甲状旁腺激素相关蛋白羧基端片段对去卵巢大鼠骨代谢的影响

目的 研究甲状旁腺激素相关蛋白(PTHrP)羧基端107-139(PTHrP107-139)对去卵巢大鼠骨代谢的影响.方法 4月龄健康雌性未孕Wistar大鼠40只,随机分为四组.假手术组(Sham组)和卵巢切除+安慰剂组(Placebo组)给予生理盐水0.2 ml/只;卵巢切除PTHrPC治疗组给予PTHrP107-139 40μg/Kg;卵巢切除+鲑鱼降钙素治疗组(CT组),给予鲑鱼降钙素15 U/kg.术后5周给药,隔日注射.治疗3个月,比较股骨、腰椎骨密度(BMD)、骨生物力学参数及骨组织形态计量学指标.结果 ①PTHrPC组和CT组大鼠股骨、腰椎BMD及骨生物力学性能明显高于Placebo组(P<0.05).②与Placebo组相比,PTHrPC和CT组的平均骨体积(TBV/TTV)明显升高,骨重建时间明显延长,而骨小梁类骨质表面(TOS)、平均类骨质宽度(MOSW)、成骨细胞表面(ObS)、骨吸收表面(OcS)、四环素单标记线占骨小梁表面的百分比(STS)、四环素双标记线占骨小梁表面的百分比(DTS)、纠正骨矿化沉积率(iMAR)较Placebo组明显下降.结论 PTHrP羧基端107-139片段主要通过降低OVX大鼠骨转换,抑制骨吸收,增加OVX大鼠的骨量,提高骨强度.     

缺碘大鼠的骨发育障碍

目的　研究碘缺乏对大鼠骨发育和骨转换的影响。方法　复制生长发育期碘缺乏大鼠动物模型 ,测定血清中TT3 、TT4、FT4含量 ,对股骨远端 2 /3进行骨计量学测定。结果　碘缺乏大鼠血清TT4、FT4含量显著下降 ,TT3 含量代偿性增加。碘缺乏大鼠骨小梁骨量较正常大鼠明显减少 ,骨小梁体积(TBV) /全部骨组织体积减少约 47% ,TBV/海绵骨体积减少约 3 5 % ,平均骨小梁板厚度减少约 3 6% ,骨小梁表面 /TBV较正常大鼠增加约 3 4% (P <0 .0 1) ,骨皮质平均厚度较正常组减少了 16% (P <0 .0 5 )。碘缺乏大鼠四环素单标记线占全部骨小梁表面的百分比、四环素双标记线占全部骨小梁表面的百分比、平均类骨质宽度、骨小梁类骨质表面占骨小梁表面的百分比、矿化沉积率和组织水平骨形成率均低于正常对照组 (P <0 .0 5或P <0 .0 1) ,矿化延迟时间 (P <0 .0 5 )和类骨质成熟时间 (P <0 .0 1)大于正常大鼠。结论发育期的骨骼对T4的缺乏非常敏感。T4降低时骨骼发育不良 ,骨小梁骨量减少 ,皮质骨的生长也受到影响。碘缺乏组大鼠成骨细胞活性降低和类骨质矿化障碍     

辛伐他汀对骨质疏松大鼠骨形成作用研究

目的　探讨他汀类药物对绝经后骨质疏松症骨形成的刺激作用和药理机制。方法　 54只 SD雌鼠随机分为 3组 :去势后给药实验组 ,去势组和对照组 ,观察术后 4、1 0和 1 6 w骨形成指标 :骨钙素 (BGP) ,骨特异碱性磷酸酶 (骨 AKP)和总碱性磷酸酶 (总 AKP) ;骨吸收指标 :尿呲啶醚 (PYD)和脱氧呲啶醚 (DPD)。同步用 IBAS计算机全自动图像分析系统对不脱钙骨组织动态观测骨形态计量学参数。结果　给药实验组在去势后 4～ 1 6 w BGP和骨 AKP明显高于单纯去势组 (分别为 P<0 .0 0 1和 P<0 .0 5) ,而尿 PYD和 DPD两组间无显著差异 (P>0 .0 5)。骨形成表面(FS)和骨小梁体积 (TBV) ,骨小梁平均厚度 (MTT)较去势组明显升高 ,尤其是 TBV和 FS(分别为 P<0 .0 0 1和 P<0 .0 1 ) ,这种差异在第 1 0周最为显著。随着给药时间的延长 (第 1 6周 ) MAR逐渐增加 (P<0 .0 0 1 )。 RS与去势组比较在所有实验周均无差异。结论　辛伐他汀可刺激骨质疏松大鼠成骨细胞活跃增生 ,促进骨形成与骨转换速率 ,并可使骨质疏松症骨组织形态改善。     

