A recent study demonstrated that in patients discontinuing DMAB after 4.6±1.6 years, a subsequent single infusion of 5 mg ZOL given six or nine months after the last DMAB injection or when bone turnover was increased, did not fully prevent increases in bone turnover and bone loss.

This randomized, open-label, interventional study aimed to investigate if treatment with ZOL could prevent increases in bone turnover and bone loss in patients previously treated with DMAB. It also determined if the timing of the administration after the last injection of DMAB influenced the outcome effect of ZOL.

The study included 61 participants with osteopenia who discontinued long-term treatment with DMAB to ZOL at three different intervals after the last DMAB injection. 59 patients completed the follow-up period. Patients were randomly assigned to receive ZOL six (6M group, n=20) or nine months (9M group, n=20) after the last DMAB injection or when bone turnover had increased (OBS; Observation group, n=21).

Using DXA (dual-energy x-ray absorptiometry) and bone turnover markers, the patients were monitored. The primary endpoints were changes in LSBMD (lumbar spine bone mineral density) six months after ZOL and the proportion of patients who failed to maintain BMD.

Six months after ZOL, LSBMD had decreased significantly by 2.1±0.9% (mean ± SEM), 4.3±1.1% and 3.0±1.1% in the 6M, 9M and OBS groups, respectively. 12 months after ZOL, LSBMD reduced by 4.8±0.7%, 4.1±1.1%, and 4.7±1.2% in the 6M, 9M, and OBS groups, respectively as depicted in Table 1:

In all groups, BMD loss above the least significant change was witnessed: At the spine: 6M:n=6 (30%), 9M: n=9 (45%), OBS: n= 9 (47%). At the total hip, the values were: 6M: n=1 (5%), 9M: n=5 (25%), OBS: n=2 (11%) as depicted in Table 2:

In the 6M group, p-CTX (p-cross-linked C-terminal telopeptide) declined initially but rapidly elevated thereafter. Six months after ZOL, p-CTX was 0.60±0.08 g/L.  In the 9M and OBS groups, p-CTX elevated rapidly. It was suppressed by ZOL but elevated again thereafter; p-CTX was 0.47±0.05 μg/L and 0.47±0.05 μg/L six months after ZOL, respectively. In the 9M group, incident vertebral fractures were observed in two women. Thus, ZOL treatment cannot fully prevent the loss of BMD in patients discontinuing DMAB.