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Byline: A. M. Schott (1,2), B. Kassai Koupai (2), D. Hans (1,4), P. Dargent-Molina (5), R. Ecochard (3), D. C. Bauer (1,6), G. Breart (5), P. J. Meunier (1) Keywords: Aging; Bone mineral density; Hip fracture; Osteoporosis; Quantitative ultrasound Abstract: In a prospective cohort of 7,598 women aged 75 and over, we analyzed the effect of age on the ability of femoral neck bone mineral density (BMD) and of ultrasound (BUA and SOS) of the calcaneus to predict hip fracture. Unadjusted regression analysis showed that the risk of hip fracture was increased 1.7 times for one standard deviation increase in age (3.7 years). Overall, for a decrease of one standard deviation in quantitative bone measures, the risk was significantly increased by 2.2 times for BMD (1.9--2.5), 1.8 for BUA (1.6--2.1), and 1.9 for SOS (1.6--2.2). However the average relative risk associated with a decrease in BMD tends to diminish with advancing age, meaning that a smaller part of the risk is explained by BMD in the very elderly. This is confirmed by the areas under the ROC curves (AUC) of BMD that are significantly better before 80 years (0.75 [0.73--0.76]) than after (0.65 [0.63--0.67] in group 80--84 years and 0.65 [0.61--0.68] in group aY=85). On the other hand, as the absolute risk increases exponentially with age, the number of hip fractures attributable to a low BMD is still important in the very elderly, the risk difference between the lowest and the highest quartile of BMD is 25 hip fractures / 1,000 woman-years in the group aY=85 compared with 16 in the two other groups. Thus, after 80, quantitative assessment of bone may still be of interest for clinical decisions. Compared with quantitative ultrasound parameters, the ability of BMD to predict hip fracture was significantly superior to that of BUA and SOS only before the age of 80 (AUC of BMD 0.75 [0.73--0.76], BUA 0.67 [0.66--0.69], SOS 0.67 [0.65--0.69]). For patients older than 80, we did not observe significant differences in AUC between DXA and QUS to predict hip fracture. Author Affiliation: (1) INSERM U 403, Hopital Edouard Herriot, 5 place d'Arsonval, Cedex 03, 69437, Lyon, France (2) Departement d'Information Medicale des Hospices Civils de Lyon, 162 avenue Lacassagne, Cedex 03, 69424, Lyon, France (3) Departement de Biostatistiques, 162 avenue Lacassagne, Cedex 03, 69424, Lyon, France (4) Nuclear Medicine Division, Geneva University Hospital, Geneva, Switzerland (5) INSERM U 149, Hopital Paul Brousse, 12 avenue Paul Vaillant-Couturier, 94800, Villejuif, France (6) Epidemiology Department, University of California San Francisco, San Francisco, California, USA Article History: Registration Date: 01/01/2003 Received Date: 29/07/2002 Accepted Date: 14/08/2003 Online Date: 17/01/2004 Article note: The named authors wrote this article on behalf of the EPIDOS Study Group. Coordinators: G. Breart and P. Dargent-Molina (epidemiology), P.J. Meunier and A.M. Schott (clinical aspects), D. Hans (DXA and ultrasound quality control), P.D. Delmas (biochemistry). Principal investigators: J.L. Sebert and C. Baudoin (Amiens), A.M. Schott and M.C. Chapuy (Lyon), C. Marcelli and F. Favier (Montpellier), C.J. Menkes, C. Cormier, and E. Hausherr (Paris), and H. Grandjean and C. Ribot (Toulouse).

