Effect of controlled zinc release on bone mineral density from injectable Zn-containing beta-tricalcium phosphate suspension in zinc-deficient diseased rats.
The purpose of this study was to evaluate the efficacy of zinc (Zn)-containing beta-tricalcium phosphate (Zn-TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D-, Ca-, and Zn-deficient diet, and induced Zn-deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure beta-TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn-TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn-TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D- and Zn-deficient diet for 9 weeks. The plasma calcium (Ca) and Zn levels, plasma alkaline phosphatase activity (ALP) and bone mineral density (BMD) of the lumbar vertebra and femora were measured. The plasma Zn levels in all the rats were between 1.1 and 2.8 microg/mL. The areas under the curves for the Ca, Zn, and ALP (Ca-AUC, Zn-AUC, and ALP-AUC) levels between 0 and 63 days were calculated. Results for the AUCs were as follows: (1) the Zn-AUCs were in the order of N10 = D20 > D10 > D0; (2) the Ca-AUCs for D0, D10 groups were significantly lower than that for the N10 group; (3) the ALP-AUCs for the D10 and D20 groups were significantly higher than that for the N10 group, and that of the D0 group was in between those. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm(2)) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body.
Otsuka
Makoto
M
Kobe Pharmaceutical University, Department of Pharmaceutical Technology, Motoyama-Kitamachi 4-19-1, Higashi-Nada, Kobe 658-8558, Japan. m-otsuka@kobepharma-u.ac.jp
Ohshita
Yuko
Y
Marunaka
Sunao
S
Matsuda
Yoshihia
Y
Ito
Atsuo
A
Ichinose
Noboru
N
Otsuka
Kuniko
K
Higuchi
William I
WI
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism*; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D002130:Calcium Phosphates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D009752:Nutritional Status; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
D001672:Biocompatible Materials; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D000469:Alkaline Phosphatase; D015032:Zinc; D002118:Calcium