D. Hans

Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study

BACKGROUNDnThe ability of ultrasonographic measurements to discriminate between patients with hip fracture and age-matched controls has until now been tested mainly through cross-sectional studies. We report the results of a prospective study to assess the value of measurements with ultrasound in predicting the risk of hip fracture.nnnMETHODSn5662 elderly women (mean age 80.4 years) had both baseline calcaneal ultrasonography measurements and femoral radiography (dual-photon X-ray absorptiometry, DPXA) to assess their bone quality. Follow-up every 4 months enabled us to identify incident fractures. 115 hip fractures were recorded during a mean follow-up duration of 2 years.nnnFINDINGSnLow calcaneal ultrasonographic variables (obtained from measurements of broadband ultrasound attenuation by, and speed of sound through the bone) were able to predict an increased risk of hip fracture, with similar accuracy to low femoral bone mineral density (BMD) obtained by DPXA. The relative risk of hip fracture for 1 SD reduction was 2.0 (95% CI 1.6-2.4) for ultrasound attenuation and 1.7 (1.4-2.1) for speed of sound, compared with 1.9 (1.6-2.4) for BMD. After control for the femoral neck BMD, ultrasonographic variables remained predictive of hip fracture. The incidence of hip fracture among women with values above the median for both calcaneal ultrasound attenuation and femoral neck BMD was 2.7 per 1000 woman-years, compared with 19.6 per 1000 woman-years for those with values below the median for both measures.nnnINTERPRETATIONnUltrasonographic measurements of the os calcis predict the risk of hip fracture in elderly women living at home as well as DPXA of the hip does, and the combination of both methods makes possible the identification of women at very high or very low risk of fracture.

How Hip and Whole-Body Bone Mineral Density Predict Hip Fracture in Elderly Women: The EPIDOS Prospective Study

Abstract: We conducted a population-based cohort study in 7598 white healthy women, aged 75 years and over, recruited from the voting lists. We measured at baseline bone mineral density (BMD g/cm2) of the proximal femur (neck, trochanter and Wards triangle) and the whole body, as well as fat and lean body mass, by dual-energy X-ray absorptiometry (DXA). One hundred and fifty-four women underwent a hip fracture during an average 2 years follow-up. Each standard deviation decrease in BMD increased the risk of hip fracture adjusted for age, weight and centre by 1.9 (95% CL 1.5, 2.3) for the femoral neck, 2.6 times (2.0, 3.3) for the trochanter, 1.8 times (1.4, 2.2) for Wards triangle, 1.6 times (1.2, 2.0) for the whole body, and 1.3 times (1.0, 1.5) for the fat mass. The areas under the receiver operating characteristic (ROC) curves were not significantly different between trochanter and femoral neck BMD, whereas ROC curves of femoral neck and trochanter BMD were significantly better than those for Wards triangle and whole-body BMD.emsp;Women who sustained an intertrochanteric fracture were older (84 ± 4.5 years) than women who had a cervical fracture (81 ± 4.5 years) and trochanter BMD seemed to be a stronger predictor of intertrochanteric ([RR = 4.5 (3.1, 6.5)] than cervical fractures ([RR = 1.8 (1.5, 2.3]).emsp;In very elderly women aged 80 years and more, hip BMD was still a significant predictor of hip fracture but the relative risk was significantly lower than in women younger than 80 years.emsp;In the 48% of women who had a femoral neck BMD T-score less than –2.5, the relative risk of hip fracture was increased by 3, and the unadjusted incidence of hip fracture was 16.4 per 1000 woman-years compared with 1.1 in the population with a femoral neck BMD T-score 5–1.

Do ultrasound measurements on the os calcis reflect more the bone microarchitecture than the bone mass?: A two-dimensional histomorphometric study

