Calcaneal Ultrasound but Not Bone Turnover Predicts Fractures in Vitamin D Deficient Frail Elderly at High Risk of Falls J. S. Chen, 1 M. J. Seibel, 2 J. Zochling, 1 L. March, 1 I. D. Cameron, 3 R. G. Cumming, 2,4 J. Schwarz, 1 J. M . Simpson, 4 P. N. Sambrook 1 1 Institute of Bone & Joint Research, University of Sydney, Sydney, Australia 2 ANZAC Research Institute, University of Sydney, Sydney, Australia 3 Rehabilitation Studies Unit, University of Sydney, Sydney, Australia 4 School of Public Health, University of Sydney, Sydney, Australia Received: 28 November 2005 / Accepted: 8 April 2006 / Online publication: 24 July 2006 Abstract Background: Biochemical markers of bone turnover have been reported to predict fracture risk independent of bone mass in postmenopausal women. We investi- gated their use in predicting fractures in the frail elderly. Methods: Cases were 151 low trauma fractures. For each case, a control was selected marched for sex, age, insti- tutiontypeandfollow-upperiod.Wemeasuredtwobone resorption markers (serum ICTP and serum CTX-I) and two bone formation markers (serum PINP and serum BAP). Quantitative Ultrasound (QUS) was measured in the calcaneus. Fractures were ascertained by x-ray re- ports. Results: The mean age of subjects was 86.8 years (± 5.8 SD)and86% werefemale.76% hadhypovitaminosisD(a serum 25 hydroxy vitamin D (25OHD) level < 39 nmol/ L)and81% hadBUA<67.4dB/MHz (correspondingto a BMD T-score < )2.5). No significant differences in bone turnover markers were detected between fracture cases and their matched controls. In contrast, there was a significant difference between cases and controls for both broadband ultrasound attenuation (BUA) and velocity of sound (VOS) (both P < 0.05). These results remained the same after adjusting for weight, lower leg length and walking aids as well as the higher falls incidence in cases than controls (average 2.7 vs 0.9 falls respectively; P < 0.001) during the follow-up period. Conclusion: In the frail elderly with vitamin D deficiency and high falls risk, calcaneal ultrasound but not markers of bone turnover were associated with fractures. Key words: Bone formation markers — Bone resorp- tion markers — Elderly — Fractures — Osteoporosis — Quantitative ultrasound Accurate assessment of fracture risk is the key step in identifying patients at ‘‘high risk’’ for osteoporosis. It is increasingly recognised that besides bone mineral den- sity (BMD), other bone related variables, such as the rate of bone turnover, determine fracture susceptibility. In this context, it has been hypothesised that accelerated bone remodelling leads to a disruption of the trabecular bone network over time and, hence, to an increase in bone fragility. Several independent studies have shown that in wo- men and men, elevated levels of bone resorption mark- ers are associated with an increased risk of vertebral and non-vertebral fractures independently of BMD [1À8]. For example, a rise in urinary deoxypyridinoline (a marker of bone resorption) by one standard deviation above the premenopausal mean has been associated with a two fold increase in hip fracture risk [1, 2, 8]. Impor- tantly, the combined measurement of bone density and bone resorption markers is a stronger predictor of future fractures than the determination of one of these vari- ables alone [2, 6]. Due to the high degree of variability in bone markers, these results are difficult to translate into the clinical setting facing the individual patient. There- fore, risk factors such as personal and maternal fracture history, low body weight and low bone mass are pres- ently considered more feasible for the practical assess- ment of fracture risk than bone markers. However, if assessment of these risk factors gives equivocal results, measurement of bone turnover may be used to improve the estimate of future fracture risk. Since vitamin D deficiency and the resulting second- ary hyperparathyroidism are associated with distur- bances of bone turnover, we examined whether the association of markers of bone turnover with incident fracture was altered in a population of predominantly vitamin D deficient elderly subjects. Methods Subjects This paper reports a case-control study of 151 pairs of older people living in residential care facilities (RCF). The partici- Correspondence to: P. N. Sambrook, Institute of Bone and Joint Research, Royal North Shore Hospital, St Leonards NSW 2065, Australia; E-mail: sambrook@med.usyd.edu.au Calcif Tissue Int (2006) 79:37À42 DOI: 10.1007/s00223-005-0287-1