Relationship between phalangeal bone density and risk of vertebral fracture.

The aims of our study were to determine the relationship between bone mineral density (BMD) measurements of the phalanges obtained with the accuDEXA and recent vertebral fractures. To determine whether osteoarthritis of the hands affects phalangeal BMD measurements, and to illustrate the conversion of phalangeal BMD measurements to absolute fracture risk estimates for clinical application. The prospective Hawaii Osteoporosis Study began in 1981, and incident vertebral fractures were identified from serial radiographs obtained at approx 2-yr intervals. Vertebral fractures occurring between 1993 and 1994 and 1997 and 1998 were compared to phalangeal BMD measurements obtained in 1997-1998. A total of 199 women participated in this case-control study. The association of the phalangeal BMD measurements with vertebral fractures was examined in age-adjusted, logistic regression models. Results are expressed as odds ratios (ORs) per SD difference in the phalangeal BMD measurements. Osteoarthritis of the hands was graded according to the Kellgren-Lawrence scale. There were 34 incident fractures since the eighth examination in 1993-1994. For vertebral fractures, the OR per SD of phalangeal BMD was 1.5 (1.0-2.1). Phalangeal BMD was not influenced significantly by established osteoarthritis (p = 0.68). Phalangeal BMD measurements obtained with the accuDEXA device relate to recent vertebral fractures and can be used to identify women at high risk of fractures. The phalangeal BMD measurements obtained with this device are not significantly influenced by the presence of osteoarthritis of the hands.     

Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk.

Low bone mineral density (BMD) is correlated with increased fracture risk. Whether greater BMD increases induced by osteoporosis drugs are related to greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and fracture risk in postmenopausal osteoporotic women receiving antiresorptive treatment. The analysis combined data from three pivotal risedronate fracture end-point trials. Women received risedronate (n = 2047) or placebo (n = 1177) daily for up to 3 yr. The BMD and vertebral radiographs were assessed periodically during 3 yr. The estimated risk of new vertebral fracture was compared between patients whose BMD increased and those whose BMD decreased. Risedronate-treated patients whose BMD decreased were at a significantly greater risk (p = 0.003) of sustaining a vertebral fracture than patients whose BMD increased. The fracture risk was similar (about 10%) in risedronate-treated patients whose increases in BMD were < 5% (the median change from baseline) and in those whose increases were >/= 5% (p = 0.453). The changes in lumbar spine BMD explained only 18% (95% confidence interval [CI], 10%, 26%; p < 0.001) of risedronate's vertebral fracture efficacy. Although patients showing an increase in BMD had a lower fracture risk than patients showing a decrease in BMD, greater increases in BMD did not necessarily predict greater decreases in fracture risk.     

Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk.

The change in BMD is a poor predictor of vertebral fracture risk after raloxifene treatment. One-year percent change in bone turnover and BMD was used to predict vertebral fracture risk. The percent change in osteocalcin was determined to be a better predictor of vertebral fracture risk than BMD. INTRODUCTION: The association between baseline BMD and fracture risk is well understood. However, the relationship between changes in BMD and fracture risk is not well defined. It has previously been demonstrated that BMD change was a poor predictor of vertebral fracture risk in raloxifene-treated women, whereas bone turnover markers were significantly associated with fracture risk. In the current analysis, we explore the prediction of vertebral fracture risk using changes in both BMD and bone turnover. MATERIALS AND METHODS: The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a randomized, placebo-controlled trial of 7705 women with osteoporosis treated with raloxifene 60 or 120 mg/day for 3 years. Markers of bone turnover were measured in one-third of the study population (n = 2503), and the present analyses include these women. Logistic regression models were constructed using one-year percent changes in BMD and bone turnover and relevant baseline demographics to predict the risk of vertebral fracture with pooled raloxifene therapy at 3 years. All covariates were standardized before modeling to facilitate direct comparisons between changes in BMD and bone turnover. RESULTS AND CONCLUSION: Prevalent vertebral fracture status (p < 0.0001), baseline lumbar spine BMD (p < 0.0001), and number of years postmenopausal (p = 0.0005) were independent predictors of fracture risk in raloxifene-treated patients. Therapy-by-change in femoral neck BMD (p = 0.02) and therapy-by-change in osteocalcin (OC; p = 0.01) were also significant for all treatment groups, indicating that changes in BMD and OC have different effects on fracture risk for the placebo and pooled raloxifene groups. The final model included significant baseline variables and change in OC (p = 0.01), whereas change in femoral neck BMD was not significant. After adjustment of each significant baseline variable, the percent change in OC was better able to predict the reduction in vertebral fracture risk than the percent change in femoral neck BMD in patients treated with raloxifene.     

