Comparison of Hounsfield Units and Vertebral Bone Quality Score for the Prediction of Time to Pathologic Fracture in Mobile Spine Metastases Treated With Radiotherapy

Dear Professor Jeffrey C. Wang, Jens R. Chapman, and Karsten Wiechert,

Editors-in-Chief of Global Spine Journal,

We extend our congratulations to Dr Patel et al for their research published in the Global Spine Journal, entitled “Antiresorptive Medications Prior to Stereotactic Body Radiotherapy for Spinal Metastasis are Associated with Reduced Incidence of Vertebral Body Compression Fracture.” Their retrospective analysis of 234 patients revealed that initiating antiresorptive agents before stereotactic body radiotherapy (SBRT) significantly lowers the risk of treatment-induced vertebral compression fractures (VCF), in contrast to initiating treatment post-SBRT. ¹ This pivotal finding could guide clinicians and surgeons in optimizing treatment protocols, potentially altering radiotherapy parameters or the timing of antiresorptive therapy to better serve patients with advanced-stage diseases.

Nevertheless, we would like to address certain aspects that deserve further discussion. In Taiwan, 2 distinct formulations of denosumab—Prolia (60 mg) and Xgeva (120 mg)—and zoledronic acid—Aclasta (5 mg) and Zometa (4 mg)—are used, each intended for different clinical indications. While Prolia and Aclasta target osteoporosis, Xgeva and Zometa aim to prevent skeletal-related events (SREs) from bone metastases. Although the majority of randomized control trials have focused only on the anti-osteoporotic effects of Prolia or Aclasta, both drugs theoretically prevent VCFs.^2,3 Given their different potency and dosing intervals, it would be of interest if the authors could provide such details, particularly to assess their efficacy in preventing VCF in the context of metastatic bone disease.

Moreover, in Taiwan, Xgeva and Zometa are approved solely for bone metastases from lung, breast, and prostate cancers, unlike in the United States where their use is more broadly applicable. Efficacy in preventing SREs from other solid tumors has not been demonstrated as strongly as for the aforementioned solid cancers.^4,5 Clarifying whether antiresorptive agents were more commonly prescribed for these specific cancers could provide deeper insights into the study’s findings and account for potential confounders, such as whether the presence of a higher proportion of lung cancer patients in specific subgroups stratified by antiresorptive agent use.

Additionally, the study did not address medication adherence and the known rebound effect associated with denosumab, which can result in an incidence of about 10% of compression fractures upon discontinuation. The observed outcome could be biased if patients’ compliance in certain subgroups was poor. Information on the frequency and compliance of medication use is crucial for interpreting the risk of adverse effects and should be considered in future reporting.^6,7

In conclusion, while the study by Dr Patel et al offers valuable insights into the timing of antiresorptive therapy about SBRT, a more detailed analysis incorporating product-specific effects, the medication uses among different cancer types, and patient adherence to different agents would enrich our understanding and application of these findings. We appreciate the opportunity to engage in this academic dialogue and look forward to further contributions from Dr Patel et al to enhance our collective knowledge and patient care in this challenging field of medicine.