雌激素对人乳腺癌细胞株MCF-7 KLK 6 mRNA和蛋白表达水平的影响

 目的： 探讨雌激素与其拮抗剂三苯氧胺对雌激素受体阳性人乳腺癌细胞株MCF-7组织激肽释放酶6（KLK 6）mRNA和蛋白（hK6）表达水平的影响。方法: 取生长良好的MCF-7细胞，在不同浓度的雌激素（17-βE2）和三苯氧胺存在下培养72 h后，收集细胞，分别采用荧光定量逆转录-聚合酶链反应和流式细胞术，检测KLK6 mRNA和蛋白表达水平的变化。结果: 实时荧光定量RT-PCR表明，当17-βE2浓度在10-12 mol/L时，与乙醇对照组无明显差异(P>0.05), 17-βE2浓度在10^-10 mol/L和10-8 mol/L时，KLK6 mRNA的相对含量显著少于乙醇对照组；流式细胞术分析表明, 代表hK6含量的相对荧光强度（AFI）显著低于乙醇对照组（P<0.01）。三苯氧胺（10^-6 mol/L）作用组KLK6 mRNA 的相对含量显著高于对照组（P<0.01）；hK6含量与对照组相比差异显著（P<0.01）。结论: 雌激素对MCF-7 KLK6 mRNA和蛋白表达水平有一定的下调作用，而三苯氧胺作用相反。     

沉默PKM2对乳腺癌他莫昔芬耐药MCF-7细胞系侵袭及迁移的影响

目的探讨PKM2下调对乳腺癌他莫昔芬(TAM)耐药MCF-7细胞系侵袭、迁移的影响。方法以浓度梯度法诱导获得乳腺癌他莫昔芬耐药细胞系(MCF-7R);细胞增殖与凋亡试剂盒(CCK-8)检测细胞增殖能力;Western blot检测细胞PKM2的表达;将表达针对PKM2的shRNA慢病毒干扰载体感染耐药细胞系,RT-q PCR、Western blot验证干扰效果,分别用Transwell侵袭实验、划痕实验检测细胞侵袭、迁移能力。结果与MCF-7细胞相比,MCF-7R细胞对他莫昔芬的抵抗能力显著增强(P0.01),PKM2的表达水平明显升高(P0.01)。稳定干扰PKM2的耐药细胞中PKM2的mRNA和蛋白水平较对照组均明显下降(P0.01),PKM2干扰后可明显抑制MCF-7R细胞的侵袭、迁移能力(P0.01)。结论 MCF-7R细胞中PKM2表达明显高于MCF-7细胞,沉默PKM2可以抑制MCF-7R细胞的侵袭和迁移能力。     

pcDNA3.1(+)-MER-Syk（L）载体构建及其对乳腺癌细胞增殖的影响

目的： 探讨乳腺癌细胞内4-OHT对MER-Syk(L)细胞定位的影响及对乳腺癌细胞增殖功能的影响。方法: 采用不表达Syk的乳腺癌细胞系MDA-MB-231,建立稳定表达融合蛋白MER-Syk(L)的细胞株;蛋白质印迹和免疫荧光染色技术检测4-OHT处理前后融合蛋白MER-Syk(L)在细胞内的位置;二苯基溴化四氮唑蓝（MTT）法分析处理前后稳态细胞的增殖能力。结果: （1）无4-OHT的处理,融合蛋白MER-Syk(L)、MER-Syk(S)和MER均位于MDA-MB-231细胞浆内;4-OHT的作用下,融合蛋白MER-Syk(L)部分移位到细胞核内,而MER-Syk(S)和MER仍然位于细胞浆内;（2）MDA-MB-231细胞核内的MER-Syk(L)蛋白能够抑制细胞的增殖和生长,而细胞浆内的MER-Syk(L)、MER-Syk(S)和MER蛋白对细胞增殖和生长功能没有影响。 结论: 4-OHT可使融合蛋白MER-Syk(L)移位到MDA-MB-231细胞核内,从而抑制细胞的增殖。     

绝经后妇女骨质疏松患者血清IGF-1、IGFBP-3与骨密度及骨代谢指标的关系

目的： 探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）与绝经后妇女骨密度及骨代谢指标之间的关系。方法： 通过检测90例绝经后妇女骨质疏松患者及70例绝经后骨量正常的健康对照组血清IGF-1、IGFBP-3、骨钙素（BGP）、I型胶原异构C端肽（β-CTX）、雌激素（E₂）、降钙素（CT）、甲状旁腺激素（PTH）、钙（Ca）、磷（P）等指标，然后同用双能X线骨密度仪检测的两组研究对象的腰椎（L2-L4）侧位、左股骨颈骨密度进行比较。结果： 绝经后骨质疏松组妇女腰椎、股骨颈骨密度显著低于对照组（均P<0.01）；血清IGF-1、IGFBP-3、E₂、CT、BGP水平均低于对照组（均P<0.01）；血清β-CTX、PTH均高于对照组（均P<0.01），血清Ca、P两组之间无差异（均P>0.05）。骨质疏松组和对照组腰椎侧位、左股骨颈BMD均与IGF-1、IGFBP-3、E₂、BGP、CT水平呈正相关，与β-CTX、PTH水平呈负相关，而与血钙、血磷无明显关系。结论： IGF-1、IGFBP-3、E₂、BGP、CT、β-CTX、PTH血清水平与腰椎、左股骨质具有明显的相关性，通过检测上述指标可考虑作为筛查绝经后妇女是否容易患有骨质疏松症的一项有价值的生化参考指标。     

绝经后骨质疏松症模型体视学测量和机理初探

目的:观测去势术后大鼠骨组织体视学的改变,复制绝经后骨质疏松症的动物模型,初步探讨骨质疏松症的发病机制。方法:将31只3月龄雌性SD大鼠随机分为卵巢切除术组(OVX)和假手术组(sham),术后28d和56d分别处死。测量子宫湿重,骨矿物密度(BMD)和骨组织形态计量参数,分析骨组织微结构的变化。结果:OVX组术后28d和56d大鼠子宫湿重和股骨远端1/3处骨密度均显著少于sham组(P＜0.05);OVX组股骨远端和胫骨近端的干骺端骨小梁面积百分率显著少于sham组(P＜0.01)。结论:卵巢切除术后大鼠股骨远端骨矿物密度和骨组织形态计量学参数稳步下降,胫骨近端骨矿物密度和骨组织形态计量学参数迅速下降而且不稳定;雌激素减少导致的骨质疏松主要发生在长骨的干骺端,骨骺受影响较少;骨组织形态计量参数中骨小梁面积百分比敏感性和稳定性较高。     

抗阻训练干预绝经后骨质疏松患者骨密度的系统综述和Meta分析

背景:抗阻训练已经被证实对于改善绝经后妇女骨质疏松患者的骨密度有所帮助,但抗阻运动的运动方式、训练强度、训练时间、训练频率,以及与不同运动(有氧运动等)方式的结合是否效果更好还有待研究。目的:评价抗阻训练对绝经后妇女骨质疏松患者骨密度的干预效果。方法:搜集抗阻训练干预绝经后妇女骨质疏松患者骨密度的相关随机对照试验,研究对象分为抗阻训练组及空白对照组,检索Pub Med、EMBASE、Web of Science、中国知网和万方医学数据库,检索的时间范围从建库到2019年12月,并且对纳入文献的相关参考文献进行检索。由2名研究者按纳入和排除标准筛选文献并提取有效数据,进行质量评价。采用Rev Man 5.3软件对最终纳入的文献数据进行Meta分析。结果与结论:①最终纳入23篇随机对照试验,对纳入的文献进行风险偏倚评价,结果显示整体文献质量为中等偏上;②Meta分析结果显示,与空白对照组相比,抗阻训练组可显著改善绝经后妇女骨质疏松患者的腰椎骨密度[SMD=0.02,95%CI(0.01,0.03),P<0.0001]、全髋骨密度[SMD=0.25,95%CI(0.06,0.44),P=0.03]、股骨颈骨密度[SMD=0.28,95%CI(0.12,0.04),P=0.0005]及大转子骨密度[SMD=0.02,95%CI(0.00,0.03),P=0.02];③提示抗阻训练有利于维持绝经后妇女骨质疏松患者的骨密度水平,可以作为绝经后妇女骨质疏松运动治疗的重要组成部分。     

乳腺癌内分泌治疗现状

内分泌治疗是雌激素受体阳性乳腺癌患的重治疗方法.随着新的内分泌药物出现,乳腺癌的内分泌治疗也取得了新的进展.目前,治疗绝经前乳腺癌患的标准用药仍是他莫昔芬,对于绝经后乳腺癌患使用芳香化酶抑制剂会获得更大的临床疗效.本文主阐述内分泌治疗在乳腺癌中的应用.     

