The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass.     

Decreased serum levels of insulin-like growth factors and IGF binding protein 3 in osteoporosis

Abstract. Objectives. The aim of the study was to investigate endogenous growth hormone (GH) secretion in patients with osteoporosis and in patients with degenerative bone diseases or no spinal disease by measuring serum insulin-like growth factors 1 and 2 (IGFs) and their major binding protein 3 (BP-3) as an indirect parameter of GH secretion. Design. A cross-sectional study. Setting. All patients were seen as out-patients of the Endocrinology Department of the University of Heidelberg where all bone parameters were measured. IGFs and BP-3 serum levels were measured at the Children's Hospital of the University of Tübingen. Subjects. A total number of 310 patients were studied. The group with primary osteoporosis and vertebral fractures (OPO) consisted of 141 patients (98 females, 43 males). Spinal degenerative bone disease or osteoarthritis (DEG) was present in 108 patients (91 females, 17 males). Sixty-one control patients (56 females, 5 males) had no spinal disease on X-ray, but presented with lower back pain. Main outcome measures. Serum levels of IGFs, BP-3, PTH and 25-vitamin D₃ were measured by radioimmunoassay. Bone mineral density (BMD) was determined using absorptiometry; anthropometric parameters and menopausal status were recorded. Results. There was no difference in age and years after menopause between OPO and DEG, but control individuals were younger. Mean IGFs and BP-3 serum levels in patients with OPO were lower (P < 0.001) than those in patients with DEG or in controls. Patients with DEG had significantly higher BP-3 levels than controls (P < 0.001). There was a significant (P < 0.05) negative correlation of BP-3 with age in females with OPO, but not in controls or in DEG patients. The IGFs did not decrease with age in any of the three groups. Binding protein 3 was positively correlated (P < 0.05) with BMD in postmenopausal women with OPO but not in controls or DEG patients. Conclusion. We conclude that systemic IGFs and IGF binding protein 3 are decreased in patients with osteoporosis. Further studies are needed to investigate whether this is as a result of diminished secretion of endogenous GH and whether this reflects the local circumstances of IGFs and IGF binding proteins in bone.     

Elevated plasma insulin-like growth factor binding protein-1 levels in Type 1 (insulin-dependent) diabetic patients with peripheral neuropathy

Summary Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between plasma IGF-I, IGFBP-1, glucose and insulin in Type 1 (insulin-dependent) diabetic patients with peripheral polyneuropathy. Plasma samples were taken at hourly intervals over an 11-h period (08.00–19.00 hours) in order to characterise secretory profiles for 15 Type 1 diabetic patients (eight neuropathic and seven non-neuropathic) and eight non-diabetic control subjects. In the non-diabetic subjects, mean plasma IGF-I levels were stable throughout the 11-h period with a range of 97 g/l–169 g/l. In contrast, mean plasma IGFBP-1 levels declined steadily from a high level of 1.99 g/l at 08.00 hours to approximately one half (0.86 g/l) at 15.00 hours. Comparison of areas under the curves revealed significant negative correlations between IGFBP-1 and glucose (–0.88, p=0.01), IGFBP-1 and insulin (–0.75, p=0.016), and IGFBP-1 and IGF-I (–0.68, p=0.03). A significant positive correlation was found between insulin and IGF-I (+ 0.89, p=0.001). The diabetic patients had markedly elevated plasma IGFBP-1 levels (area under curve, p=0.01) and lower plasma IGF-I levels (p=0.033) even though these patients were hyperinsulinaemic throughout the study period. The neuropathic diabetic patients had grossly elevated IGFBP-1 levels (–X=40 g/l at 08.00 hours) which were significantly higher (area under curve, p=0.05) than in patients without neuropathy (¯X=15 g/l at 08.00 hours). However, plasma levels of insulin and IGF-I in neuropathic and non-neuropathic subjects were similar, suggesting that the regulation of IGFBP-1 is more resistant to insulin in the neuropathic patients. In contrast to the non-diabetic subjects comparison of area under curve values revealed no positive correlation between insulin and IGF-I or negative correlations between IGF-I and IGFBP-1, and IGFBP-1 and glucose. We conclude that in Type 1 diabetes the relationships between plasma glucose, insulin, IGF-I and IGFBP-1 are clearly abnormal, and these abnormalities are more pronounced in patients with peripheral neuropathy.     

