谷康泰灵对骨质疏松模型大鼠骨形成和骨吸收功能的影响

目的　观察药物谷康泰灵对骨质疏松 (OP)模型大鼠骨形成和骨吸收功能的影响 ,为其临床治疗骨质疏松提供实验依据。方法　SD大鼠 4 4只 ,随机分为正常组 (13只 )和骨质疏松模型组 (31只 )。以维甲酸 80mg·kg- 1 ·d- 1 灌胃 15d,诱导OP模型。模型复制成功后 ,各组处死 5只 ,正常组 (8只 )继续观察 ,模型组又随机分为无措施对照组 (8只 )、谷康泰灵治疗组 (10只 ,0 0 8mg·kg- 1 ·d- 1 谷康泰灵腹腔注射 )和雌二醇治疗组 (8只 ,每只 0 0 5mg,每周 3次苯甲酸雌二醇腹腔注射 )。治疗期 30d。观察股骨松质骨区成骨细胞及破骨细胞数量和血清中AKP、TRAP活性变化。结果　与正常组相比 ,维甲酸诱导的OP模型大鼠股骨松质骨区成骨细胞功能活跃 ,数量变化不大 ;破骨细胞数量、活跃程度显著增加 ;血清中AKP和TRAP明显增高。谷康泰灵治疗后 ,OP大鼠活跃成骨细胞数量明显增加 ,破骨细胞数量显著减少 ,血清AKP活性明显增高 ,TRAP活性下降。结论　谷康泰灵对OP大鼠骨形成和骨吸收功能有显著影响 ,可刺激成骨细胞的产生增加成骨细胞的活性 ,减少破骨细胞的数量抑制破骨细胞的活性。     

Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells

Whereas continuous PTH infusion increases bone resorption and bone loss, intermittent PTH treatment stimulates bone formation, in part, via reactivation of quiescent bone surfaces and reducing osteoblast apoptosis. We investigated the possibility that intermittent and continuous PTH treatment also differentially regulates osteogenic and adipocytic lineage commitment of bone marrow stromal progenitor/mesenchymal stem cells (MSC). The MSC were cultured under mildly adipogenic conditions in medium supplemented with dexamethasone, insulin, isobutyl-methylxanthine and troglitazone (DIIT), and treated with 50 nM human PTH(1–34) for either 1 h/day or continuously (PTH replenished every 48 h). After 6 days, cells treated with PTH for 1 h/day retained their normal fibroblastic appearance whereas those treated continuously adopted a polygonal, irregular morphology. After 12–18 days numerous lipid vacuole and oil red O-positive adipocytes had developed in cultures treated with DIIT alone, or with DIIT and continuous PTH. In contrast, adipocyte number was reduced and alkaline phosphatase staining increased in the cultures treated with DIIT and 1 h/day PTH, indicating suppression of adipogenesis and possible promotion of early osteoblastic differentiation. Furthermore, intermittent but not continuous PTH treatment suppressed markers of differentiated adipocytes such as mRNA expression of lipoprotein lipase and PPARγ as well as glycerol 3-phosphate dehydrogenase activity. All of these effects of intermittent PTH were also produced by a 1 h/day treatment with AH3960 (30 μM), a small molecule, non-peptide agonist of the PTH1 receptor. AH3960, like PTH, activates both the cAMP and calcium signaling pathways. Treatment with the adenylyl cyclase activator forskolin for 1 h/day, mimicked the anti-adipogenic effect of intermittent PTH, whereas pretreatment with the protein kinase-A inhibitor H89 prior to intermittent PTH resulted in almost complete conversion to adipocytes. In contrast, the MAP kinase inhibitor PD 98059 failed to prevent the anti-adipocytic effect of intermittent PTH, suggesting that the inhibitory effect of PTH on adipocyte differentiation is predominantly cAMP-dependent. These results demonstrate a differential effect of PTH1 receptor agonists on the adipocytic commitment and differentiation of adult human bone marrow mesenchymal stem cells. This response may represent an additional mechanism that contributes to the overall bone anabolic action of intermittent PTH.     

