Mandible bone loss in osteoporosis rats

Change in the mandible during the development of osteoporosis has not been studied extensively. Thus, the present study was undertaken to clarify the target loci in the mandible during the development of experimental osteoporosis in aged female rats. Experimental osteoporosis was studied in 76 Wistar strain female rats, 35 weeks old, by means of ovariectomy and dietary calcium deficiency. The rats were divided into the following three groups: (1) group 1, unoperated basal control (Basal), maintained on a diet containing 1.0% calcium; (2) group 2, sham-operated (Sham), maintained on a diet containing 0.01% calcium; and (3) group 3, ovariecomized (OVX), maintained on a diet containing 0.01% calcium. Fifteen rats of each group, except the basal rats (10 and 6 rats), were killed at 3 and 6 months following ovariectomy, respectively. The mandible was extracted, cleaned, and then subjected to bone mineral content (BMC) and bone mineral density (BMD) analyses using a peripheral quantitative computed tomography (pQCT) bone scanner. Each mandible was scanned from the mesial margin of the first molar to distal margin of the second molar. The results showed that dietary calcium deficiency and ovariectomy caused significant decreases of trabecular and cortical BMCs and BMDs in Sham and OVX rats compared with Basal rats. Decreases due to dietary calcium deficiency were greater than those caused by ovariectomy. However, significant age-related changes were not observed in BMC and BMD in Sham and OVX rats for 3–6 months. In addition, the cortical and trabecular BMCs and BMDs obtained were found to relate to location in the mandible for each group.This work formed the basis of the presentation at the 27th European Symposium on Calcified Tissues in Tampere, Finland, May 2000 [abstract P-252, Calcif Tissue Int 66 (suppl. 1) 2000]     

Precision and accuracy of in vivo bone mineral measurement in rats using dual-energy X-ray absorptiometry

The aim of this study was to evaluate the precision and accuracy of dual-energy X-ray absorptiometry (DXA) for measuring bone mineral content at different sites of the skeleton in rats. In vitro the reproducibility error was very small (<1%), but in vivo the intra-observer variability ranged from 0.9% to 6.0%. Several factors have been shown to affect in vivo reproducibility: the reproducibility was better when the results were expressed as bone mineral density (BMD) rather than bone mineral content (BMC), intra-observer variability was better than the inter-observer variability, and a higher error was observed for the tibia compared with that for vertebrae and femur. The accuracy of measurement at the femur and tibia was assessed by comparing the values with ash weight and with biochemically determined calcium content. The correlation coefficients (R) between the in vitro BMC and the dry weight or the calcium content were higher than 0.99 for both the femur and the tibia. SEE ranged between 0.0 g (ash weight) and 2.0 mg (Ca content). Using in vitro BMC, ash weight could be estimated with an accuracy error close to 0 and calcium content with an error ranging between 0.82% and 6.80%. TheR values obtained between the in vivo and in vitro BMC were 0.98 and 0.97 respectively for femur and tibia, with SEE of 0.04 and 0.02 g respectively. In conclusion, the in vivo precision of the technique was found to be too low. To be of practical use it is important in the design of experimentation to try to reduce the measurement error. This can be achieved by performing measurements in the same position, by repeating measurements several times and by using the mean values of several BMD calculations performed by the same observer on each BMD measurement. Furthermore, better reproducibility can be obtained on the vertebra or the femur than on the tibia.     

