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      Subgroup Variations in Bone Mineral Density Response to Zoledronic Acid After Hip Fracture

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          Abstract

          Minimizing post-fracture bone loss is an important aspect of recovery from hip fracture, and determination of factors that affect bone mineral density (BMD) response to treatment after hip fracture may assist in the development of targeted therapeutic interventions. A post hoc analysis of the HORIZON Recurrent Fracture Trial was done to determine the effect of zoledronic acid (ZOL) on total hip (TH) and femoral neck (FN) BMD in subgroups with low-trauma hip fracture. A total of 2127 patients were randomized (1:1) to yearly infusions of ZOL 5 mg ( n = 1065) or placebo ( n = 1062) within 90 days of operation for low-trauma hip fracture. The 1486 patients with a baseline and at least one post-baseline BMD assessment at TH or FN (ZOL = 745, placebo = 741) were included in the analyses. Percentage change from baseline in TH and FN BMD was assessed at months 12 and 24 and compared across subgroups of hip fracture patients. Percentage change from baseline in TH and FN BMD at months 12 and 24 was greater ( p < 0.05) in ZOL-treated patients compared with placebo in most subgroups. Treatment-by-subgroup interactions ( p < 0.05) indicated that a greater effect on BMD was observed for TH BMD at month 12 in females, in patients in the lower tertile body mass index at baseline (≤22.6 kg/m 2), and in patients with baseline FN BMD T-score of ≤ –2.5; for FN BMD in patients who received ZOL for >6 weeks post-surgery; and for TH and FN BMD in patients with a history of one or more prior fractures. All interactions were limited to the first 12 months after treatment with none observed for the 24-month comparisons. (Clinical trial registration number NCT00046254.)

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          EuroQol: the current state of play.

          R. Brooks (1996)
          The EuroQol Group first met in 1987 to test the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. From the outset the Group has been multi-country, multi-centre, and multi-disciplinary. The EuroQol instrument is intended to complement other forms of quality of life measures, and it has been purposefully developed to generate a cardinal index of health, thus giving it considerable potential for use in economic evaluation. Considerable effort has been invested by the Group in the development and valuation aspects of health status measurement. Earlier work was reported upon in 1990; this paper is a second 'corporate' effort detailing subsequent developments. The concepts underlying the EuroQol framework are explored with particular reference to the generic nature of the instrument. The valuation task is reviewed and some evidence on the methodological requirements for measurement is presented. A number of special issues of considerable interest and concern to the Group are discussed: the modelling of data, the duration of health states and the problems surrounding the state 'dead'. An outline of some of the applications of the EuroQol instrument is presented and a brief commentary on the Group's ongoing programme of work concludes the paper.
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            Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

            To determine the ability of measurements of bone density in women to predict later fractures. Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Eleven separate study populations with about 90,000 person years of observation time and over 2000 fractures. Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density.
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              Osteoporosis: impact on health and economics.

              Osteoporosis is a major public health problem through associated fragility fractures. The most common sites of fracture are the hip, spine and wrist, and these have an enormous health and economic impact. All fractures result in some degree of morbidity, but fractures at the hip are associated with the worst outcomes. The worldwide direct and indirect annual costs of hip fracture in 1990 were estimated at US$34.8 billion, and are expected to increase substantially over the next 50 years. Fracture incidence varies between populations, and is set to increase over coming decades as the global population becomes more elderly. This effect will be particularly marked in the developing world, which is additionally assuming more-westernized lifestyles that predispose to increased fracture risk. Strategies to target those at high risk of fracture have been developed, but preventative measures at the public health level are also urgently needed to reduce the burden of this devastating disease.
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                Author and article information

                Journal
                J Bone Miner Res
                J. Bone Miner. Res
                jbmr
                Journal of Bone and Mineral Research
                BlackWell Publishing Ltd (Oxford, UK )
                0884-0431
                1523-4681
                December 2014
                12 December 2014
                : 29
                : 12
                : 2545-2551
                Affiliations
                [1 ]University of Maryland Baltimore, MD, USA
                [2 ]Duke University Medical Center and the Geriatrics Research Education and Clinical Center, Veterans Affairs Medical Center Durham, NC, USA
                [3 ]Oslo University Hospital, University of Oslo Oslo, Norway
                [4 ]University of Leuven Leuven, Belgium
                [5 ]St. Joseph's Healthcare, McMaster University Hamilton, ON, Canada
                [6 ]United Osteoporosis Centers Gainesville, GA, USA
                [7 ]Novartis Pharmaceuticals Corporation East Hanover, NJ, USA
                Author notes
                Address correspondence to: Jay S Magaziner, PhD, MSHyg, Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Howard Hall, Suite 200, 660 West Redwood Street, Baltimore, MD 21201, USA. E-mail: jmagazin@ 123456epi.umaryland.edu
                Article
                10.1002/jbmr.2283
                4307640
                24839241
                f4d3e2ce-f60f-4808-9b53-e734e54f0192
                © 2014 American Society for Bone and Mineral Research
                History
                : 28 January 2014
                : 02 May 2014
                : 05 May 2014
                Categories
                Original Articles

                Human biology
                clinical trials,osteoporosis,injury/fracture healing,fracture prevention,antiresorptives

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