Osteoporosis is a disease induced by bone loss as the result of a negative balance between bone resorption (by osteoclasts) and formation (by osteoblasts), under the regulation of osteocytes. Several treatments target this negative balance. Osteoclasts can be inhibited by hormones (estrogens, calcitonin) or hormone-mimetics (raloxifene). However, the most commonly used agents are the bisphosphonates that interfere the mevalonate pathway inducing osteoclasts inhibition and apoptosis.

The osteoclast express a receptor, RANK (Receptor Activator of N-kappa cells) that, when activated by its ligand, RANKL, induces differentiation and activation of the osteoclast. Most of the conditions that induce bone loss share this final common pathway. Osteoprotegerin (OPG) a decoy receptor blocks RANKL and, thus, bone resorption. Monoclonal antibodies against RANKL exert a powerful effect of bone resorption inhibition, mimicking OPG action.

Genetic variants associated to high bone mass have permitted the discovery of the Wnt pathway, essential regulator of bone formation. The Wnt-ß catenin canonical pathway is key for osteoblastic activation and bone formation. Sclerostin (SOST) and DKK1 can downregulate this signaling system decreasing bone formation. Monoclonal antibodies targeting SOST by neutralizing or DKK1 by nnnn vigorously increase bone formation. Agents like PTH may exert their anabolic effect by acting on the SOST system.

In summary, treatment of osteoporosis lies on the increasing knowledge of the mechanisms that regulate bone physiology. In this way we will be capable of improving the efficacy and safety of the pharmacotherapy of this disease.