Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures.

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.     

Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study.

The mechanisms leading to increased bone loss and skeletal fragility in women with postmenopausal osteoporosis are still poorly understood. Increased bone resorption, low serum estradiol and high serum sex-hormone-binding globulin (SHBG) recently have been reported as predictors of vertebral and hip fractures in elderly women. In a cohort of healthy untreated younger postmenopausal women aged 50-89 years (mean, 64 years), we compared baseline levels of bone markers and endogenous hormones in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with levels in the 380 women who did not fracture during a mean 5 years of follow-up. Women with levels in the highest quartile of four bone resorption markers including urinary-free deoxypyridinoline (D-Pyr), urinary type I collagen N-telopeptides (NTX), and urinary and serum type I collagen C-telopeptides (CTX) had about a 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 1.8 (1.0-3.4) for free D-Pyr, 1.7 (0.9-3.2) for urinary NTX, 2.3 (1.3-4.1) for urinary CTX, and 2.1 (1.2-3.8) for serum CTX. Serum levels of bone alkaline phosphatase (BAP) in the highest quartile were associated with an RR of fracture of 2.4 (1.3-4.2). Women with serum levels of estradiol and dehydroepiandrosterone (DHEA) sulfate in the lowest quartile had an RR of fracture of 2.2 (1.2-4.0) and 2.1 (1.2-3.8), respectively. Increased levels of SHBG and intact parathyroid hormone (PTH) were moderately associated with an increased risk of fracture. Similar results were obtained when the analysis was restricted to symptomatic vertebral and nonvertebral fractures. Adjustment of biochemical markers by hormone levels did not significantly alter the results. Women with both high bone resorption markers and low estradiol (or low DHEA sulfate) had a higher risk of fracture with RRs of 3.0-3.3 (p < 0.001). After adjustment for bone mineral density (BMD) of the hip, spine, radius, or total body, bone markers and hormones were still predictive of fracture risk with similar RRs. We conclude that high levels of some biochemical markers of bone turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are associated with increased risk of osteoporotic fracture in postmenopausal women, independently of each other and of BMD. The mechanism by which some postmenopausal women have an increased rate of bone turnover leading to an increased risk of fracture remains to be elucidated.     

Sex hormones,sex hormone binding globulin,and vertebral fractures in older men

The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N = 1463, including 1054 with follow-up data 4.6 years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade ≥ 2, N = 140, 9.6%) and new or worsening vertebral fracture (change in SQ grade ≥ 1, N = 55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤ 17 pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.     

骨转换标志物与骨密度预测老年女性骨质疏松性骨折的对比研究

目的探讨骨密度与骨转换标志物(bone turnover markers,BTMs)在老年女性骨质疏松患者中的检测意义,对比两者对骨质疏松性骨折(osteoporotic fracture,OF)的预测能力。方法收集2017年10月至2019年2月于成都医学院第一附属医院骨科住院的OF患者96例和骨质疏松患者107例,分为骨折组和非骨折组。通过双能X线吸收仪(DXA)测定骨密度,电化学发光检测BTMs:I型前胶原N端前肽(PINP)、I型胶原β-异构化C末端肽(β-CTX)、骨钙素N端分子片段(N-MID),同时测定骨代谢相关指标:碱性磷酸酶(alkaline phosphatase,ALP)、钙(Ca)、磷(P),t检验对比两组间的计量资料,采用二分类Logistic回归分析骨密度和BTMs与OF的相关性。结果骨折组的骨密度低于非骨折组,差异有统计学意义(P 0. 05);PINP、β-CTX高于非骨折组,70～90岁患者N-MID低于非骨折组,差异均有统计学意义(P0. 05);而ALP、P、Ca在两组之间相比,差异无统计学意义(P0. 05)。二分类Logistic回归分析提示腰椎及髋部骨密度、β-CTX与OF具有显著相关性,OR分别为-4. 182、-6. 929和7. 572,差异均有统计学意义(P0. 05)。PINP、N-MID与OF呈正相关,OR分别为4. 213和2. 510,差异均无统计学意义(P0. 05)。结论低骨密度、高β-CTX的骨质疏松老年女性更容易发生OF,β-CTX比骨密度预测OF的能力更强,可适时对高危人群进行相关干预管理。     

Effect of bariatric surgery on endogenous sex hormones and sex hormone-binding globulin levels: a systematic review and meta-analysis

BackgroundMost studies have shown beneficial effect of bariatric surgery (BS) on serum levels of sex hormones.ObjectiveA systematic review and meta-analysis was conducted to examine the magnitude of possible changes in levels of sex hormones following BS.SettingsElectronic databases were searched, including PubMed, Scopus, Web of Science, and Embase, for relevant studies.MethodsThe heterogeneity of the studies was examined by χ² tests and the degree of heterogeneity was estimated using I² statistic.ResultsThe results of pooled analyses revealed that BS caused a significant increase in luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) levels and conversely, decreased dehydroepiandrosterone (DHEA) and estradiol (E2) levels in males. For females, BS significantly increased LH, FSH, and SHBG levels and conversely, decreased androstenedione (AE), E2 and TT levels. Additionally, the level of progesterone (P), prolactin (PRL), free testosterone (FT) and dehydroepiandrosterone sulfate (DHEA-S) showed no significant changes in patients who had undergone BS.ConclusionBS changed most sex hormones levels including LH, FSH, TT, SHBG, AE, DHEA, and E2. It seems that BS is able to exert substantial impacts on sex hormones levels and as well as sexual function, however, larger, and more precise trials are required to specifically focus on these claims.     

Nulliparity and fracture risk in older women: the study of osteoporotic fractures.

Whether nulliparity increases fracture risk is unclear from prior studies, which are limited by small samples or lack of measured bone mineral density. No study has evaluated whether the effect of parity differs by skeletal site. We prospectively analyzed the relationship of parity to the risk of incident nontraumatic hip, spine, and wrist fractures in 9704 women aged 65 years or older participating in the Study of Osteoporotic Fractures to determine if parity reduces postmenopausal fracture risk, and if so, if this risk reduction is (1) greater at weight-bearing skeletal sites and (2) independent of bone mineral density. Parity was ascertained by self-report. Incident hip and wrist fractures were determined by physician adjudication of radiology reports (mean follow-up, 9.8 years) and spine fractures by morphometric criteria on serial radiographs. The relationship of parity to hip and wrist fracture was assessed by proportional hazards models. Spine fracture risk was evaluated by logistic regression. Compared with parous women, nulliparous women (n = 1835, 19%) had an increased risk of hip and spine, but not wrist, fractures. In multivariate models, parity remained a significant predictor only for hip fracture. Nulliparous women had a 44% increased risk of hip fractures independent of hip bone mineral density (hazards ratio, 1.44; 95% CI, 1.17-1.78). Among parous women, each additional birth reduced hip fracture risk by 9% (p = 0.03). Additionally, there were no differences in mean total hip, spine, or radial bone mineral density values between nulliparous and parous women after multivariate adjustment. In conclusion, childbearing reduces hip fracture risk by means that may be independent of hip bone mineral density.     

Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis

The role of estrogen deficiency in male osteoporosis is still under discussion. One hundred five subjects, 65 of them suffering from osteoporosis (mean age, 53.9 years) and 40 age-matched controls were studied. Osteoporosis was defined by a T score < −2.5 in the lumbar spine or at the femoral neck. Forty-one (63.1%) of the subjects had a history of low-energy fractures, involving vertebrae in 33 cases (50.8%). Osteoporosis was considered to be idiopathic in 33 subjects (50.8%) for whom no etiology could be found. We measured levels of total estradiol (pg/ml, with a detection threshold of 4 pg/ml), total testosterone (ng/ml), and their carrier protein, that is, sex hormone-binding globulin (SHBG, pmol/ml). Various markers of bone remodeling were also measured. Two of them provide an estimate of bone formation—osteocalcin (OC) and bone alkaline phosphatase (BAP). Two others evaluate bone resorption—procollagen type I C-terminal telopeptide (ICTP) and serum C-telopeptide of type I collagen (sCTX).

