The aim of any intervention in osteoporosis is the prevention of fractures at all skeletal sites in patients who have not yet fractured or of the progression of the disease in patients who have already sustained a fragility fracture. Correction of deficiencies/insufficiencies in vitamin D (and calcium) should be the first step in management. The effects of pharmacological interventions are above those obtained with calcium and vitamin D, as in clinical trials these are usually given to placebo-treated patients. The evidence of the antifracture efficacy of pharmacological interventions varies among approved agents and for treatment decisions the highest level of available evidence should be selected. Consistent with the pathophysiology of osteoporosis, pharmacological interventions are distinguished into inhibitors of bone resorption, stimulators of bone formation and compounds whose action on bone remodeling has not yet been fully elucidated, such as strontium ralenate. Of those, calcitonin, estrogens, SERMs, strontium ralenate, tibolone and PTH 1-84 cannot be considered first line of treatment due to either limited antifracture efficacy or unfavorable risk/benefit profile. Of the remaining, only the bisphosphonates alendronate, risedronate and zoledronate and the RANKL-inhibitor denosumab have been shown to reduce the risk of all osteoporotic fractures with variable efficacy. Despite the fact that the primary action of all four agents is the reduction of bone resorption and turnover, there are also considerable differences between bisphosphonates and denosumab that can be considered in clinical practice. In the absence of head-to-head studies with fracture endpoints these data together with the safety profile should be considered in therapeutic choices for individuals at risk. The Cathepsin K inhibitor odanacatib that decreases bone resorption while maintaining bone formation is not yet available for clinical use. The teriparatide paradigm illustrated the possibility of stimulating bone formation in osteoporotic patients and opened the way for the development of bone forming agents and novel forms of PTH or PTHrP are at different stages of clinical development but a synthetic analog of PTHrP (abaloparatide) given for 18 months was recently shown to decrease the incidence of vertebral and non vertebral fractures in women with osteoporosis. The recognition of the central role of the Wnt signaling pathway in bone formation provided a number of attractive targets for the development of bone building pharmaceuticals. For example, inhibition of this pathway by specific antibodies to sclerostin (romosozumab, blosozumab) represents a very promising novel anabolic therapy for patients with osteoporosis, in whom 2-year data of phase II studies are available. These new developments may allow tailoring pharmacotherapy to the specific needs and pathophysiological profile of the individual patient. Because osteoporosis is a chronic disease, knowledge of the long-term efficacy and risk profile of every individual agent prescribed is essential for proper patient care.
Disclosure of Interest S. Papapoulos Consultant for: Amgen,Axsome, Merck,Novartis, UCB, Speakers bureau: Amgen, Merck & Co
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