Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol

To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment.     

Assessment of trabecular bone structure in postmenopausal and senile osteoporosis in women by image analysis

OBJECTIVE: The aim of the study was to assess bone trabecular structure in postmenopausal and senile osteoporosis. METHODS: The study was performed on transiliac specimens obtained from women with postmenopausal (n=10) and senile osteoporosis (n=10) and on normal autopsy bone (n=7). Digitalized microradiographs were analysed using dedicated software allowing for selection of longitudinal and transversal elements. RESULTS: Significant differences between transversal and control, as well as between longitudinal and control trabecular areas were observed in senile osteoporosis (p<0.005). In postmenopausal osteoporosis, such differences were found for longitudinal trabeculae only (p<0.005). Mean longitudinal trabecular area loss in senile and postmenopausal osteoporosis as compared to control group was 57.2% and 25.7%, respectively. Respective values for transversal trabecular area were 35.0% and 59.4%. CONCLUSION: Structural anisotropy of trabecular bone is greater in postmenopausal than in senile osteoporosis and control group. The method developed allows the evaluation of bone structures in radiographs with uneven exposure.     

Calcitonin versus Clodronate in the Prevention of Ovariectomy-Induced Osteopenia in Rats

The effects of salmon calcitonin and clodronate were compared in ovariectomised rats. Sixty female Wistar rats (∼260 g in weight) were fed the same diet and had the same living conditions. The rats were divided into the following groups: 15 rats with sham ovariectomy and no drug treatment (Sham-OVX); 45 rats with bilateral ovariectomy subdivided into 15 rats not receiving drug treatment (OVX group), 15 rats treated with subcutaneous salmon calcitonin, 2 U/kg/day every 2 days (OVX + CT group) and 15 rats treated with subcutaneous clodronate, 5 mg/kg/day every 2 days (OVX + Cl group). Sixty days after surgery, the rats were sacrificed and their femurs and fifth lumbar vertebrae were dissected and cleaned of soft tissue. Femur length, vertebral height, and bone mineral content and bone mineral density of the femur and fifth lumbar vertebra by dual-energy X-ray absorptiometry were measured. Calcitonin had a significant and stronger effect in preventing ovariectomy-induced osteopenia in the femur (OVX + CT vs OVX groups, p<0.0001); both calcitonin and clodronate had a significant effect on the fifth lumbar vertebra, which was greater in the calcitonin group (OVX + CT vs OVX + Cl groups, p<0.005). These findings indicate that calcitonin has a protective effect on both the axial (trabecular bone) and peripheral (cortical bone) skeletons, but clodronate only has a protective effect on the axial skeleton. Received: 28 May 1999 / Accepted: 29 July 1999     

Amylin inhibits ovariectomy-induced bone loss in rats

Amylin (AMY), a peptide co-secreted with insulin by pancreatic beta-cells, inhibits bone resorption and stimulates osteoblastic activity. The ovariectomized (OVX) rat is an established animal model for human osteoporosis. Thus, the present experiment was performed to study the effects of AMY on estrogen deficiency-induced bone loss in rats. Thirty-one 6-month-old Wistar rats were randomized by body weight (BW) into two groups. The first underwent surgical OVX (n=21). The second was sham-operated (SH; n=10). Sixty days after surgery, 11 OVX rats were s.c. injected with rat AMY (3 microg/100 g BW/day, for 30 days; OVX+AMY), and 10 with solvent alone in the same way (0.15 ml/100 g BW; OVX). Each rat, housed in an individual cage, was fed daily the mean quantity of diet consumed the day before by SH rats. This diet contained 0.24% calcium and 0. 16% phosphorus. The 31 animals were killed on day 90. No difference in daily weight gain and BW was observed between groups. Neither AMY treatment nor OVX had any significant effect upon femoral morphology, femoral failure load, diaphyseal femoral density (representative of cortical bone) and total femoral calcium content. Nevertheless, both distal metaphyseal (representative of cancellous bone) and total femoral bone densities were higher in SH and OVX+AMY than in OVX rats. The highest plasma osteocalcin concentration was measured in OVX+AMY rats. Simultaneously, urinary deoxypyridinoline excretion was lower in OVX+AMY than in OVX rats. These results indicate that in OVX rats, AMY treatment inhibited trabecular bone loss both by inhibiting resorption and by stimulating osteoblastic activity.     

Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats

The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in the proximal tibial metaphysis of intact and ovariectomized rats. Rats were ovariectomized at the beginning of the study. On day 7 of the study, 5-mg slow release pellets of tamoxifen or placebo were implanted sc. All of the rats were killed on day 28 of the experiment. Sections of the proximal tibial metaphysis were stained for acid phosphatase and evaluated histomorphometrically. Ovariectomy resulted in marked loss of bone. Compared to the values in sham-operated animals, the trabecular bone at a sampling site in the secondary spongiosa of ovariectomized rats was reduced by more than 60%, the length of trabecular bone surface covered by osteoclasts was increased by 563%, the percentage of trabecular bone surface covered by osteoclasts was increased by 567%, the mean osteoclast size was increased by 84%, and the number of nuclei per osteoclast was increased by 38%. In contrast, treatment of ovariectomized rats for 3 weeks with tamoxifen restored the histomorphometric measurements to values comparable to those in sham-operated animals. 17 beta-Estradiol increased trabecular bone fractional area in ovariectomized and sham-operated rats, and administration of tamoxifen to estrogen-treated, ovariectomized, and sham-operated animals produced a further increase in trabecular bone. In summary, 1) ovariectomy resulted in large increases in both the number and activity of osteoclasts, 2) the increased bone resorption associated with ovariectomy produced a net loss of trabecular bone, and 3) treatment of ovariectomized rats with tamoxifen prevented these skeletal changes. The results indicate that in the rat, tamoxifen mimics the effects of estrogen on trabecular bone at concentrations that are not uterotropic.     

去卵巢大鼠骨髓源性破骨样细胞增殖、分化的改变及雌激素的影响

目的　通过体外骨髓细胞培养诱导破骨样细胞 (osteoclast likecells ,OLC)的形成 ,观察去卵巢对成年大鼠OLC形成及活性的影响以及给予雌激素后的改变。　方法　 3月龄SD大鼠分为对照组、去卵巢组及雌激素替代组。术后 12周处死大鼠 ,取股骨分离骨髓细胞 ,在条件培养液中诱导其向破骨细胞分化。活体观察OLC形成情况并于培养的第 6天行细胞染色 ,以抗酒石酸酸性磷酸酶(TRAP)染色 (+)、细胞核≥ 3个的细胞为OLC ,计数各组OLC及骨陷窝。　结果　 3组中去卵巢组OLC出现早且数量〔(2 7 75± 0 92 )个 /玻片〕明显高于其它两组〔(17 93± 0 6 9)个 /玻片和 (12 81±0 6 1)个 /玻片 ,P <0 0 1〕。雌激素处理能明显抑制OLC的形成 ,但雌激素替代组的OLC仍多于对照组 (P <0 0 5 )。骨陷窝形成的变化与OLC数量改变一致。　结论　本实验结果显示大鼠去卵巢后 ,骨髓干细胞分化形成OLC数量明显增多 ,且活性增强。补充雌激素能够有效抑制OLC形成增加及其活性增强。故雌激素抑制骨吸收的机制至少部分是作用于骨髓干细胞向破骨细胞的分化。     

Binge alcohol treatment increases vertebral bone loss following ovariectomy: compensation by intermittent parathyroid hormone

