Bruce R. Troen, M.D.

Educational Interests
I was active in organizing the Medical Genetics Pathway, which is committed to providing expanded opportunities for medical students in genetics and hopefully lay the foundation for future careers in Medical Genetics.

As a molecular biologist, I regularly have student fellows in my laboratory engaging in benchtop research.  Finally, as a geriatrician, I regularly teach medical students and house officers while attending on the in-patient wards.

     I have several major foci of research: osteoporosis, longevity/aging mechanisms, and frailty, all of which result in great morbidity in the elderly.   We are investigating the molecular basis of bone resorption, which leads to decreased bone mineral density and subsequent fractures. Bone resorbing cells (osteoclasts) synthesize large quantities of cathepsin K, which is one of the major effectors of osteoclastic bone resorption. We are studying the factors that govern both the formation and differentiation of osteoclasts and the regulation of cathepsin K expression. We employ a broad range of techniques including in situ and real time quantitative RT-PCR, northern and western analyses, transient transfection analyses with cathepsin K promoter-reporter gene plasmids, chromatin immunoprecipitation (ChIP) assays, electromobility shift assays (EMSA's), transduction of siRNA targeted at disruption of osteoclastogenesis and cathepsin K expression, bone pit resorption assays, and transgenic mice. Our studies will provide insight into molecular genetic events in the osteoclast that underlie the pathogenesis of osteoporosis. Eventually this information will permit us to devise strategies to alter cathepsin expression and thereby modulate bone resorption and the destructive potential of the osteoclast.
      Given my perspective as both a geriatrician and molecular biologist, I am also investigating the broader mechanisms that underlie the development of age-related syndromes/diseases and their impact upon the quality of life and longevity. Specifically, we are examining the role of sirtuin activating compounds (STACs, i.e. - resveratrol and resveratrol mimetics) upon both osteoblast and osteoclast formation and gene expression using in vitro culture systems and in vivo murine models. We are also studying mesenchymal stem cell proliferation and differentiation in mature, ovariectomized, and aged mice (both wild-type and senescence accelerated) treated with STACs. Our goals are to determine whether STACs: 1) alter the self-renewal as well as the commitment and/or differentiation of marrow mesenchymal stem cells, 2) maintain the stem cell pool during aging, thus contributing to the mechanisms leading to increased lifespan (e.g. - enhanced stem cell-mediated tissue repair), 3) alter body composition (e.g. - increase bone mineral density, decrease bone marrow fat, and/or decrease visceral adiposity, and 4) enhance muscle performance and mobility in elderly animals. In order to elucidate more precisely and completely the role and impact of sirtuin activation, we are also working to create animal models with both age and tissue/cell specific over expression of sirtuins.
      We are also studying the impact of vitamin D supplementation in the elderly. We have established that 2,000 IU/day of cholecalciferol is safe and are undertaking a study to examine whether this dose alters physical performance. We are also studying body composition and biomarkers of bone turnover, insulin sensitivity, and inflammation.
      I am committed to the elucidation of aging and age-related diseases and to the application of that knowledge to improve care. Our ultimate goal is to develop interventions to prevent and reverse the adverse changes that occur with aging and age-related diseases.

 

Duque, G., Demonteiro, O., and Troen, B.R.  The Prevention and Treatment of Senile Osteoporosis and Hip Fractures, Minerva Medica, in press.

Duque, G. and Troen, B.R.  Osteoporosis.  In "Hazzard's Principles of Geriatric Medicine and Gerontology" – 6th edition (Halter, Ouslander, Tinetti, Asthana, High, Studenski, Eds.) McGraw-Hill, New York, NY, in press.

Cherniack, E.P., Troen, B.R. and Levis, S. Hypovitaminosis D in the elderly: from bone to brain.  J Nutr Health Aging. 12(6):366-73, 2008. PMID: 18548173 Duque, G. and Troen, B.R.  Understanding the Mechanisms of Senile Osteoporosis: New Facts for a Major Geriatric Syndrome.  J Am Geriatr Soc, 56:935–941, 2008.