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses.

Published meta-analyses have investigated the relationship between changes in BMD and fracture risk reduction observed with antiresorptive agents, with inconsistent results. Many factors may affect the outcome of such analyses. Our work explores some of these factors and illustrates the need for caution in interpreting the results of meta-analyses. INTRODUCTION: The role of the increase in bone mineral density (BMD) in fracture risk reduction observed in osteoporotic patients treated with antiresorptive drugs is unclear. We examined the effects of study selection, the use of summary statistics or individual patient data (IPD) as the basis for the analyses, and the choice of BMD values used on the outcome of meta-analyses. MATERIALS AND METHODS: To evaluate the effects of study selection, we performed Poisson regression analyses using the results from a number of published studies. To evaluate the effects of using individual patient data instead of summary statistics, we simulated the IPD for vertebral fracture to match the summary statistics for published trials and compared these results with those based on meta-regression using summary statistics. We also evaluated the effect of varying the BMD increase with treatment (3-8%) used in predicting the fracture risk reductions in these simulations. RESULTS: The Poisson regression, which found a statistically significant relationship between nonvertebral fracture risk and spinal BMD when 18 trials of varying designs, duration, and sample size were included in the analysis (p = 0.02), was no longer significant when the analysis was based on the 7 large studies that were placebo-controlled, at least 3 years in duration (at least 1000 patient-years). Meta-analyses of simulated IPD from 12 trials of six antiresorptive agents gave accurate results regardless of the proportion of vertebral risk reduction assumed to be related to BMD change, whereas meta-regression based on summary statistics always produced an estimate around 50%. When the actual data from two risedronate studies were analyzed, the meta-regression based on summary statistics demonstrated a stronger correlation between BMD change and fracture risk reduction than the results based on the IPD analysis. In predicting the fracture risk reduction, the use of the average BMD gain (3%) observed in all studies in the calculations produced an overall fracture risk reduction very similar to the one observed clinically. In contrast, the use of a large BMD gain (8%) produced a substantially higher estimated fracture risk reduction and resulted in a high proportion of fracture risk reduction being attributed to BMD change. CONCLUSIONS: Many factors may influence the outcome of meta-analyses, and caution should be used in interpreting the results of such analyses when exploring the relationship between BMD changes and fracture risk reduction with antiresorptive therapy of osteoporosis.     

International variations in hip fracture probabilities: implications for risk assessment.

It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan [TW]], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong [HK]], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.     

The relationship between bone mineral density and fracture risk

Osteoporosis is a disorder characterized by low bone density and impaired bone strength which is an important risk factor for fracture in older adults. The diagnosis of osteoporosis in postmenopausal women is now based on bone density testing by dual energy x-ray absorptiometry but not other methodologies. However, a specific but arbitrary diagnostic threshold must be distinguished from a strategy to assess fracture risk. In untreated postmenopausal women and older men, bone density is an important, but not the only, determinant for fracture risk. Combining bone density measurements with other independent and validated risk factors for fracture provides a much more accurate assessment of an individual patient’s risk for fracture than does bone density alone. The most important of these other risk factors are age and prior fracture history. Clinical guidelines will move away from recommending treatment at specific T scores toward intervention thresholds based on absolute fracture risk. By basing who to treat on fracture probability, therapy can be targeted to those patients who would receive the greatest benefit.     

Relationship between radiologic morphology of the bone lengthening formation and its complications.