Decreased bone formation in osteoporotic patients compared with age-matched controls

Summary In order to study trabecular bone remodeling in postmenopausal osteoporosis we compared bone biopsies of 44 osteoporotic women aged 50–70 to those of 23 nonosteoporotic women, matched for age, who had a bone biopsy during anesthesia for knee arthritis. Trabecular bone volume, mean wall thickness, osteoblastic surfaces, labeled surfaces, and bone formation rate were decreased in osteoporotic women compared with control women. The osteoclast number and the osteoclastic surfaces were the same in the two groups. The normal distribution of the histomorphometric static parameters in osteoporotic patients did not allow the separation of subgroups. These data indicate that decreased bone formations is a major contributing factor leading to trabecular bone loss in postmenopausal osteoporosis.     

辛伐他汀体外促进骨形成作用的初步研究

目的 研究辛伐他汀(Simvastatin)对成骨细胞分化、增殖及骨形成的作用。方法 用RPMI 1640培养液分别对水囊引产胎儿及新生大鼠颅顶骨进行组织培养,并将等量的胎儿或大鼠的颅顶骨骨组织分为实验组(辛伐他汀1μmol/L)和对照组,除动态观察比较不同培养液中成骨细胞的增殖状况外,将培养7d后的颅顶骨组织块制成半薄或超薄病理切片,于光镜下和电镜下进行形态学观察,并用测微尺测量新生骨组织厚度,记录成骨细胞数;同时,对留取的培养液测定其中的碱性磷酸酶(AKP)及骨钙素(BGP)的含量。结果 在培养过程中,可见实验组胎儿和新生大鼠颅骨成骨细胞生长活跃,数量多;对照组成骨细胞生长缓慢,数量少,可见大量成纤维细胞。培养7d后可见实验组胎儿及大鼠颅骨新生骨组织的厚度均明显高于对照组(P<0.01);其单位长度(0.3 mm)新生骨组织内成骨细胞数均明显高于对照组(P<0.01)。透射电镜下可见实验组成骨细胞处于活化状态,胞浆内有丰富的细胞器,少见破骨细胞,而对照组成骨细胞处于衰老状态,细胞器少见,可见大量破骨细胞。实验组培养液中AKP及BGP均明显高于对照组(P<0.01)。结论 辛伐他汀在体外实验中具有促进成骨细胞分化、增殖和促进新骨形成的作用;他汀类药物可作为预防、治疗骨质疏松症的有价值的候选药物。     

Vertebral deformity in chinese men: prevalence, risk factors, bone mineral density, and body composition measurements

The present study was performed to evaluate possible interactions between estrogen and progesterone on peak cancellous bone mass. Ovariectomized (OVX) growing rats were treated with 17β-estradiol (4.8 μg/day), progesterone (4.8 mg/day), a combination of the two sex steroids, or with vehicle for 14 days beginning 7 days after OVX. The tibiae were removed for histomorphometric analysis of the proximal metaphysis. OVX and growth each resulted in net resorption of cancellous bone at a sampling site adjusted for longitudinal bone growth. Estradiol and progesterone treatment each antagonized bone loss by inhibiting the decrease in trabecular number. Estradiol increased but progesterone had no effect on trabecular thickness. Progesterone did not influence either osteoclast number or the resorption of the pretreatment fluorochrome label. Estradiol reduced osteoclast number and inhibited label resorption, the latter change being accentuated by combination treatment. Estradiol reduced and progesterone enhanced the mineral apposition and bone formation rates. The results indicate that estradiol and progesterone have independent activities on cancellous bone turnover during growth. Whereas estradiol reduced bone turnover, progesterone had a stimulatory effect on bone formation. These findings suggest that progesterone has a role in establishing and maintaining peak cancellous bone volume during growth. Received: 28 June 1999 / Accepted: 11 January 2000     

Reduced bone formation in patients with osteoporosis associated with inflammatory bowel disease

The pathophysiology of bone loss associated with inflammatory bowel disease has not been clearly defined. In this study we have performed a detailed histomorphometric analysis of iliac crest bone obtained from 19 patients with inflammatory bowel disease in whom a diagnosis of osteoporosis had been made. Eleven subjects were receiving prednisolone at the time of their biopsy. Comparison with control values demonstrated a highly significant reduction in trabecular bone area in the patient group (p<0.001). Wall width, adjusted appositional rate and bone formation rate were all significantly reduced in the patient group (p<0.001) and the formation period was significantly increased (p<0.001). Resorption cavities were slightly smaller in the patient group, differences in maximum cavity depth and cavity length achieving statistical significance (p<0.005 andp<0.05 respectively). The mineral appositional rate was significantly reduced in the patients with inflammatory bowel disease (p<0.001) and the mineralization lag time significantly increased (p<0.001); however, osteoid area, perimeter and seam width were not significantly different from controls. These results demonstrate that osteoporosis associated with inflammatory bowel disease is characterized by reduced bone formation at the cellular and tissue level; the proportionately greater change in wall width than in resorption cavity depth is consistent with a negative remodelling balance. Although none of the patients had osteomalacia as defined by the criteria of increased osteoid seam width and mineralization lag time, the higher mineralization lag time in the patient group indicates a mild mineralization defect.     

Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male

Summary Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization. The dramatic histological response to hormonal replacement confirms the importance of androgens in bone modeling and remodeling.     

骨髓间充质干细胞移植对去卵巢骨质疏松骨量影响的实验研究

目的 探索骨髓间充质干细胞（BMSCs）移植对去卵巢骨质疏松大鼠骨密度的影响。方法 雌性SD大鼠随机分为空白对照组（A组）、模型组（B组）、细胞治疗组（C组）、雷诺昔芬药物治疗组（D组）。通过去卵巢建模成功后,C组通过尾静脉移植BMSCs,D组口服雷诺昔芬抗骨质疏松药物。结果 与A组相比,B组腰椎和股骨骨密度均明显降低（P＜0.01）。MSCs治疗后,C 组中的骨密度得到明显改善,并与B组比较具有统计学差异（P＜0.01）,亦优于D组。结论 BMSCs可以有效改善去卵巢大鼠骨质,这为绝经后骨质疏松的治疗提供了一种新的方法,为进一步临床应用提供了实验支持。     

Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone)

Thiazolidinediones are insulin-sensitizing agents and in clinical use for the treatment of type II diabetes. Under specific experimental conditions, these molecules induce adipogenic differentiation of mesenchymal precursor cells at the expense of osteoblasts in vitro, suggesting possible negative effects on the skeleton. We measured effects of the thiazolidinedione BRL49653 on bone tissue of intact and estrogen-deprived skeletally mature adult female Wistar rats (6–9 months old). Weight gain and decreased plasma triglyceride levels confirmed the effectiveness of the treatment. However, no change in bone mass or fat marrow volume was observed in intact rats treated for 8 weeks with 5, 10, or 20 mg/kg of BRL49653. Study of marrow cultures established at necropsy revealed a higher responsiveness to adipogenic differentiation protocols of cultures established from the 10-mg/kg group compared to vehicle control. In a second study, the effects of thiazolidinedione treatment on the skeleton of estrogen-deprived rats were investigated. Application of 10 mg/kg of BRL49653 for 12 weeks resulted in enhanced bone loss (+31%; pQCT) and increased fat marrow volume (+117%; histomorphometry) compared to vehicle-treated OVX control. Interestingly, osteoblast number was comparable in both cases. Bone resorption parameters were significantly increased in the treatment group (+27% osteoclast number, +30% eroded surface). Enhanced bone loss due to treatment was consistently observed in the tibia, femur, and the lumbar spine. Our data indicate that thiazolidinediones may enhance bone loss induced by estrogen deprivation.     

Strontium ranelate does not stimulate bone formation in ovariectomized rats

INTRODUCTION: Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium. METHODS: Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed. RESULTS: SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca. CONCLUSION: These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.     

