骨形态计量学观察睾酮对雄性去势大鼠松质骨的影响

目的 通过骨形态计量方法观察雄激素替代疗法对去睾丸致骨质疏松大鼠不同部位松质骨的影响。方法30只4月龄SD雄性火鼠，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组每日生理盐水5ml／kg，D组每日甲基睾丸酮片1．8mg／kg，灌胃90d。实验结束，处死全部大鼠，取胫骨上段和第5腰椎进行不脱钙骨制片，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 大鼠去睾丸后胫骨上段骨量下降，骨形成和骨吸收都增加；腰椎骨量也下降，骨吸收也增加，但骨形成表现为降低。睾酮能阻止去睾丸后胫骨上段的骨量丢失（％Tb．Ar＋44．8％，P〈0．05），降低骨高转换；但不能完全阻止腰椎的骨量丢失，只能抑制骨吸收，对骨形成影响不大。结论 雄激素替代治疗能阻止雄激素水平下降造成的大鼠松质骨的骨量丢失，胫骨上段对雄激素的敏感性比腰椎部位的高。     

不同骨密度骨质疏松性椎体压缩骨折骨组织形态与骨代谢标志物分析

目的 观察不同骨密度骨质疏松椎体压缩骨折(osteoporotic vertebral compression fracture,OVCF)骨组织形态学特征及骨代谢标志物变化规律.方法 将136例OVCF患者按不同骨密度(T值)分为3组:I组,-3.5相似文献   

骨形态计量学观察丹参骨宝对环磷酰胺大鼠胫骨上段的影响

目的用环磷酰胺造成大鼠的骨丢失，观察丹参骨宝的影响。方法用4．5mg·kg^-1·d^-1的环磷酰胺灌胃给大鼠，连续15d，造成大鼠骨丢失；用丹参骨宝进行预防给药。实验结束后，取大鼠左侧胫骨上段进行不脱钙包埋切片作骨组织形态计量学测量。同时观察大鼠胸腺、脾脏的重量指数，以及外周血白细胞数量。结果环磷酰胺可使大鼠外周血白细胞数量和脾脏指数明显下降，本实验剂量的丹参骨宝不能有效对抗这种免疫抑制。环磷酰胺通过明显抑制骨形成而导致骨量减少，骨显微结构退化等典型骨质疏松特征的出现。丹参骨宝能通过增加骨的沉积矿化率，促进成骨活性而增加环磷酰胺大鼠的骨量，改善骨微观结构。结论丹参骨宝可有效预防环磷酰胺所引起的大鼠骨丢失，其预防机制与促进骨的矿化沉积率，增加骨形成活性有关。     

Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies

Denosumab, a human monoclonal antibody against RANKL, reversibly inhibits osteoclast‐mediated bone resorption and has been developed for use in osteoporosis. Its effects on bone histomorphometry have not been described previously. Iliac crest bone biopsies were collected at 24 and/or 36 months from osteoporotic postmenopausal women in the FREEDOM study (45 women receiving placebo and 47 denosumab) and at 12 months from postmenopausal women previously treated with alendronate in the STAND study (21 continuing alendronate and 15 changed to denosumab at trial entry). Qualitative histologic evaluation of biopsies was unremarkable. In the FREEDOM study, median eroded surface was reduced by more than 80% and osteoclasts were absent from more than 50% of biopsies in the denosumab group. Double labeling in trabecular bone was observed in 94% of placebo bones and in 19% of those treated with denosumab. Median bone‐formation rate was reduced by 97%. Among denosumab‐treated subjects, those with double labels and those with absent labels had similar levels of biochemical markers of bone turnover. In the STAND trial, indices of bone turnover tended to be lower in the denosumab group than in the alendronate group. Double labeling in trabecular bone was seen in 20% of the denosumab biopsies and in 90% of the alendronate samples. Denosumab markedly reduces bone turnover and also reduces fracture numbers. Longer follow‐up is necessary to determine how long such low turnover is safe. © 2010 American Society for Bone and Mineral Research.     

Effect of calcitonin on bone histomorphometry and bone metabolism in rheumatoid arthritis

Summary Twenty-four women (mean age±SD 49±13 years) with classical or definite rheumatoid arthritis (disease duration 15±8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P< 0.001). There was also a significant increase (P< 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA.     

