Table 2.
Studies evaluating the efficacy of antiresorptives following denosumab discontinuation *.
| Study, Year | Study Type, | n (% Female) | Dmab Duration | Post-Dmab Antiresorptive Regimen | % LS BMD Change (% Mean Dmab Gain Preserved) (% pts Preserved BMD **) |
% TH BMD Change (% Mean Dmab Gain Preserved) (% pts Preserved BMD **) |
% FN BMD Change (% Mean Dmab Gain Preserved) (% pts Preserved BMD **) |
VFs | Non-VFs | Comments |
|---|---|---|---|---|---|---|---|---|---|---|
| Freemantle, 2012 [70] | RCT | 115 (100) | 1 y | ALN, 1 y | 0.6 (100) (NR) | 0.4 (100) (NR) | −0.1 (100) (NR) | 0 | 1 humerus | − DAPS study—primary aim: compliance |
| Lehmann, 2017 [75] | Case series | 22 (100) | 2.5 y | ZOL, 1 infusion | −3.8 (61.2) (NR) | −1.7 (56.4) (NR) | −0.6 (73,9) (NR) | 0 | 1 calcaneous | − BMD measured 2.5 yrs after ZOL |
| Leder, 2017 [76] | Follow-up of RCT | 28 (100) | 2 or 4 y | 1 y, ZOL (n = 8); ALN (n = 8); IBN (n = 2); Dmab (n = 10) | −1.2 (NR) (NR) | NR (NR) (NR) | −0.6 (NR) (NR) | 0 | 1 tibia (stress) | − DATA follow-up − 36% of pts received Dmab |
| Reid, 2017 [77] | Case series | 6 (100) | 7 y | ZOL, 1 infusion | −9.2 (50.3) (NR) | NR (NR) (NR) | NR (NR) (NR) | NR | NR | − Follow-up of FREEDOM pts − BMD reported 2 y after ZOL |
| Horne, 2018 [72] | Case series | 16 (100) | 2 y | 1 y, ZOL (n = 11), RIS (n =5) | ZOL: −5 (73) (NR) RIS: −9.9 (41) (NR) |
ZOL: −1.5 (87) (NR) RIS: −3.9 (64) (NR) |
NR (NR) (NR) | NR | NR | − Follow-up of FRAME pts (1 y romosozumab or placebo before Dmab) − ZOL was given with up to 6 mo delay |
| Anastasilakis, 2019 [46] | RCT | 27 (100) | 2.4 y | ZOL, 1 infusion | 12 mo: 1.7 (100) (NR) 24 mo: 0.1 (100) (11.1) |
NR (NR) (NR) | 12 mo: NR (100) (NR) 24 mo: NR (100) (14.8) |
1 | 0 | − After Dmab study |
| Everts-Graber, 2020 [78] | Retrospective observational | 120 (100) | 2–5 y (mean 3 y) | ZOL, 1 infusion | −3.3 (66) | −2.2 (49) | −1.5 (57) | 3 | 4 (1 calcaneus, low energy—1 distal radius, low energy—1 pubic, high energy—1 humerus, high energy) | − BMD measured 2.5 y after ZOL |
| Everts-Graber, 2020 [79] | Retrospective | 193 (100) | mean 2.5 y | ZOL 1 infusion (n = 171), OR Other (n = 22) (IBN (n = 6), ALN (n = 10), SERMs (n = 6)) | ZOL: −3.6 (NR) (NR) Other: −3.2 (NR) (NR) |
ZOL: −2.5 (NR) (NR) Other: −3.4 (NR) (NR) |
ZOL: −1.6 (NR) (NR )Other: −3.4 (NR) (NR) |
5 (3 on ZOL, 1 on IBN, 1 on SERM) | 3 (all on ZOL) | − The 120 pts of the previous study were included to this study − BMD measured 1–4 y (median 26 mo) after ZOL |
| Kendler, 2020 [71] | Post-hoc analysis of RCT (see DAPS above) | 115 (100) | 1 y | ALN, 1y | 0.6 (100) (84.1) | 0.4 (100) (92.4) | −0.1 (100) (78.3) | 0 | 1 humerus | |
| Kondo, 2020 [80] | Retrospective observational | 30 (96.7) | <3 y (average 1.5 y) | ZOL, 1 infusion | 1.8 (100) (NR) | NR (NR) (NR) | 2.1 (100) (NR) | 0 | 0 | |
| Laroche, 2020 [73] | 18 (100) | 1–4 y (mean 39 mo) | RIS, 3 mo + 9 mo follow-up without RIS | −4.6 (NR) (NR) | −1.8 (NR) (NR) | NR (NR) (NR) | 1 | 0 | ||
| Makras, 2020 [81] | Extension of RCT (see afterDmab above) | 23 (100) | 2.4 y | ZOL, 1 infusion | 36mo: −1.75 (100) (82.6) | NR (NR) (NR) | 36 mo: NR (100) (95.6) | 0 | 1 metatarsal | − In 4 pts LS BMD and in 1 pt FN BMD decreased to T-score < −2.5 |
| Solling, 2020 [63] | RCT | 59 (88.5) | 4.6 y | ZOL, 1 infusion 6 mo after last Dmab dose (6M) OR 9 mo after last Dmab dose (9M) or when turnover increased (OBS) | 6M: −4.8 (NR) (65) 9M: −4.1 (NR) (65 )OBS: −4.7 (NR) (63) |
6M: −2.6 (NR) (15) 9M: −3.2 (NR) (35) OBS: −3.6 (NR) (37) |
6M: −3.0 (NR) (20) 9M: −3.5 (NR) (30) OBS: −4.6 (NR) (37) |
2 | 2 (1 rib, low energy—1 humerus, high energy fracture) |
Abbreviations: ALN, alendronate; BMD, bone mineral density; Dmab, denosumab; FN, femoral neck; IBN, ibandronate; LS, lumbar spine; mo, months; n, number of patients; NR, not reported; pts, patients; RCT, randomized clinical trial; RIS, risedronate; SERM, selective estrogen receptor modulator; TH, total hip; VF, vertebral fracture; non-VF, non-vertebral fracture; y, year; ZOL, zoledronate. * case reports and small case series (<5 subjects) are not reported in the Table. ** different definitions were used among studies to define when a patient would be considered as having preserved his/her BMD.