BACKGROUND: Postmenopausal estrogen deficiency and alcohol abuse are known risk factors for osteoporosis. Previous studies of the combined effect of alcohol and ovariectomy on bone loss using chronic alcohol-feeding models have not demonstrated additional alcohol-induced bone loss in ovariectomized (OVX) animals. Binge alcohol treatment causes rapid bone loss in male rats. We hypothesized that binge alcohol would cause additional bone loss in OVX rats. METHODS: Ninety-six adult (400 g) female Sprague-Dawley rats (48 sham-operated and 48 OVX, pair fed) were randomly divided into 4 treatment groups: (a) saline-treated, (b) binge alcohol-treated (3 g/kg alcohol as a 20% weight to volume alcohol/saline solution, intraperitoneal (IP), 3 times per week), (c) parathyroid hormone (PTH)-treated (80 microg/kg, SC, 5 d/wk), and (d) binge alcohol plus PTH. Rats were treated for either 2 or 4 weeks. Following treatment periods, blood was collected for alcohol concentration (BAC) measurements; lumbar vertebrae were removed for bone mineral density (BMD) levels, trabecular microarchitecture assessment, and vertebral compressive strength analysis. RESULTS: Peak binge BACs averaged 300 mg/dL. Alcohol and OVX decreased cancellous BMD: alcohol and OVX treatment in combination caused additional cancellous BMD loss and significant cortical BMD reductions. Compressive strength was also decreased by OVX and alcohol. Combination treatment resulted in further declines in bone strength. Micro-CT analysis revealed a significant effect of combined OVX and alcohol treatment resulting in decreased trabecular bone volume/total volume (BV/TV). Intermittent PTH administration compensated for losses of BMD, compressive strength, and restored BV/TV deficits caused by OVX, alcohol, or their combination. CONCLUSIONS: Bone loss following OVX can be significantly increased by concurrent binge alcohol treatment. The effects of alcohol and OVX are compensated by concurrent intermittent treatment with PTH. These results suggest that postmenopausal women who abuse alcohol may place their skeleton at additional risk for osteoporotic fracture.     

Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10?mg/kg per day)+Feno (25?mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ～50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (～45%) and bone mineral density (BMD; ～60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.     

Moderately High Consumption of Ethanol Suppresses Bone Resorption in Ovariectomized but not in Sexually Intact Adult Female Rats

Epidemiological studies suggest that moderate consumption of alcoholic beverages may be beneficial for bone in postmenopausal women. To investigate prospectively these uncontrolled obsewations, female rats were divided in four groups of 10 animals each and treated with 1) ovariectomy (OVX) and 2.5% ethanol diet (OVX-ETOH group), 2) OVX and control diet (OVX-C group), 3) sham surgery and 25% ethanol diet (SHAM-ETOH group), or 3) sham surgery and control diet (SHAM-C group). Three weeks after surgery, bone histomor-phometfy revealed that the OVX-C group, as expected, had lower trabecular bone volume and higher parameters of bone formation and resorption than the SHAM-C group (p < 0.01). Intake of ethanol did not change these parameters in the SHAM rats, but in the OVX rats it was associated with sharp reduction in parameters of bone resorption (p < 0.01) without a concomitant effect on parameters of bone formation. The cytokines are believed to contribute to accelerated bone resorption during the early postmenopausal period. Indeed, the peripheral blood monocybc cells (PBMC) from the OVX-C rats produced higher amounts of TNF-α than the PBMC from the SHAM-C rats (p < 0.05) and administration of ethanol prevented this increase in OVX rats but had no effect in SHAM rats. In summary, short-tetm intake of moderate doses of ethanol was associated with markedly different eftects in rats with and without ovarian function. Although ethanol had no significant effect on the bone tissue and TNF-α production of the SHAM rats, it was associated with markedly lower parameters of bone resorption and less TNF-α production in the OVX animals. This suggests that exposure to low-dose ethanol may protect from osteopenia following cessation of ovarian function.     

