Following BMD in Patients on Bisphosphonates: Another Perspective

A recent posthoc analysis of the FIT trial concluded that if women take bisphosphonates, they will have a decrease in fracture risk. An accompanying editorial supported the conclusion by Bell et al. that monitoring patients with BMD testing using DXA is unnecessary. In the perspective by Watts et al. in this issue of the JBMR, several arguments are made to justify DXA monitoring of therapeutic response in osteoporotic patients. What is the conscientious clinician to do when well-regarded experts cannot agree on a very important issue that comes up in practice every day? In the United Kingdom, bone densitometers are relatively rare, and use of technology is discouraged. In the United States, bone densitometers are common, and although their use may be declining because of decreased reimbursement, the United States is often at the forefront in the use of technology. Perhaps this is an issue of medical culture, but regardless of location, we are expected to practice evidence-based medicine. Clinicians who read BMD tests and see women and men with osteoporosis need an answer. What should we tell patients, colleagues, and trainees about following DXA in patients taking bisphosphonates? We are supposed to be the experts. Let us look at some of the arguments of Watts et al. First, it is true that subjects who are selected to participate in randomized, controlled trials often differ from many patients we see in practice. Those of us who have participated in clinical trials know that inclusion criteria often disqualify patients with osteoporosis that would not exclude them from using the same medication after it has been approved by the FDA. Second, we hold posthoc analyses in lower regard than planned analyses. Third, bisphosphonates are not all alike in their actions on both BMD and bone turnover markers, and perhaps on fracture risk reduction. For example, the currently available preparations of generic alendronate specifically have not been tested for their potency to change fracture surrogates (BMD, bone turnover markers) or fracture risk. Can we extrapolate the effects of the various generic alendronate preparations to the results of randomized, controlled trials using the preparation of alendronate subsequently released as Fosamax? On the other hand, the women in the FIT trial dosed with daily alendronate obviously adhered to therapy, because virtually all responded to treatment with either increased or stable BMD and reduced fracture risk. As pointed out by Chapurlat et al., even those women whose BMD decreased >4% (at 1 yr, importantly) had fewer vertebral fractures. Many of us who read BMD tests offer clinical recommendations with our report. Some recent observations of patients in one of our practices illustrate the potential value of DXA testing: a man took alendronate for 1 yr and then stopped. The DXA scans repeated 1 yr after stopping the medication showed statistically significant increases in the BMD of the spine and hip. The DXA report included a recommendation that his primary physician restart alendronate. Would the discovery of an early response to treatment have happened had he not undergone the DXA study? A second patient stopped alendronate before undergoing invasive dental work to insert implants. His BMD was unchanged 2 yr after the pretreatment DXA. The DXA report included a similar recommendation to restart alendronate once the mouth had healed. We have managed a number of patients who discontinued oral bisphosphonate therapy because of worsening gastroesophageal reflux (GERD). The DXA report provides an opportunity to suggest the use of intravenous zoledronic acid or ibandronate as an alternative to no therapy or continued symptoms with the oral bisphosphonates. Whereas some primary physicians may have had experience in switching such patients to intravenous therapy, others may have not have been aware of alternate treatment or are not experienced in the use of the intravenous treatment. Thus, there is at least anecdotal evidence that some patients indeed benefit from repeat DXA studies. Clearly, there is a need for studies on the optimal intervals between DXA tests. At the recent annual meeting of the Endocrine Society, one of us presented the results