The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure

To evaluate the effects of primary hyperparathyroidism (PHPT) on bone mass and structure, we have studied the iliac crest biopsies of 27 patients, 10 males (28-68 yr old) and 17 females (26-72 yr old) with mild PHPT after in vivo tetracycline labeling. All patients had mild hypercalcemia in the absence of any other cause and elevated levels of PTH without radiological evidence of bone disease. Static parameters of bone turnover (osteoid surface, osteoid volume, and eroded surface) were elevated in both men and women compared to normal values; the midmolecule RIA for PTH (PTHMM) was positively correlated with osteoid surface (r = 0.44; P less than 0.025) and eroded surface (r = 0.58; P less than 0.005). Dynamic parameters of bone turnover (mineralizing surface, expressed as double plus half single labeled surface, and bone formation rate at tissue level) were elevated compared to normal values; PTHMM was positively correlated with double plus half single labeled surfaces (r = 0.33; P less than 0.05) and with bone formation rate at the tissue level (r = 0.37; P less than 0.05). The mineral apposition rate was within the limits of normal values and positively correlated with PTHMM (r = 0.34; P less than 0.05). Histomorphometric parameters of bone structure [cancellous bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and total bone density (TBD)] were compared to those in 20 autopsy control subjects, 12 men (33-60 yr old) and 8 women (27-75 yr old). BV/TV and Tb.N were significantly higher in PHPT patients than controls (P less than 0.02 and P less than 0.001, respectively). Tb.Sp was significantly lower in PHPT patients than controls (P less than 0.001), whereas Tb.Th was not significantly different between PHPT patients and controls. Ct.Th was significantly lower in PHPT patients than in controls (P less than 0.001), whereas TBD was not significantly different between the two groups. BV/TV was negatively correlated with age in both controls and PHPT patients. Tb.N showed a negative correlation and Tb.Sp a positive correlation with age in controls (r = -0.47; P less than 0.05 and r = 0.52; P less than 0.02, respectively), but they were not significantly dependent on age in PHPT patients. Tb.Th, while showing no significant age-related change in controls, was negatively correlated with age in PHPT patients (r = -0.42; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

雄性ApoE基因敲除小鼠不同时期骨密度和骨微结构的改变

目的 观察ApoE基因敲除(ApoE-/-)小鼠的骨微结构、骨密度、骨矿含量(BMC)的变化,探讨ApoE在骨重建中的作用.方法 15、28和40周龄雄性ApoE-/-纯合子小鼠以及同性别、同周龄的野生型小鼠共48只,应用显微CT测定小鼠右侧股骨远端松质骨和皮质骨的骨微结构参数,双能X线骨密度仪(DXA)测定左侧股骨骨密度.并分析骨微结构、骨密度、BMC相关性.结果 与野生鼠相比,不同时期ApoE-/-鼠的股骨松质骨体积骨密度(vBMD)、组织骨密度、BMC、骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)明显增加(P<0.05),骨面积分数(BS/BV)、骨小梁间隔(Tb.SP)和结构模型指数明显减低(P<0.05).股骨皮质骨内径周长、皮质骨外径周长、皮质骨面积、骨髓腔面积、截面总面积和截面惯性矩增加,而皮质骨骨密度、皮质骨BMC和皮质骨厚度变化不明显.DXA测定显示28周龄ApoE-/-鼠的总体骨密度明显高于野生型鼠(P<0.05),15和40周龄ApoE-/-鼠总体骨密度与对照组相比,无统计学差异.28周龄ApoE-/-鼠vBMD与BMC、BV/TV、Tb.Th、BS/BV和皮质骨BMC明显相关,相关系数分别为0.955、0.944、0.834、0.923和0.903,而与其他参数不相关.结论 ApoE-/-鼠表现出骨量增加,提示ApoE在骨重建中起重要作用.     