There was no significant difference in estradiol levels between controls and osteroporosis patients. We did not find any significant correlation between estradiol levels and spinal bone mineral density (BMD) (r = 0.15, P > 0.05), and the relationship between estradiol levels and BMD at the femoral neck was weak (r = 0.25, P < 0.05). On the other hand, SHBG was significantly higher in the osteoporotic patients than in controls (P < 0.01). This difference persisted after adjustment for body mass index (BMI) and after exclusion of patients with a condition known to increase SHBG levels. Moreover, this carrier protein was negatively correlated with BMD at the femoral neck (r = −0.37, P < 0.01) and at the lumbar spine (r = −0.27, P < 0.05). SHBG also correlates strongly with sCTX (r = 0.37, P < 0.01). Finally, logistic regression analysis showed that serum SHBG concentration was significantly associated with the presence of fractures; the odds ratio of having a fracture was 2.04 [95% confidence interval (CI) 1.2–3.4, P < 0.01] for each increase of 1 standard deviation (SD) in the patient's SHBG level. The stronger relationship was nearly the same for the whole group and for patients with idiopathic osteoporosis.

This study therefore suggests that SHBG may play a key role in male patients with idiopathic or secondary osteoporosis. It shows that serum SHBG concentration is increased in middle-aged men with osteoporosis and is correlated with hip, spine BMD, and sCTX levels. Finally, our findings are in agreement with previous studies which suggest that serum SHBG is a new biological marker of fracture risk in men.     

性激素结合球蛋白与某些生殖系统疾病的相关性

性激素结合球蛋白(SHBG)是主要由肝细胞合成的一种多功能蛋白质,是运输性激素的重要载体,生理作用主要是运输性激素、调节性激素活性、降低性激素代谢清除速率、稳定血清中有活性的性激素水平,将性激素运输到靶组织。随着SHBG结构与功能、受体与信号传导、基因多态性研究的不断深入,许多生殖系统疾病与血清SHBG水平及其基因多态性有关。本文将对SHBG与生殖系统疾病的关联性研究作一综述。     

The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002     

Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study.

It has been suggested that low serum 17beta-estradiol (E2) and sex hormone-binding globulin (SHBG) may predict hip fracture in postmenopausal women. We have investigated the predictive value of serum E2 and SHBG concentrations and urinary deoxypyridinoline (D-Pyr) and type I collagen breakdown products (CTX) in a large prospective cohort of 7,598 healthy elderly ambulatory women (EPIDOS study), aged 75 years or more. We performed a nested case control study, by matching 212 patients with incident hip fracture with 636 controls. Mean follow-up was 3.3 years (maximum, 4.9 years). Women having serum E2 below the limit of detection (3 pg/ml), that is, 2% of the population, were not at higher risk, with a relative hazard (RH) of 1.59 (95% CI = 0.45-5.55). Women having serum E2 below 5, 6, 7, or 8 pg/ml, in the lowest quartile, or below the median had no increased risk of hip fracture. In contrast, women having serum E2 in the highest quartile (i.e., > or = 10 pg/ml) were protected, with an RH of 0.66 (0.44-0.98) that did not remain significant after adjustment for weight (RH = 0.71 [0.47-1.06]). High serum SHBG values with different cut-offs tended to be associated with an increased risk of hip fracture. Women in the highest quartile had an RH of 2.5 (1.37-4.61), compared with those in the lowest quartile, that decreased markedly after adjustment for body weight (1.61 [0.99 -2.62]). The highest quartile of the ratio E2/SHBG, which is an index of free E2, was associated with a lower hip fracture risk (RH = 0.6 [0.4-0.91]) that was no longer significant after adjustment for weight. In contrast, urinary D-Pyr and CTX, when elevated above the upper limit of premenopausal values, were predictive of hip fracture, with an RH of 2.07 (1.49-2.9) and 1.67 (1.19-2.32), respectively, even after adjustment for body weight, serum E2, and SHBG. We conclude that in healthy elderly French women over 75 years of age, serum E2 and E2/SHBG in the highest quartile are associated with a lower risk of hip fracture and that this association is explained by a higher body weight. In addition, serum levels of E2 and SHBG do not account for the increased risk of hip fracture associated with high levels of bone resorption markers.     

