Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density

Abstract

For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values.

Pharmacology of bisphosphonates

“…Long‐term PK might also be determined by the binding properties of the BPs (in conjunction with their potency), which might to some extent explain the differences in loss of the anti‐resorptive effect after treatment discontinuation with alendronate or risedronate. In a head‐to‐head study comparing the effect of stopping alendronate, risedronate or ibandronate, all bone turnover markers (BTMs) increased after treatment withdrawal, but remained below the pretreatment baseline with less suppression of BTMs for the risedronate group as compared to alendronate and ibandronate up to 48 weeks following treatment discontinuation . The only head‐to‐head study comparing the PK of BPs in humans used accelerator mass spectrometry to demonstrate that after intravenous administration, whole body retention (WBR) of risedronate was less than alendronate [51.0 vs 55.5%, respectively after 24 h; 33.8 vs 44.9%, respectively after 4 weeks] .…”

“…This difference in retention might explain the difference in loss of the anti‐resorptive effect between alendronate and risedronate, albeit the differences in both WBR and BTM levels seem relatively small. Interestingly, the change in bone mineral density (BMD) 96 weeks after treatment discontinuation with alendronate, risedronate or ibandronate was the same, again illustrating our incomplete understanding of the clinical and translational pharmacology of BPs.…”

“…BTMs, in combination with BMD, are used successfully to monitor so‐called drug holidays from BPs . These “drug holidays” aim to avoid administering BPs continuously for more than a few years.…”

MANAGEMENT OF ENDOCRINE DISEASE: Treatment breaks in long-term management of osteoporosis

“…This perspective is focused on treatment breaks in patients treated with alendronate or zoledronic acid as these are the treatments investigated in clinical trials large enough to investigate fractures in patients off treatment. Similar studies have not been performed for the other bisphosphonates available, but the recent TRIO study suggests that the off treatment effect on bone turnover markers are similar between the mostly used oral bisphosphonates (33). On the contrary, these considerations do not apply to treatment with denosumab, where a rebound activation of bone turnover and a rapid bone loss are seen when stopping the treatment.…”

Treatment of Osteoporosis with Bisphosphonates: Is Vitamin D Necessary?

“…If the patient has a very low bone mineral density (BMD), or BMD is lost during the annual controls, or the resorption markers are elevated, it is necessary to consider either the reinitiation of the BP or the beginning of another antiosteoporotic medication [4,5]. Likewise, if high risk indicators (such as falls, new fractures, diagnosis of diabetes, or indication of glucocorticoid therapy) appear in the course of follow-up, BP must be reindicated, or another treatment must be started [6].…”