Studies of combinations of osteoporosis medications expanded at the American Society for Bone and Mineral Research (ASBMR) 2012. Previous meetings featured alternating the anabolic, Teriparatide (Forteo) with a Bisphosphonate Antiresorptive, usually Alendronate (generic Fosamax), and, more recently, simultaneous Alendronate and Forteo. This time we heard about the first study of Denosumab (Prolia) combined with Forteo. [Disclosure: I am on the Orthopedic Advisory Board for Prolia, and Speakers Bureau for Forteo]
The Bone Mineral Density (BMD) increase at one year was much better for the combination than for either drug alone. This is the same effect we have seen with previous combinations, but higher BMD numbers. This study had small numbers of patients (<200), and a short period of time (<2 years). It is not clear, whether the greater BMD of this combination is of any significance, and how well it will hold up over time. Also, BMD is not the whole story.
BMD is the easiest aspect of Fracture Risk to measure. However, bone quality (most easily evaluated by FRAX and Vertebral Fracture Assessment – VFA) is another factor. Increased bone turnover is thought to be nearly as important in the success of Forteo as the increase in bone matrix and BMD. In the combination, Prolia apparently suppresses bone turnover, leading to a greater increase in BMD. The benefit of this over the long term is not yet clear.
I have discussed my concerns with the head of Prolia research at Amgen. He expects to have further data next spring. We need several more years and several thousand patients to be sure of what this new combination does and how. But for now, it is very interesting indeed.
Jay Ginther, MD