The effect of bisphosphonate treatment on the development of sarcopenia in cancer patients with metastatic solid tumors

Aim: Sarcopenia is defined as loss of skeletal muscle mass leading to atrophy of skeletal muscles and decrease in muscle strength, easy fatigue and various metabolic problems characterized by deterioration of muscle tissue quality.In the sarcopenic process, fibrotic tissue is replaced by muscle fibers, which leads to increased fragility, dysfunction, neuromuscular junction degeneration and increased oxidative stress. There may be multifactorial causes such as sarcopenia formation, changes in endocrine functions, chronic infections, insulin resistance, nutritional insufficiency, cessation of muscle use. Sarcopenia may also develop in patients receiving cancer treatment. Like small cell lung cancer, cancer itself can cause sarcopenia. It has been shown that tolerance to chemotherapy drugs decreases and the incidence of side effects increases in patients with sarcopenia. For these reasons, combating cachexia and sarcopenia in cancer patients is an important condition. When the literature is investigated; There was no study investigating the relationship between zoledronic acid and sarcopenia. In this study, the data of patients with bone metastatic breast, lung and prostate cancer were analyzed retrospectively and the relationship between zoledronic acid dose and sarcopenia was investigated. Materials and Methods: In this study, the files of patients who were followed and followed in the Department of Medical Oncology in Ankara Atatürk Training and Research Hospital between 2006 and January, diagnosed as bone metastatic breast, lung and prostate cancer and treated with zoledronic acid (ZA) were investigated retrospectively, staging and response assessment (CT, PET) were investigated. As a result of the examinations, operated or non-operated 64 patients with bone metastatic breast, lung and prostate cancer were included in the study. Abdominal circumference (AC) and muscle area were calculated by computed tomography images of the abdomen taken during the follow-up of the patients. Siemens Workstation, Syngovia version VB10. Program was used, rectus abdominis, external abdominal oblique, internal abdominal oblique, transversus abdominis, psoas major and minor, quatratus lumborum, areas of erector spinal muscles were measured; the area of ​​the third lumbar vertebra is not included in the measurement. Sarcopenia was detected by using CT images of the abdomen taken for diagnosis at the time of diagnosis and for evaluation of treatment response at follow-up. The rates of sarcopenia determined will be compared with the prognostic clinical evaluations of the patients before and during treatment, and the relationship between total dose of zoledronic acid and sarcopenia has been tried to be determined. For statistical analysis and calculations, IBM SPSS Statistics 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0, Armonk, NY: IBM Corp.) was used. Comparison of numerical data was performed by independent sampling Mann-Whithey Test, p <0.05 was considered statistically significant. Chi-square independence test was used to compare nominal data, such as comparing muscle type and muscle loss below and above the median value. The Wilcoxon test was used to compare the muscle areas and the abdominal areas. Results: Forty of the patients were male and 24 were female. The mean age was 57.3 years (min 23,03; max 81,39). 20 patients had breast cancer, 23 patients had prostate cancer and 21 patients had lung cancer. The patients were divided into two groups, which received an average of 14 cycles of zoledronic acid treatment (min 3, max 72 cycles), the mean ZA dose was 48 mg. Patients were divided into two groups according to total ZA dose: ≤48 mg and >48 mg. Both AC and muscle area were significantly reduced in patients with total ZA dose greater than 48 mg (P=0,011; P=0,0001); in patients less than or equal to 48 mg, muscle area decreased significantly, and AC did not change significantly (P=0,011; P=0,219). Before and after ZA treatment, total ZA dose was not divided into 2 groups; muscle area decreased significantly in patients with breast cancer, but there was no significant difference in AC (P=0,002; P=0,260). Significant decrease in both muscle area and AC was detected in patients diagnosed with prostate cancer (P=0,0001; P=0,013). In patients with lung cancer; there was no statistically significant difference in both muscle area and AC. In the group with BMI≥ 30 kg/m2, the area of ​​muscle decreased significantly, while the AC margin decreased significantly (P=0,013; P=0,055). Both in the group with BMI<30 kg/m2 decreased significantly (P=0,0001; P=0,040). When the change in muscle area before and after ZA was investigated, it was found that the median muscle area decreased by 12 cm2. The median value of the decrease in muscle area was accepted as 12 cm2 threshold and divided into two groups as ≥12 cm2 and <12 cm2. Statistically significant difference was found in patients with more than 12 loss of muscle area with total ZA dose (P=0,051). In breast cancer patients, there was no significant difference in survival between muscle area reduction threshold ≥12 cm2 and <12 cm2, but the group with numerical muscle loss <12 cm2 had longer survival idi (GS=59,5±14,4 month, %95 GA: [31,2-87,9]; GS=102,5±42,7 month, %95 GA: [18,7-186,3]). In patients with prostate cancer, survival was shorter in the group with muscle loss ≥12 cm2 than in the group with <12 cm2 (GS=56±19,3 month, %95 GA: [18-94]; GS=87,8±11,8 month, %95 GA: [64,6-111]). Although there was no statistically significant difference in survival in patients with lung cancer, survival was found to be shorter in the group with muscle loss ≥12cm2 (GS=12,6±5,8 month, %95 GA: [1,2-24]; GS=24,9±6,8 month, %95 GA: [11-38,3]). In patients receiving breast cancer hormone therapy, muscle area decreased but AC did not change significantly (P= 0.006). Conclusion: In this study, we investigated the effect of ZA on sarcopenia in patients with bone metastatic breast, lung and prostate cancer who were treated with ZA. Previously supported anti-androgen therapy also caused sarcopenia, hormone therapy (aromatase inhibitors, SERM, etc.) in breast cancer patients showed a statistically significant decrease in muscle area (P=0,006). There was a statistically significant increase in sarcopenia as total ZA dose increased (P=0,0001). The study could be further expanded by including more patients with the control group in terms of including ZA among the agents causing sarcopenia. In patients with prostate cancer, both AC and muscle area were significantly reduced in patients receiving ZA greater than 48 mg, but it was not clear whether this decrease was due to the effect of anti-androgen therapy, ZA or both. Key Words: Sarcopenia, bisphosphonates, zoledronic acid, cancer, palliative treatment