类固醇激素对大鼠股骨及腰椎的骨密度影响

目的：探讨类固醇激素对大鼠股骨和腰椎的骨密度影响。方法：雄性SD大鼠分为基础对照组、实验对照组和激素模型组；用DEXA对各组的离体双侧股骨和第5腰椎进行骨密度测定。结果：与实验对照组比较，激素模型组股骨和第5腰椎的总骨密度减少了14．77％；腰椎的骨密度减少了23．00％；左、右股骨远段的骨密度分别减少了19．83％、21．37％，具显著或非常显著差异。结论：长期使用类固醇激素，会使大鼠的骨量丢失，尤以松质骨的丢失比密质骨更为明显。故出现骨质疏松时，松质骨更容易出现骨折。     

女性2型糖尿病患者的骨密度变化

目的：探讨女性2型糖尿病与骨质疏松的关系。方法：应用双能X线骨密度仪（DEXA）对56例女性2型糖尿病患者及52例女性健康对照者进行骨密度（BMD）测定,并测定糖尿病患者的空腹胰岛素及餐后2h胰岛素（2h Ins）水平,结合病程、年龄等相关因素进行分析。结果：52例健康对照组中低骨量8例,骨质疏松5例,骨密度减低的发生率为25%;56例2型糖尿病患者中,低骨量16例,骨质疏松23例,骨密度减低的发生率为69.7%,明显高于对照组,差异有显著性（P〈0.01,χ^2=21.524）,骨密度减低者胰岛素水平相对更低。结论：女性2型糖尿病患者的骨质疏松发生率高,且与年龄、病程、胰岛素水平相关。     

卵巢辐射损伤对大鼠腰椎骨密度和生物力学的影响

目的探讨大鼠卵巢辐射损伤后腰椎骨密度、微结构和生物力学的改变。方法手术暴露大鼠双侧卵巢并应用50Gy的γ射线局部照射,术后90d取大鼠腰椎,DEXA测定骨密度,扫描电镜显示微结构,并行压缩实验检测腰椎最大载荷。结果与假手术组相比,卵巢辐射组大鼠的腰椎骨密度显著减少(P<0.05),骨微结构破坏,生物力学性能下降(P<0.05)。结论卵巢辐射损可导致大鼠腰椎的骨质疏松样改变。     

Hip bone mineral density is improved by high-impact aerobic exercise in postmenopausal women and men over 50 years

Fifteen men and women (six men) between the ages of 50 and 73 years were recruited to begin keep-fit classes. They were matched for sex, age, menopausal status and mass to 15 non-exercising controls. The keepfit classes were two to three times a week and included high-impact exercise, including step and jumping exercises specifically to load the proximal femur and spine. Proximal femur, lumbar spine and total body bone mineral density (BMD) were measured at 0 and 12 months. Urinary pyridinoline (Pyr) and deoxypyridinoline (dPyr) crosslinks were measured every 6 months to assess bone resorption. Quadriceps isometric strength was measured every 6 months. BMD increased non-significantly at the femoral neck [1.57 (0.8%] and Wards triangle [1.97 (1.4%], and significantly at the greater trochanter 2.21 (0.9)% (P=0.02) in the exercise group. Femoral neck BMD decreased by −1.9(0.8)% (P=0.049) in the control group, which was significantly different from the change in the exercise group (P=0.009). BMD did not change at the Wards triangle or trochanter in the controls. Lumbar spine BMD did not change in either group. Total body BMD did not change in the exercise group, but decreased by −0.79 (0.3)% (P=0.02) in the controls. Follwing 6 months of the exercise classes, Pyr and dPyr crosslinks were significantly reduced [−19.0 (7.2)%;P=0.0019 and −20.0 (7.7)%;P=0.021 respectively]. There was no significant change in crosslinks after 1 year, and no change at any time in the controls. Quadriceps strength changed by 5.4 (3.7)% in the exercise group and by −6.9 (2.5)% (P=0.01) in the control group after 12 months, being significant between groups (P=0.008). This study suggests that high-impact, aerobic exercise in postmenopausal women and men over 50 years old is feasible and effective at maintaining muscle strength and increasing proximal femur BMD but not spine or total body BMD.     

