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Biology of Aging

Marc Drezner

Marc Drezner

M.D., University of Pittsburgh
Professor, Department of Medicine
Senior Associate Dean of Clinical & Translational Research, School of Medicine & Public Health

Regulation of Bone Mass and Mineralization

The focus of research in my laboratory is study of 1) the pharmacological interventions which regulate bone mass and thereby provide potentially effective intervention in the treatment of osteoporosis, and 2) the biological controls that regulate bone mineralization, including phosphate homeostasis, a new family of hormones, the phosphatonins, and vitamin D metabolism.

Pharmacological studies currently underway include investigation of several drugs from the bisphosphonate class of compounds to determine their efficacy in preventing the bone loss and fracture, which occurs primarily in elderly women and constitutes the disease, post-menopausal osteoporosis. In these studies, we are assessing the effects of the bisphosphonates by oral and intravenous routes in women with post-menopausal osteoporosis. Since bisphosphonates inhibit bone resorption (and consequent loss/destruction), we anticipate that these treatment regimens will slow the inevitable bone loss in older women and prevent or limit the fracture incidence in this patient population.

In additional pharmacological studies we are examining the effects of parathyroid hormone, administered by daily subcutaneous injection, on the progression of post-menopausal and steroid-induced osteoporosis. Previous studies have established that parathyroid hormone stimulates new bone formation and thereby has the potential to alter the natural progression of these diseases. Thus, we anticipate that these studies will provide additional new therapies for diseases that commonly affect the elderly population.

In studies of the biological controls of bone mineralization, we are using molecular biological techniques to discover the cause(s) of abnormal mineralization in genetically altered animal models. These studies range from investigations of bone cells in vitro to examination of bone mineralization in animals subjected to a variety of alterations in their hormonal/metabolic milieu. Efforts to date indicate that essential control of mineralization depends on regulation of a newly recognized family of hormones, the phosphatonins, which include Fibroblast Growth Factor-23 (FGF-23) and Frizzled Related Protein 4 (FRP-4). Future studies will focus on animal models with abnormalities in these hormones, such as the hyp-mouse and the transgenic (KAP-Npt2)-hyp-mouse. These models will provide essential information about the function of the phosphatonins and the necessary co-factors to alter mineralization.

Representative Publications
Drezner, M. K. (2016). Looking back: A time of challenge, change, and fun. Journal of Bone and Mineral Research, 31(9), 1633-1634. .
View publication via DOI: DOI:10.1002/jbmr.2846

Binkley, N., Lappe, J., Singh, R.J., Khosla, S., Krueger, D., Drezner, M.K., Blank, R.D. (2015). Can vitamin D metabolite measurements facilitate a "treat-to-target" paradigm to guide vitamin D supplementation? Osteoporosis International, 26(5), 1655-1660.
View publication via DOI: DOI:10.1007/s00198-014-3010-0

O'Rourke, P. P., Carrithers, J., Patrick-Lake, B., Rice, T. W., Corsmo, J., Hart, R., Drezner, M. K., & Lantos, J. D. (2015). Harmonization and streamlining of research oversight for pragmatic clinical trials. Clinical Trials, 12(5), 449-456.
View publication via DOI: DOI:10.1177/1740774515597685

Feng, J. Q., Clinkenbeard, E. L., Yuan, B., White, K. E., & Drezner, M. K. (2013). Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia. Bone, 54(2), 213-221.
View publication via DOI: DOI:10.1016/j.bone.2013.01.046

Dempster, D. W., Compston, J. E., Drezner, M. K., Glorieux, F. H., Kanis, J. A., Malluche, H., . . . Parfitt, A. M. (2013). Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the asbmr histomorphometry nomenclature committee. Journal of Bone and Mineral Research, 28(1), 2-17.
View publication via DOI: DOI:10.1002/jbmr.1805

Yuan, B., Feng, J. Q., Bowman, S., Liu, Y., Blank, R. D., Lindberg, I., & Drezner, M. K. (2013). Hexa-D-arginine treatment increases 7b2*PC2 activity in hyp-mouse osteoblasts and rescues the hyp phenotype. Journal of Bone and Mineral Research, 28(1), 56-72.
View publication via DOI: DOI:10.1002/jbmr.1738

Drezner, M. K., & Golden, R. N. (2012). Transforming the research environment and culture for the betterment of health in Wisconsin. Wisconsin Medical Journal, 111(2), 89-90.

Yuan, B., Feng, J. Q., Bowman, S., Liu, Y., Blank, R. D., Lindberg, I., & Drezner, M. K. (2012). Hexa-D-Arginine treatment increases 7B2*PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype. Journal of Bone and Mineral Research, 28(1), 56-72.
View publication via DOI: DOI:10.1002/jbmr.1738

Binkley, N., Gemar, D., Engelke, J., Gangnon, R., Ramamurthy, R., Krueger, D., & Drezner, M.K. (2011). Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly, in older adults. The Journal of Clinical Endocrinology & Metabolism, 96(4), 981-988.
View publication via DOI: DOI:10.1210/jc.2010-0015

Rieselbach, R. E., Remington, P. L., Drezner, M. K., & Golden, R. N. (2011). Expanded community health center--academic medical center partnerships. Wisconsin Medical Journal, 110(4), 168-169.

