Lower bone mineral density in children with type 1 diabetes is associated with poor glycemic control and higher serum ICAM-1 and urinary isoprostane levels

The purpose of the study was to investigate bone mineral density (BMD) in children with type 1 diabetes (DM1) and to establish the relationships between BMD, physical activity, glycemic control, and markers of systemic oxidative stress and inflammation. We studied 30 children with DM1, aged 4.7–18.6 years, and 30 healthy subjects, matched by sex, age, and body mass index (BMI). Mean duration of DM1 was 5.4 ± 3.4 years and mean glycosylated hemoglobin (HbA_1c) level over 12 months was 9.8 ± 1.5%. Lumbar and total bone mineral density (BMD, g/cm²) were measured by dual-energy X-ray absorptiometry (DXA). We calculated the apparent volumetric lumbar BMD (BMDvol, g/cm³) and total mineral content adjusted for age and height (BMCadj), and measured plasma intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein (hs-CRP), and urinary 8-iso-prostaglandin F_2a (F₂-IsoPs). Calcium (Ca) intake was assessed by questionnaire and physical activity by questionnaire and accelerometer (ActiGraph, count/h). Total BMCadj and lumbar BMDvol were significantly lower in children with DM1 than in controls (101.8 ± 7.7 vs. 107 ± 5.7%, P = 0.005; 0.32 ± 0.08 vs. 0.36 ± 0.09 g/cm³, P = 0.05, respectively). These differences were mostly caused by the differences in boys. Plasma ICAM-1 and hs-CRP levels were significantly higher in the DM1 group compared to the controls. Ca intake and urine F₂-IsoPs levels were similar between the groups. Diabetic boys were less active than controls (18231 ± 6613 vs. 24145 ± 7449 count/h, P = 0.04). In the DM1 group, lumbar BMDvol correlated inversely with urinary F₂-IsoPs (r = −0.5; P = 0.005) and plasma ICAM-1 levels (r = −0.4; P = 0.02), and also with HbA_1c levels after adjustment for age (r = −0.45; P < 0.05). Total BMCadj correlated inversely with HbA_1c levels (r = −0.4; P = 0.02). We conclude that children with DM1, particularly boys, have lower BMD. Poor glycemic control, elevated markers of oxidative stress, and inflammation are associated with lower BMD.     

COLIA1 polymorphism contributes to bone mineral density to assess prevalent wrist fractures

Wrist fractures associated with postmenopausal women are only partially explained by osteoporosis. Recent studies have shown that polymorphism of an Spl binding site in the first intron of the collagen I alpha 1 gene (COLIA1) may determine risk for vertebral and nonvertebral fractures in post-menopausal women independent of bone mass. We investigated the relationship between the COLIA1 polymorphism, lumbar spine and femoral neck bone mineral density (BMD), ultrasound stiffness of the heel, anthropometric variables, and risk for wrist fractures in 126 Czech postmenopausal women with low bone mass who suffered one or more wrist fracture in the last 5 years and in 126 postmenopausal women with low bone mass without any fracture. Genotypes for the Spl COLIA1 polymorphism were determined by polymerase chain reaction, digestion with Ball restriction enzyme, and agarose gel electrophoresis. The test discriminates two alleles, S and s, which correspond to the presence of guanine and thymidine, respectively, at the first bases in the Spl-binding site in the first intron of the gene for CO-LIA1. No significant differences were found between the fracture and control group with regard to age, weight, and years since menopause. However, BMD of the lumbar spine and femoral neck and ultrasound stiffness of the heel were significantly lower in patients with prevalent wrist fracture. Femoral neck BMD was the strongest determinant of prevalent fracture of the wrist. COLIA1 genotyping significantly strengthened prediction of prevalent fracture of the wrist. After multivariate adjustment, women in the Ss group had 2.0 times the risk of the women in the SS group (95% confidence interval [CI] = 1.1-3.8), and the women in the ss group had 2.8 times the risk of the women in the SS group (95% CI = 0.5-14.6). The overall gene-dose effect was an odds ratio of 2.1 per copy of the "s" allele (95% CI = 1.2-3.8). In the stepwise logistic regression, COLIA1 acted synergistically with femoral neck BMD and weight in increasing prediction of wrist fracture. The results demonstrate that COLIA1 Sp1 polymorphism is associated with an increased risk of wrist fracture in postmenopausal women independent of BMD and may be helpful in clinical practice by identifying patients with an increased fracture risk.     

