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. 1981 Jul;104(1):41–49.

Histomorphometric Evaluation of the Effects of Intermittent 1,25-Dihydroxycholecalciferol Administration on Cortical Bone Remodeling in Adult Dogs

Wanda B High, Charles C Capen, Hugh E Black
PMCID: PMC1903742  PMID: 6894823

Abstract

The effects of intermittent low doses (1.25 μg daily, administered intravenously for 6 days and withdrawn for 14 days for 3 complete cycles) of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) on cortical bone were determined and compared in ribs with steady state and regionally accelerated remodeling in adult intact female dogs. The bone changes were analyzed by dynamic bone histomorphometric methods, using tetracycline and DCAF (2,4 BIS) N, N' di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bones before treatment and after 60 days of intermittent 1,25-(OH)2D3 administration. Serum calcium and phosphorus levels increased during 1,25-(OH)2D3 administration. Urinary hydroxyproline excretion increased during the first interval of 1,25-(OH)2D3 administration but was not changed significantly during the last two intervals. In normal cortical bone (11th rib) following the administration of 1,25-(OH)2D3 there was a marked decrease in the activation frequency, bone formation rate, osteoid seam thickness, seam circumference, and mean appositional rate. Although recruitment of new remodeling sites was decreased after 1,25-(OH)2D3, previously existing remodeling units continued to completion. These effects resulted in a preponderance of mature osteons in normal cortical bone. The morphometric changes in cortical bone (9th rib) exposed to both 1,25-(OH)2D3 and periosteal elevation were characterized by a marked increase in both the activation frequency and bone formation rate and associated with a decrease in the osteon formation time. Other morphometric parameters that were increased included radial closure rate, numbers of osteoid seams and resorption cavities, ratio of bone resorbing to forming sites, percentage labeled and circumference of osteoid seams, and total and cortical bone areas. The combined effect of periosteal elevation and 1,25-(OH)2D3 were markedly different from those observed with 1,25-(OH)2D3 alone. These findings suggest that the rapid bone turnover induced by tissue injury will mask or alter the effects of hormones on bone remodeling when studied over a relatively short period of time.

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Selected References

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