药物治疗老龄骨质疏松大鼠骨显微结构与骨组织形态学指标的变化

目的确定各种药物治疗动物骨质疏松的效果。方法以去卵巢法复制动物骨质疏松模型,以中药、西药、VK,钙剂进行治疗,饲养15 w后处死大鼠、取大鼠胫骨,采用德国蔡司公司生产的扫描电子显微镜观察各组大鼠胫骨纵断面的骨显微结构(骨小梁排列情况),采用成都泰盟公司BI-2000医学图像分析系统观察各组大鼠胫骨切片骨形态计量学指标。结果模型组骨小梁周长、骨小梁面积、骨小梁相对体积、骨小梁平均厚度、骨小梁平均间距小于正常对照组、中药组、西药组、维生素K(VK)组(P<0.05)。模型组与钙剂组各项指标差异不显著(P>0.05),模型组胫骨骨小梁排列稀疏,孔隙较大,正常对照组骨小梁细密,中药组、西药组,通过治疗骨小梁修复较好,钙剂组和VK组骨小梁排列有一定稀疏,有一定孔隙。结论模型组骨纤维结构发生改变,骨组织形态计量学指标发生改变;中药、西药治疗骨组骨组织形态计量学指标与正常对照组接近,中药、西药对治疗骨质疏松都具有一定效果。     

维生素E对去卵巢大鼠骨组织计量学的影响

目的：探讨VitE对去卵巢大鼠骨组织形态计量学的影响，方法：3月龄雌性SD大鼠36只，分对照组（Sham)，去卵巢组（OVX），去卵巢＋雌激素组（OVX＋E）和去卵巢＋维生素E组（OVX＋VE），后两组在去卵巢术后分别己烯雌酚0．0225mg.kg^-1.d^-1和Vit E 250mg.kg^-1.d^-1灌胃，每周6d,持续90d，用图像分析仪观测胫骨近端骨计量学参数。结果：与Sham比较，OVX大鼠的骨大梁面积（Tb,Ar)减少，骨小梁间隙（Tb.Sp)增宽，出现明显的骨质疏松，VE使OVX大鼠Tb.Ar 32%,,Tb.Sp-15%，破骨细胞数－18％，结论：VE有一定的抗原发性骨质疏松的作用。     

绝经后大鼠骨组织中IL-6、TNFα与骨形态计量的变化

目的探讨白细胞介素-6(IL-6)、肿瘤坏死因子α(TNFα)对绝经后骨质疏松症骨形态计量学的影响.方法行开腹输卵管峡部结扎后切除双侧卵巢建立绝经后骨质疏松大鼠模型,检测骨组织培养液中(RPMI1640) IL-6、TNFα活性含量,同步用IBAS计算机全自动图象分析系统对不脱钙组织作形态计量学测量,并与对照组比较.结果去势后早期(＜4 w)即有骨组织中IL-6、TNFα升高(均P＜0.05),并持续在较高水平.随着绝经期的延长(4～22 w),骨小梁体积(TBV)和平均厚度(MTT)减少,骨吸收表面(RS)增大(P＜0.002).骨组织中IL-6、TNFα和骨吸收指标在绝经后4～22 w升高的程度无显著性.结论骨微环境中破骨细胞释放一定量的IL-6、TNFα可能与绝经后骨质疏松发生有关,其持续增高可能致骨小梁组织结构变化.     