The objective was to study the different types of lengthened bone regeneration and their development during the various phases of the process to correlate them with patient factors and the surgical technique used, and to establish a possible relation between the development of the bone lengthening formation and the problems or complications. The authors studied the radiographs of a random group of 55 patients taken at three points during the course of treatment. The callus was classified with regard to its transverse diameter and the presence or absence of hypodense areas. The overall callus type was significantly influenced by the etiology, the osteotomy site, and the percentage lengthened. The percentage by which the limb was lengthened at the beginning of the process influences the overall morphology of the callus. Poor callus had been lengthened the most, atrophic callus the least. There was a correlation between the morphology of the overall callus at the end of treatment and the percentage lengthened, and between the percentage lengthened and the presence of bands at the end of treatment. The authors also found a significant correlation between age and the appearance of bands at the end of distraction. A central band was found among younger patients. The type of osteotomy affected the overall callus at the end of distraction and at the end of treatment and also influenced the transverse diameter. All the elongations with poor bone formation at the end of treatment were found to have undergone a diaphyseal osteotomy. The most common complication at the first follow-up and at the end of distraction was angulation. The diameter of the callus and the presence of bands at the end of treatment were significantly related to the complications. Fracture occurred in the first 2 weeks after removal of the external fixator in 88% of cases and in the third and fourth week in the rest. However, the segment had no significant influence on the appearance of complications. Lengthened callus with incomplete trabecular formations and hypodense areas at the end of the treatment has a high risk of fracture at the end of treatment. Callus with axial deviation, hypodense areas, or an insufficient transverse diameter during the lengthening procedure must be manipulated so that it reaches the maturing phase in better condition.     

中老年骨量异常人群血清骨代谢生化指标与FRAX骨折风险相关性分析

目的研究中老年骨量减少或骨质疏松人群的血清骨代谢生化指标,探讨血清骨代谢生化标志物对受试者骨折风险的影响。方法研究84例中老年骨量减少或骨质疏松受试者资料,记录相关人口统计学数据,检测受试者骨密度和血清骨代谢生化指标,使用骨折风险评估工具(FRAX)计算个体10年骨折发生的概率。根据FRAX计算结果,将受试者分为骨质疏松骨折高风险组和低风险组,t检验比较二组年龄、性别、体质量指数、骨质疏松比例、股骨颈、髋部和腰椎的骨密度以及血清骨代谢生化指标的差异; Pearson或Spearman相关分析了解各临床指标与FRAX骨折概率的相关性; Logistic回归分析影响FRAX骨折风险的因素。结果骨折高风险组的年龄、骨质疏松患者比例明显高于低风险组,股骨颈和髋部骨密度以及血清25-羟基维生素D_3[25-Hydroxyvitamin D_3,25(OH) D_3]水平明显低于低风险组,差异有统计学意义(P0.05),其中高风险组和低风险组25(OH) D_3水平的中位数和(最小值～最大值)分别为20.61(12.19～43.24)和29.97 (11.91～72.70);年龄与两个骨折概率均呈正相关(P0.05),股骨颈和髋部骨密度以及血清25(OH) D_3水平与两个骨折概率均呈负相关(P0.05),其中25(OH) D_3水平与两个骨折概率的相关系数r值均为-0.51; Logistic回归分析显示,股骨颈骨密度和血清25(OH) D_3是FRAX骨折风险的重要相关因素。结论血清25(OH) D_3可能是预测中老年骨量减少或骨质疏松人群脆性骨折风险较敏感的骨代谢标志物。     