Soy moderately improves microstructural properties without affecting bone mass in an ovariectomized rat model of osteoporosis

Soy protein is reported to prevent bone loss in both women and rat models of osteoporosis. However, the role of soy isoflavones on the trabecular microarchitectural properties needs to be explored. In the present study, we examined whether soy protein with graded doses of isoflavones reverses loss of bone mineral density (BMD), bone mineral content (BMC), and trabecular microstructure in an ovariectomized (Ovx) osteopenic rat model. Seventy-eight 9-m old female Sprague-Dawley rats were either sham-operated (Sham; 1 group) or Ovx (5 groups) and fed a semi-purified casein-based diet. After 90 days, the occurrence of bone loss was confirmed using dual energy X-ray absorptiometry. Thereafter, rats were assigned to the following treatments: Sham, Ovx (control), Ovx + 17beta-estradiol (E(2); 10 microg/kg body wt. twice per week), Ovx + soy protein depleted of isoflavones (Soy-; 0.06 mg isoflavones/g protein), Ovx + soy protein with normal isoflavone content (Soy; 3.55 mg isoflavones/g protein), and Ovx + isoflavone-enriched soy protein (Soy+; 7.10 mg isoflavones/g protein). After 125 days of treatment, rats were euthanized, and tibia and lumbar bones were collected for the assessment of BMD, BMC, and trabecular microarchitectural properties using X-ray microcomputed tomography. None of the treatments had an effect on BMD or microarchitectural properties of the lumbar vertebra. However, Soy treatment significantly increased tibial BMC and BMD by 10% and 4.5% compared with Ovx control, but the increase in BMD was not enough to reach the BMD levels of the Sham control group. The Soy+ diet positively affected the tibial architectural properties including trabecular thickness, separation, and number. In summary, our findings suggest that soy protein does not restore bone loss in osteopenic rats; however, higher doses of isoflavones may be required to reverse the loss of tibial microstructural properties.     

Trabecular bone remodeling and bone mineral density in the adult cat during chronic dietary acidification with ammonium chloride

Ammonium chloride (NH4Cl) is used as a urinary acidifier in the treatment and prevention of feline urologic syndrome. It is reported to cause alterations in calcium and bone metabolism in humans, dogs, and rats. Adult cats with normal renal function were fed 1.5% NH4Cl for 6 months to study the effects of chronic dietary acidification on trabecular bone remodeling of the iliac crest and bone mineral density (BMD) of lumbar vertebral trabecular bone and femoral cortex. Histomorphometric analyses of iliac crest biopsies were performed before and after treatment. Static and dynamic parameters of bone resorption and formation were determined. Single-energy quantitative computed tomography (SEQCT) was used to measure lumbar trabecular and femoral cortical BMD. There were no significant treatment effects in iliac crest trabecular bone remodeling or BMD of the vertebrae and femora. Bone remodeling activity decreased with time in both acidotic and control cats. Vertebral BMD increased with time in both groups of cats, whereas no change was seen in the femora. Thus, chronic dietary acidification for 6 months with therapeutic levels of NH4Cl produced no significant changes in trabecular bone remodeling or bone mineral density in adult cats.     

生髓健骨胶囊对酒精性骨质疏松大鼠骨密度、骨矿含量影响的研究

目的从基因分子水平探讨酒精性骨质疏松(alcoholic osteoporosis,AOP)大鼠的发病机制,观察生髓健骨胶囊对AOP大鼠骨密度(bone mineral density,BMD)、骨矿含量(bone mineral content,BMC)表达的影响,探讨生髓健骨胶囊对AOP大鼠模型的中药防治作用机理。方法选取成年雄性(清洁级)SD大鼠120只,称体重,随机分为4组,每组各30只,用白酒灌胃法造模,同时分别给予生理盐水、碳酸钙阿法D3、生髓健骨胶囊灌胃给药。于造模8、12、16周末取材,检测股骨上端BMD、BMC指标。结果检测造模干预8、12、16周后BMD、BMC指标变化,模型组BMD、BMC与正常组比较明显降低,且差异有统计学意义(P0.01),结果表明饮酒大鼠确实存在骨量减少,BMD、BMC降低;中药干预组BMD、BMC与模型组相比显著升高(P0.01);中药干预组BMD、BMC与西药对照组相比,明显升高(P0.05)。结论通过观察生髓健骨胶囊对AOP大鼠的实验指标,证明了生髓健骨胶囊能够提高AOP大鼠骨密度,增加骨矿含量,抑制矿物质丢失,改善大鼠的骨代谢。     