他汀药物序贯疗法防治去势大鼠骨质疏松实验研究

目的 观察他汀药物序贯疗法对去势大鼠骨质疏松的影响，为临床用药提供实验依据。方法 SD雌性大鼠50只，分5组，每组10只，即假手术组、去势组、去势 二磷酸盐组、去势 他汀组及去势 二磷酸盐 他汀 钙与维生素ADFR组。各组均在给药2个月时分别进行尿脱氧吡啶啉(Dpd)、肌酐(Cr)及血清骨钙素(BGP)测定。服药100d时处死大鼠进行骨密度及骨组织形态计量学测量。结果 去势组尿中Dqd／Cr、与血清BGP增高(P＜0．01)，药物治疗后Dpd／Cr均较去势组降低(P＜0．01)，二磷酸盐组血清BGP值较去势组下降(P＜0．01)，他汀组和序贯疗法组BGP值与去势组差异元显著性(P＞0．05)。骨计量学测定指标中，去势组类骨质表面(TOS)、平均类骨质宽(MOSW)、骨矿化前沿四环素标记率(STS，DTS)、成骨细胞表面(TBOS)、骨吸收表面(TBCS)和骨矿化沉积率增高，骨体积(TBV)、骨矿化延迟时间(MLT)及骨重建单位时间(δ)缩短。药物治疗后各组骨体积均较去势组增加(P＜0．01)，以序贯疗法组最好，已接近假手术组的数值。二磷酸盐组，TOS、MOSW、TBOS和TBCS均显著低于去势组，δ值显著比去势组延长，也明显比假手术组高(P＜0．01）。他汀组TBCS值较去势组增加，δ值相似；序贯疗法组TBOS与去势组相似，TBCS显著减少，δ值也有延长但与假手术组差异无显著性。结论 他汀类药可促进骨转换，增加成骨细胞活性，加快类骨质生成，缩短骨重建时间；二磷酸盐在抑制骨吸收的同时也抑制成骨细胞活性，减慢类骨质生成速度并抑制类骨质矿化，显著延长骨重建周期；序贯组集二药物的优点，克服了单一用药的缺点，在促进骨形成，抑制骨吸收上，明显优于二者单独用药。     

去卵巢大鼠椎体松质骨骨小梁微结构改变及其对生物力学的影响

目的观察骨质疏松和正常状态下椎体松质骨的微观结构改变,分析其对骨生物力学的影响。方法将12只4月龄雌性Lewis大鼠随机分为去卵巢组(OVX)组和假手术组(Sham),每组各6只。OVX组行双侧卵巢切除术,假手术组仅显露双侧卵巢。术后6个月处死动物,取尾椎(L_(4-7))行Micro-CT分析及生物力学测试。结果去卵巢6个月后,OVX组大鼠体积骨密度(vBMD)和组织骨密度(tBMD)较Sham组显著降低,松质骨骨小梁的骨体积分数(BV/TV)和数目(TB.N)都明显低于Sham组,骨小粱表面积密度(BS/BV)、结构模拟指数(SMI)和间距(Tb.Sp)显著高于Sham组,差异有统计学意义。但2组间骨小梁厚度(Tb.Th)差异无统计学意义。生物力学测试结果表明,去势6个月后,OVX组大鼠骨质生物力学性能显著下降。骨小梁力学性能与骨小梁体积分数(Adjusted R~2=0.750和数目(Adjusted R~2=0.861)呈正线性相关,而与结构模拟指数(Adjusted R~2=0.716)和骨小梁间距(Adjusted R~2=0.830)呈负线性相关。结论松质骨骨小梁微观结构的改变可影响骨质的生物力学性能,二者之间具有一定的线性关系。     

雌激素对牙槽骨影响的动物实验研究

目的 研究雌性大鼠卵巢切除后雌激素缺乏时对牙槽骨的影响。方法 采用骨密度测定骨小梁参数，包括骨小梁体密度(TBV)，骨小梁板厚度(MTPT)和平均骨小梁板间隙(MTPS)，同时监测骨Ca^2 ，Mg^2 含量，血清Ca^2 、Mg^2 、P^3 、ALP及空腹尿Ca／Cr值。结果 雌激素水平低下与牙槽骨骨密度降低有正相关关系，骨小量参数也有相应的改变，给予去除卵巢鼠雌激素治疗后骨密度有所增加。结论 雌激素缺乏也能引起牙槽骨骨质疏松。     

