Bone / Osteoporosis Research Group


Our research focuses on preclinical testing of potential new treatments for postmenopausal osteoporosis. These studies are performed in the ovariectomized rat, which becomes estrogen deficient soon after surgery and exhibits bone changes strikingly similar to those of postmenopausal women. Bone samples are embedded in plastic, sectioned with a precision microtome, stained, and subjected to microscopic analyses with a computer-assisted quantitative system. The effects of a treatment on bone mass, levels of bone resorption and formation, and bone cell populations are monitored.

a)image 1

b)image 2

c)image 3

Proximal tibial metaphyses from a control rat (a), an untreated ovariectomized rat (b), and an ovariectomized rat treated with basic fibroblast growth factor (bFGF) (c). Note the reduced amount of black-stained bone in the untreated ovariectomized rat and the blue-stained areas indicative of new bone formation in the ovariectomized rat treated with bFGF. Von Kossa / tetrachrome stain, x40.

Adapted from: Liang H, S Pun, and TJ Wronski. 1999. Bone anabolic effects of basic fibroblast growth factor in ovariectomized rats. Endocrinology 140(12):5780-5788.


In addition to histomorphometry, RNA is isolated from selected bone samples and subjected to Northern analyses and RNase protection assays. These molecular biology techniques are used to determine changes in gene expression for bone matrix proteins and several cytokines and growth factors that may serve as mediators for the skeletal effects of a treatment. The importance of this field of research is emphasized by the policy of the Federal Drug Administration (FDA) to require supporting data from the ovariectomized rat model as an essential prerequisite for approval of a new therapy for postmenopausal osteoporosis.

Research Group Members:

Thomas J. Wronski, Ph.D.
Professor

Ignacio Aguirre, DVM, Ph.D.
Research Assistant Professor