成都地区骨峰值的研究

目的了解成都地区骨峰值（ＰＢＭ）的基本情况,为骨质疏松（ＯＰ）的防治提供依据。方法随机抽取成都地区２０～４９岁人群除外心肝肺肾、内分泌等慢性病及骨代谢疾病３６８名,进行了腰椎（Ｌ２－４）正位和髋部的双能Ｘ线骨密度（ＢＭＤ）的测量。结果２０～４９岁人群的ＢＭＤ相对稳定,男性腰椎骨峰值见于２０～２９岁,值为１．０７５±０．１１４（ｇ／ｃｍ＾２）;女性见于３０～３９岁,值为１．１０６±０．１１３（ｇ／     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

ABSTRACT: BACKGROUND: Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. METHODS: Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. RESULTS: Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. CONCLUSION: The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.     

Correlation between densitometric and hystomorphometric values in isolated vertebrae of Sprague-Dawley rats

Summary The study of bone mass in experimental animals usually requires invasive techniques. Dual energy X-ray absorptiometry (DEXA) may be an alternative as a non-invasive method (1). Bone mineral density (BMD) and bone mineral content (BMC) of 62 vertebrae of Sprague Dawley rats (SDr) measured by DEXA densitometry were compared with histomorphometric bone volume measurements, and a statistically significant correlation was found (r=0.79 and 0.75, respectively, p<0.001). In conclusion, DEXA is an accurate and feasible technique for the study of trabecular bone mass in SDr.     

Validation and application of dual-energy X-ray absorptiometry to measure bone mineral density in rabbit vertebrae.

The rabbit could be a superior animal model to use in bone physiology studies, for the rabbit does attain true skeletal maturity. However, there are neither normative bone mineral density (BMD) data on the rabbit nor are there any validation studies on the use of dual-energy X-ray absorptiometry (DXA) to measure spinal BMD in the rabbit. Therefore, our aim was twofold: first, to investigate whether DXA could be used precisely and accurately to determine the bone mineral content (BMC). bone area (BA). and BMD of the rabbit lumbar spine: Second. to evaluate the new generation fan-beam DXA (Hologic QDR-4500) with small animal software by comparing two DXA methodologies QDR-1000 and QDR-4500 with each other, as well as against volumetric bone density (VBMD) derived from Archimedes principle. As expected. there was a magnification error in the QDR-4500 (BMC, BA. and BMD increased by 52%. 38%. and 10%, respectively, when the vertebrae were positioned flat against the scanning table). With the magnification error kept constant (vertebrae positioned 10 cm above the scanning table to match the height in vivo). there were no differences among the mean BMC. BA. and BMD of the rabbit vertebrae (Ll-L7) in vivo and in vitro using the QDR-4500 (p > 0.05). BMC, BA, and BMD differed between QDR-1000 and QDR-4500 in vitro because of a magnification error when the vertebrae were flat on the table (p <0.0001). and, consequently. the machines did not correlate with one another (p > 0.05). However, the BMC, BA, and BMD of the two DXAs did significantly correlate with each other in vivo and in vitro when the magnification error was compensated for (r = 0.44 and 0.52. i2 = 0.45 and 0.63. and 12 = 0.41 and 0.60. respectively. p < 0.05-0.008). The BMC and BMD (in vivo and in vitro) of the rabbit vertebrae measured by QDR-4500 was significantly correlated with VMBD, ash weight, and mineral content (,2 = 0.67-0.90,j <0.01-0.0001). Therefore, the QDR-4500 can be used to yield precise and accurate measurements of the rabbit spine.     