Few studies have analyzed the relationship between ultrasound measurements (US) and corresponding histomorphometric parameters of the calcaneus. To address this question we have compared US and histomorphometric parameters in 17 whole human os calcis from amputation or necropsy. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and bone mineral density (BMD) were measured on the whole foot at the calcaneal site using an Achilles device and a DPX-L densitometer (Lunar). The os calcis was dissected and a 1-cm-wide transcortical parallelepiped extracted with a biopsy needle, focused on the center of the measured area. Histomorphometry was performed on undecalcified biopsies. Structural and connectivity parameters were measured on 7-microns-thick sections with both automatic (Biocom) and semiautomatic analyzers (Ibas 1, Kontron). We found that all ultrasonic and densitometric parameters reflected the true amount of bone and were correlated with only some of the parameters reflecting bone microarchitecture. From stepwise regression analysis, we found that 68%, 67%, 72%, and 74% of the variance of SOS, BUA stiffness, and BMD, respectively, were explained significantly by trabeculae thickness only. Ultrasonic measurements appear to reflect bone quantity rather than bone microarchitecture. The current conclusion is fairly negative with respect to the ability of ultrasound to assess structural parameters, but our limited sample size did not give enough power to our study to reach statistically significant correlations. In addition, the calcaneus is anisotropic and the ultrasound interaction in bone is a three-dimensional phenomenon. So, a three-dimensional study rather than a two-dimensional one should be performed.

Different Morphometric and Densitometric Parameters Predict Cervical and Trochanteric Hip Fracture: The EPIDOS Study

We used an experimental software measuring the hip axis length (HAL) and bone mineral density (BMD) in specific regions of the lower and upper part of the femoral neck on dual‐energy X‐ray absorptiometry scans. To determine whether these parameters were significant predictors of the type of hip fracture, we measured 167 healthy women (controls), 24 women with trochanteric, and 42 women with cervical hip fractures within the EPIDOS prospective cohort. EPIDOS is a multicenter prospective study on risk factors for hip fracture performed in 7575 elderly women living at home, aged 75–95 and conducted in five French centers (Amiens, Lyon, Montpellier, Paris, Toulouse). Measurements were performed on data acquired at baseline before the occurrence of fracture. In the cervical fracture group, HAL was significantly longer than in controls (94.2 vs. 92.3, p = 0.03), and the associated odds ratio (OR) adjusted for age, weight, and total femoral neck BMD was significant (OR = 1.64, 95% confidence interval [CI] 1.06–2.55). In contrast, HAL was not significantly different from controls in the trochanteric fracture group. Femoral neck diameter was not a predictor of fracture. The upper and lower femoral neck BMD was lower in the trochanteric fracture group than in controls, and both measurements predicted trochanteric femoral neck fracture. In contrast, the prediction of cervical femoral neck fracture was enhanced by measuring only the upper part of the femoral neck (OR = 2.79 vs. 1.97 for the total femoral neck) while BMD of the lower part was not different from controls. Hip axis length is a predictor of femoral neck fracture. Femoral neck BMD distribution is different between cervical and trochanteric fractures. These results support the hypothesis of a different pathophysiological mechanism between the two types of hip fractures.

Ultrasound measurements on os calcis: Precision and age-related changes in a normal female population

We performed ultrasound measurements in the calcaneus of 512 healthy women. Broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were obtained with a Lunar Achilles ultrasonic instrument. Subjects studied were one group of 67 women working in our hospital (group A) and two groups which are part of two large prospective cohort studies (groups B and C). Group B consisted of 244 women aged 31–79 years randomly selected from a large insurance company, and group C consisted of 201 women aged 74–91 years randomly selected from the electoral rolls. Dual-energy X-ray absorptiometry (DXA) measurements of femoral neck and total body were performed with a Hologic QDR 2000 for group B and with a Lunar DPX Plus for group C. The in vitro precision of the Achilles, estimated by measuring a phantom daily for 45 days, was 0.84% for BUA and 0.12% for SOS. We assessed the in vivo short-term precision in 20 healthy volunteers working at the hospital, measured three times each. The coefficients of variation were 0.93% (±0.21) for BUA and 0.15% (±0.03) for SOS. The precision error was compared with the true variation, to obtain a standardized coefficient of variation. We analysed the three groups pooled together (n=512) and found for BUA an average 20% decrease and for SOS a 5% decrease between the ages of 20 and 90 years. We also performed separate analyses of subjects younger than 50 and older than 50 years, and within each 10-year age group we found that BUA was stable or slightly increased from 20 to 50 years and then decreased after 50. In contrast, SOS did not increase but decreased from the age of 20. We compared DXA measurements of the femoral neck and the total body with ultrasound measurements in groups B and C. In both groups the correlations were better with total body DXA than with femoral neck and spine DXA.

