ApoE gene polymorphisms, BMD, and fracture risk in elderly men and women: the Rotterdam study.

To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5,857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. INTRODUCTION: The E*4 allele of the E*2, E*3, E*4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. MATERIALS AND METHODS: The study population consisted of 5,857 subjects (2,560 men; 3,297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4,814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. RESULTS AND CONCLUSIONS: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE*4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures.     

Osteoporosis and Apolipoprotein E Genotype in Older Adults: The Rancho Bernardo Study

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45–95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p= 0.21 and p= 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women. Received: 26 July 2000 / Accepted: 13 October 2000     

The Assessment of Bone Mass in Men

Bone mineral density (BMD) is widely used in postmenopausal women to identify who should be given therapy for prevention and treatment of osteoporosis and to monitor the efficacy of treatment. There is still uncertainty about how to interpret BMD in men, and few prospective studies exist on the relationship between BMD and fracture risk. Men should be considered for measurement of BMD if they have suffered low trauma fractures, have prevalent vertebral deformities, have radiographic osteopenia, are over age 75, or have conditions that increase their risk for bone loss, such as hypogonadism, glucocorticoid use, or generally poor health. There is insufficient information to recommend a more widespread BMD screening. The World Health Organization has developed criteria for interpreting BMD which are widely used. Patients with BMD at least 2.5 SD below the young adult mean (T-score < -2.5) have osteoporosis, and those with BMD between 1 and -2.5 SD below the young adult mean (-2.5 < T-score < -1.0) have osteopenia. However, the BMD criteria that should be used to identify men in need of therapeutic intervention are still debated. Using male-specific hip BMD cutoffs, approximately 3-6% of U.S. men 50 years and older were estimated to have osteoporosis and 28-47% to have osteopenia. The corresponding figures in women were 13-18% with osteoporosis and 37-50% with osteopenia. Greater accumulation of skeletal mass during growth, slower rate of bone loss, and shorter life expectancy in men contribute to the lower prevalence of osteoporosis relative to women.     

Apolipoprotein E gene polymorphism and bone loss: estrogen status modifies the influence of apolipoprotein E on bone loss.

The identification of genes that contribute to bone mineral density (BMD) and bone loss has widespread implications for the understanding and prevention of osteoporosis. The objective of this study was to examine the relationship between the presence and absence of the apolipoprotein E*4 (APOE*4) allele and both BMD and annualized percentage rate of change in BMD at the lumbar spine and hip in a population of 392 healthy, pre-, peri-, and postmenopausal white women participating in the Women's Healthy Lifestyle Project. APOE genotype was analyzed by restriction enzyme analysis from genomic DNA. BMD at the lumbar spine and hip was measured at baseline and after a mean of 2.5 years using dual-energy X-ray absorptiometry (DXA). In premenopausal women, there were no significant differences in BMD or in the annualized percentage rate of change in BMD at the spine or hip when comparing women with and without the APOE*4 allele. In contrast, spine bone loss was significantly greater in peri- and postmenopausal women having an APOE*4 allele than in women without this allele (-1.75 + 1.5% per year vs. -0.98 +/- 1.4% per year, respectively, p = 0.018). Among peri- and postmenopausal women currently using hormone replacement therapy (HRT), there were no differences in the annualized percentage rate of change in spine BMD; whereas, among non-HRT users, there was a 2-fold higher rate of spine bone loss in women with an APOE*4 allele compared with women without this allele (-2.31 +/- 1.5% per year vs. -1.27 +/- 1.3% per year, respectively, p = 0.033; APOE*4 x HRT interaction, p = 0.076). In conclusion, this study shows the importance of APOE*4 allele in spine bone loss in peri- and postmenopausal women and, more importantly, it provides evidence for a genetic and lifestyle interaction in modulating spine bone loss.     

Influence of Insurance Benefit Criteria on the Administration Rate of Osteoporosis Drugs in Postmenopausal Females

Background

Preventive measures need to be implemented to lower the incidence of osteoporotic fractures. Osteoporotic fractures increase morbidity and mortality as well as impose a socioeconomic burden; however, current research is limited to the administration rates of osteoporosis drugs for Korean postmenopausal females.