High bone mineral density is associated with high body mass index

Summary  High BMD is an infrequent finding. In this retrospective cohort study of women 50 years and older, we documented a strong association between high BMD and high BMI. Introduction  High bone mineral density (BMD) has been associated with genetic disorders and a variety of dietary, endocrine, metabolic, infectious and neoplastic diseases that in many cases warrant medical attention. Since body mass index (BMI) is closely correlated with BMD, we sought to explore the relationship between these two parameters in older women. Methods  We conducted a retrospective clinical cohort study of 16,500 women 50 years and older who underwent baseline BMD testing between May 1998 and October 2002. Mean T-scores and Z-scores, and the proportions of women with high BMD (T-score +2.5 or greater, Z-score +2.0 or greater), were assessed according to BMI category. Results  Higher BMI category was associated with higher mean T-scores and Z-scores at all sites (P < 0.001). The proportion of women with high BMD increased with each BMI category (P for trend <0.05). In women with a lumbar spine T-score of +2.5 or more, 43.5% were obese with BMI > 30 kg/m² (55.6% for the femoral neck and 73.1% for the total hip). For women with a lumbar spine Z-score of +2.0 or more, 37.2% were obese (42.0% for the femoral neck and 50.9% for the total hip). There was no evidence of a paradoxical increase in fracture rates in women with high BMD. Conclusions  High BMD is closely associated with elevated BMI in women. This should be taken into consideration prior to initiating extensive investigations for rare pathologies. This study was supported in part by an unrestricted educational grant from the CHAR/GE Healthcare Development Awards Programme.     

2型糖尿病患者骨密度变化及血清IGF-1水平

目的 观察2型糖尿病患者不同性别、不同年龄阶段以及肥胖与非肥胖状态下IGF-1血清浓度及前臂骨密度水平。方法2型糖尿病100人,根据年龄、体重分别进行分组。ELISA法测定血清IGF-1浓度,双能X线骨密度检测仪(DEXA)测量前臂超远端(尺桡骨远端1/10交界处)及中远端(尺桡骨远端1/3交界处)骨密度(BMD)、骨矿含量(BMC)及T积分。结果 骨质疏松症的患病率为14％(<50岁组)到73％(>70岁组),总患病率为33％(超远端)和27％(中远端)。其中女性患病率为47.7％和22.7％,男性为21.4％和30.4％。BMD、BMC、IGF-1血清水平随增龄逐渐低降,50岁以后女性BMD、BMC较男性显著下降。肥胖者的:BMD、BMC较非肥胖者高,非肥胖女性骨质疏松症的患病率升高。IGF-1在男性与女性之间及肥胖与非肥胖者之间均无差异。结论 2型糖尿病非肥胖者的骨密度低于肥胖者,女性低于男性,非肥胖女性易在前臂超远端发生骨质疏松症。:IGF-1不受性别和体重的影响,随增龄逐渐减少。     

CA repeat polymorphism of the TNFR2 gene is not associated with bone mineral density in two independent Caucasian populations

Osteoporosis has a strong genetic component, but the genes involved are poorly defined. Genome-wide scans in multiple populations have identified chromosome 1p36 as one region linked to bone mineral density (BMD). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is a positional and functional candidate gene in osteoporosis. In this study, we conducted linkage and association tests between the CA repeat polymorphism of the TNFR2 gene and BMD in two large independent samples using the quantitative transmission disequilibrium test (QTDT) program. The first group of subjects was composed of 1836 individuals from 79 multigeneration pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 nuclear families. We found no evidence of association or linkage for spine or hip BMD in the samples of the multigenerational pedigrees or nuclear families. Through testing for association and for linkage, our data do not support the TNFR2 gene as a QTL underlying hip or spine BMD variation in our Caucasian populations.     

