Femur strength index predicts hip fracture independent of bone density and hip axis length.

INTRODUCTION: Proximal femoral bone strength is not only a function of femoral bone mineral density (BMD), but also a function of the spatial distribution of bone mass intrinsic in structural geometric properties such as diameter, area, length, and angle of the femoral neck. Recent advancements in bone density measurement include software that can automatically calculate a variety of femoral structural variables that may be related to hip fracture risk. The purpose of this study was to compare femoral bone density, structure, and strength assessments obtained from dual-energy X-ray absorbtiometry (DXA) measurements in a group of women with and without hip fracture. METHODS: DXA measurements of the proximal femur were obtained from 2,506 women 50 years of age or older, 365 with prior hip fracture and 2,141 controls. In addition to the conventional densitometry measurements, structural variables were determined using the Hip Strength Analysis program, including hip axis length (HAL), cross-sectional moment of inertia (CSMI), and the femur strength index (FSI) calculated as the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter. RESULTS: Femoral neck BMD was significantly lower and HAL significantly higher in the fracture group compared with controls. Mean CSMI was not significantly different between fracture patients and controls after adjustment for BMD and HAL. FSI, after adjustment for T score and HAL, was significantly lower in the fracture group, consistent with a reduced capacity to withstand a fall without fracturing a hip. CONCLUSION: We conclude that BMD, HAL, and FSI are significant independent predictors of hip fracture.

Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment.

CONTEXT: Large segments of the population at risk for osteoporosis and fracture have not been evaluated, and the usefulness of peripheral measurements for short-term prediction of fracture risk is uncertain. OBJECTIVES: To describe the occurrence of low bone mineral density (BMD) in postmenopausal women, its risk factors, and fracture incidence during short-term follow-up. DESIGN: The National Osteoporosis Risk Assessment, a longitudinal observational study initiated September 1997 to March 1999, with approximately 12 months of subsequent follow-up. SETTING AND PARTICIPANTS: A total of 200 160 ambulatory postmenopausal women aged 50 years or older with no previous osteoporosis diagnosis, derived from 4236 primary care practices in 34 states. MAIN OUTCOME MEASURES: Baseline BMD T scores, obtained from peripheral bone densitometry performed at the heel, finger, or forearm; risk factors for low BMD, derived from questionnaire responses; and clinical fracture rates at 12-month follow-up. RESULTS: Using World Health Organization criteria, 39.6% had osteopenia (T score of -1 to -2.49) and 7.2% had osteoporosis (T score

Future methods in the assessment of bone mass and structure.

There have been major advances in the diagnosis of osteoporosis over the last few decades not only in the definitions that are now used but also in the technology that is available. The future will see further development of the techniques currently in common clinical use, such us dual energy X-ray absorptiometry and quantitative ultrasound. In addition new techniques for assessing bone structure, including MRI and fractal analysis of X-rays, may add significantly to our understanding of the pathophysiology of osteoporosis and to the prediction of fracture risk.

Update on bone density measurement.

Bone densitometry is a clinically accepted technique for assessing fracture risk and evaluating skeletal change. The proper clinical use of densitometry requires an understanding of the available techniques, their appropriate application, and the potential sources of measurement error. Recent clinical guidelines recommend that all women over the age of 65 years and all postmenopausal women with risk factors should have their bone density assessed. With the advent of smaller portable devices, bone density measurements are now widely available. In particular, ultrasound techniques, which do not use radiation, have particular promise for widespread screening applications. Peripheral densitometry alone cannot adequately address all clinical questions, particularly the question of monitoring subtle changes in bone density. For this purpose, central densitometers are still preferred. For any bone density measurement to be clinically useful, it must be performed with careful attention to detail, particularly with regard to instrument calibration, patient positioning, measurement analysis, and interpretation.

Discordance in patient classification using T-scores.

