The determination of HRQoL of a patient is a multifaceted and subjective concept that necessitates global participation from individuals in diverse countries.7,8,22 Variations in sociocultural background, educational and economical status of the patients can have a huge impact on their ability to cope with a disease and its subsequent side effects.23 While zoledronic acid is effective in reducing skeletal-related events, it is not exempt from potential side effects and adverse reactions. The collateral effects of the drug and many co-factors, such as comorbidities (e.g., diabetes), smoking, dental interventions, and concurrent medications (e.g., corticosteroids), have been reported to play a role in exacerbating the risk of MRONJ and its associated complications.12,15,24
Consistent with previous research,11,14–16 our findings indicate that MRONJ predominantly affects older individuals (≥ 60 years), with a higher incidence among females and greater predilection for mandible as presented in Table 1. Intravenous bisphosphonates, like zoledronate demonstrate greater potency, rapid binding and higher accumulation in the bone.7,8,10 It has been suggested that MRONJ is less aggressive with smaller extent of lesion when oral bisphosphonates are used as compared intravenous counterparts, potentially yielding better global quality of life scores.25,26 Within our cohort, we found a significant correlation between global health status of the patients and drugs linked to MRONJ as well as the route of administration. Cancer patients with MRONJ, who received zoledronic acid had lowest global health status scores. Conversely, patients solely treated with oral bisphosphonate likely experienced fewer adverse effects leading to better perceived global health status.
Our results also demonstrated significant variation in global health status among different stages of MRONJ demonstrating the trend of declining quality of life as the MRONJ stage advances, which is consistent with previous studies.12,14,16 Cancer patients with Stage 0 or Stage 3 MRONJ had lower global health status scores compared to those with Stage 1 or Stage 2 MRONJ. Patients with Stage 0 MRONJ may initially experience non-specific symptoms, akin to an abrupt impact, eventually advance to Stage 3, reflecting a significant deterioration in overall health status.10,16 This aligns with the findings of the study conducted by J Murphy et al,12 which emphasize that the decline in quality of life is not necessarily a steady or predictable linear decrease.
A robust positive correlation was evident between maxilla and emotional functioning score indicating that patients with maxillary MRONJ had higher or better level of emotional compared to cases wherein MRONJ affects the mandible or both jaws. This corroborates with Ruggiero et al.26 findings where patients with maxillary involvement were five times more likely to experience positive outcomes compared to those with the disease in other locations. By recognizing the potential emotional challenges associated with the location of MRONJ, healthcare professionals can offer targeted interventions and psychological support to improve the patient’s emotional well-being.
Numerous comorbid conditions (e.g., diabetes mellitus, chemotherapy, hypertension, obesity, smoking) share a common pathophysiologic process, namely, oxidative stress. Oxidative stress adversely affects bone homeostasis and has been linked to delayed healing and osteonecrosis.27,28 As suggested by Fleisher et al.,27 the interplay of oxidative stress and biofilm formation may serve as the initial trigger for both MRONJ and ONJ unrelated to antiresorptive drugs. In our present study, significant association was observed between presence of comorbidities, bone metastasis, history of dental extraction, pus discharge and extraoral swelling and adverse scores in various domains of EORTC HN35 QLQ such as pain, senses problem, problems with teeth, need for pain killer, nutritional supplements, feeding tube and weight gain. Thus, risk factors evaluation for each patient before the treatment initiation with bisphosphonates or other associated drugs is crucial.
Our study exhibits several notable strengths that contribute to the robustness of our findings. Firstly, it addresses a significant gap in the existing literature by conducting a comprehensive evaluation of the quality of life in the Indian population involving cancer patients affected by MRONJ. Secondly, we have employed validated quality of life instruments, the EORTC QLQ C30 and EORTC QLQ H&N35, which have been documented as effective tools for assessing the quality of life in cancer patients with MRONJ. This choice of assessment tools enhances the reliability and comparability of our results with previous studies. A key strength of the study also lies in its approach as it explores a wide range of patient related, disease related and MRONJ related variables. While our study provides valuable insights, it is important to acknowledge its limitations. Being a cross-sectional study, it did not test a specific hypothesis, mainly due to the smaller subgroups of MRONJ patients resulting from its overall low incidence.7,9,11 Together with the EORTC QLQ-C30 and EORTC QLQ-H&N35, our study also explored the association between oral health status and MRONJ in our sample which is discussed in part 2 of this research article. Future research should encompass long-term prospective studies collaborating multiple healthcare institutions to collect data from diverse patient populations with MRONJ enabling the identification of predictive factors and a comprehensive assessment of QoL over time comparing different treatment strategies.