Original articleEffect of feeding on bone turnover markers and its impact on biological variability of measurements
Introduction
Biochemical markers of bone turnover may be of value to predict the rate of bone loss and the risk of osteoporotic fracture and to monitor treatment response in metabolic bone diseases, particularly osteoporosis.11 Bone turnover markers are subject to biological variability, which may influence clinical interpretation. These factors include the effects of circadian rhythms, dietary calcium intake, growth, aging, sex hormone status, gender, and for urine-based markers the requirement to correct for urine dilution using creatinine concentration.13 Day-to-day variability (coefficient of variation [CV]) levels of 5%–13% for formation markers and 6%–34% for resorption markers have been observed under clinical research conditions in several studies.13 In clinical practice, it is important to minimize the impact of different sources of biological variability.11
There is increasing evidence that a variety of dietary factors may result in acute changes in bone turnover. This is a source of biological variability, although the potential importance of acute changes in dietary intake has never been systematically examined. Thus, calcium supplements may suppress resorption within a few hours5 and recent studies have shown that acute ingestion of glucose may decrease bone resorption.3, 4 Other dietary components may induce analytical artifacts; for example, dietary intake of gelatine may increase excretion of hydroxyproline, but not urinary pyridinolines.9 In addition, the circadian rhythm of bone turnover is attenuated by food intake throughout the 24 h cycle.7, 21
Standardization of dietary intake prior to sampling could improve the performance of these measurements in clinical practice. First, standardization of sampling conditions could reduce measurement variability. Although it has been suggested11 that all markers of bone turnover should be assessed in the fasting state, there is as yet little evidence to support this assertion. Second, recent dietary intake may influence the reference range.
The aims of this study were to determine the effect of fasting or feeding on: (1) the concentration of markers of bone turnover; (2) analytical and within-subject variability; and (3) the clinical interpretation of results. A wide spectrum of analytes are examined to establish if changes in diet represent an important feature of biological variability for commercial assays currently available for use in research and clinical practice.
Section snippets
Subjects
Twenty healthy premenopausal women (mean age of 33 years, range 21–45 years) were recruited from the staff at the Northern General Hospital, Sheffield. All participants completed a lifestyle, general health, and osteoporosis risk factor questionnaire. Women were excluded if they had any disease known to affect bone metabolism, had sustained a fracture during the preceding 12 months, or were taking any medication known to affect bone metabolism apart from an oral contraceptive (n = 9). Four
Results
All bone formation and resorption markers were significantly lower in the fed state (Table 1) with the exception of bone ALP. Mean percentage differences between the fasting and fed state for individual subjects are shown in (Figure 2). The magnitude of the decrease with feeding ranged from 3.8 ± 0.9% for PINP (p < 0.0001) to 17.8 ± 2.6% (p < 0.0001) for sβCTX. The decrease was observed for both serum markers (range 3.8%–17.8%) and urine markers (range 7.0%–7.9%). The decrease in formation
Discussion
There is increasing evidence that food intake may result in acute changes in bone turnover. A marked circadian rhythm has been observed for bone turnover markers.15, 22 Fasting attenuated the circadian rhythm observed for sCTX and uCTX, but not for OC, which suggests dietary changes may partially contribute to the circadian rhythm.7, 21 Nonfasting samples have frequently been collected during clinical studies,2, 11, 19, 27 but the importance of feeding for different markers remains unknown. The
Acknowledgements
The authors thank all the volunteers from the Osteoporosis Centre and the Department of Orthopaedics for participating in the study. We also thank Debbie Swindell, Joanne Li, and Alison Eagleton for their assistance. Roche Diagnostics, Penzberg, Germany, provided an unrestricted grant toward the cost of the bone turnover markers assays.
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