Vitamin D deficiency and bone mineral density in postmenopausal women receiving aromatase inhibitors for early breast cancer

Objective

Aromatase inhibitors (AI) treatment leads to an increased risk of bone loss and fractures. In a group of women with early breast cancer (EBC) and baseline Vitamin D deficiency (<30 ng/ml) who are treated with AI, we aim to describe: serum levels of Vitamin D, bone mineral density (BMD), calcium intake, and the increase of serum 25(OH)D accomplished in 3 months of treatment with Vitamin D supplements.

Study design

Prospective, non-randomized clinical trial.

Methods

In 232 consecutively included women with EBC in treatment with AI, we assessed baseline calcium intake, serum levels of 25(OH)D, BMD and, spine X-ray. All received Calcium and Vitamin D supplements, and those with vitamin deficiency received 16,000 IU Vitamin D every 2 weeks. Serum levels of 25(OH)D were newly assessed after treatment. All the baseline evaluation was performed before starting AI treatment.

Results

Mean age at baseline (±SD) was 63.2 ± 8.8 years. In 150 (64.9%) cases, the women had been treated previously with tamoxifen; 101 (43.7%) started exemestane, 119 (51.5%) letrozole, and 11 (4.8%) anastrozole. The AI were initiated within 6 weeks after surgery or after the last cycle of chemotherapy.At baseline, 88.1% had 25(OH)D levels <30 ng/ml, 21.2% had severe deficiency (<10 ng/ml), and 25% of the participants had osteoporosis. Mean daily calcium intake was low (841 ± 338).We found a significant association between 25(OH)D levels and BMD at baseline, which remained significant in femoral neck BMD after multivariate adjustment.Plasma 25(OH)D levels improved significantly at 3 months follow-up in those treated with high dose Vitamin D supplements: mean increase 32.55 ng/ml (95%CI 28.06–37.03).

Conclusions

Our study suggests a high prevalence of commonly unrecognized Vitamin D deficiency in women with EBC treated with AI, a known osteopenic agent. Our results support the need for a routine assessment of 25(OH)D levels and, when necessary, supplementation in these patients.     

Effect of natural early menopause on bone mineral density

OBJECTIVES: Early menopause (EM) is included among the risk factors for osteoporosis. Several studies have shown that women with early menopause have lower bone mineral density (BMD) than those with normal expected age of menopause. The aim of our cross-sectional study was to investigate the effects of time of menopause on vertebral bone mass in healthy postmenopausal women and to evaluate if early menopause is a risk factor for lower vertebral BMD. METHOD: We studied 782 who had never received drugs acting on bone mass. The study population was divided into three groups: women with early, normal (NM), and late (LM) menopause. Our study population was further categorized in 5-year age segments between 45 and >75. RESULTS: The three groups examined did not differ for age, age at menarche, body mass index (BMI), and vertebral BMD, while there were significant differences in age at menopause and years since menopause. Our study showed that women with EM presented significantly lower vertebral BMD than NM and LM in 50-54 age segments. Beyond 55 years, EM, NM, and LM women had no differences in lumbar BMD values. CONCLUSIONS: In conclusion, controversial data demonstrated that the absolute amount of bone loss is greater after early menopause than after normal or late menopause, even if a slight effect of early menopause on bone mass cannot be excluded.     

