Purpose: Denosumab (DMAB) decreases bone resorption and fracture risk. After discontinuation, however, bone resorption increases, bone mass is lost and fractures have been reported. The aim of the study was to investigate if infusion of zoledronic acid (ZOL) could prevent increases in bone turnover and bone loss in patients previously treated with DMAB and if the timing of the first infusion of ZOL is important.
Methods:The study was a 2-year randomized, open label, interventional study in patients with osteopenia after DMAB treatment for an average of 4.6 years. ZOL was administrated 6 months (6M group, n=20) or 9 months (9M group, n=20) after the last DMAB injection or when bone turnover was increased (OBS group, n=20). Patients in the OBS and the 9M groups were monitored monthly and if s-carboxy-terminal collagen crosslinks (s-CTX) increased > 1.26 ug/l (50% above the range for postmenopausal women and elderly men) or if a patient suffered a fragility vertebral or hip fracture, ZOL was administered. DXA was performed after 3 months in the OBS group, and if BMD decreased > 5%, ZOL was administered. The patients were monitored with DXA 6, 12 and 24 months after treatment. ZOL was re-administered if BMD decreased > 5% or if s-CTX increased > 1.26 ug/l. We report the analysis of the outcome 12 months after the initial ZOL. The study is ongoing.
Results: A total of 60 postmenopausal women and men, mean age 67.7 (range 51-85) years were enrolled in the study. In the OBS group 1, 2, 6, 1 and 0 patients fulfilled the CTX or BMD criteria for treatment 1, 2, 3, 4 and 5 months after baseline. The remaining 10 patients were treated 6 months after baseline according to protocol. In the 9M group 2 patients fulfilled the CTX criteria at month 2. Nineteen patients (32%) fulfilled the criteria for re-retreatment during the follow-up. Twelve months after ZOL BMD was decreased at the lumbar spine by 4.8±0.7%, 4.2±1.1%, and 4.9±1.4% in the 6M, 9M and OBS groups, respectively (p≤0.006 for all without differences between groups) and at the total hip BMD by 2.6±0.5%, 3.3±0.8%, and 3.8±0.9% in the 6M, 9M and OBS groups, respectively (p≤0.001 for all without differences between groups). Mean CTX was within the postmenopausal reference range 6 and 12 months after the initial treatment in all 3 groups.
Conclusion: Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia.