Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys

Journal of Bone and Mineral Research

Volumn 30, Issue 4, 2015, Pages 657-669

  Kostenuik, Paul J ^a   Smith, Susan Y ^b   Samadfam, Rana ^b   Jolette, Jacquelin ^b   Zhou, Lei ^a   Ominsky, Michael S ^a  

^a AMGEN INC   (United States)

^b CHARLES RIVER LABORATORIES   (United States)

Author keywords

Alendronate; Bone Strength; Calcium Homeostasis; Denosumab; Osteoporosis

Indexed keywords

ALENDRONIC ACID; ALKALINE PHOSPHATASE; CALCIUM; CARBOXY TERMINAL TELOPEPTIDE; DENOSUMAB; BONE DENSITY CONSERVATION AGENT;

ADULT; ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOMECHANICS; BONE DENSITOMETRY; BONE DENSITY; BONE MASS; BONE REMODELING; BONE STRENGTH; BONE TURNOVER; CALCIUM BLOOD LEVEL; CALCIUM HOMEOSTASIS; CONTROLLED STUDY; CORTICAL BONE; DRUG EFFICACY; DRUG SAFETY; DRUG SUBSTITUTION; FEMALE; FLUOROCHROME STAINING; MACACA FASCICULARIS; MORPHOMETRICS; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; OVARIECTOMY-INDUCED OSTEOPOROSIS; POROSITY; PROTEIN BLOOD LEVEL; SURFACE PROPERTY; TRABECULAR BONE; X RAY BONE DENSITOMETER; ANIMAL; BONE; DRUG EFFECTS; HOMEOSTASIS; METABOLISM; OVARIECTOMY; PHOTON ABSORPTIOMETRY; PHYSIOLOGY;

ABSORPTIOMETRY, PHOTON; ALENDRONATE; ANIMALS; BONE AND BONES; BONE DENSITY CONSERVATION AGENTS; CALCIUM; DENOSUMAB; FEMALE; HOMEOSTASIS; MACACA FASCICULARIS; OVARIECTOMY;

EID: 84925405908     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2401     Document Type: Article

References (38)

1. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361: 756-765.
2. Smith MR, Egerdie B, Toriz NH, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009; 361: 745-755.
3. Kostenuik PJ, Nguyen H, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009; 24: 182-195.
4. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004; 19: 1059-1066.
5. Ominsky MS, Stouch B, Schroeder J, et al. Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys. Bone. 2011; 49: 162-173.
6. Kostenuik PJ, Smith SY, Jolette J, Schroeder J, Pyrah I, Ominsky MS,. Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody. Bone. 2011; 49: 151-161.
7. Smith SY, Recker RR, Hannan M, Muller R, Bauss F,. Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomogus monkeys. Bone. 2003; 32: 45-55.
8. Russell RG, Xia Z, Dunford JE, et al. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann NY Acad Sci. 2007; 1117: 209-257.
9. Van Beek E, Pieterman E, Cohen L, Lowik C, Papapoulos S,. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun. 1999; 255: 491-494.
10. Baron R, Ferrari S, Russell RG,. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 2011; 48: 677-692.
11. Recknor C, Czerwinski E, Bone HG, et al. Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol. 2013; 121: 1291-1299.
12. Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial. J Bone Miner Res. 2009; 24: 153-161.
13. Roux C, Hofbauer LC, Ho PR, et al. Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: Efficacy and safety results from a randomized open-label study. Bone. 2013; 58: 48-54.
14. Zebaze RM, Libanati C, Austin M, et al. Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone. 2014; 59: 173-179.
15. Nakamura T, Matsumoto T, Sugimoto T, et al. Fracture risk reduction with denosumab in japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014; 99: 2599-2607, jc20134175.
16. Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2010; 25: 72-81.
17. Cummings SR, Cosman F, Eastell R, Reid IR, Mehta M, Lewiecki EM,. Goal-directed treatment of osteoporosis. J Bone Miner Res. 2013; 28: 433-438.
18. Block GA, Bone HG, Fang L, Lee E, Padhi D,. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res. 2012; 27: 1471-1479.
19. Maalouf NM, Heller HJ, Odvina CV, Kim PJ, Sakhaee K,. Bisphosphonate-induced hypocalcemia: report of 3 cases and review of literature. Endocr Pract. 2006; 12: 48-53.
20. National Research Council Guide for the care and use of laboratory animals. 2011; 8th ed. Washington, DC: The National Academies Press.
21. Balena R, Toolan BC, Shea M, et al. The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates. J Clin Invest. 1993; 92: 2577-2586.
22. Stroup GB, Kumar S, Jerome CP,. Treatment with a potent cathepsin K inhibitor preserves cortical and trabecular bone mass in ovariectomized monkeys. Calcif Tissue Int. 2009; 85: 344-355.
23. Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res. 1987; 2: 595-610.
24. Allen MR, Burr DB,. Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. J Bone Miner Res. 2007; 22: 1759-1765.
25. Okada N, Kawazoe K, Teraoka K, et al. Identification of the risk factors associated with hypocalcemia induced by denosumab. Biol Pharm Bull. 2013; 36: 1622-1626.
26. Prolia U.S.; Prescribing Information. FDA/Amgen. 2014. http://pi.amgen.com/united
27. Jiang Y, Zhao J, van Audekercke R, Dequeker J, Geusens P,. Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties. Calcif Tissue Int. 1996; 58: 30-39.
28. Allen MR, Burr DB,. Changes in vertebral strength-density and energy absorption-density relationships following bisphosphonate treatment in beagle dogs. Osteoporos Int. 2008; 19: 95-99.
29. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB,. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000; 15: 613-620.
30. Allen MR, Reinwald S, Burr DB,. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Int. 2008; 82: 354-360.
31. Kostenuik P,. On the evolution and contemporary roles of bone remodeling. Osteoporosis. 4th ed.; Chapter 37. New York: Elsevier 2013: pp 873-914.
32. Mashiba T, Turner CH, Hirano T, et al. Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures. Bone. 2001; 29: 271-278.
33. Ominsky MS, Stolina M, Li X, et al. One year of transgenic overexpression of osteoprotegerin in rats suppressed bone resorption and increased vertebral bone volume, density and strength. J Bone Miner Res. 2009; 24: 1234-1246.
34. Halazy-Nagy JM, Rodan GA, Reszka AA,. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone. 2001; 29: 553-559.
35. Burgess T, Qian YX, Kaufman S, et al. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol. 1999; 145: 527-538.
36. Ohishi M, Chiusaroli R, Ominsky M, et al. Osteoprotegerin abrogated cortical porosity and bone marrow fibrosis in a mouse model of constitutive activation of the PTH/PTHrP receptor. Am J Pathol. 2009; 174: 2160-2171.
37. Lin JH, Chen IW, Duggan DE,. Effects of dose, sex and age on the disposition of alendronate, a potent antiosteolytic bisphosphonate, in rats. Drug Metabol Dispos. 1992; 20: 473-478.
38. Reid IR, Miller P, Brown JP, et al. Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies. J Bone Miner Res. 2010; 25: 2256-2265.