应用pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松建模效果的对比研究

目的比较pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松的建模效果的能力。方法16只8月龄Wistar雌性大鼠(平均体重350g)随机分为模型组(卵巢切除组)与对照组(卵巢假切除组)。术后3个月,取大鼠左侧股骨。应用肢体计算机断层扫描(pQCT)与双能X线骨密度仪(DXA)对骨质疏松建模效果进行对比研究:(1)确定pQCT与DXA测量精度,即计算重复测量的精度误差;(2)比较应用两种骨密度仪所测得的对照组、模型组的骨密度、骨矿含量、骨几何结构参数及其相关系数。结果(1)pQCT总骨及松质骨体密度的测量精度误差分别为2.27%与2.00%,而DXA骨面密度的测量精度误差为3.36%。(2)模型组pQCT总骨体密度和松质骨体密度分别低于对照组8.2%和15.0%犤(模型组-对照组)/对照组×100%犦,差异有显著性(P<0.01);而模型组DXA骨面密度低于对照组3.0%,差异无显著性(P>0.05)。模型组pQCT总骨骨矿含量低于对照组3.7%,差异无显著性(P>0.05),而松质骨骨矿含量低于对照组11.4%,差异有显著性(P<0.05);模型组DXA骨矿含量低于对照组3.0%,差异无显著性(P>0.05)。(3)DXA骨矿含量与pQCT总骨骨矿含量之间呈正相关(r=0.82,P<0.001);DXA骨投影面积与pQCT骨体积之间亦呈正相关(r=0.52,P<0.05);DXA骨面密度与pQCT总骨体密度之间无相关关系(r=0.14,P>0.05)。DXA     

Milk, rather than other foods, is associated with vertebral bone mass and circulating IGF-1 in female adolescents

Summary  Low calcium intake hampers bone mineral acquisition in adolescent girls. This study explores dietary calcium sources and nutrients possibly associated with vertebral mass. Milk intake is not influenced by genetic variants of the lactase gene and is positively associated with serum IGF-1 and with lumbar vertebrae mineral content and density. Introduction  Low calcium intake hampers bone mineral acquisition during adolescence. We identified calcium sources and nutrients possibly associated with lumbar bone mineralization and calcium metabolism in adolescent girls and evaluated the possible influence of a genetic polymorphic trait associated with adult-type hypolactasia. Methods  Lumbar bone mineral content (BMC), bone mineral density (BMD), and area, circulating IGF-1, markers of bone metabolism, and −13910 LCT (lactase gene) polymorphism; and intakes of milk, dairy products, calcium, phosphorus, magnesium, proteins, and energy were evaluated in 192 healthy adolescent girls. Results  After menarche, BMC, BMD, serum IGF-1, and serum PTH were tightly associated with milk consumption, but not with other calcium sources. All four parameters were also associated with phosphorus, magnesium, protein, and energy from milk, but not from other sources. Girls with milk intakes below 55 mL/day have significantly lower BMD, BMC, and IGF-1 and higher PTH compared to girls consuming over 260 mL/day. Neither BMC, BMD, calcium intakes, nor milk consumption were associated with −13910 LCT polymorphism. Conclusions  Milk consumption, preferably to other calcium sources, is associated with lumbar BMC and BMD in postmenarcheal girls. Aside from being a major source of calcium, milk provides phosphates, magnesium, proteins, and as yet unidentified nutrients likely to favor bone health.     

Effect of treadmill exercise on vertebral and tibial bone mineral content and bone mineral density in the aged adult rat: Determined by dual energy X-ray absorptiometry

Summary Dual energy X-ray absorptiometry (DXA; Hologic QDR-1000W) in an ultrahigh-resolution mode, was used to examine the changes in tibial/fibula and vertebral L4 +L5 bone mineral content (BMC) and bone mineral density (BMD) in each 14-month-old female rat at 0, 9, and 16 weeks of study. Twenty rats were randomized by a stratified weight method into two groups, control and exercised. Exercise consisted of running on a flat-bed treadmill, 17 m/minute, 1 hour/day and 5 days/week. As compared with the control group, a significant increase in tibia/fibula BMC and vertebral BMD was apparent at 9 weeks after exercise training (P=0.014 by 2-way analysis of variance). The slope of the gain of the tibia/fibula BMC and BMD by 16 weeks of training was ninefold and fivefold higher than that of the control group (P<0.01 and P<0.05, respectively, by Mann-Whitney test). The correlation coefficient (r) between the final dry weight of excised bone and the final BMC of the intact rat was 0.843 and 0.71 for tibia/fibula and vertebrae, respectively. In summary, we found that in the aged rat, by 9 weeks, exercise increases BMC and BMD in the tibia, whereas in the vertebrae, only increases in the BMD were found. This study demonstrates that this precise and accurate DXA technique is useful in a longitudinal study of in vivo bone mineral changes in the rat over time by taking into account the individual variation between animals as well as changes between groups.     