结缔组织生长因子在去卵巢大鼠骨丢失中的作用

目的通过检测绝经后骨质疏松(PMOP)模型大鼠骨组织中结缔组织生长因子(CTGF)的表达水平,探讨CTGF在去卵巢(OVX)大鼠骨丢失中可能的作用。方法 3月龄成年雌性Sprague/Dawley(SD)大鼠30只,随机分为3组,每组10只:(1)Sham组;(2)OVX组;(3)OVX+E组。用药12 w后,检测大鼠股骨及腰椎骨密度(BMD)后处死大鼠,应用免疫组化法观察骨组织中CTGF的表达水平。结果与Sham组相比,OVX组大鼠BMD下降,骨小梁周边CTGF阳性细胞表达增多且增强;OVX+E组BMD与Sham组比较无明显差异,骨小梁周边CTGF阳性细胞呈微量表达。相关分析显示,OVX组大鼠骨组织中,CTGF与BMD呈负相关;Sham组与OVX+E组大鼠骨组织中,CTGF与BMD无明显相关性。结论在OVX大鼠骨组织中BMD下降,CTGF表达增强,推测CTGF在PMOP的发病机制中可能发挥重要作用,且雌激素能阻止CTGF的过度表达。     

Assessment of changes due to the long-term effect of estrogen and calcium deficiency in the trabecular bone structure in rats

OBJECTIVE: To assess structural changes, especially structural anisotropy, of rat bone trabecular system 6 months after ovariectomy followed by low-calcium diet. METHOD: The study was carried out on the group of 32 female rats, half of which were ovariectomized at the age of 75 days. The animals were divided into 4 groups: one receiving a normal diet (N), another receiving a low-calcium diet (LCa), ovariectomized rats receiving a normal diet (OVX), and ovariectomized animals receiving a low-calcium diet (OVX+LCa). After 6 months the animals were killed, bone specimens were collected and cut into sections of 6 microm thickness. Digital images of the sections were analyzed using a software package enabling analysis of the transversal and longitudinal trabeculae. RESULTS: Significant changes in trabecular structure due to a low-calcium diet (trabecular bone volume loss of 19%), ovariectomy (53%) and ovariectomy combined with low-calcium diet (71%) were observed. In all the analyzed groups, the percentage loss (as compared with controls) of transversal trabeculae was more significant than the loss of longitudinal trabeculae. In the LCa group, transversal trabecular loss was 39%, longitudinal 25%, in (Ovx): 63% and 54%, respectively, and in OVX + LCa: 77% and 72%. The structural anisotropy coefficient, defined as the ratio of transversal to longitudinal trabecular surface area was 0.64 for (N), 0.50 for LCa, 0.49 for OVX, and 0.54 for OVX+LCa groups. CONCLUSIONS: The effect of ovariectomy and low-calcium diet on trabecular structure can be assessed quantitatively by means of analysis of transversal and longitudinal trabeculae associated with the main direction of strain. The degree of transversal trabecular loss is much higher than the longitudinal trabecular loss; the difference becomes smaller with the progress of bone destruction, being greatest in the LCa group, the smallest in the (OVX+ LCa) group.     

用Micro-CT评价大鼠骨质疏松合并骨性关节炎模型

目的利用Micro-CT技术,建立一种骨质疏松合并骨性关节炎的大鼠模型,为进一步进行骨质疏松合并骨性关节炎的药物研究提供动物模型。方法SD雌性大鼠18只,随机分成假手术(Sham)组、去卵巢(OVX)组和OVX+碘乙酸钠(OVX+MIA)组。去卵巢手术4 w后,在Sham和OVX组大鼠右侧膝关节腔内注射无菌生理盐水,而OVX+MIA组大鼠注射碘乙酸钠(40 mg/ml)。碘乙酸钠注射12 w后处死取材,取右侧股骨和胫骨进行Micro-CT扫描和重建。结果与Sham组比较,OVX组和OVX+MIA组大鼠股骨松质骨骨密度、骨体积分数、骨小梁数量和连接密度均明显减小(P<0.01),而骨小梁分离度和结构指数模型均明显增大(P<0.01)。与Sham组比较,OVX+MIA组胫骨关节面内侧软骨厚度、软骨体积分数明显减小(P<0.05,P<0.01)。结论利用双侧OVX手术和膝关节腔中注射MIA可制备骨质疏松合并骨性关节炎的大鼠模型,而单纯双侧OVX手术不能制备骨质疏松合并骨性关节炎的大鼠模型。     

