Hormonal regulation of calcium homeostasis in two breeds of dogs during growth at different rates

Growing giant-breed dogs are more susceptible to developing skeletal disorders than small-breed dogs when raised on diets with deficient or excessive Ca content. Differential hormonal regulation of Ca homeostasis in dogs with different growth rates was investigated in Great Danes (GD, n = 9) and Miniature Poodles (MP, n = 8). All animals were raised on the same balanced diet and under identical conditions. Calciotropic and growth-regulating hormones were measured. Production and clearance of 1,25-dihydroxycholecalciferol (1,25[[OH].sub.2][D.sub.3]) were investigated with the aid of [[sup.3]H]-1,25[(OH).sub.2][D.sub.3] and renal messenger RNA abundance of 1[alpha]-hydroxylase and 24-hydroxylase. Intestinal, renal, and skeletal Ca handling were evaluated with the aid of [sup.45]Ca balance studies. Skeletal development was evaluated by radiology and histomorphometry. Great Danes had greater (P < 0.001) growth rates than MP, as indicated by the 17-fold greater body weight gain, by increased longitudinal growth reflected in the increased (P < 0.05) gain in length of the radius and ulna, and by increased (P < 0.001) growth plate thickness. These findings were accompanied in GD by greater (P < 0.05) plasma GH and IGF-I concentrations. Effects were observed for vitamin D3 metabolism, such as greater (P < 0.01) plasma 1,25[(OH).sub.2][D.sub.3] concentrations due to decreased (P < 0.01) clearance rather than increased production of 1,25[(OH).sub.2][D.sub.3], and decreased (P < 0.01) plasma 24,25-dihydroxycholecalciferol (24,25[[OH].sub.2][D.sub.3]) concentrations likely due to competitive inhibition of the production of 24,25[(OH).sub.2][D.sub.3]. These findings were accompanied in both breeds by a limited hormonal regulation of Ca and P absorption at the intestinal level, and in GD by increased (P < 0.05) renal reabsorption of inorganic P ([P.sub.i]) compared with MP, resulting in greater (P < 0.01) [P.sub.i] retention and greater (P < 0.01) plasma [P.sub.i] concentrations. Bone turnover, resorption, and formation were greater (P < 0.01) in GD than in MP. In addition, GD had more irregular (P < 0.01) growth plates than MP, accompanied by disorders of endochondral ossification. It is suggested that in GD, increased calcitonin levels and/or a relative deficiency in 24,25[(OH).sub.2][D.sub.3] at the growth-plate level may both be responsible for the retarded maturation of chondrocytes, resulting in retained cartilage cones and osteochondrosis, and this may be a pathophysiological factor for the increased susceptibility of large breed dogs to developing skeletal disorders. Key Words: Absorption, Bones, Calcium, Cholecalciferol, Dogs, Somatotropin