The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis.

In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 (p < 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.     

白介素1受体措抗剂基因多态性与上海市绝经后妇女骨密度无相关性

目的 了解白介素1受体拮抗剂（IL-1RA）基因多态性与绝经后妇女骨密度（BMD）的关系.方法 筛选370名年龄47～75岁无血缘关系的上海市汉族绝经后妇女,双能X线吸收仪检测腰椎2～4和近端股骨包括股骨颈、大转子和Ward＇s三角的BMD,按BMD值分为152例骨质疏松患者和218例对照组.IL-1RA基因型检测通过聚合酶链反应和电泳鉴定.结果 在整个人群中,IL-1RA等位基因的频率分布是A1占94.3%,A2占4.6%和A4占1.1%,等位基因频率分布符合Hardy-Weinberg定律.在骨质疏松组和对照组中IL-1RA等位基因A2型频率分布差异无显著性（x2=3.30,P=0.069）.无论是在整个人群还是各亚组中,均未发现IL-1RA基因多态性与各部位BMD有相关性.结论 本研究显示IL-1RA的基因型和等位基因频率分布与高加索人群有显著差别,IL-1RA基因多态性可能不是影响上海市绝经后妇女BMD变异或骨质疏松的遗传因子.     

绝经后女性2型糖尿病患者血糖控制与骨密度关系的观察

目的 探讨2型糖尿病绝经后女性患者血糖水平与骨密度的关系.方法 选择规律治疗1年以上的2型糖尿病绝经后女性患者30例,其中15例为血糖控制较好组[GGC组:平均年龄(61.2±1.1)岁],另外15例为血糖控制较差组[PGC组:平均年龄(63.4±0.9)岁].另设正常对照组15例[NC组:平均年龄(61.8±1.5)岁].分别测定3组成员股骨颈及L1～4水平的BMD、空腹及餐后血糖、糖化血红蛋白、空腹IGF-1、空腹C-肽、血钙、血磷、血镁、全段甲状旁腺素、碱性磷酸酶、谷氨酰转肽酶以及超敏C反应蛋白.结果 3组在iPTH和IGF-1水平上差异无显著性.糖尿病组与非糖尿病患者比较,股骨颈BMD值无统计学差异.结论 2型糖尿病绝经后女性骨密度水平与IGF-1、体重等指标相关,骨吸收增加与高血糖无明显相关.     

Low bone mineral density is not associated with angiographically determined coronary atherosclerosis in men

Summary  

This study for the first time investigates the association of bone mineral density (BMD) with angiographically determined coronary atherosclerosis in men. Our data show that the prevalence of low BMD is very high in men undergoing coronary angiography. However, neither osteopenia nor osteoporosis is associated with an increased prevalence of angiographically determined coronary atherosclerosis.     

血清瘦素与绝经后2型糖尿病女性患者骨密度的相关性研究

目的探索血清瘦素与绝经后2型糖尿病患者骨密度的相关性。方法共纳入98名2型糖尿病女性进行分析,通过双能X线骨密度仪对受试者髋部BMD进行检查,并测定T评分,按照骨密度检测结果分为骨质疏松症组(PMOPW)以及非骨质疏松组(PMW)。对照组按照BMI与骨质疏松症受试者匹配。通过酶联免疫吸附法(ELISA)测定检测血清瘦素水平。结果两组血清瘦素和BMD值差异均有统计学意义(瘦素,(18.23±8.56) ng/m L vs (22.44±9.56) ng/m L,P0.05)和(BMD,(-0.74±0.13) vs(-3.127±0.55),P0.05)。在PMOPW中,血清瘦素和BMD与体重、BMI、腰围、臀围显著相关。多元线性逐步回归分析显示PMW和PMOPW的体重和BMI是BMD的独立预测因子。未发现血清瘦素水平是两组BMD的预测因子。结论体重和BMI对2型糖尿病患者BMD影响显著,但是未发现血清瘦素与PMW和PMOPW的BMD有关。     