Florez, H. and Troen, B.R.  Fat and Inflammaging: A Dual Path to Unfitness in Elderly People? J Am Geriatr Soc, 56(3):558-60, 2008.

Yang, G., Zaidi, M., Zhang, W., Zhu, L.L., Li, J., Iqbal, J., Varbanov, A., Gross, G., Phipps, R., Troen, B.R., Sun, L..  Functional grouping of osteoclast genes revealed through microarray analysis. Biochem Biophys Res Commun. 8;366(2):352-9, 2008.

Cherniack, E.P. and Troen, B.R.  Calciotropic Hormones. In "Senile Osteoporosis: Advances in Pathophysiology and Therapeutic Approach" (Duque, G. and Kiel, D., Eds.) Springer-Verlag London Limited, pp. 34-46, 2008.

Cherniack, E.P., Levis, S. and Troen, B.R.  Hypovitaminosis D: a stealthy epidemic requiring treatment.  Geriatrics 63(4):24-30, 2008.

Cherniack, E.P., Florez, H.J., Troen, B.R.  Emerging therapies to treat frailty in the elderly.  Alternative Medicine Reviews 12(3):246-258, 2007.

Pang, M., Martinez, A.F., Fernandez, I., Balkan, W., Troen, B.R. AP-1 Stimulates the Cathepsin K Promoter in RAW 264.7 Cells. Gene 403(1-2):151-8, 2007.

Howard, G.A., Schiller, P.C., D'Ippolito, G., Cheung, H.S., Troen, B.R., Roos, B.A.  Unlocking the Mysteries of Adult Stem Cells and Regenerative Medicine.  Federal Practitioner 24(7):30-32,37, 2007.

Paniagua, M. and Troen, B.R.  The Demographics of Aging in Women. In “The Menopause: Endocrinologic Basis & Management Options” – 5th edition, (Eskin, B.A., Ed.) Taylor and Francis, Boca Raton, FL, pp. 23-34, 2007.

Troen, B.R. The Regulation of Cathepsin K Gene Expression.  Annals NYAS 1068:165-172, 2006.

Troen, B.R.  Osteoporosis in Older People: A Tale of Two Studies (and Three Treatments).  J Am Geriatr Soc May;54(5):853-855, 2006.

Duque, G. and Troen, B.R.  Skeletal Aging.  In: “Geriatric Nutrition: The Health Professional’s Handbook” 3rd edition. (Chernoff, Ed.) Jones and Bartlett, Boston, MA, pp. 325-344, 2006.

Troen, B.R. and Jurivich, D.A.  Biology of Aging.  In: “Geriatrics Review Syllabus” – 6th edition, (Pompei, P. & Murphy, J.B., eds.), New York: American Geriatrics Society, pp. 8-16, 2006.

Pang M., Martinez A.F., Jacobs J., Balkan W., Troen B.R. (2005) RANK ligand and interferon gamma differentially regulate cathepsin gene expression in pre-osteoclastic cells. Biochem Biophys Res Commun 328(3):756-763. PMID: 15694411

Zhu L.L., Zaidi S., Moonga B.S., Troen B.R., Sun L. (2004) RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during osteoclast formation. Biochem Biophys Res Commun 326(1):131-5. PMID: 15567162

Eskin B.A. and Troen B.R. (2004) Geripause: A Newly Defined Postmenopausal Phase. Menopause Management 13(4):12-17.

Troen B.R. (2004) The role of cathepsin K in normal bone resorption. Drug News Perspect 17(1):19-28. PMID: 14993931

Troen B.R. (2003) Molecular mechanisms underlying osteoclast formation and activation. Exp Gerontol 38(6):605-14. Review. PMID: 12814795

Troen B.R. (2003) The biology of aging. Mt Sinai J Med 70(1):3-22. Review. PMID: 12516005