US Patent #6,756,480 │ WO 2004060386: “Modulators of PTH and PTHrP receptors and uses for the treatment of bone disorders.”
US Patent #8,992,925 │ WO2007059136: “RANKL antibody-PTH/PTHrP chimeric molecules”
Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I. Kostenuik PJ, Halloran BP, Turner R, Morey-Holton E, Bikle D. J Bone Miner Res 14: 21-31, 1999. PMID: 9893062
RANK is the intrinsic hematopoietic cell surface receptor that control osteoclastogenesis, and regulation of bone mass and calcium metabolism. Li J, Sarosi I, Yan XQ, et al. Proc Natl Acad Sci USA 97: 1566-1571, 2000. PMID: 10677500
Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy. Capparelli C, Kostenuik PJ, Morony S, Starnes C, Weimann B, Lacey DL, and Dunstan CR. Cancer Res 60: 783-787, 2000. PMID: 10706080
Osteoprotegerin: A potential novel therapeutic agent for treatment of humoral hypercalcemia of malignancy. Capparelli C, Kostenuik PJ. Cancer Res Alert 2: 22-24, 2000.
The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared to bisphosphonates in two models of humoral hypercalcemia of malignancy. Morony S, Warmington K, Adamu S, et al. Endocrinol 146: 3235-3243, 2005. PMID: 15845617
Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone. Kostenuik PJ, Ferrari S, Pierroz D, et al. J Bone Miner Res 22: 1534-1547, 2007.
PMID: 17576164*
Prevention of glucocorticoid-induced bone loss by inhibition of RANKL. Hofbauer LC, Zeitz U, Schoppet M, et al. Arthritis and Rheumatism 60: 1427-1437, 2009. PMID: 19404943
Osteoprotegerin abrogated cortical porosity and bone marrow fibrosis in a mouse model of constitutive activation of the PTH/PTHrP receptor. Ohishi M, Chiusaroli R, Ominsky M, et al. Am J Pathol 174: 2160-2171, 2009. PMID: 19389927
Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. Drake MT, Srinivasan B, Modder UI, et al. J Clin Endocrinol Metab 95: 5056-5062, 2010.
PMID: 20631014
Bone turnover markers in peripheral blood and marrow plasma reflect trabecular bone loss but not endocortical expansion in aging mice. Shahnazari M, Dwyer D, Chu V, et al. Bone 50: 628-637, 2012.
PMID: 22154841
On the evolution and contemporary roles of bone remodeling. Kostenuik P. Osteoporosis 4th Edition, Chapter 37: 873-914. Edited by R. Marcus, D. Feldman, D. Dempster, M. Luckey and J. Cauley. Elsevier, New York, 2013.
Chronic inhibition of RANKL induces an osteoclast-independent mechanism of PTH-induced calcium mobilization. Bahar H, Maeda A, Reyes M, Dean T, Schipani E, Pajevic PD, Neer R, Kostenuik P, Potts J, Gardella T. J Bone Miner Res 29 (Suppl. 1): S251, 2014 (Abstract)
Estrogens antagonize RUNX2-mediated osteoblast-driven osteoclastogenesis through regulating RANKL membrane association. Martin A, Xiong J, Koromila T, et al. Bone 75: 96-104, 2015.
PMID: 25701138
OPG treatment prevents bone loss during lactation but does not affect milk production or maternal calcium metabolism. Ardeshirpour L, Dumitru C, Dann P, Sterpka J, VanHouten J, Kim W, Kostenuik P and Wysolmerski J. Endocrinology 156: 2762-2773, 2015. PMID: 25961842
Hypocalcemia in patients with metastatic bone disease treated with denosumab. Body JJ, Lipton A, Henry DH, et al. Eur J Cancer 51: 1812-1821, 2015. PMID: 26093811
Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats. Hohman EE, Hodges JK, Wastney ME, Lachcik PJ, Han CY, Dwyer D, Peacock M, Kostenuik PJ, Weaver CM. Bone. 2018 Nov;116:162-170. PMID: 30077758
Estrogen regulates bone turnover by targeting RANKL expression in bone lining cells. Streicher C, Heyny A, Andrukhova O, Haigl B, Slavic S, Schüler C, Kollmann K, Kantner I, Sexl V, Kleiter M, Hofbauer LC, Kostenuik PJ, Erben RG. Sci Rep. 2017 Jul 25;7(1):6460. PMID: 28744019.
Some of Dr. Kostenuik's patents and publications in the endocrinology field:
Dr. Kostenuik's interest in endocrinology research began with a post-doctoral fellowship at the UCSF/VA Endocrine Unit, where he studied osteoblast responsiveness to PTH. He would go on to invent, patent and preclinically validate several novel PTH-based therapeutic agents for osteoporosis. These molecules, designed to have long circulating half-lives that permit infrequent s.c. delivery, provided the first experimental evidence that bone-building effects of PTH therapy do not require brief PTH exposure (*PMID 17576164, below). Dr. Kostenuik's biomarker lab at Amgen measured PTH and dozens of other hormones in various metabolic diseases. The regulation of calcium and phosphorus in bone and kidney diseases remains an abiding research interest of his.
Endocrinology