Osteoporosis is a systemic skeletal disease characterized by low bone mass and deteriorated bone microarchitecture that leads to increased risk of fractures. The aim of osteoporosis treatment is to reduce the increased risk of fractures. This can be obtained by different means, including reducing the risk of falls, but also by increasing bone strength. In the past the focus was on antiresorptive therapies that worked through inhibition of the osteoclasts. Supplementation with calcium and vitamin D and hormone replacement therapy were among the first therapies available. It is controversial how strong the antiresorptive effect of calcium and vitamin D is, whereas the WHI study confirmed the antiresorptive and fracture risk reducing effects of HRT. The clinical use of HRT is limited by the adverse effects. The development of more bone targeted therapies took off in the 1960s with the discovery of the bisphosphonates. Bisphosphonates adhere to bone surfaces and prevent osteoclasts from resorbing bone. Several different bisphosphonates have been developed for the treatment of osteoporosis and the more potent bisphosphonates; risedronate, alendronate and zoledronic acid are among the most used therapies for osteoporosis today. They reduce the risk of vertebral, hip and non-vertebral fractures by approximately 70%, 40% and 20%, respectively. The interest in generating bone forming agents lead to the development of teriparatide (PTH 1-34). Teriparatide, administrated intermittently, stimulates the osteoblasts and bone formation. It is primarily used for the treatment of severe osteoporosis with the aim of not only preventing fractures in the short term, but also increasing bone mass and improving bone structure. Treatment with teriparatide should be followed by an antiresorptive treatment. In the 1990s and 2000s several important pathways in bone have been unraveled. This had lead to deveopment of new treatments; denosumab is an antibody against RANKL with a very strong antiresorptive effect. Romosozumab is an antibody against sclerostin and the first dual-acting therapy for osteoporosis. Romosozumab stimulates bone formation and inhibits bone resorption. Romosozumab is currently under clinical investigation in phase 3 trials. Recently, Abaloparatide, a PTHrP analogue has been approved for the treatment of osteoporosis. Abaloparatide has many similarities with teriparatide but is less likely to cause hypercalcemia.

Osteoporosis therapies have been developed over more than 6 decades with the focus shifting from antiresorptive, over bone forming to dual acting therapies. The challenge remaining is optimizing the use of the different therapies in a personalized approach to treatment.