老年性髋部骨折骨密度与骨形态计量学的关系

目的通过老年髋部骨折患者骨密度的测定和骨组织形态计量分析,探讨骨质疏松性骨折骨密度与骨结构的关系。方法选择低、中能量创伤所致髋部骨折需要手术治疗的老年患者30例,分为2组,男性14例,女性16例。以双能X线吸收骨密度仪(DEXA)测量患者健侧股骨近端大转子BMD。手术中用切面积1cm×1cm的环钻于患侧股骨大转子间区松质骨按统一标准定位后,钻取骨柱,进行骨组织形态计量学观察与分析。结果根据BMD测定的结果男性患者能诊断为骨质疏松症的有9例(64.29%),女性患者能诊断为骨质疏松症的有12例(75.00%)。骨组织形态计量学结果提示老年男女骨结构参数差异不明显,无统计学意义。老年男、女性股骨大转子BMD均与%Tb.Ar、Tb.Th、Tb.N、N/F成正相关,与Tb.Sp成负相关(P<0.05)。结论老年人男女两个组的股骨近端转子间区骨组织形态计量参数无明显差异,股骨近端转子间区的BMD与骨结构有一定的相关性,骨形态计量学分析较BMD更可靠、更敏感、更真实地反映骨质疏松的情况。     

Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.

Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.     

Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy.

Although low absolute values of bone mineral density (BMD) predict increased fracture risk in osteoporosis, it is not certain how well increases in BMD with antiresorptive therapy predict observed reductions in fracture risk. This work examines the relationships between changes in BMD after 1 year or 3 years of raloxifene or placebo therapy and the risk for new vertebral fractures at 3 years. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis were randomized to placebo or raloxifene 60 mg/day or 120 mg/day. Relationships between baseline BMD and changes in BMD from baseline with the risk of new vertebral fractures were analyzed in this cohort using logistic regression models with the raloxifene doses pooled. As has been observed in other populations, women with the lowest baseline lumbar spine or femoral neck BMD in the MORE cohort had the greatest risk for vertebral fractures. Furthermore, for any percentage change, either increase or decrease in femoral neck or lumbar spine BMD at 1 year or 3 years, raloxifene-treated patients had a statistically significantly lower vertebral fracture risk compared with placebo-treated patients. The decrease in fracture risk with raloxifene was similar across the range of percentage change in femoral neck BMD observed at 3 years; patients receiving raloxifene had a 36% lower risk of vertebral fracture compared with those receiving placebo. At any percentage change in femoral neck and lumbar spine BMD observed at 1 year, raloxifene treatment decreased the risks of new vertebral fractures at 3 years by 38% and 41%, respectively. The logistic regression model showed that the percentage changes in BMD with raloxifene treatment accounted for 4% of the observed vertebral fracture risk reduction, and the other 96% of the risk reduction remains unexplained. The present data show that the measured BMD changes observed with raloxifene therapy are poor predictors of vertebral fracture risk reduction with raloxifene therapy.     

绝经后女性骨折风险与肌源性因子及骨代谢指标的相关性研究

目的 探讨绝经后女性肌源性因子及骨代谢指标与骨质疏松性骨折风险的相关性。方法 研究南京中医药大学无锡附院2021年6月至2022年6月门诊绝经后女性患者215例,根据纳排标准筛选出184例,其中绝经后骨质疏松88例,骨量减少65例,正常骨量31例。收集基线资料、肌骨代谢指标（碱性磷酸酶（ALP）、I型原胶原氨基端前肽（PINP）、鸢尾素（irisin）及肌肉抑制素（MSTN）等）及BMD,应用FRAX评估软件来评估骨折风险。控制年龄、骨量、FRAX风险等级比较肌骨代谢指标、体质指数（BMI）及体表面积（BS）的差异,并对绝经后女性骨折风险和各指标进行相关性分析;多重线性回归分析骨折风险概率与相关变量间的关系。结果 不同年龄组间BMD、PMOF及PHF差异存在统计学意义（P<0.05）;不同骨量组间BMI、BS、ALP、PMOF及PHF差异存在统计学意义（P<0.05）;FRAX不同风险组年龄、BS、BMD、Ca、ALP、PINP、irisin及MSTN之间差异存在统计学意义（P<0.05）;相关性分析显示FRAX骨折概率与年龄、PINP、MSTN成正相关（P<0.05）,与BMI、BS、BMD及irisin成负相关（P<0.05）,二元Logistic回归分析显示年龄、PINP与irisin是骨折风险的重要相关因素。结论 基于适合亚洲人群的FRAX干预阈值研究,绝经后女性年龄、PINP与irisin是骨折风险评估的敏感因素,这对优化骨质疏松骨折风险模型有重要意义。     