四环素-雌酮对去卵巢山羊髂骨的有利作用

目的　山羊双侧卵巢切除 (OVX)建立绝经后骨质疏松 (PMO)动物模型 ,应用骨组织形态计量学方法观察OVX山羊对四环素 雌酮 (XW 63 0 )的治疗反应。方法　 3 1只雌性山羊随机分成 4组 ,即正常对照组、假手术组、OVX术后 6个月组、XW 63 0治疗 6个月组。在处死前第 2 1天和第 9天 ,给山羊口服四环素以标记骨组织和进行动力学研究。制备山羊髂骨不脱钙骨切片 ,应用骨组织形态计量学方法 ,观察各组髂骨骨计量学参数的变化。结果　与正常对照组和假手术组比较 ,OVX术后 6个月组的骨小梁体积比全部骨组织体积 (TBV/TTV)、骨小梁体积比海绵骨体积 (TBV/SBV)、平均骨小梁板厚度 (MTPT)、四环素双标线距离 (DDL)、平均类骨质宽度 (MOSW )、骨矿化沉积率 (MiAR)和组织水平的骨形成速率 (Svf)显著减少 (Svf:P <0 .0 5 ,其余各参数 :均P <0 .0 1) ,骨小梁表面比体积 (S/V)则显著增加 (P <0 .0 1) ,说明OVX山羊骨量丢失 ,骨小梁体积明显减小 ,骨小梁厚度下降、连接性降低 ,骨转换率降低 ,激活频率减慢 ,骨形成明显减少 ,表现为低转化骨质疏松的骨代谢特征。以上结果提示 ,骨质疏松山羊模型复制成功。与OVX术后 6个月组相比 ,XW63 0治疗 6个月组的TBV/TTV ,TBV/SBV ,MTPT ,DDL ,MOSW ,MiAR和Svf显著增加 (均P <0 .0 1)     

仙灵骨葆对去势大鼠骨量和生物力学性能的影响

目的探讨仙灵骨葆对骨质疏松(OP)大鼠骨量、骨代谢和生物力学性能的影响。方法 3月龄雌性SD大鼠24只分为3组,每组8只:正常对照组(N)、卵巢切除组(OVX)、卵巢切除+仙灵骨葆治疗组(XLGB)。除N组外,其余两组行卵巢切除术,6 w后XLGB组给予药物干预:250 mg.kg-1.d-1,OVX组给予等量生理盐水,8 w后处死所有大鼠。留取尿液、血清检测血PINP值、尿DPYD/Cr、NTX/Cr值。取左侧股骨行骨密度测定,取左侧胫骨制备硬组织不脱钙切片,备行骨组织形态计量学检测,取右侧股骨行三点弯曲试验,检测其最大载荷。结果 OVX组血PINP、尿DPYD/Cr、尿NTX/Cr值显著高于N组,XLGB能显著降低血PINP、尿DPYD/Cr、尿NTX/Cr值,但仍显著高于N组。OVX组股骨全长及近、中、远三段骨密度均显著低于N组,XLGB组近、远端骨密度显著高于OVX组。BV/TV在OVX组显著低于N组,XLGB组显著高于OVX组;OVX、XLGB组骨吸收指标Oc.N、Er.Pm均显著高于N组,XLGB组Oc.N、Er.Pm显著低于OVX组,BFR/BV显著高于OVX组。最大载荷三组之间无显著差别。结论仙灵骨葆灌胃可抑制卵巢切除大鼠骨量丢失,其机制与促进骨形成、抑制骨吸收,降低骨转换水平,进而维持骨量及微观结构有关。     

Sevelamer restores bone volume and improves bone microarchitecture and strength in aged ovariectomized rats

Sevelamer hydrochloride, a noncalcium phosphate binder, has been shown to reduce coronary artery and aortic calcification, and to improve trabecular bone mineral density in hemodialysis patients with chronic kidney disease. Here, we examined whether sevelamer given orally for 12 wk with normal food could restore bone volume (BV) and strength in aged ovariectomized (OVX) rats starting at 4 wk after OVX. Dual-energy x-ray absorptiometry, microcomputerized tomography, and bone histomorphometry analyses showed that OVX animals receiving sevelamer had increased trabecular BV (51%), trabecular number (43%), trabecular thickness (9%), cortical thickness (16%), mineral apposition rate (103%), bone formation rate (25%), and enhanced cortical and trabecular bone mechanical strength as compared with OVX rats. Sevelamer decreased collagen C telopeptide, increased osteocalcin levels, and decreased phosphate and magnesium levels without affecting calcium levels in the blood. Although sevelamer was not absorbed systemically, it stimulated osteoblast differentiation in BM-derived mesenchymal stem cell cultures, as evaluated by alkaline phosphatase positive colony-forming units, and inhibited recombinant human soluble receptor activator of nuclear factor-kappaB ligand-induced osteoclast differentiation, as evaluated by tartrate-resistant acid phosphatase positive cells in bone mineral-hematopoietic stem cell cultures. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis revealed that 69 proteins were differently expressed after OVX, of which 30% (20 of 69) were reversed to sham activity after sevelamer intake. PTH, fibroblast growth factor-23, and cytokine profile in serum were not significantly changed. Together, these results suggest that sevelamer in food increases the BV and improves biomechanical properties of bone in OVX rats.     

Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats

Female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX) or sham surgery (control). Groups of ovariectomized (OVX) and control rats were injected daily with low, medium, or high doses of 17 beta-estradiol (10, 25, or 50 micrograms/kg BW, respectively). An additional group of OVX and control rats was injected daily with vehicle alone. All rats were killed 35 days after OVX, and their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Trabecular bone volume was markedly reduced in vehicle-treated OVX rats relative to that in control rats (12.1% vs. 26.7%). This bone loss was associated with a 2-fold increase in osteoclast surface and a 4-fold increase in osteoblast surface. The bone formation rate, studied with fluorochrome labeling, was also significantly elevated in vehicle-treated OVX rats (0.111 vs. 0.026 micron3/micron2.day). In contrast, treatment of OVX rats with the three doses of estradiol resulted in normalization of tibial trabecular bone volume and a decline in histomorphometric indices of bone resorption and formation. Our results indicate that estrogen treatment provides complete protection against osteopenia in OVX rats. The protective mechanism involves estrogenic suppression of bone turnover. These findings are consistent with the skeletal effects of estrogen therapy in postmenopausal women.     

Pulsed electromagnetic field stimulates osteoprotegerin and reduces RANKL expression in ovariectomized rats

Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague–Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17β-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG.     

Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein

Daidzein is metabolized to equol in the gastrointestinal tract by gut microflora. Equol has greater estrogenic activity than genistein and daidzein, with its production shown to be promoted by dietary fiber. It is known that resistant starch (RS) is not absorbed in the proximal intestine and acts as dietary fiber in the colon. In this study, we investigated the combined effects of daidzein and RS intake on equol production, bone mineral density, and intestinal microflora in ovariectomized (OVX) mice. Female mice of the ddY strain, aged 8 weeks, were either sham operated (n = 6) or OVX. The OVX mice were randomly divided into 5 groups: OVX control (n = 6), OVX fed 0.1% daidzein–supplemented diet (OVX + Dz, n = 8), OVX fed 0.1% daidzein– and 12% RS–supplemented diet (OVX + Dz + RS, n = 8), OVX fed 12% RS–supplemented diet (OVX + RS, n = 8), and OVX who received daily subcutaneous administration of 17 β-estradiol (n = 6). After 6 weeks, urinary equol concentration was significantly higher in the OVX + Dz + RS group than in the OVX + Dz group. The bone mineral density of the whole tibia was higher in the OVX + Dz +RS group compared with the OVX + Dz group. The occupation ratios of Bifidobacterium spp in the cecal microflora in groups fed RS were significantly higher than those in the other groups. The present study demonstrated that RS may increase the bioavailability of daidzein.     