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

Association of KIT gene polymorphisms with bone mineral density in postmenopausal Korean women

Bone mineral density (BMD) is a major factor for determining bone strength and osteoporotic fracture risk, and is determined by environmental and multiple genetic factors. KIT, which encodes a transmembrane receptor with tyrosine kinase activity, plays an important role in the differentiation of osteoclasts. We examined the associations between KIT gene polymorphisms and BMD in postmenopausal Korean women. All exons, their boundaries, and the promoter region (approximately 1.5 kb) from 24 individuals were directly sequenced. Eighteen polymorphisms were identified, and three single-nucleotide polymorphisms (SNPs) were genotyped in all study participants (n = 946). BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. The mean age of the study subjects was 58.9 ± 7.5 years, and the mean number of years since menopause was 9.6 ± 7.9 years. None of the three SNPs (−1694G>T, +41894A>G, and +49512G>A) was significantly associated with BMD value. However, multivariate analysis showed that the ht3 (−1694T-+41894A-+49512G) was significantly associated with lower BMD at the femoral neck (P = 0.007 in the recessive model). These findings indicate that KIT-ht3 may be a useful genetic marker for osteoporosis and that KIT may have a role on bone metabolism in humans. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. S.-Y. Kim and J.-Y. Lee are co-first authors.     

Comparison between 60 matched pairs of postmenopausal black and white women: analysis of risk factors related to bone mineral density

PURPOSE: Osteoporosis is a systemic disease in which bone density is reduced, leading to weakness of the skeleton and increased vulnerability to fractures. The purpose of this study was to compare known or suspected risk factors (medical, gynecological, and lifestyle characteristics) related to bone loss between 60 matched pairs of black and white postmenopausal women. METHODS: The two racial groups were matched one for one on selective anthropometric variables [age (years), standing height (cm), and body weight (kg)] in order to equate age and body size between groups. Information on risk factors was obtained from an orally administered questionnaire and body composition variables (in addition to those used for matching) assessed by anthropometry and total body dual energy X-ray absorptiometry (DXA). Four skinfold sites (chest, triceps, mid-axillary, and abdomen) were measured with Harpendon calipers and four body circumferences (chest, forearm contracted, waist, and gluteal) were assessed with a Gulick tape. DXA radius, spine, femur, and whole body measurements were obtained on a Hologic QDR-2000 with software version 7.20. RESULTS: White women reported significantly higher proportions of alcohol use, family history of broken bones, and a greater utilization of hormones, calcium and vitamins than did black women. Black women reported a greater numbers who had other diseases (i.e., overactive thyroid, diabetes, rheumatoid arthritis, or kidney stones). Although age and body weight were similar in both groups, black women had greater lean tissue and less body fat than white women. Blacks had significantly higher bone mineral density across all body sites with the exception of the mid- and ultra-distal radius. CONCLUSION: On the basis of these data, it was concluded that part of the difference often observed in bone density between black and white postmenopausal women might be due to lifestyle factors.     

康力龙对类固醇性大鼠骨质疏松骨密度和生物力学的影响

目的　从生物力学和骨矿含量测定角度研究康力龙对类固醇性大鼠骨代谢的影响。方法　采用 3月龄雄性SD大鼠 2 8只 ,随机分为基础对照组、年龄对照组、激素模型组和康力龙预防组。后两组给醋酸泼尼松 4 5mg·kg-1,ig ,2次 /周 ;预防组还给康力龙 0 5mg·kg-1·d-1,ig。 3个月后取股骨和第 5腰椎行骨密度测定 ,再行扭转、3点弯曲和压缩试验。结果　与年龄对照组比较 ,激素模型组股骨和第 5腰椎的总骨密度减少了 14 6 4 % (P <0 0 1) ;股骨干在 3点弯曲试验时所承受的载荷减少了17 1% (P <0 0 5 ) ;其余的力学参数都出现减少的趋势。与激素模型组比较 ,康力龙预防组股骨和第 5腰椎的总骨密度有所增加 ;股骨扭转角度明显增加 72 5 % (P <0 0 5 ) ,其余的力学参数都出现增加的趋势。结论　长期使用糖皮生激素 (GC) ,会使大鼠皮质骨和松质骨的骨密度和力学性能下降 ,从而易致骨折 ;应用康力龙则能阻止GC所致骨量丢失 ,还能增加其力学性能。     

