Drug free “holiday” from bisphosphonates

I have just read another report of a possible late complication of alendronate — stress fractures of the femoral shaft. We should not be too surprised that a therapy that has been on the market for more than a decade is reported to have potential long-term adverse events, and I stress the word “potential.”

Some ask why these complications were not picked up during the initial safety and efficacy studies. The answer is straightforward: any drug that has such a high incidence of worrying adverse events that they are noted during controlled clinical trials is extremely unlikely to be approved. In the real world it has taken countless numbers of patients taking therapy to even begin to get a hint of these adverse events.

In the meantime here is a suggestion worth considering.

Bisphosphonates prevent bone loss by inhibiting bone resorption reaching a nadir after three to six months. This inhibition lasts for several months after therapy is interrupted. When I see a patient in whom serial bone density studies, done properly after two or more years of therapy, show that bone mineral density is stable I offer the patient a drug free holiday. I use the term “offer” because the patient must be informed that this is off-label use of the drug and few studies have directly addressed this concept.

I get a measurement of a biochemical marker of bone resorption. Serum and urine assays for the amino- and carboxy-terminal telopeptide of collagen cross links — NTX and CTX — are available and reimbursable. If the value is in the lower half of the pre-menopausal reference interval I feel very comfortable interrupting therapy since this indicates that the anti-resorptive therapy is indeed inhibiting resorption. I will then monitor the marker every three to four months so that I can have some idea when the inhibition of resorption is lessening. Two consecutive results showing an increase in the marker is my clue to recommend re-starting therapy.