Calcitonin therapy: is the story coming to an end?

Abstract

Clinicians who treat postmenopausal osteoporosis today have a number of proven therapeutic agents at their disposal, but this wasn’t always the case in the bone field. Just two decades ago, doctors could offer their patients only estrogen—or calcitonin. Filling the pre-bisphosphonate era treatment gap, calcitonin would become a huge commercial success: in 1992, more than 900 million US dollars’ worth of calcitonin was sold worldwide. Even 10 years later, more than 4 million prescriptions for Miacalcin, a salmon calcitonin nasal spray, were dispensed just in the US alone. If sales are the guide, calcitonin was a blockbuster drug in its day. In 2012, the landscape of osteoporosis treatment looks dramatically different. Having long been overshadowed by bisphosphonates, which were first approved for clinical use in the mid-1990s, calcitonin now represents only a sliver of the market for osteoporosis medications; in many regions, including the US, it has been many years since calcitonin played a meaningful role in the clinic. Considering this greatly diminished presence, it is perhaps unsurprising that a July 2012 recommendation by the European Medicines Agency (EMA) that physicians no longer use calcitonin to treat osteoporosis met with little attention at the time. After conducting a risk– benefit review of available clinical data, the EMA’s Committee for Medicinal Products for Human Use (CHMP) found a small but significant increase in cancer incidence in patients taking calcitonin-containing medicines for osteoporosis or osteoarthritis. What is the bone field to make of this news? Osteoporosis experts told BoneKEy that the evidence linking calcitonin to cancer is weak. Regardless, as more powerful drugs have long been available to treat osteoporosis, they say the loss of calcitonin from the therapeutic armamentarium will have little impact. In fact, as an osteoporosis therapy, calcitonin has always had many skeptics. The drug never found a secure spot in clinical practice, owing its commercial success more to the lack of availability of other osteoporosis agents rather than to evidence of efficacy. Still, if it will soon be time to write calcitonin’s epitaph, it would be unfair for that statement to focus solely on efficacy. From a historical vantage point, the clinical development of calcitonin was an important stepping stone for the bone field on the path towards more powerful osteoporosis drugs and better-designed clinical trials. However, it is from the basic science perspective that calcitonin’s influence has been most deeply felt. Calcitonin was the first paradigm of a bone resorption inhibitor, and it stimulated much fruitful laboratory research, by some of the bone field’s most respected investigators, into bone biology and peptide biology. Yet, even in that light, calcitonin is still somewhat of an enigma: 50 years after its discovery, calcitonin’s exact physiological role in humans remains unclear.