David, V., Martin, A., Hedge, A. M., Drezner, M. K., & Rowe, P. S. (2011). Asarm peptides: Phex-dependent and -independent regulation of serum phosphate. American Journal of Physiology. Renal Physiology, 300(3), F783-791.
View publication via DOI: DOI:10.1152/ajprenal.00304.2010

Khosla, S., Bellido, T. M., Drezner, M. K., Gordon, C. M., Harris, T. B., Kiel, D. P., . . . Sherman, S. S. (2011). Forum on aging and skeletal health: Summary of the proceedings of an asbmr workshop. Journal of Bone and Mineral Research, 26(11), 2565-2578.
View publication via DOI: DOI:10.1002/jbmr.488

Lu, Y., Yuan, B., Qin, C., Cao, Z., Xie, Y., Dallas, S. L., . . . Drezner, M. K., Bonewald, L. F., & Feng, J. Q. (2011). The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment. Journal of Bone and Mineral Research, 26(2), 331-340.
View publication via DOI: DOI:10.1002/jbmr.226

Zhang, R., Lu, Y., Ye, L., Yuan, B., Yu, S., Qin, C., . . . Drezner, M. K., Bonewald, L. F., & Feng, J. Q. (2011). Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. Journal of Bone and Mineral Research, 26(5), 1047-1056.
View publication via DOI: DOI:10.1002/jbmr.294

Yuan, B., Takaiwa, M., Clemens, T.L., Feng, J.Q., Kumar, R., Rowe, P.S., Xie, Y., & Drezner, M.K. (2008). Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J. Clin. Invest., 118(2), 722-34.
View publication via DOI: DOI:10.1172/JCI32702

Binkley, N., Krueger, D., Gemar, D., & Drezner, M.K. (2008). Correlation among 25-hydroxy-vitamin D assays. J. Clin. Endocrinol. Metab., 93(5), 1804-8.
View publication via DOI: DOI:10.1210/jc.2007-2340

Hollis, B.W., Wagner, C.L., Drezner, M.K., & Binkley, N.C. (2007). Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. J. Steroid Biochem. Mol. Biol., 103(3-5), 631-4.
View publication via DOI: DOI:10.1016/j.jsbmb.2006.12.066

Binkley, N., Novotny, R., Krueger, D., Kawahara, T., Daida, Y.G., Lensmeyer, G., Hollis, B.W., & Drezner, M.K. (2007). Low vitamin D status despite abundant sun exposure. J. Clin. Endocrinol. Metab., 92(6), 2130-5.
View publication via DOI: DOI:10.1210/jc.2006-2250

Shane, E., Civitelli, R., Delmas, P.D., Drezner, M., Eisman, J.A., Lindsay, R., Lorenzo, J., Miller, P., Ralston, S., Reid, I., & Siris, E. (2007). Maintaining the trust of physicians and the public in the medical literature: Report of a task force on scientific publishing of clinical trials. J. Bone Miner. Res., 22(11), 1661-7.
View publication via DOI: DOI:10.1359/jbmr.07090c

Binkley, N., Krueger, D., & Drezner, M.K. (2007). Low vitamin D status: Time to recognize and correct a Wisconsin epidemic. W.M.J., 106(8), 466-72.

Blank, R.D., Malone, D.G., Christian, R.C., Vallarta-Ast, N., Krueger, D., Drezner, M.K., Binkley, N., & Hansen, K.E. (2006). Patient variables impact lumbar spine dual energy x-ray absorptiometry precision. Osteoporosis Int., 17, 768-74.
View publication via DOI: DOI:10.1007/s00198-005-0050-5

Reginster, J.Y., Adami, S., Lakatos, P., Greenwald, M., Stepan, J.J., Silverman, S.L., Christiansen, C., Rowell, L., Mairon, N., Bonvoisin, B., Drezner, M.K., Emkey, R., Felsenberg, D., Cooper, C., Delmas, P.D., & Miller, P.D. (2006). Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann. Rheum. Dis., 65(5), 654-61.
View publication via DOI: DOI:10.1136/ard.2005.044958

Lensmeyer, G.L., Wiebe, D.A., Binkley, N., & Drezner, M.K. (2006). HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary assays. Clin. Chem., 52(6), 1120-6.
View publication via DOI: DOI:10.1373/clinchem.2005.064956

Delmas, P.D., Adami, S., Strugala, C., Stakkestad, J.A., Reginster, J.Y., Felsenberg, D., Christiansen, C., Civitelli, R., Drezner, M.K., Recker, R.R., Bolognese, M., Hughes, C., Masanauskaite, D., Ward, P., Sambrook, P., & Reid, D.M. (2006). Intravenous ibandronate injections in postmenopausal women with osteoporosis: One-year results from the dosing intravenous administration study. Arthritis Rheum., 54(6), 1838-46.
View publication via DOI: DOI:10.1002/art.21918

Couto, F.M., Chen, H., Blank, R.D., & Drezner, M.K. (2006). Calciphylaxis in the absence of end-stage renal disease. Endocr. Pract., 12(4), 406-10.

