Effects of teriparatide and bisphosphonate on spinal fusion procedure: a systematic review and network meta-analysis

PONE-D-20-09535

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Reviewer #1: The authors present the first network meta-analysis (NWA) looking at the use of Teriparatide and bisphosphonates in the setting of spinal fusion surgery, which is an important topic with high real-world relevance. While other systematic reviews have been previously conducted in the literature, this is the first to use this newer NWA statistical method. Compared with traditional pairwise meta-analyses, NMAs allow the visualization of a larger amount of evidence, estimation of the relative effectiveness among all interventions, and rank ordering of the interventions. As such, they can be helpful in determining the best available intervention by facilitating indirect comparisons of multiple interventions that have not been robustly studied in head-to-head studies.

Based off their analyses, the authors conclude that Teriparatide treatment significantly improves spinal fusion rates while bisphosphonates do not. This conclusion is properly placed in the context of the previous literature and the author's provide a nice discussion comparing/contrasting their study to similar previously conducted systematic reviews on the subject matter. That being said, while their conclusion is supported by their data, there are many challenges with these types of analyses that can limit their real-world usefulness. For a NMA to produce valid results, it is important that the distribution of effect modifiers (i.e., average patient age, gender distribution) is similar, since this balance increases the plausibility of reliable findings from an indirect comparison. In my opinion, the authors did a nice job of providing this information systematically, which helps the reader empirically evaluate the validity of the assumption of transitivity by reviewing the distribution of potential effect modifiers across trials.

Overall, the manuscript is well organized and written clearly enough to be accessible to non-specialists and the details of their methodology are sufficient to allow the analyses to be reproduced.

Reviewer #2: Excellent paper on a very important topic. You list several risk factors for pseudoarthrosis, but do not list osteopenia and osteoporosis as risk factors, but several papers have shown that these are also independent risk factors as well. You may want to include that in the paper.

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Reviewer #1: No

Reviewer #2: Yes: Ahmad Nassr