Do Markers of Bone Resorption Add to Bone Mineral Density and Ultrasonographic Heel Measurement for the Prediction of Hip Fracture in Elderly Women? The EPIDOS Prospective Study

Abstract: We have previously shown that hip bone mineral density (BMD), heel broadband ultrasound attenuation (BUA) and bone resorption markers are independent predictors of hip fracture in elderly women. We investigated whether a combination of these three parameters could improve the predictive value of a single test in a nested case–control analysis (75 hip fractures and 228 age-matched controls) of the EPIDOS prospective study comprising 7598 healthy women 75 years of age and older followed prospectively for a mean 22 months. At baseline, prior fracture, femoral neck BMD by dual-energy X-ray absorptiometry (DXA), heel BUA and urinary type I collagen C-telopeptide breakdown products (CTX) were assessed. The area under the receiver operating characteristic curve was significant for the three diagnostic tests, heel BUA being the best single predictor. The added value of urinary CTX to either BMD or BUA depends on the cutoff point chosen to define patients at risk and on the therapeutic strategy that is considered. Defining patients at risk as those with low BMD (or low BUA) or high CTX resulted in a significant increase in the sensitivity compared with BMD or BUA alone – a strategy that could be applied when a broad treatment is considered. However, this increased sensitivity was also obtained simply by increasing the BMD and BUA cutoffs, suggesting that a combination of CTX with BMD/BUA is not useful for that type of treatment strategy. Conversely, defining patients at risk as those with both low BMD and high CTX increases the specificity (88% vs 78%) with a similar number of hip fracture patients being identified (30% vs 32%) – a combination that could be useful when the strategy is to target treatment to a subset of high-risk patients. This strategy appears to be more cost-effective than bone mass measurement alone as indicated by the 37% fewer patients who need to be treated to avoid one fracture per year. If DXA or ultrasound is not available, the combination of a bone resorption marker with a history of any type of fracture after the age of 50 years gave a predictive value similar to that obtained with femoral neck BMD or heel BUA alone, for both types of treatment strategy. We conclude that the combination of urinary CTX with hip BMD could be useful for the identification of elderly women at high risk for hip fracture, resulting in higher specificity for a given sensitivity threshold than BMD measurement alone. If DXA is not available, the combination of history of fracture and urinary CTX performs as well as hip BMD to assess hip fracture risk in elderly women.

Influence of fat on ultrasound measurements of the os calcis

Measurements of the speed-of-sound (SOS) and of the broadband ultrasound attenuation (BUA) on the os calcis were recently proposed to assess osteoporotic fragility. Velocity and attenuation were measured through the heel which can be divided in three phases including hydroxyapatite, soft tissue, and fat. The aim of this study was to evaluate the influence of fat composition and heel width on SOS and BUA. This influence was determined from both in vitro investigations examining fat samples, phantoms, and cadaver heels, and in vivo ones observing adult volunteers as well as a wide sample section of healthy elderly women. Ultrasound velocities on various fat samples were significantly lower than those on distilled water (-65 m/second to -123 m/second). The excision of the surrounding soft tissue from cadaver heels made SOS steadily increase whereas the insertion of a 10 mm piece of lard in the lateral face of cadavers and volunteers heels os calcis lowered SOS about 30 m/second. ond. Furthermore, a difference of SOS was estimated at 15 m/second for a 12.5% variation of the marrow fat weight. Among 334 elderly and healthy women aged 75 and over, a significant negative correlation was found between SOS and heel width (r=-0.27; P<0.0001). On the other hand, fat composition had no significant effect on BUA measurement, and no significant relationship was found between BUA and heel width. This study demonstrates that an increase of heel width and fat thickness provides an underestimation of os calcis SOS, but has no significant effect on BUA.

