Two teriparatide studies and risedronate fracture results
Two teriparatide studies. This first study concerns teriparatide's effects on vertebral fractures and bone mineral density (BMD) in men during treatment and after discontinuation of therapy. See: Osteoporos Int. 2004 Aug 18 [Epub ahead of print], Kaufman JM and others. PMID: 15322742. Teriparatide (Forteo) has been shown to be an effective bone forming agent in men and women and to reduce fractures in women. This study was done to see if it also reduced fractures in men. Three hundred fifty-five men were in the study and treated with either 20 or 40 micro g of teriparatide once daily. A follow up study after discontinuing therapy and starting bisphosphonate (BP) antiresorptive therapy was done. If BP therapy was used spine and hip BMD levels remained higher compared to men who discontinued teriparatide and didn't take BP. In the teriparatide groups, fracture rates were reduced 51% compared to placebo (nonsignificant, p=0.07). However, the incidence of moderate and severe fractures was significantly reduced by 83% (p=0.01). The authors concluded, ". . .men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe fractures." Editor's comments: Fracture reduction is the key element that we are searching for in osteoporosis therapy. So it is important to see that teriparatide therapy decreases the incidence of fractures, especially the more severe type.
The second study concerns using teriparatide after treatment with either raloxifene (hormone therapy for women only) or alendronate (Fosamax). See: J Bone Miner R. 2004 May;19(5):745-51. Ettinger B and others, PMID: 15068497. Participants in the study were given 20 micro g daily injections of teriparatide along with 1000 mg daily calcium and 400 IU vitamin D daily for 18 months. They had all received either alendronate or raloxifene before starting the teriparatide. The authors compared outcomes using DXA and looking at bone turnover markers. What is important in this study is that prior treatment of participants with alendronate, ". . .prevents increases in BMD, particularly in the first 6 months." Editor's comments: Since substantial amounts of bisphosphonates are incorporated into bone during therapy and that it has a half-life of about ten year, it is entirely reasonable that it could be having a negative effect on teriparatide results. It is noteworthy, however, to recall that in previous studies where teriparatide was given concomitantly with bisphosphonates, that combination therapy gave better results than taking only Fosamax. But, adding the Fosamax decreased the effectiveness compared to just using Forteo. See the recent Update on this topic. So, here are the options as I see it: Before starting therapy: If there is any doubt that Forteo might be the medication of choice, start with it, don't start with a bisphosphonate planning on using Forteo later if results are unsatisfactory with the bisphosphonate. After starting therapy with Forteo: Don't combine the use of bisphosphonates. You should, however, use bisphosphonates when Forteo therapy is discontinued.
Does increased BMD mean decreased fracture risk when using risedronate? See: J Clin Densitom. 2004 Fall;7(3):255-61. Watts NB and others, PMID: 15319494. Although it is known that low BMD correlates with increased fracture risk, it is controversial whether increases in BMD after osteoporosis drug therapy also decreases fracture risk. This paper analyzed data from three studies on women who received risedronate (n=2047) or placebo (n=1177) daily for up to three years. The authors found that there was decreased fracture risk of about 10% in women whose BMD increases were <5% or were >/=5%. And the changes in lumbar spine BMD explained only 18% of risedronate's vertebral fracture efficacy. They concluded, "Although patients showing an increase in BMD had a lower fracture risk than patients showing a decrease in BMD, greater increases in BMD did not necessarily predict greater decreases in fracture risk." Editor's comments: There is often the question of the importance of the quality of bone vs. the quantity. This appears to be another study to add to that controversy. It is always reassuring to see a direct one-to-one correspondence between cause and effect. That is, if BMD increases X, fracture reduction is Y. If BMD increases 2X, fracture reduction is 2Y, etc. Life is seldom that simple, however, as appears to be the case in the study above. Apparently the quality of the bone formed (which is hard to determine with any diagnostic tests currently available) isn't necessarily directly related to increases in BMD. What is important is that fractures are reduced after taking risedronate, even though not in an exact relationship with increasing BMD.