Bone remodelling in monoclonal gammopathies of uncertain significance,symptomatic and nonsymptomatic myeloma

Summary In order to characterize the abnormalities of bone remodelling in the various stages of plasma cell disorders, we studied 60 patients (29 monoclonal gammopathies of uncertain significance (MGUS), 13 stage I myeloma, 18 stage III myeloma). We carried out histomorphometric study of bone biopsies in 34 patients and measurement of osteocalcin and the calciuria/creatinine ratio.Bone remodelling was approximately normal (BV/TV: 21.2±7, ES: 4.1±2, OS: 16.5±10) in MGUS. Stage I myeloma was characterised by parallel increases in resorption surfaces and osteoid surfaces (BV/TV: 18±5, ES/BS: 7.4±3.5, OS/BS: 24.8±11.5), of the ca/cr ratio and osteocalcin. In stage III myeloma, resorption surfaces and the ca/cr ratio showed an even greater increase while osteoid surfaces, osteocalcin and trabecular bone volume decreased (BV/TV 13.6±6, ES/BS: 12.1±6, OS/BS: 13.6±8.3). Osteocalcin and osteoid surfaces were correlated (r=0.5). There was a positive correlation between osteocalcin and the number of plasmocytes in stage 1 myeloma (r=0.64) and a negative correlation in stage III myeloma (r=0.9).Bone remodeling was normal in MGUS; bone remodelling grew with a parallel increase of formation and resorption in stage I; bone resorption increased while bone formation decreased in stage III myeloma.     

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。     

Magnetic resonance imaging of normal and osteoarthritic trabecular bone structure in the human knee

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to evaluate the trabecular bone structure in the distal femur and the proximal tibia and its to correlate the findings with different stages of osteoarthritis (OA) of the human knee. METHODS: Axial images of the distal femur and proximal tibia were obtained at 1.5 T in patients without and with mild OA and with severe OA. The spatial resolution was 195 x 195 microm(2) with a 1-mm slice thickness. Apparent measures of trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th) were calculated. RESULTS: Significant differences existed in the trabecular bone structure of the femur and tibia. Differences in trabecular bone structure between the tibia and the femur decreased with the degree of OA. The apparent BV/TV, Tb.N, and Tb.Sp in the femoral condyles could be used to differentiate healthy patients or patients with mild OA from patients with severe OA (P < 0.05). Among individuals, the structural variation of the lateral and medial femoral condyle was indicative of the extent of the disease. CONCLUSION: High-resolution MRI of the knee joint can provide a noninvasive assessment of trabecular bone structure. Trabecular bone structure, determined by high-resolution MRI, shows significant variation in patients with varying degrees of OA. The impact of OA on trabecular bone is different in the tibia than in the femur, and this difference depends on the extent of the disease.     

旋转中心偏移对显微CT松质骨定量分析的影响

目的观察旋转中心微小偏移对显微CT测量参数的影响。方法20只7月龄sD大鼠随机分为去卵巢组（OVX）和假手术组（SHAM）。手术后3周处死,应用显微cT扫描胫骨近干骺端。手动校正以获取每次扫描的最佳旋转中心,分析各旋转中心在偏移±0．5、±1．0、±1．5和±2．0像素条件下的密度及微结构参数。结果一般线性模型分析结果显示OVX组与SHAM组比较,表观骨密度、组织骨密度、骨体积分数、骨小梁数量和联接密度明显下降,骨小梁间隔明显增宽（P〈0．05）。组织骨密度、各向异性度、骨小梁面积密度和联接密度随旋转中心的偏移下降,骨体积分数和骨小梁厚度随偏移幅度的加大逐渐升高。旋转中心偏移±1．5像素内,对组织骨密度、骨体积分数、各向异性度和联接密度的测量无影响。而骨小梁厚度和骨小梁面积密度在旋转中心偏移±1．0像素内影响较小。OVX组与SHAM组各参数随旋转中心偏移的变化趋势基本一致。各参数随旋转中心偏移服从二次回归方程趋势。通过二次回归方程拟合,可以获得实际旋转中心。以该中心获取的图像质量高,并能确保定量分析数据的准确。实际旋转中心与人为校正的最佳旋转中心之间存在微小差异。结论旋转中心的微小偏移对表观骨密度、结构模型指数、骨小梁间隔和数量的测量无明显影响。组织骨密度、骨小梁厚度、骨小梁面积密度、骨体积分数、各向异性度和联接密度受旋转中心偏移影响较大。通过二次曲线方程拟合能找到正确的旋转中心,该中心与人为校正获取的最佳旋转中心存在一定误差。     