骨质疏松性骨折风险的FRAX评分与脊柱形态的相关性研究

目的:探讨骨质疏松老年人脊柱形态与全身骨折风险之间的关系。方法:2010年6月至2011年1月,应用双能X线(DEXA)测量107位老年人股骨颈及腰椎骨密度(BMD),其中男41例,女66例;年龄48~82岁,平均(67±6)岁。并对其进行骨折风险因素问卷调查,联合应用世界卫生组织(WHO)推荐的骨折风险测评工具(FRAX)对老年人进行骨质疏松性骨折风险评估,计算出每个人10年内髋部骨折概率和10年内主要的骨质疏松性骨折(脊柱、髋部、前臂或肩部骨折)概率。采用Spinalmouse测量老年人站立位的脊柱椎间夹角、脊柱曲度,并分析骨折风险概率与脊柱椎间夹角、脊柱曲度的相关性,做曲线拟合分析。结果:骨质疏松性骨折概率与直立位的T7、T8夹角,胸椎曲度,腰椎曲度成正相关(P<0.05),与前倾角成正相关(P<0.05),与其他椎间夹角无明显相关关系。结论:老年人的脊柱形态特征能够反映骨质疏松性骨折风险的高低。     

Effect of deproteination on bone mineral morphology: implications for biomaterials and aging

Bone mineral morphology is altered by processing and this is rarely considered when preparing bone as a bioimplant material. To examine the degree of transformation, a commercial, coarsely particulate bone mineral biomaterial produced by prolonged deproteination, defatting, dehydration, and heating (donor material) was compared with similar particles of human bone (recipient material) prepared optimally by low-temperature milling. The two powders were freeze-substituted and embedded without thawing in Lowicryl K4M before sectioning for transmission electron microscopy (TEM) (other aliquots were processed by traditional TEM methods). To maximize resolution, electron micrographs were image-enhanced by digitization and printed as negatives using a Polaroid Sprint Scan 45. In addition to their morphology, the particles were examined for antigenicity (specific by reference to fluorescein isothiocyanate [FITC]-conjugated fibronectin, and nonspecific by reference to general FITC-conjugated immunoglobulins). Results showed that the optimally prepared human bone fragments stained discretely for fibronectin with negligible background autofluorescence. In contrast, the bioimplant fragments stained extensively with this and any other FITC-conjugated antibody and, unlike fresh bone, it also autofluoresced a uniform yellow. This difference was also expressed structurally and, although the bioimplant mineral consisted of rhomboidal plates up to 200 nm across and 10 nm thick, the optimally prepared bone mineral was composed of numerous clusters of 5-nm-wide sinuous calcified filaments of variable density and indeterminate length (which became straight needles 50 nm long and 5 nm thick following traditional chemical TEM fixation/staining). It was concluded that the inorganic phase of bone is both morphologically and immunologically transmutable and that, in biomaterials, the transformation is apparently so great that a broad indigenous antigenicity is unmasked, increasing the likelihood of resorption or rejection. This marked change may also provide preliminary insight into a more modest natural aging phenomenon with the localized lateral fusion of calcified filaments into less flexible, more immunologically reactive fenestrated plates.     

Predicting bone loss and fracture risk with biochemical markers: A review.

Numerous studies have reported associations of biochemical markers of bone turnover with rates of change in bone density. Increasing levels of both formation and resorption markers are associated with faster rates of decline in bone mineral density. The differences in bone loss rates among persons predicted from marker levels correspond to clinically significant differences in fracture risk. Markers have also been shown to predict fracture risk directly, although increases in certain markers are associated with increased risk in some studies, and other markers with decreased risk in other studies. The associations of biochemical markers with fracture risk are similar in magnitude to those for bone density and fractures. Taken together, existing data provide convincing evidence that biochemical markers can help determine which women are at increased risk of rapid bone loss and fracture.