Fosamax® Needs a Break

“Take a break to prevent a break” might become a safety slogan for the drugs that have been used with apparent success to treat osteoporosis. Alendronate, the drug we know as Fosamax® may actually weaken bone and lead to increased fracture risk.

Alendronate belongs to a class of drugs called bisphosphonates. These chemicals were developed in the 19th century but were not investigated until the 1960s for use in disorders of bone metabolism. Their non-medical use was to soften water in irrigation systems used in orange groves. The rationale for giving them to people was that they prevented the dissolution of hydroxylapatite, the principal bone mineral, and in turn, stopped bone loss. Only in the 1990s was their actual mechanism of action explained when Merck brought Fosamax® to the marketplace.

There is little doubt that these drugs do what they are supposed to over the short term: increase bone density and decrease fracture risk.  The FOSIT study published in 1999 told us this quite clearly. This study reported on 1,908  healthy, postmenopausal women with osteoporosis, 950 of whom  took 10 mg of Fosamax® for a year, while the other 958 got a placebo. Both groups took 500 mg of calcium per day.  After a year, bone mineral density increased by almost 5 percent on average in those taking the Fosamax® compared to the placebo group. Non-spinal fractures decreased. Of those taking the drug only 19 suffered fractures compared to 37 of those taking the placebo.

From the first use of these drugs, there was always a theoretical worry. Recall that there are two main processes that occur constantly in the bone: osteoclastic activity that breaks down old bone, and osteoblastic activity that builds up new bone; this constant turnover of bone maintains healthy and strong bones. Bisphosphonate drugs stop the osteoclastic activity so that old bone is left untouched; this increases bone density measurements. The worry was that because these drugs halt normal bone turnover people using them would end up with dense, but more brittle bones. As the early studies consistently showed a rapid reduction in fracture rates, this concern faded.

Unfortunately, these early worries were not just a product of naturopathic paranoia; the problems took just a few years to show up. The May/June 2008 issue of The Journal of Orthopaedic Trauma published a report on “Low-energy femoral shaft fractures associated with alendronate use.” The authors reviewed records of 70 patients who had sustained low- energy femur fractures. That means their femurs broke without any major stress. Rather they did little things such as walking or stepping off a curb and thus triggered the breaks. These were not young people—their average age was about 75. Of these 70 patients, 25 of them (a little more than a third, or 36 percent), were taking Fosamax®. Nineteen (76 percent) of those 25 patients demonstrated a simple, transverse fracture with a unicortical break in an area of cortical hypertrophy. This is a rare and peculiar type of fracture. Only one patient of those not taking Fosamax® (2 percent) had this kind of bone break. When the statistics were worked out, the numbers tell us that Fosamax® use significantly increased risk of these fractures: the odds ratio was 139.33, 95% CI [19.0-939.4], P <0.0001). In other words, you can say that those taking Fosamax® were about 140 times more likely to get one of these rare fractures.  It took about seven years for this problem to occur. Those taking Fosamax® for less than two and a half years were not at greater risk.

A 2009 paper in Geriatrics continued this story. It tells us that, “The fractures are often preceded by pain in the affected thigh…” this paper suggests that patients not take Fosamax® for longer than five years. Another 2009 article, this one in Clinical Calcium, echoed this warning and suggested that, “… alendronate treatment might be stopped for a while after five years to prevent [these kinds of]… fractures.”

Researcher from Johns Hopkins repeated this same story in the journal Orthopedics in August 2009. Then in November 2009, doctors from New York University reported on seven different patients who had broken both legs. The average age of these patients was 61 years and on average they had taken Fosamax® for 8.6 years. One patient had broken both legs simultaneously.

Few doctors and fewer patients are paying attention to duration of Fosamax® use. Most patients will report they’ve taken Fosamax®, “for awhile.” Doctors need to start spreading the message that “for awhile” should be less than five years.

In our practice, we are suggesting a break from use after a shorter period of time, about three years. Discontinuing Fosamax® use and relying solely on naturopathic treatments, even for an interval of time, may, in the long run, prove to be a safer course of action.

Unfortunately, over the years, as Fosamax® was used with apparent benefit by so many people, many of us grew lax, thinking that our early worries were unfounded. In hindsight, this may have been a problem all along. It’s only in the last few years that enough patients have taken the drug long enough that we can actually see the results of long-term bone suppression.