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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.

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SUMMARY We have performed a double‐blind placebo controlled study of 1α‐hydroxyvita‐min D3 (1α‐(OH)D3) 2 μg daily for 6 months, in 14 patients receiving long‐term glucocorticoid treatment. Patients were matched for age, sex, underlying disease and dose of glucocorticoid. Initial values for serum calcium, phosphorus and alkaline phosphatase were in the normal range. Two of the 14 patients showed an increased serum immunoreactive parathyroid hormone (iPTH) concentration. Serum 25‐hyd‐roxyvitamin D and 1,25‐dihydroxyvitamin D (l,25‐(OH)2D) were normal but the average 24,25‐dihydroxyvitamin D (24,25‐(OH)2D) was low. The histomorphometrically determined trabecular bone volume of an iliac crest biopsy appeared to be low in 6 patients. The average active bone resorption and osteoid seams were increased, while the average osteoblast seams were within the normal range. Treatment with 1α‐(OH)D3 raised 47Ca2+ intestinal absorption and 24 h urinary Ca2+ excretion significantly at 3 and 6 months and at 6 months serum iPTH concentration and 24 h urinary hydroxyproline excretion had fallen significantly in the treated group. During treatment with 1α‐(OH)D3 the serum 1,25‐(OH)2D and 24,25‐(OH)2D levels increased significantly. In all cases of the 1α‐(OH)D3‐group, the second bone biopsy, taken at the end of the treatment period, showed a decrease of active resorption and a more positive course of trabecular bone volume than the biopsy of the placebo‐treated counterpart: trabecular bone volume remained constant or even increased in the 1α‐(OH)D3‐group. In both groups osteoid seams and osteoblast seams did not change significantly. We conclude that treatment with 1α‐(OH)D3 during 6 months inhibits the increased bone resorption seen in glucocorticoid‐induced bone disease, while bone formation is not suppressed by this therapy.

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A staining method is described using thionin, for undecalcified deacrylated bone sections. RNA is stained purplish violet, allowing still active osteoblasts to be distinguished from lining cells. Staining intensity of mineralized bone is related to the degree of mineralization. Mineralizing fronts and cement lines are visualized clearly. Lamellae show an alternate pattern. Histomorphometric parameters such as osteon thickness and interstitial bone thickness can be measured without using polarized light. The mineralizing front can be assessed and expressed as a percentage of the osteoblast-covered interface between osteoid and mineralized bone. The stain is also useful for qualitative assessment of metabolic bone disease. Thionin stained sections can be kept for at least one year when stored in the dark at 7 C.

The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms orally, twice weekly) (Group B). Histomorphometry was performed at T0, T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.