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J Clin Endocrinol Metab. 2013 Aug;98(8):3206-12. doi: 10.1210/jc.2013-1402. Epub 2013 Jun 20.

Comparative effect of zoledronic acid versus denosumab on serum sclerostin and dickkopf-1 levels of naive postmenopausal women with low bone mass: a randomized, head-to-head clinical trial.

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1
Department of Endocrinology, 424 General Military Hospital, 56429 Thessaloniki, Greece. anastath@endo.gr

Abstract

CONTEXT:

Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment.

OBJECTIVE:

The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1).

DESIGN:

This was an interventional, parallel assignment, open-label, randomized clinical trial.

SETTING:

The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece.

PATIENTS AND INTERVENTIONS:

Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up.

MAIN OUTCOME MEASURES:

Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen.

RESULTS:

Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, whereas receptor activator of nuclear factor κB ligand decreased in the zoledronic acid group (P = .004) but increased in the denosumab group (P = .037). Bone markers (procollagen type 1 N-terminal propeptide, C-terminal cross-linking telopeptide of type 1 collagen, and total serum alkaline phosphatase) decreased in both groups (all P < .001).

CONCLUSIONS:

Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1.

PMID:
23788684
DOI:
10.1210/jc.2013-1402
[Indexed for MEDLINE]
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