Untitled Document

Research

Marc Drezner

M.D., University of Pittsburgh
Professor, Department of Medicine
Head, Endocrinology, Diabetes and Metabolism Section, Dept. of Medicine
mkd@medicine.wisc.edu
http://www2.medicine.wisc.edu/home/people-search/people/staff/349/DREZNER_MARC_K/

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
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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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