Effects of vitamin K2 and calcitonin on bone resorption model induced by vitamin A in thyroparathyroidectomized rats

Abstract

Vitamin K2 is considered to have two different effects: one is to enhance bone formation, and the other is to suppress bone resorption. However, as these effects have not been observed in a single experiment, it is unclear whether bone formation can proceed during a state of accelerating bone resorption. We therefore examined the effects of vitamin K2 and calcitonin on a vitamin A-induced bone resorption model of thyroparathyroidectomized rats using bone histomorphometry and bone metabolism markers. The seven groups of male Sprague-Dawley rats (6 weeks old) were sham operation of thyroparathyroidectomy (TPTX) (sham group), TPTX (TPTX group), treated with vitamin A (20 mg/kg per day) from 11th to 20th day after TPTX (A group), treated with vitamin A and vitamin K2 (30 mg/kg per day) or its vehicle from 11th to 20th day after TPTX [K group or K (veh) group], and treated with vitamin A and calcitonin (10IU/kg/ per day) or its vehicle during the same period [CT group or CT (veh) group]. Serum and urine samples were taken for marker determination on days 10, 13, 16, and 19 of TPTX and at death on the 21st day after TPTX. Undecalcified sections (Villanueva bone stain) were made of the left tibiae and decalcified sections [tartrate-resistant acid phosphatase (TRAP) stain] of the right tibiae. In the undecalcified sections, secondary trabeculae were used for histomorphometry, and in the decalcified sections primary and secondary trabeculae were used. Serum Ca of the vitamin A-administered group was significantly higher than that of the TPTX group, but this change was inhibited by vitamin K2 or calcitonin. Serum alkaline phosphatase (ALP) in the K group was significantly higher than in all the thyroparathyroidectomized groups except the K (veh) group. In the undecalcified sections, although there was no significant difference between any of the groups in bone volume, the K group showed an increase of osteoid surface and mineralizing surface. In the decalcified sections, the K group showed a decrease of TRAP-positive areas compared to the K (veh) group in primary trabeculae. There was no significant difference between the K and K (veh) groups in secondary trabeculae. Results from the CT group were compatible with bone resorption inhibition in both bone metabolism markers and bone histomorphometry. We found that vitamin K2 enhances bone formation and suppresses bone resorption in areas with a high turnover of bone metabolism. Vitamin K2 is therefore expected to increase bone content if it is administered over an extended period.