Efficacy of switching from teriparatide to zoledronic acid or denosumab on bone mineral density and biochemical markers of bone turnover in older patients with severe osteoporosis: a real-life study

Abstract

Purpose: Osteoporosis is characterized by loss of bone mass and susceptibility to fracture. Skeletal effects of teriparatide (TPT) are not persistent after drug withdrawal and sequential therapy with bisphosphonates or denosumab (Dmab) after TPT discontinuation represents a valid option. Here, the two sequential strategies were evaluated in severe osteoporotic patients.

Methods: The study retrospectively enrolled 56 severe osteoporotic patients who received TPT for 24 months followed by 24 months of zoledronic acid (ZOL) (TPT + ZOL) or Dmab (TPT+Dmab). Clinical features, incident fractures, bone mineral density (BMD) measurements, and bone marker profiles were collected. One-way ANOVA analyzed the difference between mean T-scores at baseline, after 24 months of TPT, and after 2 doses of ZOL or after at least 3 doses of Dmab.

Results: Twenty-three patients received TPT + ZOL (19 females, 4 males; median [IR] age, 74.3 [66.9, 78.6] years) and 33 patients received TPT+Dmab (31 females, 2 males; mean [IR] age, 66.6 ± 11.3 years). Mean lumbar and hip T-scores were increased after both TPT + ZOL and TPT+Dmab (all p < 0.05 vs baseline). The size effects induced by TPT + ZOL on the lumbar and hip BMD T-scores were similar to those observed with TPT+Dmab with mean T-scores increases of about 1 and 0.4 SD, respectively. No significant between-group differences were identified. Incident fragility fractures occurred in 3 (13%) patients treated with TPT + ZOL and in 5 (15%) patients treated with TPT+Dmab.

Conclusions: Sequential TPT + ZOL therapy is likely to increase bone mineralization at the lumbar level and to stabilize it at the femoral level, similarly to what obtained with the sequential TPT+Dmab. Both ZOL and Dmab are suggested to be effective sequential treatments after TPT.

Keywords: Bone mineral density; Denosumab; Fragility fractures; Osteoporosis; Teriparatide; Zoledronic acid, Severe osteoporosis.

Fig. 1

Study design. DXA, dual-energy x-ray absorptiometry at lumbar, femur neck, and hip sites; TPT teriparatide 20 μg/day subcutaneously; ZOL zoledronic acid 5 mg/12 months intravenously; Dmab denosumab 60 mg/25 weeks subcutaneously

Fig. 2

Effect of sequential treatment with TPT + ZOL versus TPT+Dmab on lumbar, femur neck, and hip BMD T-scores. Sequential treatment with TPT + ZOL determined significant increases in mean lumbar (a) and hip (c) T-scores, while no significant change was detected in the mean neck T-score (b). Similarly, sequential treatment with TPT+Dmab determined significant increases in mean lumbar (d) and hip (f) T-scores, while no significant change was detected in the mean neck T-score (e). Panel (a), *p < 0.0001; **p = 0.0007; Panel (c), ^§p = 0.0492; Panel (d), *p < 0.0001; **p = 0.0074; Panel (f), ^§p < 0.0001; ^§§p < 0.0001; TPT, 20 μg/day sc teriparatide; ZOL, 5 mg/12 months iv zoledronic acid; Dmab, 60 mg/25 weeks sc denosumab

Fig. 3

Comparison of sequential treatment-induced BMD T-score changes in lumbar, femur neck, and hip T-scores between TPT-ZOL and TPT+Dmab patients. The change in mean T-score from baseline to the end of sequential treatment was not different between TPT + ZOL and TPT+Dmab groups at any sites. Δ, change in mean T-score; TPT, 20 μg/day sc teriparatide; ZOL, 5 mg/12 months iv zoledronic acid; Dmab, 60 mg/25 weeks sc denosumab; n, number of patients included in the analysis

Fig. 4

Correlation between baseline T-scores and sequential treatment-induced changes in T-scores. The baseline hip T-score was negatively correlated (r² = 0.351, p = 0.004) with the change in hip T-scores after TPT + ZOL sequential treatment (a). The baseline femur neck T-score was negatively correlated (r² = 0.200, p = 0.009) with the change in neck T-scores after TPT+Dmab sequential treatment (b). TPT, 20 μg/day sc teriparatide; ZOL, 5 mg/12 months iv zoledronic acid; Dmab, 60 mg/25 weeks sc denosumab

Fig. 5

Effects of sequential treatments TPT + ZOL versus TPT+Dmab on circulating bone markers. Plasma PTH levels were reduced by TPT treatment and increased by both ZOL and Dmab treatment (4a, 4e). Serum 25OHD levels were significantly increased during both the sequential treatments (4b, 4f). Serum total ALP and βCTX levels were significantly reduced after TPT + ZOL (4c, 4d) and TPT+Dmab treatments (4g, 4h). Panel (a), *p < 0.0001; **p = 0.0007; Panel (b), *p = 0.0008; Panel (c), *p = 0.0005; Panel (d), *p = 0.0133; **p < 0.0001; **p < 0.0001; Panel (e), *p = 0.0298; Panel (f), *p = 0.0290; **p = 0.0165; Panel (g), *p < 0.0001, **p < 0.0001; Panel (h), *p < 0.0001; **p = 0.0042. TPT, 20 μg/day sc teriparatide; ZOL, 5 mg/12 months iv zoledronic acid; Dmab, 60 mg/25 weeks sc denosumab