Phase 3 fracture trial of odanacatib for osteoporosis – study design

McClung, M.; Bone, HG; Dempster, David W.; Eisman, John A.; Greenspan, Susan L.; Nakamura, Toshio; Papapoulos, Socrates E.; Shih, Jhih-Yuan; Santora, Arthur C.; Verbruggen, Nadia; Rosenberg, Elizabeth; Leung, Albert

doi:10.1016/j.bone.2010.04.517

Cited by 2 publications

(1 citation statement)

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“…Phase II studies with such an inhibitor (odanacatib) showed a decrease in bone resorption with relatively less inhibition of bone formation (figure 1B) and very encouraging results on mineral density of cortical bone 9. A large phase III clinical trial with odanacatib is currently underway 10. However, all treatments targeting the osteoclasts cannot stimulate bone formation underlining the need for bone-forming agents.…”

Section: Osteoporosis and Its Treatmentsmentioning

confidence: 99%

Targeting sclerostin as potential treatment of osteoporosis

Papapoulos

2011

Annals of the Rheumatic Diseases

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In recent years, study of rare bone diseases has led to the identification of signalling pathways that regulate bone formation and provided targets for the development of novel therapeutic agents to stimulate bone formation in patients with osteoporosis. Studies of two bone sclerosing dysplasias, sclerosteosis and van Buchem disease led to the identification of sclerostin, a negative regulator of bone formation. Sclerostin binds to LRP5/6 and inhibits Wnt signalling, but its precise molecular mechanism of action is not yet known. Its expression is restricted in the skeleton to osteocytes and is modified by mechanical loading and parathyroid hormone treatment. Sclerostin deficiency reproduces the findings of the human diseases in mice, while sclerostin excess leads to bone loss and reduced bone strength. An antibody to sclerostin increased bone formation dramatically at all bone envelopes in ovariectomised rats and intact monkeys, without affecting bone resorption and improved bone strength. In initial human studies, a single injection of the antibody to postmenopausal women increased serum P1NP and transiently decreased serum CTX. Clinical phase II studies with this antibody are currently underway.

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Section: Osteoporosis and Its Treatmentsmentioning

confidence: 99%