Biological Variability in Serum and Urinary Indices of Bone Formation and Resorption in Dogs

Abstract

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.

Tartrate-resistant acid phosphatase as a biomarker of bone turnover in dog

“…Moreover, the high rate of interindividual variation found for the serum tALP activity was similar to previously data published for the dog (Allen et al, 2000;Kaneko et al, 2008). Additionally, the intra-and interindividual variations found for TRAP was similar to that found for other resorption biomarkers for this species such as ICTP in the study of Ladlow et al (2002), and similar to that found in humans in the study of Panteghini and Pagani (1995). In accordance with results obtained in studies published for man concerning the activity of the two enzymatic parameters studied in the present work, the inter-individual variability was higher than the intra-individual variation.…”

“…However, if the biological variability of a marker is high, the variability of the analytical test is not as restrictive. For a potential clinical application, it has been suggested that the variability of the analytical test to measure a specific biochemical marker should be less than or equal to half of the underlying biological variability for that parameter within the study population (Ladlow et al, 2002;Allen, 2003). The main limitation for clinical application of these parameters has been related to the difficulty in the interpretation of the individual results due to the high biological variability associated with factors like age; gender; nutrition; exercise; systemic disease; and circadian, day-to-day, and seasonal rhythms (Ladlow et al, 2002).…”

“…Furthermore, bone-derived biomarkers have also been proposed by some researchers to assess the process of bone fracture healing. In fact, several parameters seem to be suitable for reflecting the bone healing process allowing differentiation between normal and delayed or non-union processes of fracture healing (Joerring et al, 1992;Kurdy, 2000;Laurer et al, 2000;Herrmann et al, 2002;Komenou et al, 2005). Some parameters have also been presented as an aid in osteomyelitis diagnosis after osteosynthesis (Philipov et al, 1995;Southwood et al, 2003).…”

Measurement of serum carboxyterminal cross-linked telopeptide of type I collagen concentration in dogs with osteosarcoma

“…There have been several studies 8,9,[29][30][31]36,37 that examined the concentration of ICTP in clinically normal dogs or in dogs with pathologic conditions such as periodontal disease and osteomyelitis. The results of our study indicated that the mean serum ICTP concentration in dogs with osteosarcoma was not significantly increased, compared with that of clinically normal dogs.…”

“…Osteosarcomas that form in the axial skeletal regions (ie, axial osteosarcoma) are commonly treated with surgical removal with or without adjuvant radiation therapy or chemotherapy for incompletely removed lesions. [24][25][26][27][28] There are several reports 8,9,[29][30][31][32][33][34][35][36][37] in the veterinary literature regarding evaluation of various markers of bone activity and reports of markers of bone metabolism for specific diseases.…”