The prevention of osteoporotic progression by means of steroid loaded TCPL drug delivery systems.
Numerous studies have suggested that there is a link between the age-related decreases in Estradiol and adrenal androgens, and the subsequent development of senile osteoporosis. The specific objectives of this investigation were: 1) to deliver Dehydroepiandrosterone (DHEA), Diosgenin (DG), and Estradiol (E) at sustained levels by Tri-Calcium Phosphate Lysine drug delivery systems (TCPL), and 2) to study the effects of the sustained delivery of DHEA, DG, and E on the bone turnover of adult female rats following withdrawal of the endogenous hormonal milieu by means of ovariectomization (OVX). In this study, 20 female Sprague-Dawley rats were randomly divided into five groups containing four rats per group. The rats in Group 1 served as intact controls. Animals in groups 2-5 were ovariectomized, and groups 3-5 were implanted immediately with TCPL drug delivery capsules containing DHEA, DG, and E, respectively. Group 2 served as the SHAM (OVX only) group. At the end of 33 days post implantation, the vital organs, reproductive organs, and femurs were collected and evaluated. Bone histomorphometric analyses as well as mechanical strength testing was performed. Data obtained from this study demonstrated that body weights were increased in all OVX animals, and that E replacement resulted in body weights that were not significantly different from intact controls. No differences were seen in the wet weights of any vital organs. However, a decrease in the weights of the cervix and oviducts were evident in all ovariectomized groups, with the exception of the E group. Thirty-three days following OVX, the OVX-only group exhibited an increased inner medullary area, decreased thickness of the cortical layer of bone, and decreased mechanical strength. The group treated with DHEA and the group treated with E were shown to maintain both the medullary area and the cortical thickness (as compared to the intact control group). The three point bending test of the femora showed that OVX-only induced a slight decline in mechanical strength, and that DHEA and DG, but not E, showed increases in mechanical strength. Results of this experiment suggest that DHEA and E may reduce bone remodeling as evidenced by the reduction in the medullary area, and that DHEA may possibly be used in postmenopausal patients to reduce osteoporotic progression.
Scott
A
A
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Higdon
K
K
Tucci
M
M
Benghuzzi
H
H
Puckett
A
A
Tsao
A
A
Cason
Z
Z
Hughes
J
J
D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D002130:Calcium Phosphates; D003687:Dehydroepiandrosterone / Q000008:administration & dosage*; D004144:Diosgenin / Q000008:administration & dosage*; D018450:Disease Progression; D016503:Drug Delivery Systems; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D008239:Lysine; D010024:Osteoporosis / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D010052:Ovariectomy; D010710:Phosphates; D051381:Rats; D017207:Rats, Sprague-Dawley
D002130:Calcium Phosphates; D004343:Drug Implants; D010710:Phosphates; C112656:tricalcium phosphate lysine; D003687:Dehydroepiandrosterone; D004958:Estradiol; D008239:Lysine; D004144:Diosgenin