The Correlation of Regional Microstructure and Mechanics of the Cervical Articular Process in Adults

Purpose: Using micro-CT and finite element analysis to establish regional variation microarchitectures and correlation with mechanical properties of cervical articular facet trabecular bone to predict cervical spine security and material properties. Methods: A total of 144 cervical articular processes (each articular was separate to four region of interest (ROI), superior-anterior (SA), superior-posterior (SP), inferior-anterior (IA), and inferior-posterior (IP) regions) specimens with a volume of 5 × 5 × 5 mm³ were scanned by micro-CT, and allowable stress and other mechanical properties parameters in each region were calculated after mechanical testing, then the effectiveness was verified of finite element models by ABAQUS software. Results: Maximum and minimum values of C2–C7 articular processes and regions are C5 and C7 level, SA and SP regions for bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), whose variation tendency is similar to the Young’s modulus, allowable stress, BMD, maximum force and strain. Between Young’s modulus and all microstructure parameters, especially between BV/TV, bone mineral density (BMD) and Tb.Th, had higher linear regression coefficients R² = 0.5676, 0.6382, 0.3535, respectively. BMD and yield strength, BV/TV, and allowable stress also had better regression coefficients, R² = 0.5227, 0.5259, 0.5426, respectively. Conclusions: The contribution of the microstructure and mechanical properties of the C2–C7 cervical spine to the movement of the cervical spine is different and has a good correlation and the effectiveness of the finite element model is also verified that we can correctly calculate the microstructure and mechanical properties of the cervical articular process to evaluate the stability and injury risk of cervical vertebrae by the established model.     

Effect of Sevelamer Hydrochloride on Bone in Experimental Uremic Rats

Abstract: Hyperphosphatemia in dialysis patients is known to cause secondary hyperparathyroidism and high-turnover bone disease. Sevelamer hydrochloride (sevelamer) is a nonabsorbed, calcium-free phosphate-binder. We determined the effect of sevelamer on parathyroid hormone (PTH)-induced high bone turnover. Rats were sham-operated or 5/6-nephrectomized (Nx) and fed a phosphate loading diet for 16 weeks or 5/6-nephrectomized and fed a phosphate loading diet for 8 weeks and then fed the same diet containing 3% sevelamer for the subsequent 8 weeks (Nx-S). Sevelamer significantly reduced serum PTH. The relative osteoid volume (OV/BV), osteoid surface (OS/BS), eroded surface (ES/BS), mineral appositional rate (MAR), volume-referent bone formation rate (BFR/TV), and bone-referent bone formation rate (BFR/BV) were measured for vertebral bone histomorphometric analysis. All parameters were statistically higher in the Nx rats than in the sham-operated control rats. The administration of sevelamer attenuated increases in OV/BV, ES/BS, BFR/TV, and BFR/BV. For femur histomorphometric analysis, the porosity area (%) (PoAr/CtAr), osteoid surface on the periosteal surface, osteoid surface on the endocortical surface (OS/Es), mineral appositional rate on the periosteal surface, mineral appositional rate on the endocortical surface, bone formation rate on the periosteal surface, and bone formation rate on the endocortical surface (Es BFR) were calculated. All parameters were higher in the Nx group than in the control group. Sevelamer inhibited the elevation of PoAr/CtAr, OS/Es, and Es BFR. Our findings suggest that the decrease in PTH by sevelamer may be beneficial in the treatment of high PTH-induced bone disease.     

