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Osteoporosis and osteoporosis-related fractures are growing problems with the aging population and are associated with significant morbidity and mortality. At this time, other than parathyroid hormone analogs, all therapies for osteoporosis are antiresorptive. Therefore, researchers have focused efforts on development of more anabolic therapies. Understanding of the Wnt signaling pathway, which is critical for skeletal development, and the role of sclerostin in inhibition of Wnt signaling has led to the discovery of a novel therapeutic approach in the treatment of osteoporosis - sclerostin inhibition. In this review, we discuss the biology of Wnt signaling and sclerostin inhibition. We then discuss human disorders of decreased sclerostin function and animal models of sclerostin inhibition. Both have served to elucidate the effects of decreased sclerostin levels and function - increased bone mass and strength and fewer fractures. In addition, we review data from Phase I and II studies of the two humanized sclerostin monoclonal antibodies, romosozumab and blosozumab, both of which have had positive effects on bone mineral density. We conclude with a discussion of the ongoing Phase III studies of romosozumab. The available data support the potential for neutralizing sclerostin monoclonal antibodies to serve as anabolic agents in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract: Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, an essential mediator of osteoclast activity and survival. In postmenopausal women with low bone mineral density (BMD), subcutaneous denosumab decreases bone resorption and increases BMD. This post hoc analysis reports on subjects treated for up to 24 months with denosumab 60mg 6 monthly (N=39), placebo (N=39), or open-label alendronate 70mg once weekly (N=38) in a phase 2 study. Hip scans were done by dual-energy X-ray absorptiometry at baseline, 12, and 24 months; these were analyzed with hip structural analysis software to evaluate BMD and cross-sectional geometry parameters at the narrowest segment of the femoral neck, the intertrochanter, and the proximal shaft. Geometric parameters and derived strength indices included bone cross-sectional area, section modulus, and buckling ratio. At 12 and 24 months denosumab and alendronate improved these parameters compared with placebo. Denosumab effects were greater than alendronate at the intertrochanteric and shaft sites. The magnitude and direction of the changes in structural geometry parameters observed in this study suggest that denosumab treatment may lead to improved bone mechanical properties. Ongoing phase 3 studies will determine whether denosumab reduces fracture risk. [Copyright &y& Elsevier]

Summary: The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region.Purpose: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region.Methods: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version.Results: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased.Conclusions: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region. [ABSTRACT FROM AUTHOR]