2型糖尿病患者血清Metrnl水平与骨密度的相关性研究

目的 探讨2型糖尿病(diabetes mellitus type 2,T2DM)患者血清Metrnl浓度与骨密度的相关性及其影响因素。方法 选取江苏大学附属医院就诊的T2DM患者146例,对所有受试者进行糖耐量、胰岛素兴奋实验、血生化检测等。ELISA检测血清Metrnl水平。所有受试者均接受双能X线骨密度仪检测,根据骨密度结果分为T2DM合并骨密度(bone mineral density, BMD)正常组和BMD异常组。结果 与T2DM合并BMD正常组相比,T2DM合并BMD异常组血清Metrnl水平显著升高(P<0.05)。进一步在调整性别、年龄等因素后,T2DM患者血清Metrnl水平与第1腰椎(L1)、L2、L3、L2～L4、L1～L4等BMD值,以及L1～L4 T值呈显著负相关(P<0.05)。Logistic回归结果显示,T2DM患者血清Metrnl水平与骨量异常独立相关。ROC曲线模型分析结果显示,血清Metrnl预测T2DM患者骨量异常的曲线下面积为0.720(95%CI=0.638～0.802,P<0.001)。结论T2DM合并BMD异常患者血清...     

Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density

Bone strength is determined by bone mineral density (BMD) and bone structure. Dual-energy X-ray absorptiometry (DXA) measures BMD. Whether quantitative ultrasound (qUS) measures a property of bone distinct from BMD is uncertain. To evaluate this, DXA and qUS were measured in 58 fracture patients and 428 controls. To study the independent effects of age and gender on qUS measurements and control for BMD by study design rather than statistical methods, subgroups from the normative database were created and intentionally matched by the same femoral neck (FN) BMD. Speed of sound (SOS; m/sec), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI) were then compared in individuals matched by FN BMD but differing in age, gender, and presence or absence of fractures. The results are presented as percentage difference (mean +/- SD). Elderly women with the same FN BMD as young women had 1 +/- 2% lower SOS (p < 0.05), 8 +/- 15% lower SI (p < 0.05), and 4 +/- 9% lower BUA (p = 0.07). Elderly women with the same FN BMD as elderly men had 5 +/- 9% lower BUA (p < 0.05). Elderly men with the same FN BMD as young men had 1 +/- 2% lower SOS (p = 0.1), 5 +/- 14% lower SI (p = 0.2), and 1 +/- 9% lower BUA (n.s.). Young women with the same FN BMD as young men had 2 +/- 7% lower BUA (n.s.). Women with fragility fractures had 8 +/- 11% lower BUA (p < 0.001) and 13 +/- 22% lower SI (p < 0.01) than controls with no fractures matched by FN BMD, age, and gender. Men with fragility fractures had 13 +/- 12% lower BUA (p < 0.01) and 16 +/- 19% lower SI (p < 0.05) than controls with no fractures matched by FN BMD, age, and gender. Despite comparable femoral neck BMD, qUS measurements differed according to age, gender, and fracture status, suggesting that qUS may provide additional information independent of femoral neck BMD, such as differences in connectivity or other properties yet to be identified.     

