Mixed-treatment comparison of anabolic (teriparatide and PTH 1-84) therapies in women with severe osteoporosis

Abstract

Purpose:

The recent development of compounds with anabolic action on bone have increased the range of therapeutic options for the treatment of osteoporosis and the prevention of fractures. Two major PTH analogs, the synthetic full-length 1-84 PTH molecule and the recombinant 1-34 N-terminal fragment (teriparatide), are available for the treatment of osteoporosis in many countries. There have bee no comparative trials on the bone anabolic effects of these compounds.

Materials and methods:

In this study we applied a mixed treatment comparison (MTC) to compare the efficacy of teriparatide versus PTH 1-84 for the prevention of vertebral and non-vertebral fractures in women with severe osteoporosis. With this approach the relative treatment effect of one intervention over another can be obtained in the absence of head-to-head comparison. Among the candidate papers selected for analysis, two randomized controlled trials investigating the effects of teriparatide and PTH 1-84 met the selection criteria and underwent MTC analysis.

Results:

Based on a fixed-effect MTC model analysis of data from two RCTs, teriparatide (20 µg/day) showed a 70% and 94% probability of being the best treatment for the prevention of vertebral and non-vertebral fractures, respectively. Together with a lack of statistical significance, this study has additional limitations. Some differences in trial procedures and populations exist; another limitation concerns the impossibility of carrying out a randomized-effect model MTC, due to sample exiguity. Furthermore, in order to consider unknown or unmeasured differences of covariates across trials, a random-effects approach would be preferred in order to assess the presence of heterogeneity across comparisons. In contrast, in our analysis a fixed-effect MTC model only was used.

Conclusions:

Teriparatide is expected to provide a greater efficacy over PTH 1-84 with both vertebral and non-vertebral fracture prevention in postmenopausal women with severe osteoporosis.

Keywords::

• Anabolic agents
• Bone turnover markers
• Osteoporosis therapy
• PTH

Transparency

Declaration of funding

This study was conducted with unrestricted funds from ANTIAGE (a non-profit National Association for ultrasound-guided intra-articular hip therapy) whose President is Prof. Alberto Migliore.

Declaration of financial/other relationship

Prof. Alberto Migliore received grants as consultants from Ely Lilly and Nycomed for national and international studies and courses. All other authors have disclosed that they have no relevant financial or other relationship that may interfere with the proper realization of the study. CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.