Dramatic decrease of innervation density in bone after ovariectomy

Recent studies have demonstrated that bone is highly innervated and contains neuromediators that have functional receptors on bone cells. However, no data exist concerning the quantitative changes of innervation during bone loss associated with estrogen withdrawal. To study the involvement of nerve fibers in the regulation of bone remodeling, we have evaluated the modifications of innervation in a classical in vivo model of osteopenia in rats, ovariectomy (OVX). Skeletal innervation was studied by immunocytochemistry using antibodies directed against specific neuronal markers, neurofilament 200 and synaptophysin, and the neuromediator glutamate. Sciatic neurectomy, another model of bone loss due to limb denervation and paralysis, was used to validate our quantitative image analysis technique of immunostaining for nerve markers. Female Wistar rats at 12 wk of age were sham-operated (SHAM) or ovariectomized (OVX). Bone mineral density measurement and bone histomorphometry analysis of tibiae 14 d after surgery demonstrated a significant bone loss in OVX compared with SHAM. We observed an important reduction of nerve profile density in tibiae of OVX animals compared with SHAM animals, whereas innervation density in skin and muscles was similar for OVX and control rats. Quantitative image analysis of immunostainings demonstrated a significant decrease of the percentage of immunolabeling per total bone volume of neurofilament 200, synaptophysin, and glutamate in both the primary and secondary spongiosa of OVX rats compared with SHAM. These data indicate for the first time that OVX-induced bone loss in rat tibiae is associated with a reduction in nerve profile density, suggesting a functional link between the nervous system and the bone loss after ovariectomy.     

甲状旁腺素1-34对骨质疏松大鼠治疗作用的实验研究

目的探讨甲状旁腺素134(hPTH134)对骨质疏松的治疗作用以及与血钙、磷、维生素D代谢和生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型(OVX),实验动物分为4个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);hPTH134治疗组(PTH组,摘除大鼠双侧卵巢12w后用hPTH134治疗8w);盐酸雷洛昔芬治疗组(摘除大鼠双侧卵巢12w后用雷洛昔芬治疗8w);假手术组(Sham组,仅切除卵巢周围的脂肪组织约3g,术后12w纳入实验)。应用HOLOGIC第4代双能X线4500W骨密度仪测大鼠腰椎、股骨上段骨密度值(BMD);以骨形态计量学测股骨骨小梁面积、矿化沉积率;用ELISA法测定血清IGF1水平和血清25OHVitD浓度以及血淋巴细胞VitD受体(VDR)含量。结果hPTH134治疗组、盐酸雷洛昔芬治疗组均较OVX组腰椎、股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。hPTH134治疗组较盐酸雷洛昔芬治疗组股骨上段骨密度增高,两组之间差异有显著性(P<0.01)。hPTH134治疗组骨小梁面积明显增加、矿化沉积率增高。hPTH134治疗组、盐酸雷洛昔芬治疗组血清IGF1浓度值、血清25OHVitD浓度值升高,与OVX组比较差异有显著性(P<0.01)。各组血淋巴细胞VDR含量无明显变化,与OVX组比较差异无显著性(P>0.05)。结论hPTH134能够预防腰椎、股骨上段骨密度丢失,使骨小梁面积明显增加、矿化沉积率增高并且血清IGF1及血清25OHVitD浓度值升高,但对VDR含量无明显作用。     

A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients

OBJECTIVES: To determine whether risedronate (RIS) slows down trabecular bone loss in the medial compartment of the proximal tibia, a characteristic of patients with progressive knee osteoarthritis (OA). METHODS: Initially, 100 patients were randomly selected from each treatment group (each N approximately 300) comprising placebo and RIS 5 mg/day, 15 mg/day and 50 mg/week from a double blind, multi-centre, placebo-controlled, 2 yr investigation of OA knee patients in North America. Using fluoroscopic semi-flexed standard radiography, baseline and exit knee radiographs were digitized by laser scanner. Following computerized measurement of minimum medial compartment joint space width, each group was subdivided into joint space narrowing (JSN) non-progressor or JSN-progressor (JSN >or=0.6 mm measured at any point post-baseline). Computerized method of fractal signature analysis (FSA) quantified longitudinal changes separately in horizontal and vertical trabeculae in region of interest (three-fourth width of tibial compartment x 6 mm height) in the medial compartment. Following the initial study, all JSN-progressor knees within the entire patient cohort (N = 1232) were similarly analysed. RESULTS: OA knees in JSN non-progressor group had a slight decrease in FSA for vertical and horizontal trabeculae and showed no drug effect. In JSN-progressor knees, bone loss was greater in both placebo and RIS 5 mg/day groups compared with those in RIS 15 mg/day group in which trabeculae were retained, and in the RIS 50 mg/week group in which the vertical trabecular number increased significantly (P < 0.05). CONCLUSION: This preliminary study showed that patients with marked cartilage loss (JSN>or=0.6 mm) receiving RIS 15 mg/day retained vertical trabecular structure, and those receiving RIS 50 mg/week increased vertical trabecular number, thereby preserving the structural integrity of subchondral bone in knee OA.     

