Can bone turnover markers help to define the duration of bisphosphonate drug holidays?
Louise Statham1,2, Terry Aspray2 & Sharon Abdy2
Author affiliations
1Department of Pharmacy, Health & Well-being, University of Sunderland, Sunderland, UK; 2The Bone Clinic, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
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Background: On cessation of bisphosphonate treatment, while bone mineral density decreases slowly, bone resorptive markers such as C-terminal telopeptide (CTX) increase more quickly and may be useful in monitoring offset of action. Our aim was to analyse changes in CTX on stopping long-term bisphosphonate treatment to guide clinical decision-making on the duration of treatment cessation (drug holidays).
Subjects and methods: A total of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at baseline (n=138), 4 months (n=136) and 12 months (n=100). Offset of action was defined as a rise by the least significant change (LSC=33%) in CTX or CTX above the pre-menopausal mean (0.19 ug/l).
Results: Mean (SD) duration of therapy was 8 (2.7) years, with 59% stopping alendronate and 33% risedronate. At baseline, 32% of CTX measurements were above the pre-menopausal mean, while mean [median, IQR] CTX was 0.18 [0.16, IQR 0.11-0.22] ug/l rising at 4 months to 0.21 [0.20, 0.140.26] ug/l and 12 months 0.24 [0.23, IQR 0.180.29] ug/l. At 4 months, 47% patients showed a rise in CTX above LSC. At 12 months, 69% were above LSC and 66% were above pre-menopausal mean. No detectable changes in CTX were seen in 31% of patients over 12 months.
Conclusion: We found that, after at least 5 years of treatment, CTX may not be adequately suppressed in a third of patients for whom drug adherence should be reviewed. Treatment effects can wear off as quickly as four months but may also be maintained up to a year. However, monitoring of CTX can identify these patients, some of whom may need to restart treatment earlier.