In their original study report, "Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis," the World Health Organization (WHO) explicitly stated that any T-score criterion for osteoporosis is sensitive to bone mineral density (BMD) measurement site and technique, as well as the young adult reference population. Yet, the T = -2.5 criterion introduced by WHO is used for many different BMD techniques, despite the fact that it was based primarily on the relationship between forearm measurements and prevalent hip fracture in postmenopausal Caucasian females. It is reasonable to expect that a T-score threshold of -2.5 may be inappropriate for different skeletal sites and measurement techniques. This may explain the large variation in osteoporosis prevalence observed when different skeletal sites are measured. In this study, we compared the prevalence of osteoporosis (based on the T = -2.5 criterion) at different skeletal sites using the manufacturer's normative data. We determined the expected mean T-score for a 60-yr-old Caucasian female at the heel (ultrasound), hip (dual X-ray absorptiometry [DXA]), spine (PA DXA, lateral DXA, and quantitative computed tomography [QCT]), and forearm (DXA). Assuming a normal distribution of T-scores at a fixed age, we computed the expected percentage of 60-yr-old Caucasian women that would be classified as osteoporotic using the -2.5 standard deviation criterion for each technique. At age 60 yr, the expected mean T-score ranged from -2.5 (spine QCT) to -0.7 (heel). Prevalence estimates ranged from 3% at the heel to 50% for spinal QCT. It was also noted that the sites with the strongest relationship to hip fracture risk (the hip and heel) showed the least age-related T-score decline and lowest estimated prevalence. We conclude that a single T-score criterion cannot be universally applied to all BMD measurements. The discrepancies in the prevalence of osteoporosis are the result of several factors, including differences in age-related bone loss at different skeletal sites, differences in the young adult reference populations used by the various bone densitometry devices, and technology-related differences. Using estimated BMD by heel ultrasound, few patients will have T-scores below -2.5, whereas most postmenopausal women will fall below this level for spine bone density measurements performed by lateral DXA or QCT. Based on these data, it may be necessary to provide a T-score criterion specific to the type of densitometric evaluation performed.

Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma.

BACKGROUND: Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking. OBJECTIVE: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy. METHODS: Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals. RESULTS: Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment. CONCLUSION: Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.

Bone densitometry: choosing the proper skeletal site to measure.

In the last several years, many new techniques have been introduced for the measurement of bone density. At present, the clinician is faced with a choice between various technologies that provide measurements of different skeletal sites. Each of these techniques offer advantages and disadvantages for clinical use. Currently, no single technique ideally addresses all clinical requirements. Although all bone density techniques have clinical utility for assessing fracture risk, some devices offer advantages in terms of versatility (i.e., the number of skeletal sites which can be measured), ability to monitor response, cost, availability, and ease of use. Still, the question often is asked, which technique is the best to use? In clinical practice, the answer to this question will depend on the purpose of the bone density measurement. Different indications for bone mass evaluation will necessitate the measurement of different skeletal sites, which will in turn dictate which technique should be ideally used. In this article, the common clinical questions surrounding bone density measurements are reviewed, together with data supporting the appropriate skeletal site to measure to best answer these clinical questions.

Precision and discriminatory ability of calcaneal bone assessment technologies.

To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34-7.76%, 1.63-7.00%, 1.84-9.44%, and 1.99-7.04%, respectively. The %CVs for positioning, interobserver, and short-term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instruments precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88-0.93) and equivalent to DEXA of the calcaneus and hip (0.88-0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 < or = r < or = 0.91, p < 0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis.

Determinants of hip axis length in women aged 10-89 years: a twin study.

Hip axis length (HAL), a measure of femoral geometry, has been shown to predict hip fracture in white women over the age of 67 years, independently of bone mineral density at the femoral neck. A cross-sectional study of 304 pairs of female twins [176 monozygous (MZ) and 128 dizygous (DZ)], aged between 10 and 89 years, was performed to examine the influence of age, constitutional, lifestyle, and genetic factors on HAL. HAL was calculated from dual energy X-ray absorptiometry scans of the proximal femur using an automated technique with an Hologic QDR-1000W. Lean mass, fat mass, height, and weight were also measured. Maximum mean HAL was achieved by the age of 15 years. After this age there was no discernible dependency of mean HAL on age. Using within-pair differences, after adjusting for height there were no other independent constitutional or lifestyle predictors. Cross-sectionally, after adjustment for height, MZ and DZ correlations were 0.79 (95% CI: 0.73-0.84) and 0.54 (95% CI: 0.39-0.68), respectively, and independent of age. The MZ correlation exceeded the DZ correlation (p < 0.001). The best-fitting model apportioned 79% (SE 7%) of variation in height-adjusted HAL to additive genetic factors. There was marginal evidence that an environmental influence shared by twins explained 31% (SE 16%) of height-adjusted variance (p = 0.07), in which case the genetic variance was reduced to 51% (SE 15%). Adjustment for height had reduced the magnitude of total variance by 26%, and 95% of this reduction was in the additive genetic component. Applying a previously described theoretical model, approximately 10% of the increased risk of hip fracture associated with a maternal history of hip fracture could be attributed to the genetic factors determining HAL. We conclude that, in women, adult HAL is achieved by midadolescence. After adjustment for height, which is itself largely under genetic influence, other genetic factors appear to play the predominant role in explaining variation in HAL.

