The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength.
The treatment of osteoporotic women with bisphosphonates significantly reduces the incidence of bone fractures to a degree greater than can be explained by an increase in bone mineral density. In this study, 18-month Fischer 344 rats were ovariectomized and treated with a single dose of risedronate (intravenous, iv, 500 microg), zoledronic acid (iv, 100 microg) or continuous raloxifene (2 mg/kg, po, 3x/week). High resolution microCT was used to measure lumbar vertebral bone microarchitecture, the degree of bone mineralization (DBM) and the distribution of mineral. Small angle X-ray scattering was used to investigate mineral crystallinity. We found prolonged estrogen deficiency, reduced trabecular bone volume, and increased micro architecture bone compression strength lowered the degree of mineralization. Treatment with resorptive agents (bisphosphonates>raloxifene) prevented the loss of mineralization, trabecular bone volume and bone compression strength. Crystal size was not changed with OVX or with anti-resorptive treatments. In conclusion, in the aged estrogen-deficient rat model, single intravenous doses of two bisphosphonates were effective in maintaining the compressive bone strength for 180 days by reducing bone turnover, and maintaining the DBM to a greater degree than with raloxifene.
Yao
Wei
W
Department of Medicine, Aging Center, UC Davis Medical Center, Sacramento, CA 95817, USA.
Cheng
Zhiqiang
Z
Koester
Kurt J
KJ
Ager
Joel W
JW
Balooch
Mehdi
M
Pham
Aaron
A
Chefo
Solomon
S
Busse
Cheryl
C
Ritchie
Robert O
RO
Lane
Nancy E
NE
D000367:Age Factors; D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D007262:Infusions, Intravenous; D051381:Rats; D011916:Rats, Inbred F344