Long-term Use of Bisphosphonates for Osteoporosis

Bisphosphonates (listed in Box 1) are widely prescribed to prevent fractures due to the natural decline in bone strength that occurs as we age. But information about the long-term safety of these drugs is scarce.

Experts tend to disagree about when to stop bisphosphonates, but some patients remain on these drugs for many years. And growing evidence suggests that the long-term use of bisphosphonates may actually lead to hip fractures.

A July 15, 2008, New York Times article discussed a study documenting growing evidence for the long-held concern that long-term use of bisphosphonates can actually make bones brittle and more likely to fracture. In reports, several features appear to distinguish these hip fractures from those typically seen in osteoporosis: fractures occur at a different location in the hip, have unique x-ray findings, and they may be preceded by several months of severe pain at the fracture site.

Although the evidence is far from conclusive, emerging reports of a unique type of fracture in patients receiving bisphosphonates for many years point toward the drug as a possible culprit. Unlike most drugs, bisphosphonates remain in your body for many years after you stop taking them. Too little is known at this point to conclude that the benefits of prolonged bisphosphonate use outweigh the risks beyond five years.

Background

Even though we tend to think of bones as static structures, they are in a continuous process of breakdown and buildup. This process, known as remodeling, functions to repair frequent but subtle damages (“microcracks”) that occur with normal day-to-day activities. However, after our 20s (the point where bone strength is greatest), breakdown occurs at a slightly faster rate, resulting in a slow, steady decline of bone.

In the shorter term, bisphosphonates increase bone strength. They accomplish this by interfering with the cells that break down bone, slowing down or halting the natural process that often leads to osteoporosis.

Clinical trials have evaluated some bisphosphonates for up to 10 years. After five years, the number of hip fractures was the same regardless of whether the patients continued taking the drugs.

However, little is known about the effectiveness of bisphosphonates beyond 10 years. Moreover, we know even less about the long-term safety of these drugs.

What we do know is that the cells that break down bone play a critical role in repairing microcracks. Thus, with long-term suppression of remodeling by bisphosphonates, microcracks may accumulate over time. This could eventually weaken bone, leading to an increased propensity to fracture after minimal stress.

Compounding this suppression of remodeling, bisphosphonates can also lead to relatively higher levels of minerals (calcium) to proteins, compared to normal bone. A potential consequence of this is that bone could become more brittle and more likely to fracture, the concern discussed in the New York Times article.

What You Can Do

Further investigation into the risks, as well as benefits, of long-term bisphosphonate use is needed. But, because there is little evidence of benefit after five years and the long-term risks remain largely unknown, it is reasonable to discuss with your doctor discontinuing these drugs after five years. However, you should continue to take calcium and vitamin D supplements at currently suggested doses (see Box 2), regardless of whether or not you are on bisphosphonates.