Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Received: 8 June 1998 / Accepted: 7 December 1998     

Clinical utility of spine bone density in elderly women.

It is common clinical practice to obtain a bone density measurement at both the hip and spine to evaluate osteoporosis. With aging, degenerative changes in the lumbar spine may elevate the bone mineral density (BMD) results giving false assurances that the fracture risk at the spine is low. We examined the association of spine osteoarthritis and bone mineral density in 1082 community-dwelling ambulatory older women aged 50-96 years who participated in a 1992-1996 osteoporosis research clinic visit. The BMD was measured at the hip and posteroanterior (PA) and lateral lumbar spine using dual energy X-ray absorptiometry (DXA). Spine osteoarthritis was identified on the PA lumbar spine DXA images by a musculoskeletal radiologist. Forty percent of women had evidence of spine osteoarthritis (OA). Women with spine OA had a mean age of 77.4 yr (95% confidence interval [CI]: 76.5-78.2), were significantly older than women without spine OA (mean age, 66.8 yr; 95% CI: 65.9-67.7), and were more likely to have prevalent radiographic fractures (14.2% vs. 9.5%; p<0.05). Age-adjusted BMD at the femoral neck, total hip, PA spine, and lateral spine was significantly higher in women with spine OA. Women with spine OA were more likely to have osteoporosis by the World Health Organization classification at the femoral neck and total hip than those without spine OA, but less likely based on the PA spine (14.4% vs. 24.5%). Despite higher BMD levels, women with OA of the lumbar spine had higher prevalence of osteoporosis at the hip and more radiographic vertebral fractures. In elderly women 65 yr and older who are likely to have spine OA, the DXA measurement of the spine may not be useful in assessing fracture risk, and DXA of the hip is recommended for identification of osteoporosis.     

Prevalent vertebral deformities: Relationship to bone mineral density and spinal osteophytosis in elderly men and women

The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density (BMD) at the lumbar spine and femoral neck, severity of spinal degenerative disease and vertebral deformity prevalence. We performed standardized spinal radiographs in a random sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study, a population-based study of fracture risk factors. Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis. BMD was measured by dual-energy X-ray absorptiometry. The prevalence of vertebral deformities was critically dependent on the criterion used. The less strict criteria seemed to overestimate deformities at either end of the spine region analysed. However, irrespective of the criterion used, prevalence of deformity was higher in men than in women (25% vs 20% for the 3 SD criterion, 17% vs 12% for the 4 SD criterion and 27% vs 25% for the 25% criterion). Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25% criterion (OR/SD change in BMD 1.39 (p=0.02) vs 1.20 (p=0.19)), 3 SD criterion (OR/SD change in BMD 1.45 (p=0.01) vs 1.10 (p=0.34)) and 4 SD criterion (OR/SD change in BMD 1.98 (p=0.0002) vs 1.68 (p=0.008)). BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women. Severity of spinal osteophytosis was not associated with vertebral deformity. In conclusion, femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures. Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk, indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis. These findings support the use of femoral neck bone densitometry in older men and women. Moreover, these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly, with important implications for the design of clinical trials. However, irrespective of the criterion used, vertebral deformities in men are at least as common, if not more so, than in women, suggesting that vertebral osteoporotic fractures are overlooked in men.     

骨密度在髋部骨质疏松性骨折风险评估中的价值

目的评估骨密度在髋部脆性骨折风险预测中的临床价值。方法回顾性研究2014年6月至2019年6月在我院创伤骨科住院的老年髋部骨折患者72例,作为病例组,其中股骨转子间骨折31例,股骨颈骨折41例;对照组选择同期我院骨外科门诊老年体检者63例。使用DXA方法测量患者腰椎和健侧髋部(全髋部、转子间、股骨颈、Ward’s区)的骨密度;对照组测量腰椎和左侧髋部骨密度,统计分析测量结果。结果①骨折组腰椎、髋部骨密度均显著低于对照组,差异有统计学意义(P0.01);②转子间骨折组和股骨颈骨折组在腰椎和髋部区域骨密度比较差异均无统计学意义(P 0.05);③骨折组与对照组在转子间区的T值降低比例最大为122.1%,腰椎降低幅度最小为31.3%,余髋部的T值均有不同程度降低;④骨折后髋部和腰椎T值比存在倒置现象;⑤对照组和骨折组髋部骨质疏松程度比较,差异有统计学意义(P0.01);两组患者腰椎骨质疏松程度比较,差异无统计学意义(P0.05)。结论①髋部骨折患者骨密度均显著低于体检者,提示骨密度与髋部骨折具有一定相关性,但与髋部骨折类型无关;②在髋部骨折风险评估中,髋部骨密度相比腰椎更有价值;③当髋部与腰椎T值比出现倒置时,将不可避免发生髋部骨折;④骨量正常的部分患者发生了脆性骨折,而骨质疏松的部分患者却未发生骨折,表明影响骨折发生的因素除了骨密度外,可能和骨骼的微结构有关。     

