Combination or sequential teriparatide for osteoporosis treatment in denosumab-users: real-world bone mineral density outcomes

The optimal osteoanabolic strategy in denosumab (Dmab)-users remains uncertain. In treatment-naïve patients, Dmab/teriparatide (TPTD) combinations result in dramatic bone mineral density (BMD) gains at the spine and hip. However, BMD outcomes with combination Dmab/TPTD have not been investigated in patients on <i>established</i> Dmab. We retrospectively reviewed patients with osteoporosis at two Sydney centers between 2013 and 2023. Eligible patients were managed with Dmab immediately before ≥12-months TPTD. Patients were grouped according to whether TPTD was added to ongoing Dmab (<i>combination</i>) or Dmab was withheld during TPTD (<i>sequence</i>). BMD outcomes were assessed during TPTD. The total cohort (<i>N</i> = 23; 11 = combination, 12 = sequence) had mean age 77 ± 7 years and were predominantly female (87 %). Overall, prior vertebral (52 %) and non-vertebral fractures (2.4 ± 1.5) were prevalent and pre-TPTD BMD T-scores (SD) low at lumbar spine (-2.4 ± 1.2) and total hip (-2.2 ± 0.6). Median Dmab exposure was 5-doses (IQR 3-11), median overall antiresorptive exposure was 6-years (IQR 4-11) and majority (>90 %) received 18-months TPTD. Groups were similar in age, sex, Dmab and overall antiresorptive exposure, fracture prevalence, DXA interval and pre-TPTD BMD values. Combination Dmab/TPTD was associated with significant lumbar spine BMD gains (+0.080 g/cm² ± 0.059 g/cm², <i>p</i> = 0.004; +9.8 %). No significant BMD change occurred during sequential Dmab/TPTD (+0.026 g/cm² ± 0.049 g/cm², <i>p</i> = 0.107; +3.5 %). Combination Dmab/TPTD resulted in greater lumbar spine BMD gains (<i>p</i> = 0.039). Hip and femoral neck BMD remained stable in both groups. In this retrospective study, significant lumbar spine BMD gains occurred during combined Dmab/TPTD in patients on established Dmab. These results warrant prospective controlled studies to further inform optimal osteoanabolic strategies in Dmab-users.