Bone histomorphometry,bone mass,and related parameters in alcoholic males

Summary Bone mass and related metabolic variables were studied in 50 males known to be, or to have been, regular alcohol abusers. Subjects were divided into those who were still drinking and those who had abstained for at least 3 months, and the former further subdivided into moderate and heavy drinkers. Twenty-five had at least two atraumatic spinal crush fractures. In 25 cases, bone histomorphometry was carried out. Lumbar bone mineral density and iliac crest bone volume were significantly lower in spinal crush fracture cases. Parathyroid hormone, testosterone, and urinary cortisol measurements showed no difference between groups. Alkaline phosphatase and 24-hour urine hydroxyproline were higher in osteoporotics than in nonosteoporotics. On bone histomorphometry, there were essentially no differences between those with and those without fractures in terms of bone formation and resorption parameters. Drinkers showed lower osteoid seam width and fraction of osteoid covered by osteoblasts, as well as fewer osteoblasts per 10 cm of bone surface than abstainers. Mineralization lag time was prolonged, and mineralization rate per day was lower in the drinkers. Osteon formation time was prolonged in the drinkers. On the resorption side, only the osteon resorption time was significantly different in the drinkers, being prolonged. The heavy drinkers, but not the moderate drinkers, had a significantly reduced surface extent of lacunae. We conclude that alcohol consumption has clear detrimental effects on bone formation with less pronounced suppressive effects on bone resorption. In no biochemical or hormonal measurement, however, with the exception of hydroxyproline excretion and plasma alkaline phosphatase, could those who had osteoporosis be distinguished from those who did not.     

Intersample variation in bone histomorphometry: Comparison between parameter values measured on two contiguous transiliac bone biopsies

Summary In order to evaluate the intersample variations for bone histomorphometric parameters in various metabolic bone diseases, either for a group or for one single patient, two complete contiguous transiliac bone biopsies were taken in 55 subjects. The diagnoses were osteoporosis (OP), renal osteodystrophy (ROD), osteomalacia (OM), primary hyperparathyroidism (HPT), metastatic bone disease, fluorosis, thyrotoxic bone, and “normal” bone. The following histomorphometric parameters were measured: trabecular bone volume (TBV), trabecular osteoid surfaces (TOS) and volume (TOV), trabecular resorption surfaces (TRS), and calcification rate (CR). The thickness index of osteoid seams (TIOS) was calculated. The measurements were performed with both manual and computerized methods which give similar results according to our previous study. The differences between parameters values measured on both cores were expressed by the difference in percent of the mean and by the intrapair coefficient of variation. Moreover, for each parameter, the confidence interval for one subject was calculated from the residual mean square of a two-way analysis of variance. For each parameter, the intersample variation differs according to the diagnosis. Confidence interval (risk=5%) for one single subject reaches 29% for TBV in OP; 16% for TOS; 26% for TOV and TIOS in OM; 25% for TRS in ROD, and 69% in HPT, but is much lower for groups of 10 and 20 patients. These variations must be taken into account when successive biopsies are performed in one individual or in groups of patients to follow the course of a disease or evaluate the effects of a therapy.     

Preventive effects of intermittent administration of human parathyroid hormone on steroid-induced osteopenia in rats

The purpose of this study was to determine the preventive effect of intermittent administration of human parathyroid hormone (h-PTH) on bone change in steroid-treated rats; this was done by histomorphometric and biochemical analysis. Seven-month-old female Wistar rats were divided into four groups; in-each of the four groups one subgroup was treated for 4 weeks and one for 8 weeks. The groups consisted of: untreated controls, a steroid group (receiving prednisolone), a steroid + PTH group (predniso-lone and h-PTH administered simultaneously), and a steroid + PTH vehicle group. Prednisolone (2.5 mg/kg) and h-PTH (1–34) (6.0 μg/kg) were administered six times a week during the experimental period. At necropsy, bilateral tibiae were collected: one was used for preparing undecalcified sections after Villanueva bone staining, and the other for decalcified tartrate-resistant acid phosphatase (TRAP) stained sections. Biochemical analysis showed that steroids increased urinary calcium at the 8th week; however, such bone metabolic markers as serum 1,25-(OH)₂D and urinary deoxypyridinoline did not change in any treatment group. Histomorphometrically, steroid-induced osteopenia was established at the 8th week by inhibition of both bone formation and bone resorption. The simultaneous intermittent administration of PTH plus steroid, however, increased both bone formation and bone resorption, resulting in increases in bone volume beginning at 4 weeks. These results suggest that the simultaneous intermittent administration of PTH with steroid prevents steroid-induced low-turnover osteopenia by stimulating bone turnover.     

