Effects of dietary supplementation of calcium and vitamin don bone growth in growing male rats

Effects of dietary supplementation of calcium (Ca) and vitamin D(D) on bone growth in growing male rats were investigated. We performed this study using D-deficient rats of 3-month-old. In the experiment 1, the D-deficient rats were fed either low-Ca (0.22% Ca) or high-Ca (1.20% Ca) diets with oral supplementation of different amounts of D₃ (0, 0.7, 7 or 70 IU/week) for 28 days. In the dxperiment 2, the D-deficient rats were fed diets containing different concentrations of Ca (0.22, 0.44, 0.88 or 1.20%) with oral D₃ supplementation of either low-dose (0.7 IU/week) or relatively high-dose (70 IU/week) for 28 days. After the feeding period, plasma levels of Ca, 1α, 25 (OH)₂D₃, PTH, bone Gla protein were measured. Bone ash weight, bone mineral density, mechanical bone strength were also measured. In the both experiments, the plasma levels of PTH decreased to the normal levels in response to the increased amounts of dietary Ca intakes as well as D supplementation. In contrast, the bone markers increased to the respective normal levels in response to the increased amounts of dietary Ca intakes as well as D supplementation. In the experiments 1 and 2, a high correlation between the plasma levels of PTH and the bone markers was observed. These results suggest that both dietary Ca and D supplementation may affect bone growth in growing rats by controlling PTH secretion.     

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

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.     

Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats

Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol–ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength–strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet. Received: July 17, 1999 / Accepted: Sept. 20, 1999     

Efficacy and safety of edoxaban in patients early after surgical bioprosthetic valve implantation or valve repair: A randomized clinical trial

ObjectiveEarly warfarin anticoagulation is recommended in patients undergoing surgical bioprosthetic valve implantation or valve repair. It is unclear whether non-vitamin K antagonist oral anticoagulants can be a full alternative to warfarin. This study aimed to compare efficacy and safety of edoxaban with warfarin in patients early after surgical bioprosthetic valve implantation or valve repair.MethodsThe Explore the Efficacy and Safety of Edoxaban in Patients after Heart Valve Repair or Bioprosthetic Valve Replacement study was a prospective, randomized (1:1), open-label, clinical trial conducted from December 2017 to September 2019. Patients were randomly assigned to receive edoxaban (60 mg or 30 mg once daily) or warfarin for the first 3 months after surgical bioprosthetic valve implantation or valve repair. The primary efficacy outcome was a composite of death, clinical thromboembolic events, or asymptomatic intracardiac thrombosis. The primary safety outcome was the occurrence of major bleeding.ResultsOf 220 participants, 218 (109 per group) were included in the modified intention-to-treat analysis. The primary efficacy outcome occurred in 4 patients (3.7%) taking warfarin and none taking edoxaban (risk difference, ?0.0367; 95% confidence interval, –0.0720 to –0.0014; P < .001 for noninferiority). The primary safety outcome occurred in 1 patient (0.9%) taking warfarin and 3 patients (2.8%) taking edoxaban (risk difference, 0.0183; 95% confidence interval, –0.0172 to 0.0539; P = .013 for noninferiority).ConclusionsEdoxaban is noninferior to warfarin for preventing thromboembolism and is potentially comparable for risk of major bleeding during the first 3 months after surgical bioprosthetic valve implantation or valve repair.