Zoledronic Acid (ZOL) Administered Sequential to Teriparatide might Promote a Deeper Suppression of Bone Resorption than ZOL Alone

Background:
Bisphosphonate efficacy is alterated according to baseline bone turnover. Teriparatide promotes bone turnover, however, it is not known whether pretreatment with teriparatide influences bone turnover suppression induced by ZOL, thereby possibly affecting a preferred subsequent treatment timing.

Aim:
To evaluate the effect of ZOL on bone resorption suppression in a post-teriparatide versus first line scenario in osteoporotic patients.

Methods:
Patients treated with teriparatide followed by ZOL (TPT-ZOL) or with a single infusion of ZOL were retrospectively identified in a tertiary referral bone metabolism center database. Demographic, clinical, densitometric and laboratory data, including C-terminal-telopeptide-of-Type-I-Collagen (CTX) following ZOL treatment were compared between groups.

Results:
Twenty-six patients treated with TPT-ZOL and forty-one with ZOL were comparable in gender (92.3% vs 92.7% female, p=0.4) and age at ZOL administration (median [IQR]: 70.1 [63.6,77.5] vs 69.6 [64.2,76.2], p=0.6). Femoral neck T-scores, vitamin D levels and timing of CTX measurement post-ZOL (median [IQR]: 12.1 [11.0,13.1] vs 12.2 [11.3,15.8] months, p=0.6), were similar. CTX was significantly lower among patients in the TPT-ZOL group (median [IQR]: 142.1 [91.2,220.8] vs 184.2 [159.0,262.0] pg/ml, p=0.005). In a regression model controlling for age, body mass index, kidney function and timing of CTX measurement, pretreatment with TPT was a strong predictor of a CTX level lower than 150 pg/ml, following ZOL treatment (OR=5.6, 95% CI 1.6-22.4, p=0.009).

Conclusions:
ZOL administered sequential to teriparatide promotes a deeper decline in serum resorption marker than ZOL alone. It is possible that in a sequential treatment scenario, subsequent ZOL dosing interval should be modified accordingly.