Biochemical markers of bone metabolism in growing thoroughbreds: a longitudinal study J. S. PRICE*, B. F. JACKSON, J. A. GRAY y , P. A. HARRIS z , I. M. WRIGHT x , D. U. PFEIFFER, S. P. ROBINS { , R. EASTELL**, S. W. RICKETTS yy Department of Veterinary Basic Science, The Royal Veterinary College, London NW1 OTU, UK, y University of Newcastle, Newcastle upon Tyne NE2 4HH, z Equine Studies Group, Waltham Centre for Animal Nutrition, Waltham-on-the Wolds, Leics, LE144RS, x Greenwood Ellis & Partners, Newmarket, Suffolk CB8 9AQ, { Rowett Research Institute, Aberdeen AB21 9SB, **Bone Metabolism Group, University of Sheffield, Sheffield S5 7AU, yy Beaufort Cottage Stables, Newmarket, Suffolk CB8 8JS SUMMARY This study describes longitudinal changes in serum levels of biochemical markers of bone cell activity in a group of 24 thor- oughbred foals from birth to 18 months of age. The markers of bone formation included the type I collagen carboxy-terminal propeptide (PICP), the bone-specific isoenzyme of alkaline phosphatase (BAP), and osteocalcin (OC). Levels of the cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and the N-terminal propeptide of type III collagen (PNIIIP), a marker of soft tissue turnover, were also measured. Levels of all markers fell significantly between birth and 18 months of age (70±80 per cent); this decrease being most marked between 0 and 6 months. However, a transient increase in levels of the markers then occurred between 6 and 14 months of age. The timing of this increase was specific for each parameter. ICTP and OC concentrations increased between October and December. PICP concentrations increased between December and April whereas the increase in PIIINP was coincident with the peak in weight gain between April and June. Changes in BAP concentration were less distinct at this time. Season was shown to have significant effects on the biochemical markers independent from the effect of age. Concentrations of all markers decreased with increasing body weight and at any given age heavier horses had lower marker levels. These results show that biochemical markers of bone cell activity and soft tissue turnover follow characteristic patterns of change in growing thoroughbreds influenced by age, season and bodyweight. The demonstration that the reference ranges for the biochemical markers change from month to month means that single samples from individuals are of little value for monitoring bone cell activity in growing thoroughbreds. # 2001 Harcourt Publishers Ltd THE horse skeleton is prone to injury and subject to a number of growth disturbances during development including osteochondrosis, angular limb deformities and cervical vertebral malformation, which are all part of the syndrome of developmental orthopaedic diseases (DOD) (Jeffcott 1991, Hurtig and Pool 1996). Many of these conditions affect foals early in their life, although clinical signs may not be apparent until the yearling stage or until animals begin training. The incidence of lameness related to skeletal growth disorders has increased in recent years and results in significant morbidity and economic loss (O'Donohue et al 1992, Jeffcott 1993, Sandgren et al 1993a and 1993b, Jeffcott and Henson 1998). If the high prevalence of abnormal skeletal develop- ment in young horses is to be reduced, studies are required that will enable the relationship between growth, factors which affect it, and skeletal integrity to be determined. In recent years a number of studies have shown that bone marker measurements can be applied to the study of bone metabolism in horses (Lepage and Tremblay 1990, Hank et al 1993, Davicco et al 1994, Price et al 1995a and 1995b, Jackson et al 1996, Gray 1996, Lepage et al 1997 and 1998, Black et al 1998). In children, biochemical markers have been shown to be sensitive indicators of skeletal health during growth (Trivedi et al 1989 and 1991), and may be useful for assessing children with growth disorders and monitor- ing their response to treatment (Crofton et al 1995, Scariano et al 1995). It would be of great value if pre- dictive biochemical markers could be found to identify young horses which have, or are at increased risk of, abnormal skeletal development. However, before the predictive/diagnostic value of biochemical markers can be established it is neces- sary that serum concentrations in normal horses are documented and how these may be affected by external and internal variables including age, season, time of day. A number of cross-sectional studies have shown that there are age-related decreases in bone turnover in different breeds of horses (Lepage et al 1990, Davicco et al 1994, Price et al 1995a, Black et al 1998). However, no studies have examined in any detail the pattern of change in the markers within the first 2 years of life, and how they may be related to physical measurements of growth. Hence, the objective of the present study was to establish, for the first time, longitudinal changes in Research in Veterinary Science 2001, 71, 37±44 doi:10.1053/rvsc.2001.0482, available online at http://www.idealibrary.com on 0034-5288/01/010037  08 $35.00/0 # 2001 Harcourt Publishers Ltd *Corresponding author: Dr J.S. Price. E-mail: jprice@rvc.ac.uk