Association between bone turnover rate and bone microarchitecture in men: The STRAMBO study

Few data concern the relationship between bone turnover and microarchitecture in men. We investigated the association between levels of biochemical markers of bone turnover (BTM) and bone microarchitecture in 1149 men aged 19 to 85 years. Bone microarchitecture was assessed by high‐resolution peripheral quantitative computed tomography at the distal radius and tibia. Bone formation was assessed by serum osteocalcin, bone alkaline phosphatase, and N‐terminal extension propeptide of type I collagen. Bone resorption was assessed by serum C‐terminal telopeptide of type I collagen and urinary excretion of total deoxypyridinoline. BTM levels were high in young men and decreased until age 50 years. Urinary deoxypyridinoline (DPD) increased after age 70 years, whereas other BTMs remained stable. Before 50 years of age, only cortical volumetric bone mineral density (D_cort) correlated negatively with BTM levels. Between 50 and 70 years of age, D_cort and some microarchitectural parameters correlated significantly with BTM at the radius and tibia. After 70 years of age, higher BTM levels were associated with lower cortical thickness and D_cort at both the skeletal sites. At the distal radius, men in the highest BTM quartile had lower trabecular density, number (Tb.N), and thickness (Tb.Th) and more heterogeneous trabecular distribution compared with men in the lower quartiles. At the distal tibia, higher BTM levels were associated with lower Tb.N and Tb.Th in the central but not subendocortical area. Thus, in men, bone microarchitecture depends weakly on the current bone turnover rate until age 70. Thereafter, bone turnover seems to be a significant determinant of bone microarchitecture. © 2010 American Society for Bone and Mineral Research.     

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study

Summary

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events.

Introduction

Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss.

Methods

Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change).

Results

Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was ?0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p?p?=?0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04–1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p?=?0.08).

Conclusions

In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.     

性激素结合球蛋白检测在评价多囊卵巢综合征治疗中的意义

目的探讨性激素结合球蛋白(SHBG)检测在评价治疗多囊卵巢综合征(PCOS)不育患者中的意义。方法将533例PCOS不育患者按体重指数(BMI)分为非肥胖组(424例)和肥胖组(109例)并再按是否存在胰岛素抵抗(IR)分为四组。A组:非肥胖无IR组(162例)、B组:非肥胖IR组(262例)、C组:肥胖无IR组(42例)、D组:肥胖IR组(67例)。测定黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E_2)、总睾酮(T)、泌乳素(PRL)、SHBG、血糖(FBG)和胰岛素(FINS)水平,计算游离雄激素指数(FAI)及稳态模型指数(HOMA-IR)。A组、C组予达英-35;B组、D组予达英-35+盐酸二甲双胍,均治疗3月后复查各指标。停药后给予枸橼酸氯米芬(克罗米芬,CC)+人绝经期促性腺激素(HMG)促排卵治疗。比较各组排卵及妊娠情况。结果四组治疗后FAI均较治疗前降低,SHBG较治疗前升高差异有显著性;四组治疗后LH、LH/FSH比值、T较治疗前降低差异有显著性;但A组HOMA-IR、FINS较治疗前升高差异有显著性,B、D组HOMA-IR、FINS较治疗前降低差异有显著性。促排卵结果显示治疗后排卵率非肥胖组高于肥胖组(85.60%vs 68.69%,P0.01),两组治疗后有排卵患者SHBG较无排卵患者升高,FAI较无排卵患者降低;非肥胖组LH、LH/FSH比值、FINS降低(P0.05),而肥胖组FINS、HOMA-IR则降低(P0.05)。妊娠结局比较:非肥胖组和肥胖组妊娠分娩患者治疗后T、FAI、FINS、HOMA-IR较自然流产患者降低,SHBG升高(P0.05);此外肥胖组妊娠分娩患者治疗后BMI较自然流产患者降低。结论无论肥胖还是非肥胖的PCOS患者,无论是否存在胰岛素抵抗,SHBG及FAI均可作为评价治疗是否有效的指标之一,可提示促排卵治疗及妊娠结局。因此在PCOS患者治疗中检测SHBG及FAI能指导临床用药,降低流产率,对优生优育有重要指导意义。     

Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN

We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42-52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E(2)), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations ( beta=0.003, partial r2=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations ( beta=-0.216, partial r2=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period.     

