Center for Aging
Glucocorticoid-induced osteoporosis in a mouse model
Wei Yao, MD and Nancy Lane, MD

Descripion: Glucocorticoid induced osteoporosis is the most common cause of secondary osteoporosis. Glucorticoids alter bone metabolism in a number of ways including increasing osteoclast activity and decreasing osteoblast activity and lifespan. In this experiment we will determine trabecular bone architecture, bone strength, gene expression and nanoindentation and raman microspectroscopy for bone mineral to matrix ratios are influenced by bone active agents that both prevent and treat Glucocorticoid-induced bone loss. A student will learn about bone metabolism including how to measure serum markers of bone turnover, bone histomorphometry, in-vivo measurements of bone architecture and advanced techniques to study bone quality including elastic modulus mapping and raman microspectroscopy.

Duration: short 6 months/long 12 months.

Several references for the medical students to read to determine if they might be interested in the project:

1. O'Brien CA, Kai D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS 2004 Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145(4):1835-1841.
 2. Weinstein RS, Chen J-R, Powers CC, Stewart SA, Landes RD,. Bellido T, Parfitt AM, Manolagas SC 2002 Promotion of osteoclast survival and antagonism of bisphosphonate induced osteoclast apoptosis by glucocorticoids. J Clin Invest 109:1041-1048.
3. Lane NE 2001 An Update on Glucocorticoid-induced Osteoporosis. Rheumatic Disease Clinics of North America Guest Editior Lane, NE 27: 235-254.
4. Dempster D 1989 Iliac crest biopsy: Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 4:137-141.
5. Lane NE, Sanchez S, Modin G, Genant HK, Pierini E, Arnaud CD. Parathyroid hormone treatment can reverse steroid osteoporosis: results of a randomized clinical trial. Journal of Clinical Investigation 102(8):1627-1633, 1998.

A letter of invitation to the student(s):
Dear Student,
We invite you to consider doing a mentored research project in our laboratory. We are studying metabolic bone disease and we have a project in a small animal in which we induce bone loss with glucocorticoids and then study both the changes in the bone microstructure and macrostructure when we evaluate treatments used in the clinic to both prevent and treat this disease. We would expect you to spend 4-6 hours a week in the laboratory, however the hours are flexible. You can also spend more time, for example 6-8 weeks. You will learn a number of exciting experiment techniques that we use to answer our research questions including how glucocorticoids and the agents affect the genes responsible for bone mineralization used to prevent and treat this disease. We hope you will find this work interesting.