Effects of sodium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 ± 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer−NaB−). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB−), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to anova with the Tukey–Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB− groups than in the two other groups (P < 0.005–0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB− group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects. Received: May 1, 2000 / Accepted: August 11, 2000     

Bone Mass Is Preserved and Cancellous Architecture Altered Due to Cyclic Loading of the Mouse Tibia After Orchidectomy

Introduction : The study of adaptation to mechanical loading under osteopenic conditions is relevant to the development of osteoporotic fracture prevention strategies. We previously showed that loading increased cancellous bone volume fraction and trabecular thickness in normal male mice. In this study, we tested the hypothesis that cyclic mechanical loading of the mouse tibia inhibits orchidectomy (ORX)‐associated cancellous bone loss. Materials and Methods : Ten‐week‐old male C57BL/6 mice had in vivo cyclic axial compressive loads applied to one tibia every day, 5 d/wk, for 6 wk after ORX or sham operation. Adaptation of proximal cancellous and diaphyseal cortical bone was characterized by μCT and dynamic histomorphometry. Comparisons were made between loaded and nonloaded contralateral limbs and between the limbs of ORX (n = 10), sham (n = 11), and basal (n = 12) groups and tested by two‐factor ANOVA with interaction. Results : Cyclic loading inhibited bone loss after ORX, maintaining absolute bone mass at age‐matched sham levels. Relative to sham, ORX resulted in significant loss of cancellous bone volume fraction (?78%) and trabecular number (?35%), increased trabecular separation (67%), no change in trabecular thickness, and smaller loss of diaphyseal cortical properties, consistent with other studies. Proximal cancellous bone volume fraction was greater with loading (ORX: 290%, sham: 68%) than in contralateral nonloaded tibias. Furthermore, trabeculae thickened with loading (ORX: 108%, sham: 48%). Dynamic cancellous bone histomorphometry indicated that loading was associated with greater mineral apposition rates (ORX: 32%, sham: 12%) and smaller percent mineralizing surfaces (ORX: ?47%, sham: ?39%) in the final week. Loading resulted in greater BMC (ORX: 21%, sham: 15%) and maximum moment of inertia (ORX: 39%, sham: 24%) at the cortical midshaft. Conclusions : This study shows that cancellous bone mass loss can be prevented by mechanical loading after hormonal compromise and supports further exploration of nonpharmacologic measures to prevent rapid‐onset osteopenia and associated fractures.     

Brazilian normal static bone histomorphometry: effects of age,sex, and race

Bone histomorphometry values for normal individuals within different populations have been well established. We studied iliac crest bone samples from 125 healthy Brazilian subjects. The effect of sex, race, and age variables on histomorphometric parameters was evaluated. Bone volume showed a trend to decrease with age in both sexes, being significantly higher in black females and Caucasian males. Interactions among sex, race, and age had no effect on trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). However, age had a significant effect on Tb.Th and Tb.Sp, and sex had an impact on Tb.Sp. Trabecular number (Tb.N) was higher in black females than in males and was higher in Asian males than in females. Among females, Tb.N was lower in Asians than in other races and was higher in blacks than in Caucasians and or in those of mulattos. In addition, Tb.N was higher in males under 10 than in males over 50 years old, was higher in females under 10 than in females in any other age bracket, and was lower in females in the 41–50 age bracket than in younger females. Osteoid volume and osteoid surface were significantly higher in males than in females, and a significant age-related difference in osteoid thickness was observed. No significant sex-related or race-related differences were found in terms of resorption, although eroded surface decreased with age. In conclusion, sex, race, and age, as well as interactions among these three variables, were found to affect some static histomorphometric indexes in healthy Brazilian subjects.     