Discrepancies in normative data between Lunar and Hologic DXA systems.

Many studies have shown the high correlation between Lunar and Hologic DXA bone mineral density (BMD) measurements despite differences in absolute calibration. However, in clinical practice, raw BMD values (in g/cm2) are not normally used for assessing skeletal status and fracture risk. Instead, the BMD values are expressed in terms of the number of standard deviations above or below the young normal value (commonly referred to as the T-score). If the normative populations of the various systems are consistent, the standard deviation scores should also be consistent. For this reason, the World Health Organization (WHO) recently established diagnostic criteria for osteoporosis based on T-scores and not BMD. However, few studies have compared the instruments in terms of their standard deviation scores. In this study, we used linear regression to compare T-scores in 83 women at L1-4 and 120 women at the femoral neck obtained on a Lunar DPX and a Hologic QDR-1000/W system. patient BMD and T-score measurements were highly correlated between the two systems (r > 0.95). No clinically significant difference in L1-4 T-scores was seen (less than 0.1 SD). However, linear regression analysis confirmed a systematic difference of 0.9 SD between the femoral neck T-scores. This discrepancy is caused by: (1) differences in the normal populations, and (2) differences in statistical models used to determine the young normal mean and standard deviation. In an attempt to correct the discrepancy, the female young normal mean and standard deviation were recalculated for the femoral neck using published epidemiological data from NHANES and existing DXA cross-calibration equations. The Hologic young normal value (mean +/- SD) was redefined as 0.85 +/- 0.11 g/cm2, while the Lunar value was redefined as 1.00 +/- 0.11 g/cm2. When the femoral neck T-scores for the study population were recalculated on the basis of these new values, the results were equivalent between manufactures, effectively eliminating the discrepancy. However, the revised values should be confirmed by additional measurements in young normal adults.

Bilateral comparison of femoral bone density and hip axis length from single and fan beam DXA scans.

Dominant/nondominant differences in bone mineral density (BMD) have been observed in the upper extremities. However for the proximal femur, the distinction between dominant and nondominant hips is not clear. The purpose of this study is to evaluate left/right variations in femoral BMD and hip axis length (HAL) in both single beam and fan beam dual x-ray absorptiometry (DXA) scans. A total of 36 women aged 41-76 years (average age 60 +/- 10 years) received single beam and fan beam DXA scans of both proximal femora with a Hologic QDR-2000 scanner. Femoral BMD and hip axis length were determined for each scan. Left/right and single beam/fan beam correlations were determined and differences were evaluated using a two-way analysis of variance. Femoral BMD at corresponding measurement regions in opposing femora were highly correlated (r = 0.81-0.96). No significant left/right differences were detected. At the femoral neck, the mean BMD difference (+/- standard deviation) was 1.5% +/- 4.7% in a single beam mode and -0.6% +/- 6.3% in fan beam mode. Though mean values of femoral BMD were equivalent, the observed individual left/right differences were occasionally large (as high as 26% in the femoral neck). The hip axis length of the left and right hips were highly correlated and statistically equivalent. However, hip axis length using fan beam was significantly larger (7.5%) than the single beam measurement with a larger observed variation. We conclude that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality control of DXA instruments in multicenter trials.

Dual-energy X-ray absorptiometry (DXA) has become the measurement of choice for multicenter trials with bone density endpoints. When performing DXA measurements with several different systems, it is important to implement a quality assurance program to guarantee that any observed density changes are real and not due to machine and/or operator variability. In this study, we present a series of procedures based on phantom measurements designed to monitor DXA instrument stability. Techniques for longitudinal evaluation of machine performance and cross-calibration of instruments are described. These procedures are then demonstrated using quality assurance data collected from a number of different DXA scanners. Together these methods provide a defined approach to instrument quality control. Though based primarily on the use of spinal phantoms, these procedures can be generalized for use in any multicenter DXA study.

Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results.