Methods

This study represents a nationwide, observational, and cross-sectional survey that investigates the administration rates of osteoporosis drugs based upon a bone mineral density (BMD) test performed on Korean postmenopausal patients who visited outpatient orthopedic clinics. BMD test results were examined in postmenopausal female patients (50 to 80 years of age); subsequently, the patients were classified into an osteoporosis group, osteopenia group, and normal group. The administration rates of osteoporosis drugs and bisphosphonates were then analyzed. The osteoporosis group was subdivided into a T-score less than -3.0 group and a T-score between -3.0 and -2.5 group that were separately analyzed.

Results

Based on the lumbar spine BMD, the rate of administration of osteoporosis drugs in the osteoporosis group was 42.1%, which was significantly higher compared to the osteopenia group or normal group. A significantly low bone mineral density was observed in patients who were administered bisphosphonates. Based on the lumbar spine BMD, the administration rate of osteoporosis drugs in the group with a T-score between -3.0 and -2.5 (34.2%) was significantly lower than the group with a T-score less that -3.0 (46.2%). The bisphosphonate administration rate was also significantly low; however, the administration rate for osteoporosis drugs was significantly lower than that of the osteopenia group.

Conclusions

Only about 40% of Korean postmenopausal female patients with osteoporosis were administered osteoporosis drugs. The administration rate in patients with a T-score between -3.0 and -2.5 was particularly low and active treatment to prevent osteoporotic fractures is required in this group.     

Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk--The Study of Osteoporotic Fractures.

Hip fractures are common and devastating events. The apolipoprotein E*4 (APOE) allele, associated with Alzheimer's disease, has also been associated with osteoporosis in hemodialysis patients. We prospectively studied 1750 women, age >/=65 years, who underwent measurements of hip and calcaneal bone mineral density (BMD), were typed for APOE and followed for approximately 7.0 years for the occurrence of fractures and falls. Women with at least one APOE*4 allele had an increased risk of hip fracture, relative hazard (RH) (95% confidence interval) = 1.90 (1.05-3.41) and wrist fracture, RH = 1.67 (1.01-2.77) compared with women without APOE*4, even after adjusting for age, cognitive function, falling, and BMD. The effect of APOE*4 on hip fracture was greatest among women with additional (>/=3) other risk factors. Women with an APOE*4 allele were also likely to report a maternal history of fracture. The average number of falls per year did not differ by APOE*4: 0.46 for APOE*4 women and 0.41 for women without an APOE*4 allele. Women with an APOE*4 allele experienced greater weight loss which contributed to faster rates of bone loss. We conclude that women with the APOE*4 polymorphism are at substantially increased risk of hip and wrist fracture that is not explained by bone density, impaired cognitive function, or falling. Possible alternate explanations include an effect of APOE on vitamin K, bone turnover, or weight loss. The APOE polymorphism may be a candidate gene for hip fractures among community dwelling nondemented women.     

46例绝经后骨质疏松症妇女骨密度及尿吡啶啉、血清Ⅰ型前胶原肽的初步分析

本文通过对60～70岁绝经后妇女20例健康对照组、28例骨质疏松组、18例骨质疏松伴骨折组骨密度及尿吡啶啉(Pyridinoline,PYD)、血清Ⅰ型前胶原肽(Carboxy\|terminalpropeptideoftypeIprocollagen,PICP)的测定,经过比较分析结果显示46例骨质疏松患者的骨密度显著低于健康对照组,18例骨质疏松伴骨折组患者的股骨颈部位的骨密度显著低于28例骨质疏松无骨折组.46例骨质疏松患者的尿PYD、血PICP均显著高于健康对照组.由此提示绝经后妇女测量骨密度尤其是股骨上端的骨密度,结合骨吸收及骨形成的生化指标尿PYD、血PICP,能更好地预测骨质疏松及提示骨折发生的危险性.     

绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系。方法选择骨质疏松性椎体骨折的绝经后妇女23例为骨折组,无椎体骨折的25例绝经后骨质疏松妇女为对照组。两组的年龄、绝经年限、身高、体重、体重指数差异无显著性,均行胸腰椎正侧位X线摄片。用双能X线吸收仪（DXA）测量的腰椎（L2-4）前后位骨密度（BMD）、骨矿含量（BMC）和T值。结果骨折组BMD、BMC和T值均低于对照组（P〈0.01）。结论腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关。绝经后骨质疏松妇女应重视BMD变化,预防椎体骨折的发生。     

Apolipoprotein E4 is associated with reduced calcaneal quantitative ultrasound measurements and bone mineral density in elderly women