Effect of a five-week swimming program on rat bone: A histomorphometric study

Summary To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swin training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2–6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. Normal gravity would be an important cofactor in the osteogenic effects of exercise.     

Experimental study of vascularized bone grafts in rat: Effect of mechanical loading on bone dynamics

We studied the etiology of postoperative hypertrophy of vascularized bone grafts in a murine experimental model. Syngeneic grafting of revascularized ulna to rat tibia was performed with (group 1) or without (group 2) mechanical loading. The effect of simple overloading on intact bone was studied by segmental resection of the radius (group 3). Bone dynamics were examined by histomorphological measurements. Significant hypertrophy was observed in the early postoperative period in both groups 1 and group 2. After the initial phase, bone growth continued and extensive remodeling was observed in group 1, while marked bone resorption was observed in group 2. Adaptive remodeling was also observed in group 3 after surgery, but was slower than that in groups 1 and 2. Early hypertrophy of vascularized grafts did not correspond to mechanical loading. These results suggest that mechanical loading is the principal factor responsible for remodeling in vascularized bone grafts for their adaptation to a new environment.     

BEMF对卵巢切除骨质疏松大鼠治疗作用的骨形态计量学研究

目的观察BEMF对OVX—OP大鼠骨形态计量学指标的影响，探讨BEMF对卵巢切除致骨质疏松大鼠的治疗作用及机制。方法6个月龄雌性未孕Wistar大鼠40只，按体质量随机分为卵巢切除组（OVX）、假手术组（Sham）、仿生电磁场治疗组（EM）、雌激素治疗组（E）。术后8周，E组苯甲酸雌二醇肌肉注射，0．5mg／kg，1次，2周。EM组大鼠暴露于仿生电磁场治疗，1h·次^-1·d^-1，OVX、Sham组不予以任何处理，作为对照组。治疗10周后处死各组大鼠，取左侧胫骨进行骨形态计量学测定。结果治疗10周后，EM组大鼠％Tb．Ar、Tb．Th、Tb．N较OVX组显著增加（P〈0．01），Tb．sp显著降低（P〈0．01），与E组变化相似。E组、EM组大鼠成骨细胞数（％L．Pm）低于OVX组（P〈0．01）；EM组、E组仍高于Sham组（P〈0．01）；EM组高于E组（P〈0．01）。E组、EM组破骨细胞数（N．Oc）低于OVX组（P〈0．01）；EM组、E组仍高于Sham组，（P〈0．01）；EM组高于E组，差异非常显著（P〈0．01）。结论BEMF具有增加骨量、改善骨结构的作用；与雌激素的治疗作用存在不同机制。     

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     

Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats

The physiological role of gonadal androgens in regulating bone metabolism is not established. To determine if androgens antagonize the changes in cortical bone after gonadectomy, we treated orchiectomized (ORX) rats with testosterone (T) and 5 alpha-dihydrotestosterone (DHT), and ovariectomized (OVX) rats with the afore-mentioned androgens, as well as the synthetic androgen fluoxymesterone (Fl) and the nonsteroidal estrogen diethylstilbestrol (DES). OVX resulted in a rapid, sustained increase in periosteal bone formation at the tibial diaphysis, whereas ORX resulted in decreased bone formation. Androgen treatment stimulated bone formation in ORX rats and suppressed bone formation in OVX rats. A large dose of DES suppressed bone formation in OVX rats to values below the intact controls. The results of these studies demonstrate that androgens counteract the changes in cortical bone formation after gonadectomy in females as well as males, and thereby reestablish the sex difference observed in intact rats.     