2型糖尿病患者血清25-经维生素D水平与骨密度的关系

目的 探讨2型糖尿病患者不同血清25-( OH) D水平与骨密度的关系。方法 选择住院的2型糖尿病患者288例,根据25-( OH) D水平对其进行分组：25-( OH) D>30ng/mL为维生素D充足组;20ng/mL <25-( OH ) D≤30 ng/mL为维生素D不足组;l0 ng/mL <25-( OH) D <20 ng/mL为维生素D缺乏组;25-( OH) D <10ng/mL为维生素D严重缺乏组。采用双能X线骨密度仪(DXA)测量受试者腰椎L1-4、股骨颈及全髓的骨密度。分析不同水平25-( OH ) D与骨密度的关系。结果 维生素D充足组、维生素D不足组、维生素D缺乏组、维生素D严重缺乏组的患者例数(所占比例)分别为10例(3. 5%) ,74例(25.7%) ,177例(61.5%) ,27例(9.3%)。不同性别组25-( OH ) D水平无明显差异,但是女性患者的腰椎L1-4、股骨颈、全髋的骨密度均较男性低。pearscm相关分析显示25-( OH) D水平与腰椎L1-4、股骨颈、全髓的骨密度均无相关性(分别为r=0.080 P=0.262;r=0. 139 P=0. 051;r=0.068 P=0. 342)。结论 2型糖尿病患者25-( OH) D水平与腰椎L1-4、股骨颈、全髓的骨密度均无明显相关性。     

绝经后2型糖尿病妇女血脂水平和骨密度的关系

目的探讨绝经后2型糖尿病妇女血脂和骨密度改变的相关性。方法将290例绝经后2型糖尿病妇女按T值分成骨质疏松组和非骨质疏松组;检测各组患者血清总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇LDL-C)以及腰椎骨密度(BMD),然后分析血脂和骨密度的关系;对骨密度和血脂、年龄、绝经年龄等变量之间的关系进行多元逐步回归分析。结果(1)绝经后2型糖尿病妇女的HDL-C与腰椎BMD存在负相关(r=-0.305,P=0.001),LDL-C、TG、TC与腰椎BMD无相关;(2)在校正体重指数、年龄和绝经年限影响因素后,绝经后2型糖尿病妇女的HDL-C与腰椎BMD仍存在负相关(r=-0.160,P=0.018),而LDL-C、TG、TC与腰椎BMD仍无相关。(3)在多元逐步回归分析中,HDL-C(β1=-0.199,P=0.005)仍与骨密度独立相关。结论绝经后2型糖尿病妇女的HDL-C与腰椎BMD存在负相关而TC、TG、LDL-C与腰椎BMD无相关。     

绝经后2型糖尿病女性患者骨密度与血清促甲状腺激素水平的关系

目的 通过测定甲状腺功能正常的绝经后2型糖尿病妇女的骨密度,探讨正常范围内促甲状腺激素（TSH）的水平与骨密度的关系。方法 选取在我院内分泌科住院治疗的甲功正常的绝经后T2DM女性患者220例,根据血清TSH水平,以1.60 mU/L和2.90 mU/L为界,将入选患者分为3组,即A组(0.27mU/L~1.60mU/L)、B组（1.60mU/L~2.90mU/L）、C组（2.90mU/L~4.20mU/L）。比较各组的一般情况、生化指标、骨密度（BMD）的差异。结果 ①与B组相比,A组患者左股骨颈、转子和全髋部BMD降低,差异有统计学意义（P<0.05）,而AC、BC两两比较差异无统计学意义（P>0.05,P>0.05）;②对于甲功正常的绝经后T2DM女性患者,血清FT3与全髋部BMD呈正相关（r=0.292,P=0.039）,TSH、FT4与全髋部BMD无相关（r=0.078,P=0.594;r=-0.043,P=0.771）;③校正年龄、绝经年限、BMI后,FT3与全髋部BMD仍呈正相关（r=0.401,P=0.006）,TSH、FT4与全髋部BMD仍无相关（r=0.013,P=0.929;r=0.039,P=0.797）;④在多元线性回归中,FT3仍与全髋部BMD独立相关（B=0.114,P=0.006）。结论 在甲功正常的绝经后T2DM妇女中,低TSH会降低全髋BMD;血清FT3与全髋BMD呈正相关,而TSH、FT4与全髋部BMD无相关。     

