Understanding the Fosamax problem

FOSAMAX works by inhibiting bone resorption and suppressing bone turnover. Bone mineralization occurs in two phases. Primary mineralization occurs while new bone is forming. Because FOSAMAX severely suppresses bone turnover, bone remodeling and primary mineralization are inhibited. Secondary mineralization of existing bone however, continues to occur. This results in an increase in the tissue mineral content of the bone which translates to an increase in bone mineral density (BMD). Increased BMD does not necessarily correspond with reduction of fracture risk. Additionally, through the bisphosphonate mechanism of action, bone becomes highly mineralized, homogenous, brittle, and more susceptible to fracture.

MERCK knew or should have known that by inhibiting bone turnover while at the same time allowing the secondary mineralization of old bone to continue, long term FOSAMAX therapy would result in bones becoming highly mineralized, brittle and more susceptible to fracture. This is especially true given the fact that the effects of FOSAMAX on the bone accumulate and continue for years after treatment is discontinued.

MERCK’s 1997 Fracture Intervention Trial (FIT) reported a 47% reduction in the risk of new vertebral fractures and a 28% reduction in the risk of clinical fractures in postmenopausal women taking alendronate compared to those taking a placebo. Ensrud et al., Treatment with Alendronate Prevents Fractures in Women with Highest Risk, 157 Arch. of Int. Med. 2617 (Dec. 8/22, 1997).

Medical researchers in the January 19, 2008, issue of British Medical Journal revealed the manner in which bisphosphonates such as FOSAMAX are presented to reduce fracture risk for those women who actually do have osteoporosis tends to exaggerate the actual fracture reduction benefit conferred. According to the authors, published critical trials exaggerated the fracture-reduction benefits through the use of relative risk rather than in terms of absolute risk. As the authors state: Impressive sounding reductions in relative risk can mask much smaller reductions in absolute risk. By using the math of relative risk rather than absolute risk, the purported benefits of the drugs appear larger than they actually are in the general population. As a result, billions of dollars are being spent on a drug that has questionable utility for the ultimate goal of fracture reduction.

Correspondingly, when examined in a clinical setting, later observational studies revealed that the FIT study exaggerated the benefit derived from alendronate therapy in reducing the risk of fracture. The 2006 ICARO study concluded that the incidence of fractures during treatment with antiresorptive agents, including FOSAMAX, in a clinical setting is considerably higher than that observed in randomized clinical trials, especially when therapy was not supplemented with calcium and vitamin D. Silvano et al., Fracture Incidence and Characterization in patients on Osteoporosis Treatment: The ICARO Study, 21 J. Bone and Mineral Research 1565 (2006).

It is really not a question of whether a woman who has taken Fosamax for over 5 years will suffer a femur break. It will happen, and the really question is simply, “When?” Thanks, Merck for targeting and putting millions of women at huge risk for a broken femur so you could make your billions.