Subhajit Das, Julie C Crockett

Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral density (BMD) and pathological fractures which lead to significant morbidity. It is defined clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score =-2.5). Osteoporosis was a huge global problem both socially and economically - in the UK alone, in 2011 £6 million per day was spent on treatment and social care of the 230,000 osteoporotic fracture patients - and therefore viable preventative and therapeutic approaches are key to managing this problem within the aging population of today. One of the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk before they develop a fracture. We discuss the current and future possibilities for identifying susceptible patients, from fracture risk assessment to shape modeling and in relation to the high heritability of osteoporosis now that a plethora of genes have been associated with low BMD and osteoporotic fracture. This review highlights the current therapeutics in clinical use (including bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand], intermittent low dose parathyroid hormone, and strontium ranelate) and some of those in development (anti-sclerostin antibodies and cathepsin K inhibitors). By highlighting the intimate relationship between the activities of bone forming (osteoblasts) and bone-resorbing (osteoclasts) cells, we include an overview and comparison of the molecular mechanisms exploited in each therapy.