Daily and cyclic parathyroid hormone in women receiving alendronate
N Engl J Med. 2005 Aug 11;353(6):566-75, Cosman F and others. PMID: 16093465. This study was significant for several reason: 1) It tested whether there would be increased benefits to people taking alendronate (Fosamax) if they had parathyroid hormone (1-34) (Forteo) added to the alendronate regimen. The authors concluded there was improvement when Forteo is given to women already taking alendronate (about 6% increase in bone mineral density). 2) It used a cyclic regimen for the Forteo of three months on three months off during the 15-month trial. This cyclic method, which is much cheaper and involves 50% fewer injections, was almost equal to the full-time Forteo therapy. (See the abstract for details of the study methods and outcomes). This cyclic method was tried because it is known that Forteo first stimulates bone formation which is followed then by bone remodeling. It was suggested that the cyclic method stimulates the bone formation phase and avoids the bone remodeling phase--which is less beneficial. An interesting side light of this study is the breakout of bone mineral density (BMD) increase is shown, not only as the mean of all the participants, but by percentage increase amongst the various participants. Thus, 72% had an increase of at least 3%; 58% had an increase of at least 5%, 14% had an increase of at least 10 percent; and 6 percent had an increase of at least 15%. It is interesting that there could be such a huge difference in response among the participants, indeed 5 times greater increase in BMD in a small percentage of the women. And some women apparently didn't respond at all to the added Forteo. This data makes you wonder what causes that large difference. If researchers could find out, and target the high-end response for all participants, this could provide excellent results in future studies. But that is a big "if."
Editor's comments: Very often someone who needs to take Forteo to try to rapidly reduce the risk of bone fracture may have already been taking one of the bisphosphonates, such as Fosamax, for osteoporosis. This study shows that adding the Forteo to the regimen at that point will give improved results compared to taking Fosamax alone. The study didn't include a group that stopped taking Fosamax, so it is unknown if the results would have changed had the Fosamax been stopped and a group taken only Forteo. The results also show that reducing the number of Forteo injections by 50%--three months on and three months off--gives almost equal results to full-time injections. Forteo is not cheap, so the dollar savings could be significant, and that is combined with the comfort and convenience of 50% fewer injections. That combination makes the cyclic alternative quite interesting. Patients might want to discuss this with their care providers. NOTE: As often occurs, men were not included in this study, but were included in the FDA approval for Forteo. Just remember there is a slight consideration of increased prostate cancer risk with parathyroid injections, so men should discuss this with their physicians. Even on this issue the cyclic regimen would appear to be potentially beneficial since fewer injections and less medication would be used, with the probable decrease in risk.