Multigenerational exposure to genistein does not increase bone mineral density in rats

Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) were collected from these animals at necropsy at 2 years of age and subjected to dual-energy x-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. Femurs were collected, and length, cross-sectional area, and cortical bone area were measured directly. Serum was collected for measurement of pyridinoline (PYD) and alkaline phosphatase (ALP). BMD was not affected by genistein in any phase of the experiment. In female rats treated continuously with genistein, BMC and bone area were reduced in the 500 ppm group compared to the 5 ppm group in the lumbar vertebrae, and in all treatment groups compared to control in the caudal vertebrae. In both males and females treated continuously, the cross-sectional area of the femur was reduced in rats treated with 500 ppm compared to those treated with 5 ppm. In female rats treated continuously, PYD was higher in the 100 and 500 ppm groups than in the 0 and 5 ppm groups. In conclusion, the effects of genistein on reproductively-intact rats were not dramatic. High dose of genistein throughout the lifespan resulted in decreased bone size, which may reduce the force required to break the bone.     

Analysis of relationships between sex hormone dynamics and bone metabolism and changes in bone mass in surgically induced menopause

A 3-year follow-up study was performed of bone metabolism and bene changes induced by surgical menopause as a consequence of hysterectomy and oophorectomy (OVX) in 52 nonmenopausal women. We investigated 22 bone parameters and determined seven bone indices as indieators of bone mineral content by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and microdensitometry (MD). The significant correlations between levels of sex hormones and/or bone parameters and bone indices demonstrated that marked sex-steroid deficiency after surgical menopause induced bone uncoupling during high bone turnover and subsequent rapid bone loss in the early period after OVX. Principal component analysis using correlation coefficients suggested a seven-loading-factor matrix composed of bone parameters and a two loading-factor matrix composed of bone indices. Two groups of parameters—estradiol and estriol, and androstenedione together, and luteinizing hormone and follicle-stimulating hormone together—indicated that the rate of bone loss was greater in the trabecular bone than in the cortical bone. Three other groups of parameters—urine calcium, urine hydroxyproline, and serum bone Gla-protein together; serum alkaline phosphatase, serum calcium, and 1,25-dihydroxy-cliolecalciferol [1,25(OH)₂D] together; and plasma tartrateresistant acid phosphatase—indicated that bone uncoupling, with a prevalence of resorption over formation of bone, was greater in trabecular bone than in cortical bone and also that the magnitude and rate of bone loss in the axial vertebrae surpassed those in the appendicular metacarpals after OVX. Two other groups of parameters, namely, trabecular bone mineral density (D_d) and bone mineral content (D_c), both measured by DXA, and bone mineral density (L₂, L₃), measured by QCT, together; and the cortical thickness index (MCI), cortical bone mineral density (GS/D), and the ratio of GSmin/max, measured by MD, indicated that the relative rates of bone reduction at the 3-year follow-up were greater in the axial vertebrae than in the appendicular metacarpals. Thus, bone change in the trabecular bone was associated with rapid loss during the early phase after OVX, whereas that in the cortical bone was slow during the late phase.     