Prevalent Vertebral Fractures in Black Women and White Women

Vertebral fractures are the most common osteoporotic fracture. Hip and clinical fractures are less common in black women, but there is little information on vertebral fractures. We studied 7860 white and 472 black women ≥65 yr of age enrolled in the Study of Osteoporotic Fractures. Prevalent vertebral fractures were identified from lateral spine radiographs using vertebral morphometry and defined if any vertebral height ratio was >3 SD below race‐specific means for each vertebral level. Information on risk factors was obtained by questionnaire or examination. Lumbar spine, total hip, and femoral neck BMD and BMC were measured by DXA. The prevalence of vertebral fractures was 10.6% in black and 19.1% in white women. In age‐adjusted logistic regression models, a 1 SD decrease in femoral neck BMD was associated with 47% increased odds of fracture in black women (OR = 1.47; 95% CI, 1.12–1.94) and 80% increased odds in white women (OR = 1.80; 95% CI, 1.68–1.94; interaction p = 0.14). The overall lower odds of fracture among black women compared with white women was independent of femoral neck BMD and other risk factors (OR = 0.51; 95% CI, 0.37–0.72). However, the prevalence of vertebral fractures increased with increasing number of risk factors in both groups. The prevalence of vertebral fractures is lower in black compared with white women but increases with age, low BMD, and number of risk factors.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63–89 years, mean±SD 76±7 years) and 162 age-matched female controls (age 62–90 years, mean±SD 75±7 years). BMD was measured in the femoral neck and lumbar spine (L2–4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504±0.097 v 0.597±0.101,p<0.01, for femoral neck; 0.661±0.146 v 0.720±0.128,p<0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm² at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1–SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm²), total hip (800 versus 876 mg/cm²), and lumbar spine (1024 versus 1062 mg/cm²); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2–SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1–SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

肱骨近端、髋部骨折老年女性骨密度和骨代谢指标对比研究

目的对髋部、肱骨近端骨折老年女性的骨密度和骨代谢指标进行对比分析,进一步揭示上述骨折部位女性患者骨密度和骨代谢指标特征性变化情况。方法经患者及家属同意,共纳入62例老年髋部骨折女性患者(其中股骨颈骨折39例,股骨粗隆间骨折23例)、肱骨近端骨折21例,收集患者年龄、检测患者骨密度、血清骨转换指标(Ⅰ型胶原氨基端延长肽,P1NP;Ⅰ型胶原C端肽β降解产物,β-CTX)。结果肱骨近端骨折女性患者平均年龄为(66.1±8.0)岁,明显小于股骨颈骨折、粗隆间骨折女性患者(P<0.05);肱骨近端骨折女性髋部(T=-1.19±0.66)、腰椎骨密度(T=-1.67±1.00)明显高于粗隆间骨折女性髋部(T=-2.36±1.17)、腰椎骨密度(T=-2.61±1.42)(P<0.05),同时显著高于股骨颈骨折患者髋部骨密度(T=-2.33±0.99)。股骨颈骨折、股骨粗隆间骨折患者髋部、腰椎骨密度相比差异无统计学意义;三组间血清P1NP比较差异没有统计学意义,粗隆间骨折女性血清β-CTX(732.18±334.37μg/L)要明显高于肱骨近端骨折患者(529.66±292.34μg/L)(P<0.05)。结论相对于髋部骨折患者,肱骨近端骨折老年女性患者年龄较低,骨密度相对较高;骨吸收活跃可能是导致粗隆间骨折女性骨密度下降的原因。     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Epidemiology of osteoporosis in Okinawa

International comparisons of fracture incidence of the femoral neck, bone mineral density of the axial and appendicular bones, calcium intake and daily activities in aged populations are extremely important for identifying preventive measures to be taken against senile osteoporosis. We surveyed the femoral neck fracture rate for four years from 1986 to 1989 in Okinawa Prefecture, and investigated bone mineral density of the lumbar spine and proximal femur by dual photon absortiometry or dual energy quantitative computed tomography in both normal subjects and osteoporotics with spinal compression fractures or hip fractures. Information on past and current daily activities and calcium intakes were collected through interviews or questionnaires on some of these control or osteoporotic subjects. The incidence of hip fracture in Okinawa was relatively higher than that in other prefectures of Japan, but apparently lower than that in Caucasian populations. In normal subjects, the slope of the overall regression line for bone mass vs age in women was 2.2 times steeper than that in men at the lumbar spine, but it was almost identical at the proximal femur in both sexes. Middle aged women lost BMD at both skeltal sites almost 2 times faster than that of overall women. BMD values of the osteoporotics with fractures were significantly lower than those of control subjects before 70 years. The high calcium intake group (more than 600mg/day) showed significantly higher BMD values at both skeltal sites comapred to the low calcium group (less than 600mg/day). Past daily activity level was significantly correlated with BMD values of each skeltal site, but current daily activity level correlated only with BMD for the lumbar spine.