胶原氨基末端前肽(type I collagen N terminal peptide,PINP)和Ⅰ型胶原羧基端肽(type I collagen carboxy-terminal peptide,CTX-I),增加了大鼠胫骨骨密度(bone mineral density, BMD),增强了股骨极限载荷、能量和刚度,差异比较有统计学意义(P0.05)。结论缺氧诱导因子抑制剂能有效改善OVX诱导的骨质疏松症。     

Combined intervention of dietary soybean proteins and swim training: effects on bone metabolism in ovariectomized rats

Soybean proteins, a rich source of isoflavones, taken immediately after an ovariectomy prevent bone loss in rats. Exercise-induced stimuli are essential for bone growth. Few studies exist about the combined effects of swim training and soybean protein supplementation on bone metabolism. So, the purpose of this study was to investigate, in 48 female Sprague-Dawley rats (12 weeks old) the effects of an 8-week swim-training regimen (1 h/day, 5 days/week) and dietary soybean proteins (200 g/kg diet) on bone metabolism. Rats were randomly assigned to four groups: (1) ovariectomized fed with a semisynthetic control diet; (2) ovariectomized fed with a soybean protein-enriched semisynthetic diet; (3) ovariectomized trained to exercise and fed with control diet; (4) ovariectomized trained to exercise and fed with a soybean protein diet. Following the treatment period, body weight gain was identical in the four groups. Soybean protein supplementation increased bone calcium content, and reduced plasma osteocalcin values, without significant modification of calcium balance and net calcium absorption. Swim training enhanced plasma and bone calcium content and calcium balance and net calcium absorption. It did not modify either plasma osteocalcin values or urinary deoxypyridinoline excretion. Both exercise and soybean protein intake increased plasma on bone calcium without modifying net calcium absorption or bone markers. In conclusion, we demonstrated, in ovariectomized rats, that swimming exercise and dietary supplementation with soy proteins do not have synergistic effects on calcium metabolism and bone markers.     

The cost-effectiveness of risedronate treatment in Japanese women with osteoporosis

We constructed a mathematical model for assessing the cost-effectiveness of providing BMD (bone mineral density) scans to Japanese women aged 55 years and over and treating, with risedronate, those that are shown to be osteoporotic. Fracture rates, cost data, utility values, and the increased risks of fractures associated with T-score and vertebral fracture history were taken from published literature. We estimated the cost of fractures avoided due to risedronate treatment, allowing the net changes in cost, incorporating both intervention and fracture costs to be calculated. The QALYs (quality adjusted life years) gained through treatment were calculated enabling cost per QALY ratios to be presented. Further analyses were undertaken assuming treatment was reserved for older women and/or those who had sustained a vertebral fracture in the previous 2 years. Cost per QALY values were inversely related to absolute risk of fracture. Assuming a cost per QALY value threshold of US$100,000, we concluded that providing BMD scans to women aged 70 years and over who had sustained a vertebral fracture in the previous 2 years and treating those that were osteoporotic was cost-effective. However, providing BMD scans for women without a vertebral fracture in the previous 2 years was not cost-effective, even in women aged 85 years and older.     

肉桂醛对去卵巢诱导的骨质疏松大鼠模型骨密度和骨量的保护作用

目的探讨肉桂醛对去卵巢手术诱导的骨质疏松症大鼠模型中骨密度(BMD)和骨量的影响。方法 24只雌性Sprague-Dawley大鼠经过去卵巢手术或假手术。12周后大鼠被分为肉桂醛组(RGQ组)、对照组(CON组)和去卵巢组(OVX组)。检测所有大鼠股骨和腰椎骨密度(BMD),血清细胞因子肿瘤坏死因子-α(TNF-α)和IL-6(Interleu-kin)水平和进行股骨组织形态学分析。结果去卵巢手术显著降低大鼠的BMD值、骨小梁数量、小梁厚度和小梁面积;此外,显著增加骨小梁分离度和血清TNF-α和IL-6水平;和CON组比较差异有统计学意义(P0.05)。而RGQ治疗后,RGQ组大鼠大鼠的BMD值、骨小梁数量、小梁厚度和小梁面积显著增加,骨小梁分离度和血清TNF-α和IL-6水平显著降低;和CON组比较差异有统计学意义(P0.05)。结论肉桂醛对去卵巢手术诱导的骨质疏松症大鼠模型中骨密度(BMD)和骨量有保护作用。     

