Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody

Journal of Bone and Mineral Research

Volumn 26, Issue 1, 2011, Pages 19-26

  Padhi, Desmond ^a   Jang, Graham ^a   Stouch, Brian ^a   Fang, Liang ^a   Posvar, Edward ^a  

^a AMGEN INC   (United States)

Author keywords

AMG 785; ANABOLIC; BONE FORMATION; SCLEROSTIN ANTIBODY

Indexed keywords

ALKALINE PHOSPHATASE; AMG 785; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; OSTEOCALCIN; PLACEBO; PROCOLLAGEN; PROTEIN ANTIBODY; SCLEROSTIN; UNCLASSIFIED DRUG;

ADULT; ARTHRALGIA; ARTICLE; BACKACHE; BONE DENSITY; BONE TURNOVER; CONSTIPATION; CONTROLLED STUDY; COUGHING; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HEADACHE; HEPATITIS; HIP; HOT FLUSH; HUMAN; INJECTION SITE BLEEDING; INJECTION SITE ERYTHEMA; LUMBAR SPINE; MAJOR CLINICAL STUDY; MALE; NAUSEA AND VOMITING; OSSIFICATION; PHASE 1 CLINICAL TRIAL; POSTMENOPAUSE; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE;

ANTIBODIES, MONOCLONAL; BIOLOGICAL MARKERS; BONE AND BONES; BONE DENSITY; BONE MORPHOGENETIC PROTEINS; BONE REMODELING; DEMOGRAPHY; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENETIC MARKERS; HUMANS; MALE; MIDDLE AGED; PLACEBOS; TIME FACTORS;

EID: 78650958526     PISSN: 08840431     EISSN: None     Source Type: Journal    
DOI: 10.1002/jbmr.173     Document Type: Article

References (32)

1. Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003; 22: 6267-6276.
2. van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004; 199: 805-814.
3. 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: 1842-1844.
4. van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res. 2007; 22: 19-28.
5. Baron R, Rawadi G., Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007; 148: 2635-2643.
6. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005; 280: 19883-19887.
7. Semenov M, Tamai K, He X., SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005; 280: 26770-26775.
8. Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001; 68: 577-589.
9. Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001; 10: 537-543.
10. Beighton P., Sclerosteosis. J Med Genet. 1988; 25: 200-203.
11. Hamersma H, Gardner J, Beighton P., The natural history of sclerosteosis. Clin Genet. 2003; 63: 192-197.
12. Barnard AH, Hamersma H, Kretzmar JH, et al. Sclerosteosis in old age. S Afr Med J. 1980; 58: 401-403.
13. Vanhoenacker FM, Balemans W, Tan GJ, et al. Van Buchem disease: lifetime evolution of radioclinical features. Skeletal Radiol. 2003; 32: 708-718.
14. Van Hul W, Balemans W, Van Hul E, et al. Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. Am J Hum Genet. 1998; 62: 391-399.
15. Beighton P, Barnard A, Hamersma H, et al. The syndromic status of sclerosteosis and van Buchem disease. Clin Genet. 1984; 25: 175-181.
16. Balemans W, Patel N, Ebeling M, et al. Identification of a 52kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002; 39: 91-97.
17. Staehling-Hampton K, Proll S, Paeper BW, et al. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110: 144-152.
18. Loots GG, Kneissel M, Keller H, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 2005; 15: 928-935.
19. Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008; 23: 860-869.
20. 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: 578-588.
21. 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: 948-959.
22. Eddleston A, Marenzana M, Moore AR, et al. A short treatment with an antibody to sclerostin can inhibit bone loss in an ongoing model of colitis. J Bone Miner Res. 2009; 24: 1662-1671.
23. Ke HZ, Xiang JJ, Li X, et al. Inhibition of sclerostin by systemic treatment with a sclerostin monoclonal antibody enhances fracture healing in mice and rats. Abstract and Oral presented at 55th Annual Orthopaedic Research Society Meeting. February 22-25, 2009.
24. Wang W, Wang EQ, Balthasar JP., Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008; 84: 548-558.
25. Top 200 Brand Drugs by Units in 2007. Drug Topics. Accessed January 4, 2010.
26. MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2008; 148: 197-213.
27. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001; 344: 1434-1441.
28. Greenblatt D., Treatment of postmenopausal osteoporosis. Pharmacotherapy. 2005; 25: 574-584.
29. McClung MR, San Martin J, Miller PD, et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005; 165: 1762-1768.
30. Stein SA, Witkop C, Hill S, et al. Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship. Neurology. 1983; 33: 267-277.
31. Hodsman AB, Hanley DA, Ettinger MP, et al. Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003; 88: 5212-5220.
32. Fox J, Miller MA, Newman MK, et al. 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: 260-273.