Failure strength of human vertebrae: prediction using bone mineral density measured by DXA and bone volume by micro-CT

Significant relationships exist between areal bone mineral density (BMD) derived from dual energy X-ray absorptiometry (DXA) and bone strength. However, the predictive validity of BMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA in the lumbar spine may be improved by assessing BMD from lateral-projection scans, as these might better approximate the objective of measuring the trabecular-rich bone in the vertebral body, compared to the commonly-used posterior-anterior (PA) projections. Nowadays, X-ray micro-computed tomography (μCT) allows non-destructive three-dimensional structural characterization of entire bone segments at high resolution. In this study, human lumbar cadaver spines were examined ex situ by DXA in lateral and PA projections, as well as by μCT, with the aims (1) to investigate the ability of bone quantity measurements obtained by DXA in the lateral projection and in the PA projection, to predict variations in bone quantity measurements obtained by μCT, and (2) to assess their respective capabilities to predict whole vertebral body strength, determined experimentally. Human cadaver spines were scanned by DXA in PA projections and lateral projections. Bone mineral content (BMC) and BMD for L2 and L3 vertebrae were determined. The L2 and L3 vertebrae were then dissected and entirely scanned by μCT. Total bone volume (BV(tot)=cortical+trabecular), trabecular bone volume (BV), and trabecular bone volume fraction (BV/TV) were calculated over the entire vertebrae. The vertebral bodies were then mechanically tested to failure in compression, to determine ultimate load. The variables BV(tot), BV, and BV/TV measured by μCT were better predicted by BMC and BMD measured by lateral-projection DXA, with higher R(2) values and smaller standard errors of the estimate (R(2)=0.65-0.90, SEE=11%-18%), compared to PA-projection DXA (R(2)=0.33-0.53, SEE=22%-34%). The best predictors of ultimate load were BV(tot) and BV assessed by μCT (R(2)=0.88 and R(2)=0.81, respectively), and BMC and BMD from lateral-projection DXA (R(2)=0.82 and R(2)=0.70, respectively). Conversely, BMC and BMD from PA-projection DXA were lower predictors of ultimate load (R(2)=0.49 and R(2)=0.37, respectively). This ex vivo study highlights greater capabilities of lateral-projection DXA to predict variations in vertebral body bone quantity as measured by μCT, and to predict vertebral strength as assessed experimentally, compared to PA-projection DXA. This provides basis for further exploring the clinical application of lateral-projection DXA analysis.     

Mineral loss in cortical and trabecular bone during high-dose prednisone treatment

Summary To evaluate the effect of prednisone and triple treatment (sodium fluoride, calcium, and vitamin D) on trabecular and cortical bone serial bone mineral content (BMC) measurements were made at a metaphyseal (BMC_D) and diaphyseal (BMC_P) site on the forearm on 31 consecutive and previously bone-healthy patients scheduled for at least 24 weeks high-dose prednisone treatment. The patients were randomized into two further treatment groups: group I (n=16) received prednisone plus triple treatment and group II (n=15) received only prednisone. The two groups were similar with regard to age, sex, prednisone dose, and initial BMC. During 24 weeks treatment, BMC_D (partially representing trabecular bone) and BMC_P (mainly representing cortical bone) fell significantly and similarly, demonstrating that there is no preventive effect on bone mineral loss on the triple regimen. The BMC fall after 12 weeks was significantly more pronounced for metaphyseal (partially trabecular) than for diaphyseal (cortical) bone, whereas the values did not differ significantly after 24 weeks; this indicates a greater sensitivity to the hormone treatment of trabecular bone. In the entire group, the fall in BMC correlated positively with individual prednisone dose, significant at the diaphyseal site (r=0.39,P<0.05), but not at the metaphyseal site (r=0.31, P=0.08). It is concluded that corticosteroid-induced osteopenia is a diffuse bone disease which affects trabecular as well as cortical bone, suggesting that BMC measured on the forearm reflects changes in bone mineral at other locations.     