Association between self-reported prior wrist fractures and risk of subsequent hip and radiographic vertebral fractures in older women: a prospective study.

In this large prospective cohort study of elderly women, the relationships between prior wrist fracture and incident hip and radiographic vertebral fractures were significantly attenuated when adjusted for BMD. This study suggests that BMD thresholds for drug therapy to prevent osteoporotic fracture should be only modestly adjusted in those with prior wrist fracture compared with those without prior wrist fracture. Validation of such an approach would require intervention trials in patients with prior wrist fracture. INTRODUCTION: Prior wrist fracture has been identified as a risk factor for incident hip and vertebral fractures and proposed as a criterion for determining who should be offered drug therapy to prevent osteoporotic fracture, even if their hip BMD T score is > -2.5. Previously published studies of the relationships between prior wrist fracture and incident hip and vertebral fractures did not adjust for BMD. MATERIALS AND METHODS: We ascertained prior history of wrist fracture since age 50, measured calcaneal and hip BMD, and performed lateral spine films in a cohort of 9704 elderly community-dwelling women, and then followed them prospectively for incident vertebral and hip fractures. Incident vertebral fractures were defined by morphometry using lateral spine radiography at the first examination and an average of 3.7 years later. Incident hip fractures were confirmed with radiographic reports over a mean follow-up period of 10.1 years. RESULTS: Prior wrist fracture was associated with an age-adjusted 72% increased odds of incident radiographic vertebral fracture (odds ratio [OR], 1.72; 95% CI, 1.31-2.25). After adjustment for calcaneal BMD, the association of prior wrist fracture with incident radiographic vertebral fracture was attenuated (OR, 1.39; 95% CI, 1.05-1.83). Prior wrist fracture was also associated with an age-adjusted 43% excess rate of incident hip fracture (hazards ratio [HR], 1.43; 95% CI, 1.17-1.74). After adjustment for hip BMD, the association of prior wrist fracture with rate of incident hip fracture was no longer statistically significant (HR, 1.12; 95% CI, 0.92-1.38). CONCLUSION: In elderly women, prior wrist fracture is a risk factor for radiographic vertebral fracture independent of BMD. The association between prior wrist fracture and incident hip fracture is largely explained by hip BMD. Modest adjustment of BMD drug treatment thresholds for prevention of osteoporotic fractures in those with prior wrist fracture compared with those without prior wrist fracture may be reasonable, but validation of such an approach would require intervention trials in patients with prior wrist fracture.     

Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures

Age‐related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15‐year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age‐related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss. © 2013 American Society for Bone and Mineral Research     

Association of bone turnover markers with volumetric bone loss,periosteal apposition,and fracture risk in older men and women: the AGES-Reykjavik longitudinal study

Summary

Association between serum bone formation and resorption markers and cortical and trabecular bone loss and the concurrent periosteal apposition in a population-based cohort of 1069 older adults was assessed. BTM levels moderately reflect the cellular events at the endosteal and periosteal surfaces but are not associated with fracture risk.

Introduction

We assessed whether circulating bone formation and resorption markers (BTM) were individual predictors for trabecular and cortical bone loss, periosteal expansion, and fracture risk in older adults aged 66 to 93 years from the AGES-Reykjavik study.

Methods

The sample for the quantitative computed tomography (QCT)-derived cortical and trabecular BMD and periosteal expansion analysis consisted of 1069 participants (474 men and 595 women) who had complete baseline (2002 to 2006) and follow-up (2007 to 2011) hip QCT scans and serum baseline BTM. During the median follow-up of 11.7 years (range 5.4–12.5), 54 (11.4 %) men and 182 (30.6 %) women sustained at least one fracture of any type.

Results

Increase in BTM levels was associated with faster cortical and trabecular bone loss at the femoral neck and proximal femur in men and women. Higher BTM levels were positively related with periosteal expansion rate at the femoral neck in men. Markers were not associated with fracture risk.