Bone mineral density in healthy Tunisian women

Interpretation of densitometric results requires a comparison with reference bone mineral density (BMD) values of normal age and sex-matched persons. Thus the aim of this study was to determine these values for healthy Tunisian women, to estimate the prevalence of osteoporosis and to compare our findings with other populations. A cross-sectional study of 1378 Tunisian women aged between 20 and 96 years was carried out using DXA (GE-Lunar Prodigy). Subjects with suspected conditions affecting bone metabolism were excluded. Measurements were taken at the lumbar spine and femoral neck. These values were expressed at T-scores, with reference to the mean BMD values of the group aged 20–40 years. The peak bone mass, estimated in this age group was 1.174 + 0.127 g/cm² at the lumbar spine and 1.016 ± 0.118 g/cm² at the femoral site. It was attained respectively within the age of 25 years and 36 years. For both sites, the expected decline in BMD was shown when the successive age groups [40–49 years] and [50–59 years] were compared. Bone loss was rapid during the first 5 years after menopause. Thereafter BMD declined slowly but continually. The prevalence of osteoporosis in the women over 50 years of age, taking account of peak bone mass observed in our cohort, was 23.3% at the spine and 17.3% at the femoral neck with a combined prevalence of 23.4%. These rates attained respectively 30.4%, 11.8% and 32.9% when we considered the Italian values, which demonstrate the variability of osteodensitometric depending to the reference population adopted.     

Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis

BACKGROUND: Long-term post-menopausal hormone therapy (pHT) was often regarded as first-line therapy to prevent fractures in post-menopausal women, a recommendation under scrutiny given the benefit-risk profile of the Women's Health Initiative results of the estrogen-progestin combination. Apart from controlled clinical studies providing data with fractures as an end point, measures of lumbar and hip bone mineral density (BMD) may be used to assess bone-related effects of pHT. The objective of this study was to conduct a systematic review of 2-year trials, published between 1990 and December 2002, and assessing changes in BMD by any estrogen including ethinyl estradiol, any estrogen plus any progestin, or tibolone. METHODS: We searched MEDLINE, EMBASE and systematic reviews. Thirty-nine randomized, prospective, controlled 2-year trials were analysed in pre-specified groups according to the profile of the compounds. RESULTS: Virtually all pHT regimens at least maintain BMD at the lumbar spine and the hip compared with baseline; there is no apparent difference between the various estrogenic compounds. Tibolone, a synthetic progestin, appears to be as effective as any estrogen. Most trials were conducted in early post-menopausal women, fewer in women with hysterectomy and/or bilateral oophorectomy. CONCLUSIONS: The size of impact on BMD does not appear to differ between tibolone and any estrogen compound studied.     

Meta-analysis of genome-wide linkage studies for bone mineral density

Genome-wide linkage studies have shown several chromosome loci that may harbor genes that regulate bone mineral density (BMD), but results have been inconsistent. A meta-analysis was performed to assess evidence for linkage of BMD across whole genome scan studies. Eleven whole-genome scans of BMD or osteoporosis containing 3,097 families with 12,685 individuals were included in this genome scan meta-analysis (GSMA). For each study, 120 genomic bins of ~30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. A total of seven bins lie above the 95% confidence level (P=0.05) and one bin was above the 99% confidence level (P=0.01) in the GSMA of eleven linkage studies: bins 16.1 (16pter-16p12.3, Psumrnk <0.01), 3.3 (3p22.2-3p14.1), 1.1 (1pter-1p36.22), 18.2 (18p11.23-18q12.2), 6.3 (6p21.1-6q15), 20.1 (20pter-20p12.3), and 18.1 (18pter-18p11.23). GSMA was performed with seven studies with linkage scores of LOD >1–1.85 for sensitivity test, confirming the linkage on chromosome 16p and 3p and revealing evidence of new linkage in bins 10.2 (10p14-10q11.21) and 22.2 (22q12.3-22pter). In conclusion, the meta-analysis of whole-genome linkage studies of BMD has shown chromosome 16pter-16p12.3 to have the greatest evidence of linkage as well as revealing evidence of linkage in chromosomes 1p, 3p, 6, 10, 18, 20p, and 22q across studies. This data may provide a basis with which to carry out targeted linkage and candidate gene studies particularly in these regions.