氟对大鼠腰椎骨组织形态计量学的影响

目的 观察氟对大鼠腰椎的骨组织形态计量学影响.方法 90只2月龄SPF级SD大鼠,雌雄各半,按体质量随机分成9组,其中对照组分为幼年(CS)、成年(AS)、长期(NS)组,用药组分为幼年高氟(CHS)、幼年低氟(CIS)、成年高氟(AHS)、成年低氟(ALS)、幼年长期高氟(CLHS)、幼年长期低氟(CLLS)组.对照组生理盐水灌胃,用药组分别按相应时间给予不同剂量的氟化钠灌胃.实验验结束后,取腰椎制成不脱钙骨切片,行骨组织形态计量学测量.包括骨小粱面积百分数(Tb.Ar)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、单位骨小梁面积破骨细胞数(Oc.N)、破骨细胞周长百分数(%Oc.Pm)、荧光周长百分率(%L.Pm)、骨矿化沉积率(MAR)、骨小梁周长形成率(BFR/BS)、骨小梁面积形成率(BFR/BV)、骨组织总面积形成率(BFR/TV)、成骨细胞周长(Ob.PM).结果 [1]CHS组的%Tb.Ar、Tb.Th、Tb.N、%L.Pm、MAR、BFR/BS、BFR/BV、和BFR/TV[(50.63±7.44)%,(150.26±27.51)μm,(3.44±0.47)N/mm,(50.63±7.44)%,(0.85±0.03)μm/d、(8.45±2.36)μm/d×100、(381.16±41.62)%/year、(75.07±4.81)%/year]均高于CS组[(29.71±9.32%)、(1 10.93±28.19)μm、(2.68±0.34)N/mm、(24.00±1.22)%、(0.65±0.03)μm/d、(5.43±0.18)μm/d×100、(141.32±9.29)%/year、(58.14±2.3)%/year,P<0.05].CLS组的%Tb.A、Tb.Th、%L.Pm、MAR、BFR/BS、BFR/BV、BFR/TV和Ob.PM[(40.76±6.43)%、(164.25±45.65)μm、(42.02±6.12)%、(0.85±0.04)μm/d、(8.95±3.73)μm/d×100、(378.73±35.39)%/year、(73.52±8.71)%/year、(1.41±0.05)μm]均高于CS组(P均<0.05).[2]AHS组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(50.62±5.76)%、(0.51±0.05)N/mm、(1.13±0.05)%、(42.3±7.02)%、(1.28±0.09)μm/d、(12.91±1.52)μm/d×100、(390.12±43.56)%/year、(65.21±22.13)%/year]均高于AS组[(42.73±5.22)%、(0.41±0.17)N/mm、(0.77±0.52)%、(28.43±6.93)%、(0.80±0.03)μm/d、(9.83±1.44)μm/d ×100、(324.43±53.44)%/year和(48.35±9.36)%/year,P均<0.05].A15组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(51.14±6.22)%、(O.49±0.61)N/mm、(1.17±0.11)%、(45.06±6.92)%、(1.39 ±0.08)μm/d、(12.87±1.35)μm/d × 100、(394.6±50.23)%/year和(66.31±18.93)%/year]均高于AS组(P均<0.05).[3]CLHS组的Ob.PM、Oc.N和%Oc.Pm[(1.47±0.27)μm、(0.58±0.13)N/mm、(1.14±0.07)%]均高于NS组[(0.82±1.2)μm、(0.42±0.25)N/mm和(0.75±0.64)%,P均<0.05)].结论 短期染氟导致幼年、成年大鼠的腰椎成骨活动增强;长期染氟虽然增加成骨细胞数目,但是腰椎骨量增加不明显,有促进骨吸收,降低骨质量的可能,随着氟化钠使用时间的延长,逐渐表现出对生长期大鼠骨代谢和骨质量的负作用.     

