FOLLOW UP OF PATIENTS TAKING BIPHOSPHONATES FOR OSTEOPOROSIS-NO USE OF BMD IN THE FIRST THREE YEARS

July 2, 2009 — Monitoring bone mineral density (BMD) in postmenopausal women in the first 3 years after starting treatment with a potent bisphosphonate is not needed and may even be misleading, according to the results of a study reported in the June 24 Online First issue of the BMJ.

"Guidelines for treatment of postmenopausal osteoporosis differ in their recommendations for monitoring after starting bisphosphonates," write Katy J.L. Bell, from the University of Sydney in Sydney, Australia, and colleagues from the Fracture Intervention Trial. "The US National Osteoporosis Foundation and the American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment....The UK guidelines recommend that further research is needed and the North American guidelines recommend that treatment should not be stopped or changed because of a modest observed loss in density."

The goal of this secondary analysis of trial data using mixed models was to determine the value of monitoring response to bisphosphonate treatment by BMD measurement. The Fracture Intervention Trial was a randomized controlled trial comparing the effects of alendronate vs placebo on BMD after menopause. Between May 1992 and May 1993, a total of 6459 postmenopausal women with low BMD were enrolled and underwent measurement of hip and spine BMD at baseline and at 1, 2, and 3 years after randomization. The primary endpoints of the study were variation in hip and spine BMD, both between-person (treatment related) and within-person (measurement related).

After 3 years' treatment with alendronate, there was an increase in hip BMD by 0.030 g/cm². Although there was some between-person variation in the effects of alendronate, this was small vs within-person variation. In most patients (97.5%), increases in hip BMD of 0.019 g/cm² or more were attributed to alendronate treatment.

"Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading," the study authors write. "Routine monitoring should be avoided in this early period after bisphosphonate treatment is commenced."

Although improved adherence to treatment is sometimes cited as a reason for BMD monitoring, the study authors note that most adverse events occur within 3 months of starting treatment and that discussing any complaints with a healthcare professional a few months after starting therapy improves compliance.

In an accompanying editorial, Juliet Compston, from the University of Cambridge in Cambridge, United Kingdom, notes that biochemical markers of bone turnover could potentially be used for monitoring because they change rapidly in response to treatment and predict fracture risk better than BMD. However, within-person and measurement variability are too high for these markers to allow their routine use in clinical settings.

"If true non-responders to antiresorptive treatment do exist they are rare, and most cases of non-response are caused by failure to persist with treatment," the study authors write. "This is best tackled by carefully explaining the treatment to patients before they start and follow-up after about three months to discuss problems related to treatment. Routine monitoring of bone mineral density during the first few years of antiresorptive treatment cannot be justified because it may mislead patients, lead to inappropriate management decisions, and waste scarce healthcare resources."