THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis.

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2-3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.