Byline: P. Dargent-Molina (1), S. Piault (1), G. Breart (1) Keywords: Hip fracture; Osteodensitometry; Osteoporosis; Risk factors; Screening; Ultrasound Abstract: Decision to treat with an anti-osteoporotic drug should be based on individual fracture risk evaluation. We compared the discriminant value of four different screening strategies to identify elderly women with a risk of hip fracture greater than 20 per 1000 woman-years: (1) BMD screening alone, (2) quantitative ultrasound (QUS) screening alone, (3) QUS triage followed by BMD assessment for women with medium-low QUS parameters, and (4) selective BMD screening based on weight followed by clinical evaluation for women with medium-low BMD. The study population included 5910 women aged 75 years or older who participated to the EPIDOS (Epidemiologie de l'Osteoporose) prospective study. Over an average of 3.7 (+-0.8) years of follow-up, 231 women suffered a hip fracture, which corresponds to an average risk of 10.6 per 1000 woman-years. All strategies allow us to clearly distinguish a group at high risk of hip fracture (i.e. &gt 20 per 1000 woman-years) from a group at low risk (i.e. below the average risk in the cohort). QUS screening alone has a very low sensitivity (15%). The strategy using QUS as a method of triage and that combining selective BMD and clinical assessment have a sensitivity equivalent to systematic BMD screening (around 35%), with less than 50% BMD examinations. The high-risk women identified by these two strategies are not the same. A simple algorithm combining QUS, BMD, and clinical risk assessment allows an increased number of high-risk women to be identified (21%), and thus improves the sensitivity (53%). With this combined strategy, women in the high-risk group have one chance in ten of having a hip fracture over the next 4 years, whereas women in the low risk group have only one chance in 40. Author Affiliation: (1) INSERM (Institut National de la Sante et de la Recherche Medicale), 16 avenue Paul Vaillant-Couturier, Unite 149, 94 807, Villejuif Cedex, France Article History: Received Date: 27/03/2003 Accepted Date: 19/08/2003 Online Date: 30/09/2003 Article note: Members of the EPIDOS Study Group: Coordinators: G. Breart, P. Dargent-Molina(epidemiology), P.J. Meunier, A.M. Schott (clinical aspects), D. Hans (bone densitometry and ultrasound quality control), P.D. Delmas (biochemistry). Principal investigators (center): C. Baudoin, J.L. Sebert (Amiens) M.C. Chapuy, A.M. Schott (Lyon) F. Favier, C. Marcelli (Montpellier) E. Hausherr, C.J. Menkes, C. Cormier (Paris) H. Grandjean, C. Ribot (Toulouse)

Byline: P. Dargent-Molina (1), M. N. Douchin (1), C. Cormier (2), P. J. Meunier (3), G. Breart for the EPIDOS study group* (1) Keywords: Key words:Elderly -- Hip fracture -- Screening Abstract: Elderly women with very low bone mineral density (BMD) (T-score a$?-3.5) have a risk of hip fracture more than two times higher than the average risk of women of the same age. Using data from the EPIDOS prospective study, we have shown that by measuring BMD on the 50% of women who have the lowest weight, it is possible to identify the majority of these women at higher risk. In the present analysis, we assessed whether the use of clinical risk factors, in the subset of women selected for osteodensitometry and with moderately low BMD (T-score between -3.5 and -2.5), allows the identification of another subgroup of women with a risk 2 times higher than average and, thereby, increases the efficiency of selective BMD screening. We then assessed the discriminant value for hip fracture of the overall screening strategy (i.e., use of weight to select women for osteodensitometry, then use of clinical risk factors to enhance the predictive value of BMD), and compared it with the value of BMD used as a population screening tool. In total, 6933 EPIDOS participants, aged 75 years or above, were included in this analysis. Using Cox regression models, we first determined which baseline factors were most predictive of hip fracture among the 1588 women with weight below median (selection criteria for osteodensitometry in the proposed strategy) and T-score between -3.5 and -2.5. Based on the relative risk (RR) estimates from the final risk function, we calculated an individual risk score for hip fracture. We assessed the incidence of hip fracture for each value of the score, and determined the cutoff to identify women with a risk about 2 times higher than the average risk in this elderly cohort. The overall screening strategy (i.e., selective BMD measurement based on weight, followed by clinical fracture risk assessment) identifies two subgroups of higher risk women: a group with very low BMD (T-score a$?--3.5), and another group with moderately low BMD (T-score between --3.5 and --2.5) but a high fracture risk score. We calculated the total number of women classified as being at high risk, and assessed the overall sensitivity and specificity of this strategy to identify elderly women who will suffer a hip fracture. Among women with weight below median and T-score between -3.5 and -2.5, the factors most predictive of the risk of hip fracture were age, history of fall, ability to do the tandem walk (test of dynamic balance), gait speed and visual acuity. A simple additive score based on these factors (except visual acuity) allows a high-risk group (risk about 2 times higher than average) to be clearly distinguished from a low-risk group (risk below average). Overall, the proposed strategy identifies approximately 15% of the women in the cohort as being at high risk, i.e., 543 women with T-score a$?-3.5 and 503 women with -3.5 &lt T-score a$?-2.5 and a high fracture risk score. The sensitivity for hip fracture is equal to 37% and the specificity to 85%, which is equivalent to the discriminant value of BMD as a population screening tool. In elderly women, the use of a simple clinical risk score, in women with previous BMD values, allows the number of high-risk women identified to be increased. Overall, the proposed screening strategy (use of weight to select women for osteodensitometry, and then use of clinical risk factors to enhance the predictive value of BMD) has the same discriminant value for hip fracture as BMD used as a population screening tool. Author Affiliation: (1) INSERM Unite 149, Villejuif, FR (2) Service de Rhumatologie A, CHU Cochin, Paris , FR (3) Service de Rhumatologie et de Pathologie Osseuse, Hopital E. Herriot, Lyon, France, FR Article note: Received: 20 November 2001 / Accepted: 11 February 2002