利塞膦酸钠联合雷洛昔芬治疗绝经后骨质疏松症疗效分析

目的观察利塞膦酸钠联合雷洛昔芬治疗绝经后女性骨质疏松症的效果。方法将148例绝经后女性骨质疏松症患者随机分为治疗组和对照组,治疗组给予利塞膦酸钠联合雷洛昔芬治疗,对照组给予利塞膦酸钠治疗。在治疗前及治疗后12个月分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标、激素水平及研究期间药物不良反应和VAS评分的变化。结果药物治疗后12个月,两组腰椎(L1～4)及左侧股骨颈的骨密度明显增加,治疗组的骨密度显著高于对照组(P0. 05);血清雌激素和孕酮水平均明显下降,皮质醇水平明显上升,与治疗前相比差异有统计学意义(P0. 05),而对照组与治疗前相比差异无统计学意义(P0. 05);治疗后两组血清P1NP及β-CTX较治疗前明显下降、BAP和BGP较治疗前明显上升,比较差异有统计学意义(P0. 05),治疗组较对照组的改善更为明显(P0. 05);治疗后两组患者VAS评分较治疗前显著降低,比较差异有统计学意义(P0. 05),治疗组较对照组降低得更为明显(P0. 05);两组患者在研究期间的药物不良反应无统计学意义(P0. 05)。结论利塞膦酸钠联合雷洛昔芬治疗骨质疏松症较单独使用利塞膦酸钠治疗的效果更为显著,且不增加药物副作用。     

The long-term effects of ovariectomy on bone metabolism in sheep

Osteoporosis and associated fractures are major public health concerns, and as such require appropriate large animal models to further our understanding of this disease. Although sheep appear to be an ideal model with which to study bone loss caused by estrogen depletion, limited data are available concerning the long-term effect of ovariectomy on bone in sheep. The goal of the present study was to observe the ovariectomy-induced changes in bone mass, structure, and metabolism in sheep over a period of 18 months. Six ewes were ovariectomized (OVX) and compared to an age-matched control group by analyzing bone mineral density, trabecular structure, biochemical markers of bone formation and resorption, and plasma estrogen levels. Bone loss (13%, P < 0.01) occurred during the first 4 months after surgery, then stabilized and returned to pre-OVX levels for the remainder of the study. Trabecular architecture was also altered and tended toward osteopenia with recovery to baseline values. Markers of bone formation and resorption were elevated up to 6 months postovariectomy, after which time levels returned to baseline values. Although estradiol measurements demonstrated a clear decline following surgical ovariectomy, levels returned to normal after 6 months. Therefore, the detrimental effect of ovariectomy on sheep bone metabolism seems to be reversible, with normal bone parameters being reestablished within 6 months after surgery. These data seem to indicate that the sheep is not an appropriate model for human postmenopausal osteoporosis.     

人参水煎剂防治去卵巢大鼠骨量丢失的骨形态计量学观察

目的 探讨人参水煎剂对去卵巢大鼠骨量丢失的骨形态学改变及其预防作用。方法4.5月龄SD雌性大鼠,按体重随机分为基础组、假手术组、去卵巢组、已烯雌酚阳性用药组、人参低剂量用药组、人参高剂量用药组,共给药10周,取胫骨上段骨组织包埋,不脱钙骨切片,用全自动图像分析仪及松质骨形态计量学软件进行测量和分析,观察人参对骨形态计量学参数的影响。结果 去卵巢10周后骨量丢失和破骨细胞活性、骨形成及骨转换率增加,差异有显著性(P<0.01)。低剂量的人参能使骨量增加26.6％,高剂量能使骨量增加35.1％,高低两剂量人参能使大鼠的骨吸收和骨转换率均下降,差异有显著性(P<0.01或0.05),不抑制藕联的骨形成。结论去卵巢大鼠骨量丢失,骨转换率增高,出现明显的骨质疏松;已烯雌酚(10μg·kg-1·d-1)能抑制骨吸收,也抑制骨形成。人参有增加骨量的趋势,增加骨形成,并对子宫无刺激作用,有弱的预防去卵巢大鼠的骨量丢失作用。     

不同运动强度对去势大鼠骨质疏松软骨形态的影响

目的探讨不同运动强度在去势SD大鼠骨质疏松中的应用效果及对软骨形态的影响。方法 2017年9月至2018年11月在中山大学附属第三医院中心实验室取40只SD大鼠作为研究对象,采用切断输卵管及切除卵巢方法建立大鼠骨质疏松模型。取同期实验的SD健康大鼠10只作为假体手术组。根据大鼠处理方法不同分为模型对照组、低强度组、中等强度组及高强度组,每组10只。模型对照组常规饲养,低强度组跑台训练10 m/min,中等强度组进行20 m/min跑台训练,高强度组进行25 m/min跑台训练,每天1 h,连续训练6周。比较不同组大鼠训练6周后关节软骨mankin score评分、关节软骨厚度、血清钙、磷及MMP-3水平、HE及番红染色情况。结果①中等强度组简易精神状态评价(MMS)评分低于低强度组、高强度组及模型对照组(P0.05);低强度组MMS评分低于高强度组及模型组(P0.05);中等强度组关节软骨厚度高于低强度组、高强度组及模型对照组(P0.05);②中等强度组血清钙、血清磷水平低于低强度组、高强度组及模型对照组(P0.05);③模型对照组软骨表面光滑,呈圆形或椭圆形;低强度组大鼠人软骨表面相对光滑,细胞数量相对较多,排列规则,染色加深;中载荷运动组软骨表面光滑,染色明显增粗,基质染色较深,染色均匀;高强度组潮线不规则,染色相对较浅。结论中等运动强度用于去势大鼠骨质疏松中效果理想。