顺铂对雌性大鼠骨密度影响的实验研究

目的本文通过对去势雌性大鼠的动物实验研究，观察顺铂对骨代谢、骨密度的影响，并探讨其可能机制。方法将三月龄雌性SD大鼠30只，随机分为对照组和化疗组，每组15只。各组大鼠均用1％戊巴比妥钠腹腔内麻醉，行双侧卵巢切除术。术后1W开始用药，每两周用药1次，共6次。对照组腹腔内注射生理盐水1ml；化疗组腹腔内注射顺铂2mg／kg溶于1ml生理盐水中。术后13W处死各组动物，处死前用代谢笼收集24h空腹尿标本，自动生化分析仪测定尿钙浓度并计算出24h排泌量。氯胺T氧化法测尿羟脯氨酸(HOP)浓度并计算出24h排泌量；麻醉动物，开腹后下腔静脉取血离心，放免法测骨钙素(BGP)、血尿素氮(BUN)；取腰椎L4-6椎体，双能X线骨密度测量仪测腰椎骨密度。结果化疗组与对照组相比，骨密度降低，24h尿HOP及24h尿Ca定量升高，均有显著意义，血BGP无差异。结论本实验表明顺铂对大鼠的骨代谢存在直接的不良影响，使骨吸收增加，表现为松质骨骨密度降低。     

Bone density and shape as determinants of bone strength in IGF-I and/or pamidronate-treated ovariectomized rats

Areal bone mineral density (BMD) is a major determinant of bone strength and thereby of fracture risk. Other factors including trabecular microarchitecture and bone dimensions also contribute to bone strength. To investigate the relative importance for bone strength of BMD and bone dimensions, the relations between strength and the latter variables were evaluated under different experimental conditions in ovariectomized rats. Bone strength was assessed in compression and bending with measurement of BMD by dual-energy X-ray absorptiometry. Interventions were designed to increase trabecular BMD in rats with estrogen deficiency-induced bone loss (OVX) by treatment with pamidronate, an inhibitor of bone resorption, or to modify bone dimensions, particularly diameter, by administration of the growth factor IGF-I. In OVX rats, pamidronate treatment increased BMD with a commensurate increase in bone strength at the level of lumbar vertebrae and femoral neck (r=0.789,p<0.0001 andr=0.535,p<0.001, respectively). IGF-I increased the external diameter of midshaft tibia and femoral neck, which also correlated with bone strength (r=0.678,p<0.0001 andr=0.507,p<0.0002, respectively). Thus, both bone dimensions and BMD contributed to the determination of bone strength. In conclusion, adult rats with estrogen deficiency-induced bone loss represent a useful experimental model for investigating bone strength and its determinants such as BMD and external bone dimensions.     

ONO-5334, a cathepsin K inhibitor,improves bone strength by preferentially increasing cortical bone mass in ovariectomized rats

This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy resulted in significant elevation in urinary deoxypyridinoline and plasma C-terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after surgery. Peripheral quantitative computed tomography analysis showed that total, trabecular, and cortical bone mineral content (BMC) decreased in the proximal tibia, which was paralleled with a significant decline in bone strength. Treatment with ONO-5334 (0.12, 0.6, 3 or 15 mg/kg) once daily for 8 weeks dose-dependently restored the decrease in total BMC and bone mineral density (BMD) in the proximal tibia and suppressed urinary deoxypyridinoline and plasma CTX levels. Alendronate (1 mg/kg, once daily) also fully restored these bone mass parameters. Separate analysis of trabecular and cortical bones, however, showed that ONO-5334 only partially restored trabecular BMD and BMC at 15 mg/kg, whereas alendronate fully restored these parameters. On the other hand, ONO-5334 increased both cortical BMD and BMC with an effect more potent than that of alendronate. Bone geometric analysis indicated that ONO-5334 at 15 mg/kg decreased endosteal circumference without affecting periosteal circumference, resulting in marked increase in cortical thickness. Interestingly, the effects of ONO-5334 on bone strength parameters were more prominent than those of alendronate, although the two test compounds had a similar effect on total BMC. Taken together, our results indicate that ONO-5334 has pharmacological characteristics different from those of alendronate and may offer a unique therapy for patients with osteoporosis.