Conclusion

This data corroborates the notion from few previous studies that both envelopes are metabolically active and that BTM levels may moderately reflect the cellular events at the endosteal and periosteal surfaces. However, our results do not support the routine use of BTM to assess fracture risk in older men and women. In light of these findings, further studies are justified to examine whether systemic markers of bone turnover might prove useful in monitoring skeletal remodeling events and the effects of current osteoporosis drugs at the periosteum.

     

Kinetic of bone turnover markers after osteoporotic vertebral compression fractures in postmenopausal female

Background

Osteoporotic fracture occurs mostly at the spine, in which the commonest one is vertebral compression fracture. Bone turnover markers (BTMs) can be applied to assess bone formation and resorption activity. Nevertheless, there are few reports on BTMs changes after osteoporotic vertebral compression fracture. The aim of this study is to investigate the kinetics of bone turnover markers after osteoporotic vertebral compression fractures in postmenopausal female.

Methods

Three hundred nine postmenopausal female patients with osteoporotic vertebral compression fractures were included in the study. Fasting blood samples were obtained to analyze the serum concentration of bone turnover markers including osteocalcin (OC), β-isomerized type I collagen amino-terminal peptide (β-CTX), alkaline phosphatase (ALP), type I procollagen amino-terminal peptides (PINP), calcium, and phosphorus. According to periods long after vertebral fracture, all the cases were divided into seven phases: phase 1 (within 3 days), phase 2 (3 days to 1 week), phase 3 (1 to 2 weeks), phase 4 (2 to 4 weeks), phase 5 (4 to 12 weeks), phase 6 (12 to 24?weeks), and phase 7 (24?weeks to 1 year). Comparisons among the phases and kinetics during the phases were conducted.

Results

All the kinds of BTM’s serum concentration began to increase within 3 days after vertebral fracture in phase 1. Osteocalcin and β-CTX had two peaks, the first one in phase 2 (21.4?±?6.0?ng/ml and 0.72?±?0.17?ng/ml, respectively) and the second in phase 6 (25.8?±?7.5?ng/ml and 0.89?±?0.23?ng/ml, respectively). The peak of ALP arrived in phase 4 at the value of 123.9?±?25.7?U/L. PINP reached its peak value (69.50?±?16.82?ng/ml) in phase 6. Serum phosphorus arrived at its first peak (1.21?±?0.13?mmol/L) in phase 2 and the second peak (1.23?±?0.13?mmol/L) in phase 4. Serum calcium reached the first peak (2.30?±?0.07?mmol/L) in phase 3 and the second peak (2.34?±?0.08?mmol/L) in phase 5.

Conclusion

The time-dependent variations of BTMs based on the fracture healing process of inflammation, regeneration, and remodeling occur after vertebral fracture. Kinetics of BTMs after vertebral fracture as well as the reference value at each period were established in the present study. It is helpful to assess vertebral fracture healing process according to the kinetics of BTMs.

     

骨转换标志物CTX-1和PINP预测骨质疏松骨折的研究进展

骨质疏松性骨折作为老年人群中的常见病,已成为全球性公共卫生问题,但目前对其发生风险的预测方法有限且准确度不足。近期研究发现骨转换标志物可能对预测骨质疏松性骨折发生有应用前景,现综述近年来有关骨转换标志物(CTX-1和PINP)对骨质疏松性骨折风险预测的研究进展,为临床筛查骨质疏松性骨折发生的高风险人群提供新思维。     

椎体骨质疏松骨折患者骨转换生化标志物的临床研究

目的 探讨骨转换生化标志物对于绝经后骨质疏松椎体骨折的预测价值。方法 73例绝经后骨质疏松症患者分为骨折组及非骨折组,分别测定血清I型原胶原氨基端前肽（PINP)、I型胶原交联羧基末端肽（CTX)及骨密度并比较。结果 绝经后骨质疏松骨折组患者的骨转换生化标志物水平明显高于非骨折组,其差异有显著性;而两者骨密度的差异无显著性。结论 骨转换生化标志物可以作为预测绝经后骨质疏松骨折的重要指标。