The comparison of patient data among different dual x-ray absorptiometry (DXA) scanners is complicated because no universally accepted cross-calibration procedure or standard currently exists. This study was performed under the auspices of the International DXA Standardization Committee to establish appropriate cross-calibration parameters. Posteroanterior (PA) lumbar spine measurements of 100 women, ages 20-80 years (mean 52.6 +/- 16, range of BMD = 0.4-1.6 g/cm2) were obtained on a Norland XR26 Mark II, a Lunar DPX-L, and a Hologic QDR 2000 densitometer using standard procedures (pencil beam mode for all three scanners). Area, BMC, and BMD results from the different scanners were compared for all patients. In addition, the European spine phantom (ESP) and the European spine phantom prototype (ESP prototype), as well as standard phantoms from all three manufacturers, were evaluated on the three systems. To achieve universal scanner calibration, we used the intercept and slope of the patient's correlations and the value of the middle vertebra of the ESP as a reference point in a series of standardization formulas, and we have expressed the results as sBMD (mg/cm2). The correlations of the patients' spinal BMD values were excellent for each of the three scanner pairs. The average absolute difference in patient spinal BMD values (L2-4) between Hologic and Norland was 0.012 g/cm2 (1.3%); it was 0.113 g/cm2 (11.7%) between Hologic and Lunar and 0.118 g/cm2 (12.2%) between Norland and Lunar. The phantoms' regression lines approximated those of the patient regression lines, and the phantoms with only one measurement point were very close to the patients' regression lines. After applying the standardization formulas, the average absolute differences for the 100 patients were 28 mg/cm2 (2.7%) for Hologic/Norland, 23 mg/cm2 (2.2%) for Hologic/Lunar, and 29 mg/cm2 (2.8%) for Norland/Lunar. Average BMD results for the patients before correction were 0.972 mg/cm2 for Hologic, 1.100 g/cm2 for Lunar, and 0.969 g/cm2 for Norland. After correction, sBMD results for patients were 1045 mg/cm2 for Hologic, 1047 mg/cm2 for Lunar, and 1043 mg/cm2 for Norland. The standardization approach as performed in our study provided compatibility of DXA results obtained on different scanners.

Automated evaluation of hip axis length for predicting hip fracture.

The hip axis length has been shown in previous studies to be predictive of hip fracture independent of age and femoral bone density. The first studies of hip axis length were performed by manual measurement of dual x-ray absorptiometry (DXA) scan printouts. In this study, an automated analysis procedure is defined using software tools provided by the DXA manufacturer. Manual and automatic hip axis length measurements in 198 women were highly correlated (r = 0.98). Because of scaling factors of the printout, the automatic measurement was 58% longer than the manual value. Precision of the automatic measurement, based upon triplicate DXA scans of 33 women, was 0.07 cm or 0.68%. To define normative data, the hip axis length was measured from femoral DXA scans of 471 female volunteers aged 40-92 scanned on 14 different Hologic QDR-1000 systems. Mean hip axis length was 10.5 cm, with a standard deviation of 0.62 cm. No significant relationship between hip axis length and age was found (r = 0.07, P = 0.15). Based on previously reported odds ratios corrected for femoral bone density, age, height, and weight, an automatic hip axis length measurement of 11.0 cm is associated with a twofold increase in hip fracture risk compared with a woman with an average hip axis length. A hip axis length value of 11.6 cm increases hip fracture risk by a factor of 4 compared with a woman with a normal hip dimension. We conclude that the hip axis length can be easily incorporated into existing DXA hip analysis software in combination with a bone density measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group.

Compared with white women, Asian women have about a 40%-50% and blacks a 50%-60% lower risk of hip fracture, but the reason for this racial difference is not known. Women with a shorter hip axis have a lower risk of hip fracture. To test the hypothesis that a shorter hip axis length could account for the lower risk of hip fracture among Asian and black women, we measured hip axis length in 135 Caucasian, 74 Asian and 50 black women. The mean hip axis lengths of Asian and black women were significantly shorter (1.2 and 0.7 standard deviations, respectively) than that of the whites (p < 0.0001). We estimate that, compared with white women, Asians would have a 47% lower risk (95% confidence interval: 32%-63%) and blacks would have a 32% (15%-45%) lower risk of hip fracture because of their shorter hip axis. We conclude that a shorter hip axis length might be a major factor accounting for Asian women's lower risk of hip fracture and might contribute to the lower risk in black women.