Byline: D. M. Black (1), M. Steinbuch (2), L. Palermo (1), P. Dargent-Molina (3), R. Lindsay (4), M. S. Hoseyni (2), O. Johnell (5) Keywords: Key words:Bone mineral density -- Fracture risk -- Hip fracture -- Osteoporosis -- Postmenopausal women -- Risk assessment Abstract: Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women. Author Affiliation: (1) University of California, San Francisco, CA, USA, US (2) Procter &amp Gamble Pharmaceuticals, Cincinnati, OH, USA, US (3) INSERM Unit 149, Villejuif Cedex, France, FR (4) Helen Hayes Hospital, Regional Bone Center, West Haverstraw, NY, USA, US (5) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden, SE Article note: Received: 7 November 2000 / Accepted: 23 May 2001

Byline: P. Dargent-Molina (1), F. Poitiers (1), G. Breart (1) Keywords: Key words:Bone densitometry -- Elderly women -- Osteoporosis -- Screening Abstract: Currently, few elderly women have a measurement of bone mineral density (BMD). The aim of this study was to assess the potential value of a two-step screening process to identify the elderly women who are at greatest risk of fracture because of very low BMD: (1) use simple clinical criteria to select women who are highly likely to have a very low BMD and (2) measure the BMD of the women so selected. We used baseline data from 6958 women aged 75 years or older who were participants in the EPIDOS prospective study of risk factors for hip fracture. The outcome variable was very low BMD measured at the femoral neck by dual-energy X-ray absorptiometry and defined as a T-score a$?-3.5. The factors most predictive of very low BMD were low weight, history of fracture after the age of 50 years, slow gait, balance impairment, low grip strength, and dependence for instrumental activities of daily living. A score based on the risk function including these factors has a sensitivity of 80% at the median cut-off. Hence, by measuring the BMD of only half the population, 80% of the women with very low BMD can be identified. Weight is the strongest determinant of very low BMD and has approximately the same sensitivity as the complete score. In conclusion, a risk score for very low BMD based on simple criteria such as weight could be a useful clinical tool to select elderly women for bone densitometry. Author Affiliation: (1) INSERM UniteA' 149, Villejuif, France, FR Article note: Received: 13 July 1999 / Accepted: 19 April 2000

Byline: P. Dargent-Molina (1), A. M. Schott (2), D. Hans (2), F. Favier (3), H. Grandjean (4), C. Baudoin (5), P. J. Meunier (2), G. Breart (1) Keywords: Key words:Elderly -- Hip fracture -- Osteodensitometry -- Osteoporosis -- Screening -- Ultrasound 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. Author Affiliation: (1) INSERM Unit 149, Villejuif, FR (2) INSERM Unit 403, Hopital E. Herriot, Lyon, FR (3) INSERM Unit 500, Montpellier, FR (4) INSERM CJF 94-06, Toulouse , FR (5) INSERM Unit 21, Villejuif, France, FR Article note: Received: 13 April 1998 / Accepted: 23 May 1998

Byline: P. Garnero (1), P. Dargent-Molina (2), D. Hans (1), A. M. Schott (1), G. Breart (2), P. J. Meunier (1), P. D. Delmas (1) Keywords: Key words:Bone markers -- DXA -- Hip fracture -- Osteoporosis -- Risk factors -- Ultrasound 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. Author Affiliation: (1) INSERM Unit 403, Hopital E. Herriot, Lyon, France , FR (2) INSERM Unit 149, Villejuif, France, FR Article note: Received: 24 November 1997 / Revised: 3 March 1998

Byline: A. M. Schott (1), C. Cormier (2), D. Hans (1), F. Favier (3), E. Hausherr (4), P. Dargent-Molina (4), P. D. Delmas (1), C. Ribot (5), J. L. Sebert (6), G. Breart (4), P. J. Meunier (1) Keywords: Key words: Aging -- Bone mineral density -- Hip fracture -- Osteoporosis -- 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/cm.sup.2) of the proximal femur (neck, trochanter and Ward's 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 Ward's 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 Ward's 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. Author Affiliation: (1) INSERM U 403, Hopital Edouard Herriot, Lyon, FR (2) Service de Rhumatologie, Hopital Cochin, Paris, FR (3) INSERM CJF 93-06, Montpellier, FR (4) INSERM U149, Villejuif, FR (5) Service d'Endocrinologie, Hopital Purpan, Toulouse, FR (6) Service de Rhumatologie, Hopital Nord, Amiens, France., FR Article note: Received: 19 May 1997 / Accepted: 16 October 1997

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society, in collaboration with the International Association of Gerontology and Geriatrics for the European Region, the European Union of Medical Specialists, and the International Osteoporosis Foundation-European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.