Antiresorptive agents form an important part of the treatment strategy in almost every patient with osteoporosis. They are used both as the primary treatment option and as a means of maintaining gains in bone mass after bone anabolic therapy. Marketed drugs in this category comprise bisphosphonates, SERMs, calcitonin, and denosumab. By virtue of their effect on bone remodeling, potent antiresorptives have the potential to cause hypocalcaemia in susceptible patients (especially in the face of hypovitaminosis D or partial hypoparathyrodism) and they all delay the removal of old bone tissue. Though they share an ability to reduce bone resorption, there are also great differences. Bisphosphonates are stored in bone, though with differences in binding kinetics within the drug family, whereas other antiresorptives (apart from the mixed action drug strontium ranelate) are not. The optimum duration of antiresorptive treatment is 28 and may be different in different patients and with different drugs. Concerns directly related to the mechanism of action include Osteonecrosis of the Jaw (ONJ) and atypical femur fractures (AFF). Both outcomes are clearly overrepresented among bisphosphonate users but confounding by indication is a concern. The rate of AFF appears to be much too low to be determined from clinical trials and these are usually of relatively short duration. In addition, original x-rays are no longer available from phase III trials for assesment of criteria for atypical fracture. For ONJ, the strongest information comes from the oncology setting where frequent i.v. dosing is the norm. Non-skeletal adverse events are not uncommon and vary by drug class. Most are mild. Associations between oral bisphosphonates and oesophageal cancer are controversial, and will be discussed, as are associations between bisphosphonates and cardiovascular outcomes.
Declaration of interest: Conflict of Interest: Grant / Research support from Novartis, Nycomed, Amgen, Merck Speakers Bureau with Nycomed, Merck, Eli Lilly.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.