Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in Ovariectomized Cynomolgus Monkeys

Journal of Bone and Mineral Research

Volumn 32, Issue 4, 2017, Pages 788-801

  Ominsky, Michael S ^a   Boyd, Steven K ^b   Varela, Aurore ^c   Jolette, Jacquelin ^c   Felx, Melanie ^c   Doyle, Nancy ^c   Mellal, Nacera ^c   Smith, Susan Y ^c   Locher, Kathrin ^a   Buntich, Sabina ^a   Pyrah, Ian ^a   Boyce, Rogely W ^a  

^a AMGEN INC   (United States)

^b UNIVERSITY OF CALGARY   (Canada)

^c CHARLES RIVER LABORATORIES   (United States)

Author keywords

BIOMECHANICS; BONE HISTOMORPHOMETRY; Bone QCT microCT; OSTEOPOROSIS; THERAPEUTICS ANABOLICS

Indexed keywords

COLECALCIFEROL; COLLAGEN TYPE 1; PARATHYROID HORMONE; ROMOSOZUMAB; MONOCLONAL ANTIBODY;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; ASH ANALYSIS; BONE BIOPSY; BONE DENSITOMETRY; BONE DENSITY; BONE EXAMINATION; BONE MASS; BONE MINERAL; BONE MINERALIZATION; BONE QUALITY; BONE STRENGTH; BONE STRUCTURE; CONTROLLED STUDY; CORTICAL BONE; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DUAL ENERGY X RAY ABSORPTIOMETRY; ENDOCORTICAL BONE; FEMALE; FEMORAL NECK; FEMUR DIAPHYSIS; FINITE ELEMENT ANALYSIS; ILIAC BONE; LUMBAR SPINE; MACACA FASCICULARIS; METAPHYSIS; MORPHOMETRY; MUSCULOSKELETAL SYSTEM PARAMETERS; NONHUMAN; OSSIFICATION; OVARIECTOMY; PARATHYROID HORMONE BLOOD LEVEL; PERIOSTEUM; POROSITY; PROTEIN BLOOD LEVEL; PROXIMAL FEMUR; RADIUS; RIB; TRABECULAR BONE; TREATMENT DURATION; VERTEBRA BODY; VITAMIN BLOOD LEVEL; ANIMAL; DIAGNOSTIC IMAGING; DIAPHYSIS; DRUG EFFECTS; METABOLISM; PHOTON ABSORPTIOMETRY;

ABSORPTIOMETRY, PHOTON; ANIMALS; ANTIBODIES, MONOCLONAL; BONE DENSITY; DIAPHYSES; FEMALE; FEMUR NECK; MACACA FASCICULARIS; OVARIECTOMY; RADIUS;

EID: 85006827382     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.3036     Document Type: Article

References (33)

1. Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009; 24 (4):578–88.
2. Poole KE, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB.J. 2005; 19(13):1842–4.
3. Ke HZ, Richards WG, Li X, Ominsky MS. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012; 33(5):747–83.
4. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011; 26(1):19–26.
5. McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014; 370(5):412–20.
6. Li X, Niu QT, Warmington KS, et al. Progressive increases in bone mass and bone strength in an ovariectomized rat model of osteoporosis after 26 weeks of treatment with a sclerostin antibody. Endocrinology. 2014; 155(12):4785–97.
7. Ominsky MS, Niu QT, Li C, Li X, Ke HZ. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. J Bone Miner Res. 2014; 29(6):1424–30.
8. Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010; 25(5):948–59.
9. Niu Q, Boyce R, Ominsky M. Romosozumab (sclerostin antibody) increases wall thickness in remodeling units in cynomolgus monkeys after 28 weeks. J Bone Miner Res. 2015; 30(S1):MO0154.
10. Ominsky MS, Boyce RW, Li X, Ke HZ. Effects of sclerostin antibodies in animal models of osteoporosis. Bone. 2016.
11. European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. Effective May 31, 2007. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003405.pdf. Accessed March 17, 2016.
12. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Osteoporosis: nonclinical evaluation of drugs intended for treatment guidance for industry. Draft guidance. Effective June 1, 2016. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM506366.pdf. Accessed July 12, 2016.
13. Jerome CP, Burr DB, Van Bibber T, Hock JM, Brommage R. Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis). Bone. 2001; 28(2):150–9.
14. Fox J, Miller MA, Newman MK, Recker RR, Turner CH, Smith SY. Effects of daily treatment with parathyroid hormone 1-84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys. Bone. 2007; 41(3):321–30.
15. Fox J, Miller MA, Newman MK, Turner CH, Recker RR, Smith SY. Treatment of skeletally mature ovariectomized rhesus monkeys with PTH(1-84) for 16 months increases bone formation and density and improves trabecular architecture and biomechanical properties at the lumbar spine. J Bone Miner Res. 2007; 22(2):260–73.
16. Saito M, Marumo K, Kida Y, et al. Changes in the contents of enzymatic immature, mature, and non-enzymatic senescent cross-links of collagen after once- weekly treatment with human parathyroid hormone (1-34) for 18 months contribute to improvement of bone strength in ovariectomized monkeys. Osteoporos Int. 2011; 22(8):2373–83.
17. Doyle N, Smith SY, Varela A, Hattersley G. Abaloparatide (BA058), a human PTHrP analog: correlation of in vivo bone mass gains and improved bone strength in the osteopenic cynomolgus monkey. Presented at: ASBMR 2014 Annual Meeting; September 12-15, 2014; Houston, TX, USA.
18. Smith SY, Jolette J, Turner CH. Skeletal health: primate model of postmenopausal osteoporosis. Am J Primatol. 2009; 71(9):752–65.
19. 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(2):162–73.
20. Cain CJ, Rueda R, McLelland B, Collette NM, Loots GG, Manilay JO. Absence of sclerostin adversely affects B-cell survival. J Bone Miner Res. 2012; 27(7):1451–61.
21. Boyce RW, Paddock CL, Franks AF, Jankowsky ML, Eriksen EF. Effects of intermittent hPTH(1-34) alone and in combination with 1,25(OH)(2)D(3) or risedronate on endosteal bone remodeling in canine cancellous and cortical bone. J Bone Miner Res. 1996; 11(5):600–13.
22. Attisano R, Gust DA, Wilson ME, Meeker T, Gordon TP. Immunomodulatory effects of estrogen and progesterone replacement in a nonhuman primate model. J Clin Immunol. 2002; 22 (5):263–9.
23. High WB. Effects of orally administered prostaglandin E-2 on cortical bone turnover in adult dogs: a histomorphometric study. Bone. 1987; 8(6):363–73.
24. Agerbaek MO, Eriksen EF, Kragstrup J, Mosekilde L, Melsen F. A reconstruction of the remodelling cycle in normal human cortical iliac bone. Bone Miner. 1991; 12(2):101–12.
25. Ross RD, Edwards LH, Acerbo AS, et al. Bone matrix quality after sclerostin antibody treatment. J Bone Miner Res. 2014; 29(7):1597–607.
26. Taylor S, Ominsky MS, Hu R, et al. Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats. Bone. 2016; 84:148–59.
27. Ma YL, Zeng Q, Donley DW, et al. Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis. J Bone Miner Res. 2006; 21(6):855–64.
28. Lindsay R, Cosman F, Zhou H, et al. A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res. 2006; 21(3):366–73.
29. Miller MA, Bare SP, Recker RR, Smith SY, Fox J. Intratrabecular tunneling increases trabecular number throughout the skeleton of ovariectomized rhesus monkeys treated with parathyroid hormone 1-84. Bone. 2008; 42(6):1175–83.
30. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016; 375(16):1532–43.
31. Recker RR, Benson CT, Matsumoto T, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res. 2015; 30(2):216–24.
32. Chouinard L, Felx M, Mellal N, et al. Carcinogenicity risk assessment of romosozumab: a review of scientific weight-of-evidence and findings in a rat lifetime pharmacology study. Regul Toxicol Pharmacol. 2016; 81:212–22.
33. Recknor CP, Recker RR, Benson CT, et al. The effect of discontinuing treatment with blosozumab: follow-up results of a phase 2 randomized clinical trial in postmenopausal women with low bone mineral density. J Bone Miner Res. 2015; 30(9):1717–25.