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New treatments of osteoporosis

By Bente L. Langdahl


AbstractOsteoporosis is characterized by low bone mass, deteriorated bone architecture and increased risk of is fractures. The current available treatments of osteoporosis comprise antiresorptive and anabolic treatments. Bisphosphonates and RANKL antibody are the most widely used antiresorptive treatments while teriparatide is the only available anabolic treatment of osteoporosis. A common feature of antiresorptive as well as anabolic treatment is that bone resorption and formation remain coupled. Both types of treatment therefore establish a period of positive balance but because of the coupling, this period is temporary.The focus of this review is two new classes of anti-osteoporosis treatments; inhibition of cathepsin K and inhibition of sclerostin. Through very different mechanisms of action both may prove capable of uncoupling resorption and formation. Cathepsin K is a lysosomal cysteine protease that degrades bone matrix proteins including collagen type I. Animal and human studies have demonstrated that inhibition of cathepsin K leads to increased bone mass across species and reduced fracture risk in postmenopausal women.Sclerostin activates the Wnt canonical pathway and stimulates bone formation through stimulation of osteoblast differentiation, proliferation and survival. Short-term studies of antibody mediated inhibition of sclerostin in animals and postmenopausal women have consistently shown stimulation of bone formation and reduced or unaltered bone resorption. Clinical studies in postmenopausal women have shown increases in bone mass.If these two new treatments demonstrate anti-fracture efficacy at the same level or better as the best of the currently approved treatments, they will become valuable tools for improving the treatment of osteoporosis

Publisher: The Korean Society of Osteoporosis. Production and hosting by Elsevier B.V.
Year: 2015
DOI identifier: 10.1016/j.afos.2015.07.007
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