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。     

骨细胞GLP-1受体表达对2型糖尿病大鼠骨微结构的影响

目的观察2型糖尿病大鼠股骨颈骨细胞表达胰高血糖素样肽-1受体(GLP-1R)阳性细胞百分数的变化,探讨骨组织GLP-1R变化对骨微结构的影响。方法雄性Wistar大鼠60只,随机分为实验组(30只)和对照组(30只),实验组采用高糖高脂饲料喂养至12周时加小剂量链脲佐菌素腹腔注射诱导糖尿病模型,对照组采用普通饲料喂养。分别于造模成功时和成模后第12周,处死10只大鼠作为糖尿病0周组(DM0w组,n=10)和糖尿病12周组(DM12w组,n=10),对照组分别于同期各处死10只大鼠作为正常对照(NGT0w组,n=10;NGT12w组,n=10)。经腹主动脉采血测定空腹血糖(FBG)、胆固醇(TC)、三酰甘油(TG)。取近端股骨颈,制备脱钙和不脱钙骨切片,备免疫组化检测GLP-1R阳性的骨细胞,采用Simple软件分析骨小梁形态计量学指标:骨小梁占骨髓腔体积百分比(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)。采用单因素方差分析比较各组大鼠股骨颈表达GLP-1R阳性的骨细胞百分数,BV/TV、Tb.Th、Tb.N的变化,采用Pearson行相关分析。结果与同期对照组相比,DM0w组、DM12w组大鼠FBG、TC、TG升高(均P0.05);与同期对照组相比,DM0w组、DM12w组大鼠股骨颈表达GLP-1R阳性骨细胞百分数和BV/TV、Tb.Th均减少(均P0.05);与DM0组相比,DM12组大鼠股骨颈表达GLP-1R阳性的骨细胞百分数、BV/TV、Tb.Th、Tb.N均减少(均P0.05);Pearson相关分析显示大鼠股骨颈GLP-1R阳性骨细胞百分数与股骨颈BV/TV、Tb.Th、Tb.N均呈正相关,相关系数分别为r=0.803,P0.05;r=0.545,P0.05;r=0.771,P0.05。结论糖尿病大鼠股骨颈骨细胞GLP-1R的表达减少,同时BV/TV、Tb.N减少,Tb.Th变薄,骨细胞GLP-1R的表达可能是影响2型糖尿病骨微结构的因素之一。     

Segmental variations in trabecular bone density and microstructure of the spine in senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis

The senescence-accelerated mouse strain P6 (SAMP6) is a model of senile osteoporosis, which possesses many features of senile osteoporosis in humans. So far, little is known about the systemic bone microstructural changes that occur at the cervical, thoracic, and lumbar vertebrae. In this study, we therefore investigated segmental variations of vertebral trabecular bone mineral density (BMD) and three-dimensional microstructure in SAMP6 and the normal control mouse (SAMR1) at 12 months of age using quantitative micro computed tomography (micro-CT) and image analysis software. The vertebral height and vertebral cross-sectional area (CSA) increased, while vertebral trabecular BMD and trabecular bone volume fraction (BV/TV) decreased from the cervical to lumbar spine both in SAMR1 and SAMP6. As compared with SAMR1, the thoracic vertebral CSA had a tendency to be low and the lumbar vertebral CSA was significantly declined in SAMP6. The vertebral trabecular BMD, BV/TV, trabecular thickness (Tb.Th), and trabecular number (Tb.N) significantly decreased in cervical, thoracic and lumbar spine of SAMP6. Trabecular bone pattern factor (TBPf) was higher at the lumbar spine and the structure model index (SMI) of the lower thoracic and lumbar spine was higher in SAMP6. These results indicate that vertebral trabecular bone microstructures are remarkably heterogeneous throughout the spine in both SAMR1 and SAMP6. The decrease of vertebral trabecular bone density in SAMP6 advanced faster caudally than cranially within the spine, similar phenomena were observed in humans. These findings highlight the relevance of SAMP6 for studies of vertebral fragility associated with senile osteoporosis.     

