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Hormonal regulation of calcium homeostasis in two breeds of dogs during growth at different rates¹

M. A. Tryfonidou^*,2, M. S. Holl^*, M. Vastenburg, M. A. Oosterlaken-Dijksterhuis^*, D. H. Birkenhäger-Frenkel, W. E. van den Brom^* and H. A. W. Hazewinkel^*

^* Department of Clinical Sciences of Companion Animals and and Division of Diagnostic Imaging,Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands; and and Department of Pathology, Erasmus University, Rotterdam, The Netherlands

² Correspondence:
Yalelaan 8 (phone: 31-30-2539411; fax: 31-30-2518126; E-mail:
M.A.Tryfonidou{at}vet.uu.nl).

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]₂D₃) were investigated with the aid of [³H]-1,25(OH)₂D₃ and renal messenger RNA abundance of 1-hydroxylase and 24-hydroxylase. Intestinal, renal, and skeletal Ca handling were evaluated with the aid of ⁴⁵Ca 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)₂D₃ concentrations due to decreased (P < 0.01) clearance rather than increased production of 1,25(OH)₂D₃, and decreased (P < 0.01) plasma 24,25-dihydroxycholecalciferol (24,25[OH]₂D₃) concentrations likely due to competitive inhibition of the production of 24,25(OH)₂D₃. 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_i) compared with MP, resulting in greater (P < 0.01) P_i retention and greater (P < 0.01) plasma P_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)₂D₃ 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