High-impact exercise frequency per week or day for osteogenic response in rats

The frequency per week or day of high-impact, low-repetition jump exercise for osteogenic response was assessed by two experiments. In the first experiment, 48 11-week-old rats were randomly divided into five groups: a sedentary control (W0: n = 8), one exercise session per week (W1: n = 10), three exercise sessions per week (W3: n = 10), five exercise sessions per week (W5: n = 10), and seven exercise sessions per week (W7: n = 10). In the second experiment, 30 11-week-old rats were randomly divided into three groups: a sedentary control (D0: n = 10), one exercise session per day (D1: n = 10), and two exercise sessions per day (D2: n = 10). One exercise session consisted of 10 continuous jumps. After 8 weeks of the exercise period, the jump exercise increased the fat-free dry weight of the tibia in the W1 (7.5%, n.s.), W3 (12.6%, P < 0.01), W5 (12.0%, P < 0.01), and W7 (19.8%, P < 0.001) groups compared with the W0 group. The jump exercise also increased the fat-free dry weight in the D1 (12.0%, P < 0.001) and D2 (13.0%, P < 0.001) groups compared with the D0 group. These increases were accompanied by increased bone strength and cortical area at the mid-shaft. The results in the present study suggest that for bone gain, it is not always necessary to do high-impact exercise every day, although exercising every day does have the greatest effect. The results in this study also suggest that there is little additional benefit if bones are loaded by two separate exercise sessions daily.     

Dietary fish oil results in a greater bone mass and bone formation indices in aged ovariectomized rats

Postmenopausal bone loss and the possible progression to osteoporosis is a major health concern. Until recently, hormone replacement therapy (HRT) was the standard for preventing the development of osteoporosis and possible hip fractures following menopause. However, because of some adverse effects of HRT, new therapies, lifestyle habits, and nutritional interventions are being developed and better characterized in their ability to prevent bone loss after menopause. One such option is to increase the amount of fish oil consumed in the diet. The goal of the current research was to determine the impact of fish oil supplementation on bone mass, density, formation, and resorption in an aged ovariectomized rat model. Twelvemonth-old female retired breeder Sprague-Dawley rats were fed a control (Control) or fish oil (Fish) diet. Two weeks following the introduction of the diets, the rats were either sham-operated (Sham) or bilaterally ovariectomized (OVX). Ten weeks after surgery, indices of bone mass and bone histomorphometry were measured. Bone mineral content (BMC) of the whole femur was significantly higher in the Fish/OVX than in the Control/OVX, and the differences were most pronounced in the distal and proximal ends of the femur. However, the Fish/Sham and the Control/Sham did not differ in the measures of BMC. Although the Control/OVX had significantly lower cortical area and greater endosteal perimeter compared with the Control/Sham, the differences were not significant between the Fish/Sham and the Fish/OVX. In addition, the Fish/OVX had a significantly larger percent double-labeled surface and mineral apposition rate at the endocortical surface than the Control/OVX. Our findings suggest that fish oil supplementation has a positive effect on bone metabolism and might be a possible intervention to slow the loss of bone observed following menopause.     

Effects of treadmill exercise on bone mass,bone metabolism,and calciotropic hormones in young growing rats

The aim of the present study was to examine the effects of exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. Twenty 6-week-old female Wistar rats were randomized into the following four groups with 5 animals each: 7 weeks of exercise, 7 weeks of sedentary control, 11 weeks of exercise, and 11 weeks of sedentary control. The exercise regimen consisted of running on a treadmill at 25m/min for 1h each day on 5 days a week. After each period of exercise, the bone mineral content (BMC) of the tibia and fifth lumbar spine was measured by dual-energy X-ray absorptiometry, using a Lunar DPX-L instrument. The femoral length and levels of bone markers and calciotropic hormones were also assessed. Seven and 11 weeks of exercise increased the serum osteocalcin and 1,25-dihydroxyvitamin D₃ levels, and decreased the serum parathyroid level. Seven weeks of exercise decreased the urinary deoxypyridinoline level, and 11 weeks of exercise increased the serum alkaline phosphatase level and decreased the serum tartrate-resistant acid phosphatase level. As a result, 7 and 11 weeks of exercise increased the femoral length and tibial BMC, but did not alter the lumbar BMC. The present study demonstrates that treadmill exercise stimulates bone formation and suppresses bone resorption, increases the serum 1,25-dihydroxyvitamin D₃ level, and decreases the serum parathyroid hormone level, resulting in an increase in bone mass with stimulation of longitudinal bone growth, especially at weight-bearing sites, in young growing rats. Further studies with long-term exercise may be needed to obtain a positive effect on the lumbar BMC.