Shane, E., Goldring, S., Christakos, S., Drezner, M., Eisman, J., Silverman, S., & Pendrys, D. (2006). Osteonecrosis of the jaw: more research needed. J. Bone Miner. Res., 21(10), 1503-5.
View publication via DOI: DOI:10.1359/jbmr.060712

Feng, J.Q., Ward, L.M., Liu, S., Lu, Y., Xie, Y., Yuan, B., Yu, X., Rauch, F., Davis, S.I., Zhang, S., Rios, H., Drezner, M.K., Quarles, L.D., Bonewald, L.F., & White, K.E. (2006). Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat. Genet., 38(11), 1310-5.
View publication via DOI: DOI:10.1038/ng1905

Binkley, N., Drezner, M.K., & Hollis, B.W. (2006). Laboratory reporting of 25-hydroxyvitamin D results: Potential for clinical misinterpretation. Clin. Chem., 52(11), 2124-5.
View publication via DOI: DOI:10.1373/clinchem.2006.074922

Hansen, K.E., Binkley, N., Christian, R., Blank, R.B., Vallarta-Ast, N., Krueger, D., Drezner, M.K., & Blank, R.B. (2005). Interobserver reproducibility of criteria for vertebral body exclusion. J. Bone Miner. Res., 20, 501-508.
View publication via DOI: DOI:10.1359/JBMR.041134

Hansen, K.E., Vallarta-Ast, N., Krueger, D., Gangnon, R., Drezner, M.K., & Binkley, N. (2004). Use of the lowest vertebral body to diagnose lumbar osteoporosis in men: Is "cherry picking" appropriate? J. Clin. Densitom., 7(4), 376-381.
View publication via DOI: DOI:10.1385/JCD:7:4:376

Binkley, N., Krueger, D., Cowgill, C.S., Plum, L., Lake, E., Hansen, K.E., DeLuca, H.F., & Drezner, M.K. (2004). Assay variation confounds the diagnosis of hypovitaminosis D: A call for standardization. J. Clin. Endocrinol. Metab., 89, 3152-3157.
View publication via DOI: DOI:10.1210/jc.2003-031979

Fujiwara, I., Aravindan, R., Horst, R., & Drezner, M.K. (2003). Abnormal regulation of renal 25-hydroxyvitamin D-1α-hydroxylase activity in hyp-mice: A post-transcriptional defect. J. Bone Miner. Res., (18)3, 434-442.
View publication via DOI: DOI:10.1359/jbmr.2003.18.3.434

Thompson, D.L., Sabbagh, Y., Tenenhouse, H.S., Roche, P.C., Drezner, M.K., Salisbury, J.L., et al. (2002). Ontogeny of Phex/PHEX protein expression in mouse embryo and subcellular localization in osteoblasts. J. Bone Miner. Res. 2, 311-20.
View publication via DOI: DOI:10.1359/jbmr.2002.17.2.311

Drezner, M.K. (2002). Osteomalacia and rickets. In L. Goldman and J.C. Bennett (Eds.), Cecil textbook of medicine (22nd ed.). Philadelphia: W.B. Saunders Company.

Drezner, M.K. (2002). Bone disease resulting from inherited disorders of the renal tubule. In F. Coe, & M.J. Favus (Eds.), Disorders of bone and mineral metabolism (2nd ed.). Philadelphia: Lippincott, Williams and Wilkins.

Hans, D., Genton, L., Drezner, M.K., Schott, A.M., Pacifici, R., Avioli, L., Slosman, D.O., & Meunier, P.J. (2002). Monitored impact loading of the hip: Initial testing of a home-use device. Calc. Tissue Int., 71, 112-120.
View publication via DOI: DOI:10.1007/s00223-001-2063-1

Gold, D.T., Lyles, K.W., Harper, K.D., Shipp, K.M., & Drezner, M.K. (2001). Unexpected consequences of osteoporosis: An evolving basis for treatment decisions. In R. Marcus, D. Feldman, & J. Kelsey (Eds.), Osteoporosis (2nd ed.). San Diego, CA: Academic Press.

Weber, T.J., & Drezner, M.K. (2001). Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Metabolism, 50, 912- 915.

Nesbitt, T., Thomas R, Quarles, L.D., & Drezner, M.K. (1999). Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: Evidence for the pathophysiological role of PHEX in XLH. J. Bone Miner. Res., 14, 2027-2035.
View publication via DOI: DOI:10.1359/jbmr.1999.14.12.2027

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