男性2型糖尿病患者骨密度的变化

目的 观察男性2型糖尿病患者骨密度的变化。方法 采用双能X线吸收法（DEXA）测定811例男性2型糖尿病患者腰椎正位1～4椎体（L1-4）、左侧髋部股骨颈（Neck）、大转子（Troch）、转子内区（Imer）、髋部总体（Total）和华氏三角（ward’s）的骨密度。结果 （1）男性2型糖尿病患者L1-4骨密度的改变先随年龄增加而逐渐降低，60岁之后又逐渐增高；Neck、Troch、Inter、Total和Ward’s区骨密度随年龄增加而逐渐降低，特别是Ward’s区骨密度下降显著。（2）病程在各年龄段对骨密度无明显影响。（3）超重组骨密度〉正常体重组〉低体重组。结论 病程对男性2型糖尿病患者骨密度无影响，Ward’s区是观察骨密度变化的敏感区域。     

双能X线骨密度仪测定83例2型糖尿病人骨密度分析

目的 了解2型糖尿病患腰椎及髋部骨矿物密度的变化。方法 双能X线骨密度仪测定2型糖尿病病人共83例(年龄40—79岁)，其中男性43例，女性40例；健康对照组71例(年龄40—79岁)，男性38例，女性33例。对比分析糖尿病组与同性别同龄正常组的测量结果，另根据病程将糖尿病组分为大于5年及小于5年组，并对2组结果进行分析。结果①糖尿病组与健康对照组比较，腰椎及髋部骨密度差异无显性；②病程大于5年与小于5年的2型糖尿病患间骨密度差异无显性。结论 2型糖尿病是否引起骨矿物密度降低或增高有待进一步研究。     

Chronic hemodialysis is associated with lower trabecular bone score,independent of bone mineral density: a case-control study

Summary

We measured trabecular bone score (TBS) in 98 patients on permanent hemodialysis (HD) and 98 subjects with similar bone mineral density and normal kidney function. TBS was significantly lower in HD patients, indicating deteriorated bone microarchitecture, independent of bone mass. This might partially explain the increased fracture risk in HD.

Purpose

In the general population, trabecular bone score (TBS) was shown to predict fracture independent of bone mineral density (BMD). In end-stage renal disease patients on hemodialysis (HD), the value of TBS is beyond that of BMD in currently unclear. Our aim was to assess lumbar spine (LS) TBS in HD patients compared with subjects with normal kidney function matched for age, sex, and LS BMD.

Methods

We assessed TBS and LS and femoral neck (FN) BMD in 98 patient on permanent HD (42.8% males; mean age 57.5?±?11.3 years; dialysis vintage 5.5?±?3.8 years) and 98 control subjects (glomerular filtration rate?>?60 mL/min) using DXA. We simultaneously controlled for sex, age (±?3 years), and LS BMD (±?0.03 g/cm²).

Results

HD patients had significantly lower LS TBS (0.07 [95% CI 0.03–0.1]; p?=?0.0004), TBS T-score (0.83 SD [95% CI 0.42–1.24]; p?=?0.0001)) and TBS Z-score (0.81 SD [95% CI 0.41–1.20]; p?=?0.0001) than matched controls. TBS significantly correlated with LS BMD in both HD patients (r?=?0.382; p?=?0.001) and controls (r?=?0.36; p?=?0.002). The two regression lines had similar slopes (0.3 vs. 0.28; p?=?0.84) with different intercepts (0.88 vs. 0.98). TBS adjustment significantly increased the 10-year fracture risk from 3.7 to 5.3 for major osteoporotic fracture and from 0.9 to 1.5 for hip fracture.

Conclusions

HD patients have lower TBS than controls matched for LS BMD, indicating altered bone microarchitecture. Also, the magnitude of TBS reduction in HD patients is constant at any LS BMD. Adjustment for TBS partially corrects the absolute 10-year fracture risk.