Oral calcitonin in the management of osteoarthritis: hope or fantasy?

Osteoarthritis (OA) is a progressive disorder characterized by destruction of articular cartilage and subchondral bone, and is associated with synovial changes [1,2]. This degenerative condition affects aging men and women [3]. The two most affected locations for pain and physical disability in adults are hip and knee [4]. Owing to its important prevalence worldwide, OA represents a huge burden for each affected individual, for public health resources utilization [5]. Based on their benefit:risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid has recently been considered as of potential interest for the symptomatic m anagement of OA [6]. Structural modification of the joint is considered to be the most important determinant of OA progression. Several drugs and nutriceuticals have been evaluated as possible disease-modifying OA drugs, and their effects on progression of OA have been published in the past years. These include orally administered glucosamine sulfate, chondroitin sulfate, doxycycline, risedronate and diacereine, and intermittent courses of intra-articular injections of hyluronan [7–9]. Calcitonin (CT) is a polypeptidic hormone that has been recognized for more than 30 years as an inhibitor of osteoclast activity. Although the physiological role of calcitonin in humans has not been fully elucidated, many studies have suggested that it has beneficial effects on the clinical and biological disturbances of diseases that are characterized by excess bone re modeling [10]. For many years, it has been necessary to administer calcitonin parenterally by either intramuscular or subcutaneous injections. Unfortunately, there are several drawbacks to injection – it is nonphysiological and has no relationship to either the site or the rhythm of release of endogenous calcitonin. Furthermore, the effects of injectable calcitonin are poorly reproducible and not well accepted by patients. In some cases, the injection of calcitonin produces unpleasant reactions, including nausea, vomiting, flushing of extremities and vertigo. The drawbacks of injectable calcitonin have stimulated interest in alternative routes of delivery. Substantial evidence of bioavailability and bioefficacy sufficient to produce clinical effects equivalent to those of parenteral administration of calcitonin are currently available for three alternative routes: nasal spray, oral a dministration and rectal suppository [11–13]. It was recently suggested that calcitonin might be an asset in the management of OA [14].