Some studies have reported an association between the apolipoprotein E4 (APOE4) allele and reduced bone density and increased propensity to fracture, but this remains controversial as other studies have not found an association between APOE4 and bone density or fracture. No information is available concerning the effect of the APOE4 allele on quantitative ultrasound (QUS) parameters. We therefore examined this issue in a population-based study of 1332 healthy elderly women, examining the effect of the APOE4 allele on QUS parameters at the calcaneus and comparing this to dual-energy X-ray absorptiometry (DEXA) bone mineral density (BMD) at the hip. In addition, we examined the effect of the APOE4 allele on fracture. Subjects who had at least one APOE4 allele (n = 308) had lower calcaneal QUS parameters and lower hip BMD at the total hip, trochanter, and intertrochanter, but not the femoral neck, compared to subjects without an APOE4 allele (n = 1024) after adjustment for age, body mass index (BMI), and smoking. The decrement in QUS parameters and BMD was approximately 2%. Those subjects having an APOE4 allele were also more likely to fall into a low bone density group, defined by a T score of <1 SD below the young normal range (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.08-2.22). We compared both prevalent and incident nontraumatic fractures over 2 years in the APOE4-present group compared with the APOE4-absent group. There were 354 subjects who entered the study with a history of one or more prevalent fractures, and 104 subjects sustained a nontraumatic fracture during the study. These fractures were not associated with the presence of the APOE4 allele, but a 2% decrement in BMD was unlikely to be associated with a statistically observable increase in fractures in this study. The APOE4 allele was not associated with a difference in any biochemical measures of bone formation or resorption, or in estrogen concentration, nor was it associated with a difference in BMI. Therefore, we conclude that the APOE4 allele is associated with a consistent decrease in both QUS parameters at the calcaneus and BMD at the clinically important hip site, and that this is not associated with differences in biochemical measures of bone formation or resorption.     

Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis

Objective

We systematically assessed bone mineral density (BMD), bone turnover markers (BTM), and fractures in a large cohort of patients with Indolent Systemic Mastocytosis (ISM).

Methods

Eighty-two patients (mean age 48 years, 37 women) with ISM were studied. BMD was measured by dual X-ray absorptiometry at the lumbar spine and proximal hip. The serum markers of bone turnover included bone-specific alkaline phosphatase, C-telopeptides of type I collagen, and serum osteocalcin. Previous clinical fractures were registered and spine X-ray was obtained from all patients.

Results

Three women were excluded for concomitant diseases associated to osteoporosis. Osteoporosis according with the WHO classification (T-score < − 2.5) was found in 16 patients (20.0%) (7 females and 9 men). Mastocytosis-related low BMD (Z-score at either the spine or the hip < − 2) was found in 3 women (9%) and 13 men (28%). The BMD was generally lower at the spine than at the hip. No significant correlation was observed between serum tryptase levels and T or Z-score BMD. One or more moderate or severe vertebral fractures were found in 17 patients (12 men); in 11 of them Z-score values were > − 2 or not valuable at the spine. No significant difference was found in the prevalence of mastocytosis-related low BMD and/or vertebral fractures between patients with or without skin involvement. Two patients had radiographic and densitometric osteosclerosis-like characteristics. In osteoporotic patients higher, normal or lower serum BTM were found, without correlations with serum tryptase levels, while in patients with osteosclerosis both BTM and serum tryptase values were particularly increased.

Conclusions

Vertebral osteoporosis and fractures are frequent in patients with ISM. Spine X-ray and densitometric examination are warranted in all patients, also without skin involvement and particularly in males; Z-score other than T-score BMD must be evaluated. Patients with idiopathic osteoporosis should be evaluated for mast cell disease. Both high than low BTM can be observed in patients with osteoporosis while osteosclerosis is characterized by high bone turnover and serum tryptase levels.     

Bone mass effects of a BMP4 gene polymorphism in postmenopausal women

The pathogenesis of osteoporosis involves both genetic and environmental factors. On the basis of linkage data suggesting gene effects on bone density at chromosome 14q and data locating the BMP4 gene to 14q, we performed a positional candidate study to examine a possible association of BMP4 gene polymorphisms, hip bone density (n = 1012) and fracture rates (n = 1232) in postmenopausal women (mean age 75). On genotype analysis of the three selected single nucleotide polymorphisms (SNP), the 6007C > T polymorphism was associated with total and intertrochanteric hip BMD and BMD was lower in the 32% of subjects homozygous for the C allele. This polymorphism codes for a nonsynonymous amino acid change with the T allele coding for valine, while the C allele codes for alanine. The difference in BMD was 3.1% (TT vs. CC) and 2.3% (CT versus CC) for the total hip (P = 0.023), and 3.7% (TT vs. CC) and 2.8% (CT versus CC) for the intertrochanter site (P = 0.012). Haplotype analysis demonstrated 6 haplotypes of frequency greater than 2%. A major haplotype defined by G-C-T alleles in SNPs -5826G > A, 3564C > T and 6007C > T respectively, showed association with high bone mass. No SNP showed association with fracture rates. We conclude that a polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton.     

Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial

Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.     

Relationship between dental panoramic radiographic findings and biochemical markers of bone turnover.

We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs. INTRODUCTION: Recent studies suggest that mandibular inferior cortical shape and width on dental panoramic radiographs may be useful screening tools for low skeletal bone mineral density (BMD) or increased risk of osteoporotic fracture. However, little is known as to whether these measures are associated with bone turnover. We investigated relationships among dental panoramic radiographic findings, spine BMD, and biochemical markers of bone turnover in postmenopausal women. MATERIALS AND METHODS: Of 609 women who visited our clinic for BMD assessment between 1996 and 2002, 82 Japanese postmenopausal women, 46-68 years of age (54.1 +/- 4.9 years), were recruited for this study. Mandibular inferior cortical shape (normal, mild/moderate erosion, severe erosion) and width were evaluated on dental panoramic radiographs. BMD at the lumbar spine (L2-L4) was measured by DXA and categorized as normal (T-score > -1.0), osteopenia (T-score, -1.0 to -2.5), or osteoporosis (T-score < -2.5). Bone turnover was estimated by serum total alkaline phosphatase (ALP) and urinary N-telopeptide cross-links of type I collagen (NTx), corrected for creatinine. RESULTS: The odds of low spine BMD in subjects with any cortical erosion were 3.8 (95% CI, 1.2-12.5). Mandibular cortical erosion was significantly associated with increased NTx (p < 0.001) and ALP (p < 0.05) levels. The associations of spine BMD with NTx and ALP were similar. Mandibular cortical width was significantly associated with spine BMD but not with NTx and ALP levels. CONCLUSIONS: Our results suggest that mandibular inferior cortical shape on dental panoramic radiographs may be an indicator of bone turnover and spine BMD in postmenopausal women. Dentists may be able to identify postmenopausal women with increased risk of osteopenia and osteoporosis on routine dental panoramic radiographs.     

Association between Osteoporotic Vertebral Compression Fractures and Age,Bone Mineral Density,and European Quality of Life-5 Dimensions in Korean Postmenopausal Women: A Nationwide Cross-sectional Observational Study

BackgroudThe purpose of this study was to investigate the characteristics of osteoporotic vertebral compression fractures (OVCFs) in Korean postmenopausal women and the association between OVCFs and clinical factors such as age, bone mineral density (BMD), and quality of life.MethodsAccording to the population distribution in four regions in Korea, 1,281 postmenopausal female patients were recruited from nationwide orthopedic outpatient clinics. Radiologic, asymptomatic, and within 3 months of OVCF groups were analyzed based on age, fracture location, and prevalence according to BMD. In addition, BMD, T-score, body mass index, and European Quality of Life-5 Dimensions (EQ-5D) were investigated in the three groups, and the differences between groups were compared and analyzed.ResultsThe prevalence of radiologic OVCFs at the T11–L1 was 3.7 times higher in the 70s group (44.0%) than in the 50s group (11.9%). Femur and total hip BMD were significantly lower in patients with thoracolumbar junction fractures than in patients with L2–5 fractures, whereas no difference was observed in lumbar spine BMD. Of the three OVCF groups, the within 3 months of OVCF group had the lowest lumbar spine T-score of −2.445. The asymptomatic OVCF group also showed significantly lower lumbar spine T-score than did the group without radiologic OVCFs (p < 0.001). The EQ-5D showed a significant decrease in the radiologic OVCF group (p < 0.001) and within 3 months of OVCF group (p < 0.001).ConclusionsThe prevalence of OVCFs in the thoracolumbar junction rapidly increases with old age and low BMD in Korean postmenopausal women. Femur and total hip BMD are more predictive of thoracolumbar junction fractures than lumbar spine BMD. Patients with radiologic OVCFs had a significantly lower quality of life than no OVCF group. Therefore, this study shows it is important to treat and prevent osteoporosis before an OVCF occurs.     