老年男性骨质疏松症患者血清转化生长因子β1测定及其临床意义

目的探讨转化生长因子β1(TGF-β1)与老年男性骨质疏松症的相关性。方法测定老年男性骨质疏松组(36例)与年龄相匹配的对照组(40例)的血清TGF-β1水平及其他生化指标,同时用双能X线骨密度仪测定腰椎及股骨的骨密度及骨矿含量。结果骨质疏松组的腰椎、股骨各个测量部位的骨密度与对照组比较,差异具有统计学意义(P<0.05)。老年男性骨质疏松组TGF-β1含量明显低于对照组[分别为(9.82±6.15)ng/ml和(17.29±7.83)ng/ml,P<0.05]。而血钙、血磷、血碱性磷酸酶水平在2组间差异无显著性。骨质疏松组与对照组的腰椎、股骨各个测量部位的骨密度及骨矿含量均与血清TGF-β1呈正相关,而与血钙、血磷、血碱性磷酸酶水平无关。结论血清TGF-β1水平与骨密度及骨矿含量具有一定的相关性,测定血清TGF-β1水平有助于老年男性骨质疏松症的诊断。     

老年住院病人血清胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3与衰弱的相关性研究

目的探讨老年住院病人血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平与衰弱的相关性。方法纳入2018年1月至2019年6月老年医学科年龄≥65岁的住院病人195例,进行衰弱表型评估和老年综合评估,采用ELISA法检测血清IGF-1、IGFBP-3水平,分析其与衰弱的相关性。结果与无衰弱、衰弱前期病人相比,衰弱病人血清IGF-1、IGFBP-3水平显著下降,差异有统计学意义(P<0.05)。有序多分类Logistic回归分析显示血清IGF-1(OR=0.943,95%CI0.894~0.994,P<0.05)、IGFBP-3(OR=0.397,95%CI0.259~0.607,P<0.001)水平与衰弱显著相关。结论血清IGF-1、IGFBP-3水平与老年住院病人衰弱显著相关,可能成为老年人衰弱的预测指标。     

Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with Type 1 (insulin-dependent) diabetes mellitus

Summary Serum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A_1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at midpuberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin-like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I.     

The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with Type 1 (insulin-dependent) diabetes mellitus

Summary Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s. c. dose of recombinant insulin-like growth factor I (40 g/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1±28.2 ng/ml, mean±SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4±4.0 compared with 33.6±5.8 mU/l; p=0.01), as were the insulin requirements for euglycaemia (0.25±0.02 compared with 0.31±0.04 mU · kg^–1 · min^–1; p=0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9±2.7 compared with 67.9±16.0 mU/l; p=0.001) but no significant differences in ketone or lactate levels were detected. Recombinant insulin-like growth factor I in a s. c. dose of 40 g/kg body weight leads to a significant reduction in overnight growth hormone levels and insulin requirements in adolescents with Type 1 diabetes.     

类风湿关节炎患者骨质疏松及其相关因素的初步调查

目的探讨类风湿关节炎（RA）患者中骨质疏松（OP）的发生情况及其相关危险因素。方法采用GEInsight／Achillesexpress高频率声波（超声波）检测右跟骨的骨质状态,测量90例RA患者和80名年龄、性别基本匹配的健康志愿者的跟骨骨密度（BMD）,按WHO确定的诊断标准将RA患者和正常受试者各分为3组,即骨量正常、骨量减少和骨质疏松组。采用问卷形式调查患者的性别、年龄、体重、身高、吸烟史、钙剂摄人、骨折家族史、RA病程及糖皮质激素应用等因素,分析其与OP的相关风险。结果RA患者骨量正常、骨量减少和骨质疏松组的构成比与对照组相比较差异有统计学意义（P〈0．05）。提示RA患者中发生OP的概率较对照组发生更大。在年龄、性别无明显差异的情况下,RA病程、吸烟、激素、骨折家族史是增加OP的危险因素。多因素Logistic分析得到的回归模型：RA伴发骨质疏松=-0．530＋0．164X病程＋3．304X吸烟＋1．783X骨折家族史。结论RA患者较健康志愿者更易发生骨量减少和骨质疏松。RA患者BMD的降低和OP的发生是多因素的,其中RA病程是RA患者发生OP的独立危险因素,早期诊断与治疗对预防RA患者发生OP具有重要意义。     

呼吸暂停综合征对胰岛素样生长因子-1与心泵功能的关联分析

目的分析阻塞性睡眠呼吸暂停综合征(OSAS)对胰岛素样生长因子-1(IGF-1)及心脏功能的影响,并探讨OSAS患者IGF-1与心脏功能的相关性。方法应用分层抽样法,分别就诊于我院的健康体检者及OSAS患者中,随机选取80例健康体检者及80例OSAS患者为观察对象。以选取的健康体检者为对照组,以选取的OSAS患者作为观察组。对比两组间血清IGF-1含量、右房内径(RA)、左房内径(LAD)、右室内径(RV)、左室舒张末内径(LVED)及左室射血分数(LVEF)差异。并分析IGF-1与RA、LAD、RV、LVED及LVEF相关性。结果观察组IGF-1含量、RV、LVED及LVEF明显低于对照组(P0.05)。观察组RA、LAD明显高于对照组(P0.05)。观察组中重度组IGF-1含量、RV、LVED及LVEF最低,RA、LAD最高(P0.05)。IGF-1含量与RV、LVED及LVEF存在正向直线相关性,与RA、LAD存在负向直线相关性(P0.05)。结论 OSAS可显著影响患者的IGF-1及心脏功能,且IGF-1与心脏功能间存在显著的相关性。     