Influence of anthropometric parameters on ultrasound measurements of os calcis

Few data have been published concerning the influence of height, weight and body mass index (BMI) on broadband ultrasound attenuation (BUA), speed of sound (SOS) and Lunar “stiffness” index, and always in small population samples. The first aim of the present cross-sectional study was to determine whether anthropometric factors have a significant influence on ultrasound measurements. The second objective was to establish whether these parameters have real effect on bone or whether their infuence is due only to measurement errors. We measured, in 271 healthy French women (mean age 77±11 years; range 31–97 years), the following parameters: age, height, weight, lean and fat body mass, heel width, foot length, knee height and height of the external malleolus (HEM). Simple linear regression analyses between ultrasound and anthropometric parameters were performed. Age, height and heel width were significant predictors of SOS; age, height, weight, foot length, heel width, HEM, fat mass and lean mass were significant predictors of BUA; age, height, weight, heel width, HEM, fat mass and lean mass were significant predictors of stiffness. In the multiple regression analysis, once the analysis had been adjusted for age, only heel width was a significant predictor for SOS (p=0.0007), weight for BUA (p=0.0001), and weight (p=0.0001) and heel width (p=0.004) for the stiffness index. Besides their statistical meaning, the regression coefficients have a more clinically relevant interpretation which is developed in the text. These results confirm the influence of anthropometric factors on the ultrasonic parameter values, because BUA and SOS were in part dependent on heel width and weight. The influence of the position of the transducer on the calcaneus should be taken into account to optimize the methods of measurement using ultrasound.

Separate and Combined Value of Bone Mass and Gait Speed Measurements in Screening for Hip Fracture Risk: Results from the EPIDOS Study

Abstract: Based on data from the EPIDOS prospective study, we have shown that femoral bone mineral density (BMD), calcaneal ultrasound measurements and fall-related factors are significant predictors of the risk of hip fracture. The goal of the present investigation, in the same cohort of elderly women, was (1) to assess and compare the value of femoral BMD, calcaneal broadband ultrasound attenuation (BUA), gait speed and age for identifying elderly women at high risk of hip fracture and (2) to determine whether combining two or more of these measurements would improve predictive ability over single measures. A total of 5895 elderly women had baseline measurements of femoral neck BMD by dual-energy X-ray absorptiometry, calcaneal BUA and gait speed. During an average of 33 months of follow-up, 170 women suffered a hip fracture. We compared the sensitivity and specificity of single and combined measures for three specific cutoff levels to define high risk, i.e., the median, the top quartile and the top decile of risk. We found that femoral BMD, calcaneal BUA, gait speed and age have approximatively the same discriminant value to identify women at high risk of hip fracture even though certain measures and combinations of measures have a significantly higher sensitivity for certain cutoff levels. The sensitivity of the available screening tools is low, even when they are combined: to obtain a sensitivity of about 80%, approximately 50% of the population must be considered to be at high risk.

Effects of a new positioner on the precision of HIP bone mineral density measurements

In an attempt to reduce patient positioning errors, the authors tested the use of a new hip‐specific positioning tool, OsteoDynes Hip Positioner System (HPS). The HPS is an “A” frame splint designed to abduct both legs approximately 15° to hold them in full extension at the hips and knees and to lock the feet in a neutral position. Seventy volunteer women aged 35–82 years were randomly assigned in two age‐matched groups (mean age 56 years). Each group underwent two consecutive femur dual X‐ray absorptiometry (DXA) scans with intermediate repositioning using the HPS system and two others utilizing the standard hip positioner provided with Hologic and Lunar scanners. One technician performed all scans using a Hologic QDR 1000‐Plus and Lunar DPX‐Plus densitometer. One hundred and fifty volunteer women aged 50–84 years (mean age, 64 years) were recruited in a multicenter study for the assessment of precision. Each subject underwent three consecutive femur DXA scans with intermediate repositioning using the HPS system. The coefficient of variation (CV) was significantly improved at the femoral neck by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only moderately altered at other sites. Similar results were found with the Lunar densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8 with a similar trend but no significant difference at the other regions. No statistical difference was noted between the femoral neck BMD measured with the HPS system and with the standard positioners in either group. The mean precision of data obtained on the QDR 1000+ was 0.8% (range 0.1–1.4) for the femoral neck BMD, 1.1% (range 0.1–3.0) for the trochanter BMD, 2.3% (range 0.2–5.2) for Wards triangle BMD, and 0.8% (range 0.1–1.9) for the total femur BMD. The mean precision of data obtained on the QDR 2000 was 0.7% (range 0.1–2), 1% (range 0.1–4.9), 2.6% (range 0.3–5.7), and 0.7% (range 0.1–1.8), respectively. In conclusion, data obtained with the new OsteoDynes HPS seem capable of reducing patient positioning errors for the hip measurement. Its use is likely to improve confidence in hip bone mineral density measurements.