大鼠去卵巢后不同时期骨微结构和力学性能的变化特征

目的揭示大鼠在去卵巢后不同时期腰椎松质骨微结构退变的变化特征,探讨骨整体力学性能下降的同时可能存在的各种适应性代偿性变化。方法50只7月龄SD大鼠随机分为基线、去卵巢组（OVX组）和假手术组（SHAM）。基线组10只,其余每组均20只。实验开始时先将基线组10只处死,OVX组和SHAM组分别在手术后3周、15周各处死10只,留取动脉血清及腰椎标本,骨微结构、力学和生化指标的测定。结果去卵巢后3周时OVX组表观骨密度、骨体积分数、骨小梁厚度和骨小梁数量均较SHAM和基线降低（P〈0．05）,各向异性度较基线下降（P〈0．05）而与SHAM组无统计学差异。骨小梁面积密度、骨小梁间隔和结构模型指数均较SHAM和基线组增加（P〈0．05）。去卵巢后3周时OVX组最大应力、弹性模量、血清TRAP-5b和骨细胞密度均低于基线（P〈0．05）而与SHAM组无统计学差异。去卵巢后15周时OVX组表观骨密度、骨体积分数、骨小梁数量和联接密度、最大应力、TRAP-Sb和骨细胞密度均较SHAM和基线组降低（P〈0.05）,骨小梁结构模型指数、骨小梁间隔和各向异性度均较SHAM和基线组增加（P〈0．05）,骨小梁面积密度和厚度均与SHAM和基线组无统计学差异。结论大鼠去卵巢后腰椎骨量快速丢失,骨微结构逐渐退变,而血清TRAP-5b水平下降及骨细胞密度、骨小梁各向异性度和厚度的适应性增加,可能在一定程度上代偿骨力学性能的下降,有利于维持骨结构的完整性。     

Increased bone volume and bone mineral content in xylitol-fed aged rats.

BACKGROUND: Our previous studies have shown that dietary xylitol supplementation protects against the loss of bone mineral after ovariectomy. The ovariectomy-induced decrease in trabecular bone volume is significantly retarded by dietary xylitol. Objective: To study whether dietary xylitol can protect against bone loss also during aging, a long-term experimental study was performed with rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into two groups. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were continuously fed the same diet supplemented with 10% (w/w) xylitol. The rats were killed after 20 months. Their tibiae were used for the analyses of bone density and trabecular bone volume, and their femurs were used for the scanning analyses with peripheral quantitative computed tomography (pQCT). RESULTS: The tibial density of the xylitol-fed aged group (1.73 +/- 0.14 g/mm(3)) was significantly greater than that of the aged group without xylitol (1.56 +/- 0.14 g/ mm(3)). The trabecular bone volume of the xylitol-fed rats was 21.2 +/- 4.0%. It was significantly greater than that of the rats not receiving xylitol (9.3 +/- 4.3%). The pQCT-measured cortical bone mineral density and the pQTC-measured cortical bone mineral content of the femoral diaphysis were significantly greater in the xylitol-fed group than in the control group. The trabecular bone mineral density and the trabecular bone mineral content of the femoral distal metaphysis were also significantly greater in the xylitol-fed group than in the non-xylitol group. The total bone mineral density and the total bone mineral content of the femoral neck in the xylitol-fed aged group significantly exceeded those in the aged group without xylitol supplementation. CONCLUSIONS: A continuous moderate dietary xylitol supplementation leads to increased bone volume and increased bone mineral content in the long bones of aged rats. This indicates a xylitol-induced protection against aging-related osteoporotic changes.