Significant differences in UK and US female bone density reference ranges

Abstract

In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic (-2.5<T-score<-1.0) and osteoporotic (T-score<-2.5) arms of the study. The comparison with data from two independent studies showed that UK women aged >45 years with a typical body mass index of 28 kg m(-2) have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p<0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg(-1). In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment.