Objectives: To determine whether nonsteroidal anti-inflammatory drugs (NSAIDs) have an adverse effect on bone healing by evaluating all available human randomized controlled trials (RCTs) on this subject.Data Sources: A comprehensive search of electronic databases (PubMed, MEDLINE, and Cross-References) until October 2018 comparing the occurrence of nonunion in patients who received NSAIDs to the control group through RCTs.Study Selection: Inclusion criteria were English-only studies, and the type of studies was restricted to RCTs.Data Extraction: Two authors independently extracted data from the selected studies, and the data collected were compared to verify agreement.Data Synthesis: Nonunion was the main outcome evaluated in each study. Regression analysis was used to estimate the relative risk comparing the duration and the type of NSAIDs by calculating the odds ratio (OR) for dichotomous variables. Studies were weighed by the inverse of the variance of the outcome, and a fixed-effects model was used for all analyses.Conclusions: Six RCTs (609 patients) were included. The risk of nonunion was higher in the patients who were given NSAIDs after the fracture with an OR of 3.47. However, once the studies were categorized into the duration of treatment with NSAIDs, those who received NSAIDs for a short period (<2 weeks) did not show any significant risk of nonunion compared to those who received NSAIDs for a long period (>4 weeks). Indomethacin was associated with a significant higher nonunion rate and OR ranging from 1.66 to 9.03 compared with other NSAIDs that did not show a significant nonunion risk.

Background: Metastasis to the bone is one of the most common complications associated with advanced cancer. Patients with bone metastases are at risk of devastating skeletal related events, including pathological fractures. Purpose: The aim of this study was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject. Methods: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures. Results: Four RCTs (7,320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumor types were combined (odds ratio [OR] 0.86, 95% confidence interval [CI], 0.74 to 0.99, P = 0.04). Denosumab was favored, although not statistically significant, over ZA in endodermal origin (breast and prostate) (OR 0.85, 95% CI, 0.68 to 1.05, P = 0.13) and mesodermal origin tumors (solid tumors and multiple myeloma) (OR 0.87, 95% CI, 0.71 to 1.06, P = 0.16). Discussion: Denosumab moderately reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases with statistical significance. When pathological fractures were grouped by tumor origin (endodermal or mesodermal), no statistical difference was observed between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens.

Study Design: Meta-analysis of randomized controlled trials (RCTs). Objectives: The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of spinal cord compression in patients with spine metastases from advanced cancers, by evaluating all available RCTs on this subject. Methods: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of spinal cord compressions in spine metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were spinal cord compression. Results: Three RCTs (5274 patients) were included. Denosumab was not significantly superior to ZA in reducing the likelihood of spinal cord compression, when all tumor types were combined (odds ratio [OR] 0.92, 95% confidence interval [CI; 0.66, 1.28], P = .66). Denosumab was not significantly favored over ZA in endodermal origin (breast and prostate; OR 0.72, 95% CI [0.43, 1.19], P = .20) and mesodermal origin tumors (solid tumors and multiple myeloma; OR 1.10, 95% CI [0.72, 1.69], P = .66). Conclusion: Denosumab does not significantly reduce the likelihood of spinal cord compressions in comparison to ZA in patients with spine metastases. When spinal cord compressions were grouped by tumor origin (endodermal or mesodermal), there remained no significant difference between denosumab and ZA. Further long-term studies are needed to determine the effectiveness of these treatment regimens.

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