Rizzoli, Rene

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I90. NOVEL THERAPEUTIC TARGETS WITH POTENTIAL TOINFLUENCE BONE/MUSCLERene Rizzoli11HUG/Specialites de Medicine, University of Geneva, Geneva,SwitzerlandThe prevention of fragility fracture relies on the triad of balancednutrition, including calcium, protein and vitamin D; physical exercise;and pharmacological therapies. The goals of these measures are tomodify the two main components of fracture risk, which aremechanical overload, i.e. falls, and mechanical incompetence, i.e.bone fragility. For the latter, new regimens are in development aimedat increasing bone mass and particularly bone strength, by influencingcellular and biochemical pathways not targeted by available anti-osteoporosis agents. For instance, to transmit to the osteoblast signalsof mechanical loading or parathyroid hormone, osteocytes are usingthe WNT/beta-catenin pathway. This pathway is becoming the targetof pharmacological intervention to decrease the expression ofnegative regulators of bone formation like sclerostin. Phase III trials,monoclonal antibodies against sclerostin, tested either againstplacebo, or alendronate, over 1 year, followed by denosumab, areongoing. Odanacatib is a selective inhibitor of cathepsin K, which wastested in a 2-year phase IIb dose-ranging study given once weekly orplacebo, and in extensions. Continuous treatment up to 8 yearsresulted in further gains in BMD. Bone-resorption markers remainedreduced, while there was no significant change in bone-formationmarkers. The results from a phase III trials have demonstrated aconsistent antifracture efficacy on vertebral and non-vertebral, includ-ing hip fractures. Other agents targeting these pathways are underdevelopment. Combined and/or sequential therapies with availableagents are further considered. For the age-related reduction in musclemass and performance, characterizing sarcopenia, various agentsaffecting the myostatin activin receptor system are under clinicaldevelopment. In a phase II trial, monoclonal anti-myostatin antibodieswere shown to increase appendicular lean mass and muscle power, asassessed by a stair climbing test. Interestingly, pathways such asmuscle derived IGF-I during muscle contraction, or myostatin arecapable of influencing bone turnover as well.Disclosure statement: R.R. has received speaker or advisory boardfees from Amgen, MSD, GSK, Servier, Danone and Takeda fordelivering lectures.INVITED SPEAKER ABSTRACTS Thursday 30 April 2015 i17

I90. Novel Therapeutic Targets with Potential to Influence Bone/Muscle

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I90. Novel Therapeutic Targets with Potential to Influence Bone/Muscle

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