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. Methods One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20–71 years underwent cross‐sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x‐ray absorptiometry. BMD data were available for 102 age‐ and gender‐matched population‐based control subjects. Results After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T‐ and Z‐scores at the hip, femoral neck and spine were lower compared with age‐matched control subjects (P ≤ 0.048). Female Type 1 patients and control subjects had similar BMDs and T‐ and Z‐scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. Conclusions Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age‐matched control subjects. Impaired bone formation may occur in Type 1 diabetes.     

老年代谢综合征患者血胰岛素样生长因子1与代谢综合征的关系

目的了解代谢综合征(metabolic syndrome,MS)患者血胰岛素样生长因子1(IGF1)水平及其与MS的关系。方法按2005年国际糖尿病联盟(IDF)颁布的MS定义,将老年患者465例分为MS组255例和对照组210例。查空腹血糖、胰岛素、C肽、餐后2 h血糖、血脂全套、血IGF1并计算体质指数(BMI)。两组按是否并存糖尿病再分为糖尿病和非糖尿病两个亚组。结果(1) MS组除高密度脂蛋白胆固醇(HDL-C)低于对照组外,其他血液指标均高于对照组(P<0．01);两组IGF1水平与年龄、BMI均呈负相关(P<0．05)。(2)MS糖尿病组IGF1(163．5±128．1)μg／L、胰岛素(14．3±10．5)mU／L高于MS非糖尿病组(114．0±52．6)μg／L、(8．46±4．4)mU／L,C肽(1．1±0．4)μg／L低于MS非糖尿病组(2．5±0．4)μg／L,均为P<0．01;IGF1水平与胰岛素、C肽无相关性,与冠心病呈负相关(P<0．05)。(3)对照糖尿病组IGF1(129．2±49．1)μg／L低于对照非糖尿病组(136．6±80．5)μg／L,胰岛素(14．1±11．7)mU／L、C肽(3．28±2．23)μg／L高于对照非糖尿病组(10．3±6．1)mU／L、(2．9±1．7)μg／L,P<0．01或0．05。对照组IGF1与C肽负相关,与甘油三酯正相关;对照糖尿病组IGF1与胰岛素、C肽负相关(均为P<0．01或0．05)。结论MS患者存在高血IGF1现象,这与单纯糖尿病患者低IGF1不同;MS患者IGF1水平较低时发生冠心病的机率较高。     

A risk assessment tool (OsteoRisk) for identifying latin American women with osteoporosis

OBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scoresor=50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS: A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index <=-2; 65.6% were osteoporotic), moderate-risk patients (-2< index <=1; 26.7% were osteoporotic), and low-risk patients (index>1; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil. CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.     

The prevention or treatment of age-related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF-I or rhTGFβ): a perspective

Boonen S, Broos P, Dequeker J, Bouillon R (Department of Internal Medicine, Division of Geriatric Medicine, the Arthritis and Metabolic Bone Disease Research Unit, the Department of Traumatology and Emergency Surgery and the Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium). The prevention or treatment of age-related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF-I or rhTGFβ): a perspective (Review). J Intern Med 1997; 242 : 285–90.
Both insulin-like growth factor-I (IGF-I) and transforming growth factor β (TGFβ) have powerful modulatory effects in a variety of tissues. A major target of action is the skeletal system, where they enhance bone formation and decrease matrix degradation, thus playing a part in the maintenance of bone mass. Because of the potent mitogenic effect of these agents on osteoblasts, recombinant IGF-I (rhIGF-I) and recombinant TGFβ (rhTGFβ) have potential as drugs to stimulate bone formation in the prevention and treatment of osteoporosis. Using biochemical markers, subcutaneous rhIGF-I therapy has been shown to increase bone turnover and bone formation in nonosteoporotic older people. However, a corresponding increase in bone mass has not yet been documented nor have there been reports yet on the effects of systemically administered rhTGFβ in humans. Further investigation is required to define the clinical potential of rhIGF-I and rhTGFβ as therapeutic agents in age-related osteoporosis.     