The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group

Summary

Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.

Introduction

Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of?≤??2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.

Methods

Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.

Results

The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to ?2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.

Conclusions

As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.     

Comparison between T-score-based diagnosis of osteoporosis and specific skeletal site measurements: prognostic value for predicting fracture risk.

T-score-based diagnosis of osteoporosis might lead to diagnostic misclassification when using multiple-site bone mineral density (BMD) measurements. To compare the diagnostic concordance of T-score-based diagnosis of osteoporosis among different skeletal sites and its correlation to osteoporotic fracture, we studied 1200 postmenopausal women with (441) and without (759) fragility fracture after measuring BMD at the femoral neck, Ward's triangle, trochanter, and spine. Agreement rates of T-score-based diagnosis of osteoporosis were statistically different between pairs of measurements taken at different skeletal sites (McNemar test, p < 0.001). Fragility fractures poorly matched T-score-based diagnosis of osteoporosis (Cohen and Younden indexes <0.4). Technique inaccuracies support these discrepancies as also shown by the large range of T-score values (from -2 to -3) with similar abilities to predict fractures by ROC curve area comparison. Concordance rates between T-score and fragility fracture diagnosis of osteoporosis (marginal homogeneity test, p < 0.001) were also different across the various measurement sites. Our data show that the T-score leads to diagnostic inconsistencies among different skeletal sites and low concordance with fragility fracture based diagnosis of osteoporosis. Integration of the T-score with multiple risk assessment from clinical sources should be tested to better diagnose osteoporosis and related fracture risk.     

Use of Lowest Single Lumbar Spine Vertebra Bone Mineral Density T-Score and Other T-Score Approaches for Diagnosing Osteoporosis and Relationships with Vertebral Fracture Status

For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1–L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1–L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1–L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1–L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.     

Trabecular Bone Score: A Noninvasive Analytical Method Based Upon the DXA Image

The trabecular bone score (TBS) is a gray‐level textural metric that can be extracted from the two‐dimensional lumbar spine dual‐energy X‐ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross‐sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment. © 2014 American Society for Bone and Mineral Research.     

Use of a Swedish T-score reference population for women causes a two-fold increase in the amount of postmenopausal Swedish patients that fulfill the WHO criteria for osteoporosis

The WHO criteria for osteoporosis are based on bone mineral density (BMD) values in comparison to a reference population of healthy young adults. The aim of this study was to create BMD references for ethnic Swedish women, and to investigate whether the use of these T-score measurements influence the amount of Swedish postmenopausal patients that are diagnosed as having osteoporosis. A bone density reference was created by measuring a population-based sample of 335 randomly selected Swedish women aged 20-39yr. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, proximal femur, and total body. These locally derived T-score values were subsequently used to diagnose a sample of 300 consecutive postmenopausal Swedish patients referred to the Uppsala Osteoporosis Unit. There was a slight age-dependent decrease in femoral neck BMD, whereas no age effect was seen at other sites such as total hip, lumbar spine, or total body. This suggests that the cohort represents the steady state BMD at the ages of expected peak bone mass in Swedish women. The correlation between BMD measures at different sites differed from r=0.55 (lumbar spine BMD vs femoral neck BMD [FNBMD]) to r=0.92 (total hip BMD vs FNBMD). Central DXA-generated T-scores were calculated from this cohort, and these were significantly higher (0.3-0.5 SD) as compared with manufacturers and NHANESIII reference populations. This indicates that young Swedish women have a higher peak bone mass than the subjects included in the reference populations currently used for clinical measurements. The T-score in total hip derived from the investigated cohort was subsequently used to diagnose 300 clinical patients (mean age 63yr) referred for a DXA scan by their physicians. The use of this locally established and ethnic representative, T-score reference increased the prevalence of osteoporosis in femoral neck and total hip with 53-106%. A Swedish female BMD reference representing peak bone mass has been established and the normative data are presented. Notably, this cohort has considerably higher BMD as compared to the NHANESIII and manufacturer's reference populations. The use of the present T-score reference therefore causes approximately a 2-fold increase in the amount of Swedish postmenopausal women that fulfill the WHO criteria for osteoporosis. This demonstrates the problems with using T-score as diagnostic threshold for osteoporosis and is an argument for future strategies to obtain standardized densitometric cut-offs, for example, mg/cm(2).