Risedronate prevents the loss of microarchitecture in glucocorticoid-induced osteoporosis in rats

Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1. Control: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 mug/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 microg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31+/-1 vs 35+/-1%, p<0.05; Tb.Th: 43+/-2 vs 50+/-3 microm, p<0.01; Ac.f: 1.8+/-0.2 vs 1.6+/-0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.     

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.     

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     

Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy

CONTEXT: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. OBJECTIVE: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. DESIGN: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. SETTING: The trial was conducted at 11 clinical study sites. PATIENTS: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. INTERVENTIONS: Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered. MAIN OUTCOME MEASURES: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. RESULTS: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. CONCLUSIONS: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.     

Decreased bone strength in HLA-B27 transgenic rat model of spondyloarthropathy

OBJECTIVE: To investigate the nature of osteopenia/osteoporosis in spondyloarthropathy, an inflammatory disorder, using the HLA-B27 transgenic rat model. METHODS: HLA-B27 transgenic rats were housed individually and sacrificed at the peak of their disease (8-month-old). The spine and femurs were removed and stored in saline at -20 degrees C until analysis. The bone structure and strength were determined using a micro-computed tomography (micro-CT) device (Scanco Medical) and mechanical testing (Instron 5543). Vertebral bodies and femurs were scanned to determine trabecular structural properties in terms of bone volume (BV/TV), trabecular thickness, and spacing. After scanning, the mid-shaft femurs were subjected to a 3-point bending test (along anterior-posterior direction), the femoral necks were tested in bending, and the vertebral bodies (L4) were tested in compression. Structural (ultimate/yield load, stiffness) and apparent material (ultimate/yield stress, modulus) strength parameters were then determined. RESULTS: The majority of the bone structural and strength parameters were significantly lower (P < 0.05) in the HLA-B27 transgenic rats as compared with control littermates. Micro-CT data suggested that the transgenic animals had lower BV/TV and trabecular thickness in their vertebral bodies. The poor trabecular structure observed in HLA-B27 rats is also indicative of the poor biomechanical strength properties in the vertebral bodies as well. CONCLUSION: The HLA-B27 transgenic rats develop bone fragility similar to that seen in spondyloarthropathy and may be an important model for the study of osteoporosis in spondyloarthropathy.     

Bone loss in hypothyroidism with hormone replacement. A histomorphometric study

To determine the influences of hormone replacement on bone tissue in primary hypothyroidism, a histomorphometric study on undecalcified transiliac bone specimens was performed before treatment in ten patients, during the first month of treatment in 16 patients, and after more than six months of treatment in 15 patients. There were no obvious clinical or biologic signs of excessive replacement therapy. Before treatment, trabecular resorption surfaces were lower and bone cortical thickness was increased. From as early as the first month of treatment, trabecular resorption surfaces and cortical porosity were higher than normal but cortical thickness was still increased. After more than six months of treatment there was a significant loss of trabecular (decreased trabecular bone volume) and cortical (normal mean cortical width; increased porosity) bone with hyperremodeling (increased trabecular resorption surfaces and trabecular osteoid surfaces). This osteoporosis is similar to that observed in hyperthyroidism.     

The effects of binge alcohol exposure on bone resorption and biomechanical and structural properties are offset by concurrent bisphosphonate treatment

BACKGROUND: Chronic alcohol consumption reduces bone mass and strength, increasing fracture risk for alcohol abusers. Mechanisms underlying this vulnerability involve modulation of bone remodeling. Direct effects of alcohol on bone formation have been documented; those on bone resorption are less well studied. Skeletal effects of exposure to high blood alcohol concentrations (BAC's) attained during binge drinking have not been studied. We examined the effects of repeated binge-like alcohol treatment on bone resorption, bone mineral density and vertebral compressive strength in adult male rats treated with the aminobisphosphonate, risedronate. METHODS: A binge alcohol exposure model was developed using intraperitoneal (IP) injection to administer a 20% (vol/vol) alcohol/saline solution (3 g/kg, 1X/day) on four consecutive days for 1, 2 or 3 weeks in 400 g rats, with and without weekly risedronate treatment (0.5 mg/kg, 1X/week). Total serum deoxypyridinoline (Dpd) a crosslink of bone type collagen released during resorption was measured by ELISA. Bone mineral density (BMD) was measured using peripheral quantitative computed tomography (pQCT). Vertebral compressive strength was determined using an Instron materials testing machine. Trabecular integrity was analyzed by computer-aided trabecular analysis system (TAS). RESULTS: Peak BAC's averaged 308.5 +/- 12 mg/dL; average BAC was 258.6 +/- 28.7 mg/dL at time of euthanasia. No significant effects of treatment were observed after 1 or 2 weeks of binge alcohol exposure. At 3 weeks of alcohol treatment serum Dpd was significantly increased (205%, p < 0.05) over controls. Bone mineral density (BMD) in cancellous bone of distal femur and lumbar spine were significantly decreased (34% and 21% respectively, p < 0.01) after 3 weeks of binge treatment. Vertebral (L4) compressive strength (maximum load sustained before failure) also decreased (27%, p < 0.05) after 3 binge alcohol cycles. Risedronate maintained the Dpd level (p < 0.01), BMD (p < 0.001) and vertebral structural biomechanical properties (p < 0.01) of binge-treated rats at control levels (E vs ER). Indices of trabecular architectural integrity [Trabecular bone volume/tissue volume (BV/TV), bone area (BAR) and trabecular separation (Tb.Sp)] analyzed at week 3 showed (BV/TV) and (BAR) were significantly reduced in alcohol-binged rats (p < 0.01), while (Tb.Sp) was significantly increased (p < 0.01). Risedronate also maintained the trabecular architectural indices of binge-treated rats at control levels (E versus ER, p < 0.01). CONCLUSIONS: In adult male rats, BAC's reflective of those attained during alcoholic binge drinking may affect the skeleton in part by stimulating bone resorption, an effect mitigated by risedronate.     

Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice

It was previously shown that strontium ranelate (SR; S12911-PROTOS, Institut de Recherches Internationales Servier, Courbevoie, France) can modulate bone metabolism in rats and mice. To determine the long-term effects of SR on vertebral bone metabolism in adult mice, the compound or the vehicle was given in the diet to normal male and female mice for 104 weeks at the dose of 200, 600, or 1,800 mg/kg/d corresponding to 0.78, 2.34 or 7.01 mmol Sr(2+)/kg/d. SR dose-dependently increased plasma strontium concentration, as well as exposure to the drug. Histomorphometric analyses of indices of bone volume, bone formation, and resorption were determined in the endosteal vertebral bone. SR significantly increased the trabecular bone volume by 25% and 59% in females treated with SR 600 and 1,800 mg/kg/d, respectively. This was associated with a 27% and 62% increase in mineralized bone volume. Bone volume was also significantly increased by 17% and 38% in male mice treated with SR 200 and 1,800 mg/kg/d, respectively. In parallel, SR increased the osteoblastic surface by 131% in males. In addition to this stimulatory effect on bone formation, a 52% decrease in osteoclastic surface, and a dose-dependent decrease in osteoclastic number (30% to 47%), was observed in female mice. Finally, SR even at the highest dose tested did not alter the osteoid thickness, indicating no deleterious effect on bone mineralization. Altogether, these findings show that SR simultaneously increases bone formation and decreases bone resorption in male or female mice, which results in increased vertebral bone mass in both genders without deleterious effect on bone mineralization.