Characterization of insulin-like growth factor binding proteins (IGFBP) and regulation of IGFBP-4 in bone marrow stromal cells

Summary. Bone marrow stromal cells synthesize and secrete insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBP). IGFBPs may modulate the action of IGF-I or IGF-II on haemopoiesis. However, the specific IGFBPs produced by various stromal cell types have not been identified. We examined six different stromal phenotypes for IGFBP protein and IGFBP-1 to -6 mRNA expression. [¹²⁵I]IGF-I ligand blot analysis of conditioned medium demonstrate different patterns of IGFBP secretion by each cell type. The most prominent IGFBPs were 24 and 29 kD species, consistent with IGFBP4 and IGFBP5, respectively. RNase protection assays demonstrate that, overall, stromal cells express IGFBP-2 to -6 mRNAs, with IGFBP4, IGFBP5 and IGFBP6 mRNAs predominating. Since agents that modulate cAMP levels may influence haemopoiesis via the release of stromal-derived cytokines, we determined the effect of forskolin, a cAMP agonist, on IGFBP4 expression in TC-1 cells. Forskolin (10 ⁵ M) up-regulated IGFBP4 mRNA and protein secretion in a time-dependent manner. These findings suggest that IGFBP-4, -5 and -6 released by stromal cells may be key modulators of the haemopoietic response to IGFs. Release of IGFBP4 by agents that increase cAMP may be an important mechanism involved in regulating IGF bioavailability in the marrow microenvironment.     

血清IL-6水平与2型糖尿病患者骨质疏松关系的探讨

目的 探讨血清白介素-6（IL-6）水平与2型糖尿病（T2DM）患者骨质疏松的关系。方法 测定74例T2DM患者及46例年龄、体重指数（BMI）相匹配的健康对照者的血清IL-6水平、骨密度（BMD）、血清骨钙素（BGP）、抗酒石酸磷酸酶（TRAP）、尿羟脯氨酸CHOP）,两组进行比较。结果 血清BGP、BMD水平T2DM患者明显低于对照组（P〈0.01,P〈0.05）;TRAP、尿HOP、血清IL-6水平显著高于对照组（P〈0.05）,IL-6与BMD呈显著负相关。结论 T2DM患者骨密度降低,其原因与IL-6水平升高有一定关系。     

慢性心力衰竭患者血清胰岛素样生长因子-1及其结合蛋白的变化及意义

目的 通过对慢性心力衰竭患者血清中胰岛素样生长因子（insulin-like growth factor,IGF）-1及其相关结合蛋白的浓度测定,研究IGF-1及其相关结合蛋白对慢性心力衰竭的影响.方法 选取2012年6月至2013年12月江西省人民医院心内科慢性心力衰竭患者184例,按纽约心脏病协会心功能分级分为3组（心功能Ⅱ级组、Ⅲ级组和Ⅳ级组）,并选取正常人群63例作为对照组,测定其血清总IGF-1,游离IGF-1（Free IGF-1）、IGF结合蛋白（insulin-like growth factor-binding protein,IGFBP）-1,IGFBP-3浓度.对各组数据进行统计学分析,比较各组之间的血清总IGF-1,Free IGF-1、IGFBP-1,IGFBP-3浓度差异.结果 心功能Ⅳ级组血清总IGF-1,FreeIGF-1,IGFBP-3浓度明显高于心功能Ⅲ级组,心功能Ⅲ级组血清总IGF-1,Free IGF-1,IGFBP-3浓度明显高于心功能Ⅱ级组,差异有统计学意义（P＜0.01）.结论 血清IGF-1浓度随着慢性心力衰竭患者心功能变差而升高,说明IGF-1对患者心功能的恢复可能有明显的促进作用.     

Association of tumor necrosis factor receptor 1 gene polymorphism with bone mineral density

Background:   Estrogen deficiency in postmenopausal women causes an increased production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α. These cytokines are associated with an increase of bone turnover and an acceleration of bone loss. Tumor necrosis factor-α is known to promote osteoclastogenesis via TNFR1, one of the tumor necrosis factor receptors (TNFR). Therefore, the purpose of the present report was to investigate the association of TNFR1 gene polymorphism with bone mineral density (BMD) in postmenopausal Japanese women.
Methods:   The question of whether a polymorphism of the TNFR1 gene would correlate with osteoporosis in 320 unrelated healthy postmenopausal women in Japan, was investigated. A single nucleotide polymorphism (SNP) located at Pro12 (CCA to CCG) in exon 1 of TNFR1 was utilized.
Results:   The subjects were categorized into three genotypes: AA, AG, and GG. The frequency of each genotype was 72.2%, 23.8%, and 4.0%, respectively. The association of this polymorphism with BMD of the lumbar spine and total body, and several bone metabolic markers was then examined. Concerning the TNFR1 gene, the AA group had significantly low total body BMD, compared with the AG + GG group (Z score; 0.285 vs 0.568; P  = 0.03), although BMD of the lumbar spine was not statistically different.
Conclusion:   These results suggest an association between this SNP of the TNFR1 gene and BMD, and an involvement of TNFR1 in postmenopausal osteoporosis among Japanese.