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

High-affinity nuclear binding sites for 17 beta-estradiol (17 beta E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. Sprague-Dawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17 beta E2 (24 microliters/day at 0.01-1 nM), 17 alpha-estradiol (17 alpha E2) (24 microliters/day at 1 nM), or phosphate-buffered saline (NaCl, 8 g/liter; KCl, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4.7H2O, 2.16 g/liter) was infused for 8 days. The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% +/- 1.7% to 9.6% +/- 1.1%; mean +/- SEM), a 2-fold increase in osteoclast number (to 4.0 +/- 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% +/- 2.9%), a 9-fold increase in osteoblast number (to 11.3 +/- 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% +/- 1.7%). The local infusion of 17 beta E2 for 8 days into OVX rats (i) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17 beta E2, respectively; (ii) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 17 beta E2). Phosphate-buffered saline infusion was without effect. Infusion of 17 alpha E2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 17 beta E2. The local infusion of 17 beta E2 or 17 alpha E2 had no effect on body or uterine weight. We conclude from these findings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation.     

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.     

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.     

A comparison of assays used for the detection of antibodies to DNA

Summary To determine whether the osteopenia of rheumatoid arthritis (RA) is due to reduction of trabecular bone mass (TBV) and/or cortical width (CW), we evaluated these parameters by bone histomorphometry; we also measured the calciotropic hormones parathormone(PTH) and calcitonin (CT), vitamin D [25(OH)D] and the biological markers of bone remodeling in a group of patients with RA. Study subjects were divided into Group C — premenopausal patients, and Group A — menopausal patients and men of the same ages. These groups were compared to two agematched control groups, B and D. In both A vs. B and C vs. D, TBV and CW were significantly lower in patients. There were no differences in PTH or CT, but 25(OH)D was significantly reduced, and BGP, OHP/Cr and AP were raised in patients. Patients also exhibited TBV loss in more than 55% and CW loss in more than 98%. These changes suggest that the decline in bone mass, mainly cortical, but also trabecular, is due to increased bone turnover and enhanced resorption and seem to reflect intrinsic alterations of RA.     

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.     

Heterogeneity of fracture syndromes in postmenopausal women

Studies were performed on 32 women with vertebral crush fractures (mean age, 65.1 yr) and 27 patients with recent hip fractures (mean age, 83.6 yr). Histomorphometric analysis of undecalcified transiliac crest biopsies revealed significant differences between the two fracture groups. Trabecular bone volume (TBV) was significantly lower in vertebral fracture than in hip fracture patients (12.0 +/- 4.4% (+/- SD) vs. 14.8 +/- 3.6%; P = 0.014), while thickness of cortices was significantly lower for hip fracture than for vertebral fracture patients (436 +/- 231 vs. 823 +/- 465 microns; P less than 0.001). The TBV and radial bone mass (measured by absorptiometry on the shaft) for the vertebral fracture group were significantly lower than age-expected values. For the patients with hip fractures, the TBV was significantly above the expected value, and radial bone mass was not significantly different from the expected value. Other quantitative histological measurements did not generally differ between the two fracture groups and were compatible with normal or increased bone remodeling. The serum PTH in the hip fracture group was significantly increased above that expected in normal women of similar age. These data demonstrate the anatomical heterogeneity of osteoporotic fracture syndromes. Patients with vertebral fractures have an early deficit of trabecular bone for their age, while those with hip fractures have a deficit of both cortical and trabecular bone compared to women of age 50 yr, but the deficit is not excessive compared to others of similar age without fractures.