Biological variability in serum and urinary indices of bone formation and resorption in dogs

Serum and urinary assays of bone markers provide a noninvasive alternative to bone biopsy in the study of bone metabolism in humans. Many of the commercial assays that were originally developed for use in humans have been shown to cross-react in dogs, and it should therefore be possible to use these assays to study bone remodeling in dogs. The interpretation of bone marker data in humans is hampered by extensive inter- and intra-subject variability. The specific aim of this study was therefore to determine the extent of biological variability in bone markers in dogs. Serum and urine samples were collected every 4 hours over a 24-hour period (short-term study), and every week over a 12-week period (long-term study). Serum bone-specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (Dpd) and N-terminal telopeptide of collagen (NTx) were measured with commercial enzyme immunoassays. Serum osteocalcin (OC) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP) were measured with commercial radioimmunoassays. In the short-term study, statistically significant diurnal rhythms were identified for OC, BALP, ICTP, and Dpd. No clear rhythm was evident for NTx. There was no evidence of statistically significant long-term variability in marker excretion over the 12 weeks. Our findings confirm the utility of these assays in dogs. However, as in humans, care must be taken to ensure that specimens are collected at a consistent time of day. Moreover, given the inherent variability in marker excretion in individual animals, the most appropriate use for these assays is as a screening tool for cohort studies, rather than as a diagnostic or prognostic tool in the individual animal.