Calcitonin (but not calcitonin gene-related peptide) increases mouse bone cell proliferation in a dose-dependent manner,and increases mouse bone formation,alone and in combination with fluoride

Summary Previousin vitro studies have shown that salmon calcitonin had direct effects to increase parameters associated with embryonic chicken bone formation and to increase mouse and chicken osteoblast-line cell proliferation. The current studies demonstrate increased cell proliferation (i.e., [³H]-thymidine incorporation into DNA and tetrazolium salt reduction/deposition) in the osteoblastic murine cell line MC-3T3-E1 in response to salmon calcitonin (P<0.005) and to human calcitonin (P<0.005), but not to human calcitonin gene-related peptide. The current studies also show that salmon calcitonin increased several indices of murine bone formation. We found that 72 hours of exposure to salmon calcitonin [at 5 mU/ml—about 0.37 nM; mU/ml = milliunits of calcitonin activity/ml incubation medium (at 4,000 U/mg protein)] increased net⁴⁵Ca deposition (121% of control,P<0.05), net [³H]-proline incorporation 149% of control,P<0.001), and alkaline phosphatase activity (146% of control,P<0.01), in neonatal mouse half-calvaria. The calcitonin-dependent increase in alkaline phosphatase activity was not affected by co-incubation with 1 nM parathyroid hormone. Co-incubation with fluoride (which also increased net [³H]-proline incorporation and alkaline phosphatase activity in neonatal mouse half-calvaria,P<0.05, for each) enhanced the osteogenic response to low-dose calcitonin, (i.e., co-incubation with fluoride shifted the biphasic calcitonin dose-response curve to a range of lower calcitonin concentrations). The calcitonin-fluoride combinations had proportional effects on net [³H]-proline incorporation and alkaline phosphatase in the treated mouse calvaria (r=0.78,P<0.005).     

Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats

The skeletal effects of flurbiprofen (Fb), a nonsteroidal antiinflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm² of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.     

Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations

Introduction Statins are drugs that inhibit HMG Co-A reductase and have been shown to enhance bone formation in vitro and in vivo in rodents. However, the statins currently used for cholesterol-lowering have been selected for their capacity to target the liver where their effects on cholesterol synthesis are mediated and they undergo first pass metabolism. When given in lipid-lowering doses, these agents do not likely reach sufficient blood concentrations to reliably cause substantial increases in bone formation in humans. Moreover, statins are inactivated by cytochrome P450 enzymes, resulting in even less peripheral distribution of the biologically active moieties beyond the liver. Method To investigate whether an alternate method of administration might produce beneficial effects on bone formation, we administered lovastatin by dermal application to rats to circumvent the first-pass effects of the gut wall and liver. Results We found that the statin blood levels measured by HMG Co-A reductase activity were higher, maintained longer and less variable following transdermal application than those following oral administration. Also the increased circulating statin levels were associated with significantly enhanced biological effects on bone. After only 5 days of administration of transdermal lovastatin to rats, there was a 30–60% increase in trabecular bone volume, and 4 weeks later, we observed more than a 150% increase in bone formation rates. There was also a significant increase in serum osteocalcin, a marker of bone formation. We also found that lovastatin administered transdermally produces these profound effects at doses in the range of 1% of the oral dose, without any evidence of the hepatotoxicity or myotoxicity that can occur following oral statin administration. Several doses (0.01–5 mg kg⁻¹ day⁻¹) and dosage schedules were examined, and collectively the data strongly suggest a powerful anabolic effect but with an unusually flat dose-response curve. Conclusion These results show transdermal application of statins produces greater beneficial effects on bone formation than oral administration does. GE Gutierrez, IR Garrett, G Rossini and GR Mundy are all employees of and hold stock in OsteoScreen Ltd.     

中国围绝经期妇女体脂含量与骨密度关系的初步研究

目的探讨肌肉、脂肪含量与围绝经期骨质疏松妇女骨密度之间的关系。方法利用双能X线骨密度测量仪(美国,Hologic DiscoveryA型)测量门诊围绝经期妇女(90例,年龄:45~52岁(47.3±8.2))骨密度与体脂含量;同时测量登记受试者的年龄、身高、体重。结果结果显示,21%受试者腰椎和股骨骨量降低,全身脂肪含量(20675.129±5080.44)g与腰椎骨密度(0.91±0.177)g/cm2(P>0.05,r=-0.17)和髋部骨密度(0.99±0.102)g/cm2(P>0.05,r=0.158)没有相关性,肌肉含量(39790.80±6551.54)g与腰椎骨密度没有相关性(P>0.05,r=0.078),但是与髋部骨密度高度正相关(P<0.05,r=0.216)。体重(63.01±9.39)kg和腰椎(P<0.05,r=0.217)和髋部(P<0.05,r=0.305)骨密度高度正相关;BMI指数(24.6751±3.45637)与腰椎(P<0.05,r=0.244)和髋部(P<0.01,r=0.339)骨密度高度正相关。结论研究结果表明BMI指数和肌肉含量与围绝经期妇女髋部骨密度高度相关。     

Dickkopf‐1 regulates bone formation in young growing rodents and upon traumatic injury

The physiological role of Dickkopf‐1 (Dkk1) during postnatal bone growth in rodents and in adult rodents was examined utilizing an antibody to Dkk1 (Dkk1‐Ab) that blocked Dkk1 binding to both low density lipoprotein receptor‐related protein 6 (LRP6) and Kremen2, thereby preventing the Wnt inhibitory activity of Dkk1. Treatment of growing mice and rats with Dkk1‐Ab resulted in a significant increase in bone mineral density because of increased bone formation. In contrast, treatment of adult ovariectomized rats did not appreciably impact bone, an effect that was associated with decreased Dkk1 expression in the serum and bone of older rats. Finally, we showed that Dkk1 plays a prominent role in adult bone by mediating fracture healing in adult rodents. These data suggest that, whereas Dkk1 significantly regulates bone formation in younger animals, its role in older animals is limited to pathologies that lead to the induction of Dkk1 expression in bone and/or serum, such as traumatic injury. © 2011 American Society for Bone and Mineral Research     

Casodex (a nonsteroidal antiandrogen) reduces cancellous,endosteal, and periosteal bone formation in estrogen-replete female rats

Testosterone has been implicated in the preservation of the skeleton in women and female rats. In this study we investigated the role of androgens in estrogen-replete female rats by giving Casodex (pure nonsteroidal anti-androgen) daily and analyzing the effects on the skeleton using static and dynamic histomorphometric parameters after 3 weeks. There was a significant reduction in the bone formation rate in both the cancellous bone of the tibial metaphysis and in the periosteal and corticoendosteal diaphyseal bone (90%, 30%, and 100% reduction, respectively, compared with control animals, which was unaccompanied by a change in the indices of bone resorption. Casodex had no effect on cancellous bone volume and cortical bone area but this can be accounted for by the short duration of the experiment. The serum levels of dehydroepiandrosteronesulfate and androstenedione were significantly reduced in the Casodex-treated rats compared with the control animals and there was no difference in the plasma levels of estrone, estradiol, or testosterone between the two groups. This study demonstrates that androgens play a physiological role in regulating osteoblast activity in female rats.     

老年女性腰椎骨密度与年龄及椎旁体质成分相关性分析

目的探讨不同腰椎椎体骨密度(bone mineral density,BMD)与年龄及同层面椎旁腰大肌、竖脊肌、腹部脂肪、血管钙化情况的关系。方法收集体检中心行腰椎检查的老年女性90名,采用定量CT(quantitative CT,QCT)及后处理软件测量L2-L4椎体骨密度及三椎体同层面椎旁体质成分。统计学处理应用配对t检验、Pearson相关分析和多元逐步回归分析等。结果①3组椎体BMD均与年龄均呈负相关(P0.05),L2BMD、L3BMD均与双侧腰大肌、竖脊肌密度成正相关(r=0.233~0.301,P均0.05)。而L4BMD显示与双侧竖脊肌密度及腹部脂肪面积有良好的相关性,均呈正相关。②多元逐步回归分析显示除年龄外,肌肉是影响BMD的重要因素。年龄是唯一全部进入3组腰椎BMD回归方程,并呈负相关,是影响腰椎BMD的重要因素。结论老年女性的腰椎骨密度与椎旁腰大肌、竖脊肌密度,腹部脂肪面积及年龄密切相关,除年龄外椎旁肌肉密度对骨密度影响最大。QCT扫描更加直观、精确显示椎骨与椎旁体质成分情况,可作为测量诊断骨质疏松、体质成分的新手段。     

