Prevalence of severe suppression of bone turnover (SSBT) in patients on longterm bisphosphonate (BP) therapy

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Conference Proceeding

Publication Date


Publication Title

Journal of Bone and Mineral Research


In vivo tetracycline labeling of bone is a gold standard maker to determine the rate of bone turnover (or bone remodeling). Severe suppression of bone turnover (SSBT) is commonly defined as complete absence of tetracycline labeling in cancellous bone. However, it is inappropriate to assume that bone with tetracycline labeling, no matter how little, as having normal bone turnover. In the current study, we developed reference range for bone turnover based on the results from healthy premenopausal women, the lower limit of which as the cutoff to define SSBT. The bone turnover-related variables, including mineralizing surface (MS/BS, %), mineral apposition rate (MAR, μm/day), bone formation rate (BFR/BS, μm3 /μm2/ year) and activation frequency (Ac.f, /year), were determined in iliac bone biopsies obtained from 43 healthy premenopausal white women. The reference range was defined as a 95% interval with 2.5% of the values less than the lower limit and 2.5% were more than the upper limit. SSBT was defined when BFR/BS and/or Ac.f fell below the lower limit. The same measurements were performed on iliac bone biopsies from postmenopausal healthy women and from patients on long-term BP therapy (all postmenopausal) with and without atypical femur fracture (AFF). The results are shown in Table 1. Since wall thickness to calculate Ac.f may not be detected in some patients with BP exposure, we suggest BFR/BS as more appropriate variable to define bone turnover. In postmenopausal women, the prevalence of SSBT was < 5% in cancellous bone, and none in whole biopsy. In contrast, the prevalence of SSBT increased to approximately 60% in cancellous bone and 30% in whole biopsy in BP-treated patients, both of which were significantly higher than those in postmenopausal women. However, there was no significant difference in the prevalence of SSBT between BP treated patients with and without AFF. In conclusion, this study confirms that BP exposure can significantly increase the risk of SSBT in postmenopausal women. Although the prevalence of SSBT was similar in BP-treated patients with and without AFF, a higher trend was seen in patients with AFF.




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