title: Hormonal regulation of calcium homeostasis in two breeds of dogs during growth at different rates.
abstract: 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 alpha-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 (Pi) compared with MP, resulting in greater (P < 0.01) Pi retention and greater (P < 0.01) plasma Pi 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.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands. M.A.Tryfonidou@vet.uu.nl
authors.forename: M A
authors.initials: MA
authors.lastname: Tryfonidou
authors.forename: M S
authors.initials: MS
authors.lastname: Holl
authors.forename: M
authors.initials: M
authors.lastname: Vastenburg
authors.forename: M A
authors.initials: MA
authors.lastname: Oosterlaken-Dijksterhuis
authors.forename: D H
authors.initials: DH
authors.lastname: Birkenhäger-Frenkel
authors.forename: W E
authors.initials: WE
authors.lastname: van den Brom
authors.forename: H A W
authors.initials: HA
authors.lastname: Hazewinkel
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002136:Calcium, Dietary / Q000008:administration & dosage*; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D004285:Dogs / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D010758:Phosphorus / Q000378:metabolism / Q000493:pharmacokinetics; D011859:Radiography
chemical_list: D002136:Calcium, Dietary; D004100:Dihydroxycholecalciferols; D010758:Phosphorus; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002118:Calcium