Computed tomographic measurements of thigh muscle cross‐sectional area and attenuation coefficient predict hip fracture: The health,aging, and body composition study

Fatty infiltration of muscle, myosteatosis, increases with age and results in reduced muscle strength and function and increased fall risk. However, it is unknown if increased fatty infiltration of muscle predisposes to hip fracture. We measured the mean Hounsfield unit (HU) of the lean tissue within the midthigh muscle bundle (thigh muscle HU, an indicator of intramuscular fat), its cross‐sectional area (CSA, a measure of muscle mass) by computed tomography (CT), bone mineral density (BMD) of the hip and total‐body percent fat by dual X‐ray absorptiometry (DXA), isokinetic leg extensor strength, and the Short Physical Performance Battery (SPPB) in 2941 white and black women and men aged 70 to 79 years. Sixty‐three hip fractures were validated during 6.6 years of follow‐up. Proportional hazards regression analysis was used to assess the relative risk (RR) of hip fracture across variations in thigh muscle attenuation, CSA, muscle strength, and physical function for hip fracture. In models adjusted by age, race, gender, body mass index, and percentage fat, decreased thigh muscle HU resulted in increased risk of hip fracture [RR/SD = 1.58; 95% confidence interval (CI) 1.10–1.99], an association that continued to be significant after further adjustment for BMD. In models additionally adjusted by CSA, muscle strength, and SPPB score, decreased thigh muscle HU but none of the other muscle parameters continued to be associated with an increased risk of hip fracture (RR/SD = 1.42; 95% CI 1.03–1.97). Decreased thigh muscle HU, a measure of fatty infiltration of muscle, is associated with increased risk of hip fracture and appears to account for the association between reduced muscle strength, physical performance, and muscle mass and risk of hip fracture. This characteristic captures a physical characteristic of muscle tissue that may have importance in hip fracture etiology. © 2010 American Society for Bone and Mineral Research     

仫佬族绝经前与绝经后女性体成分和骨密度的相关性研究

目的研究仫佬族绝经前与绝经后女性体成分和骨密度的相关关系,探讨体成分的变化对骨密度的影响。方法随机选取广西仫佬族成年女性200名,追溯其三代均为仫佬族,应用TANITA-MC180人体成分分析仪测定其肌肉量、脂肪量等体成分指标,采用SONOT3000超声骨密度仪测定其右侧跟骨的骨硬度指数。结果 (1)绝经前女性的体重、去脂体重、肌肉量、皮下脂肪量、躯干脂肪量、四肢肌肉量、推定骨量、骨硬度指数和T值等均显著高于绝经后女性(P0.01);而绝经前女性的内脏脂肪面积、腰臀比显著低于绝经后女性(P0.01)。(2)绝经前女性和绝经后女性的骨质疏松检出率分别为6%和45%,差异具有统计学意义(P0.01)。(3)相关分析发现肌肉量、四肢肌肉量和躯干肌肉量与骨密度之间存在显著的正相关关系(P0.01或P0.05),而当控制年龄和绝经状态后体成分和骨密度之间没有相关性;根据年龄分组后发现,≥50岁组的肌肉量各指标与骨密度存在较显著的关联(P0.05),而50岁组的体成分与骨密度不存在关联性(P0.05)。(4)多重逐步回归分析发现只有绝经状态、躯干肌肉量和内脏脂肪量与骨密度相关,而躯干肌肉量对骨密度影响最大。结论仫佬族绝经后女性的骨质疏松症发生率显著高于绝经前女性;控制年龄和绝经因素后,只有躯干肌肉量与骨密度较显著相关,结果可为骨质疏松症的预防和诊断提供理论依据。     

Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats

The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague–Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.