Bone metastases are present in more than a quarter of patients with metastatic medullary thyroid carcinoma (MTC), most often with an osteolytic morphology, which is associated with increased risk for complications and decreased survival, according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Approximately 10% to 15% of patients with MTC with a palpable thyroid nodule are found to have distant metastases, which are associated with an unfavorable prognosis. Previous studies have reported that bone is the second most common site of distant metastases in this population. Bone metastases can occur with various growth patterns, including osteolytic, osteoblastic, or mixed pattern. The disruption between bone formation and bone resorption can lead to significant skeletal complications, including pathological fractures, requirement of radiation therapy or surgery, spinal cord compression, or hypercalcemia of malignancy.
The goal of the current retrospective study was to explore the characteristics and distribution of bone metastases in MTC, skeletal complications, effects of different bone metastases morphologies, and the effect of antiresorptive therapy.
The researchers retrieved data on 114 patients (77% sporadic MTC; 23% hereditary MTC) from 4 German tertiary care centers between 1973 and 2016. All patients were diagnosed with MTC and bone metastases, and the median follow-up was 5.8 years from MTC diagnosis and 2.2 years from diagnosis of bone metastases. Bone metastases morphology was osteolytic in 32%, osteoblastic in 25%, mixed in 22%, and unknown in 21% of cases.
The percentage of bone metastases among all patients with MTC was 11%, whereas among those with metastatic MTC, it was 29%. In almost all cases, patients with bone metastases also had nonosseous metastases. Approximately half of the patients (47%) with MTC and bone metastases had developed skeletal complications, including bone radiation (50%), pathological fractures (32%), and surgery to the bone (12%). The risk for skeletal complications was greater among patients with osteolytic metastases, who accounted for 42% of all skeletal complications; only 17% of skeletal complications occurred in patients with osteoblastic bone metastases (P =.047).
Furthermore, the location of bone metastases had a significant effect on the occurrence of complications, as metastases located in the spine, ribs, and scapula were more likely to be involved in skeletal complications.
Although the occurrence of skeletal complications was not associated with impaired overall survival, the morphology of bone metastases had a significant effect on mortality. In post hoc analysis and after multivariate adjustment, the presence of osteolytic metastases was found to be an independent risk factor for impaired overall survival (hazard ratio, 3.85; 95% CI, 1.52-9.77; P =.005) compared with osteoblastic metastases.
In a group of patients who received treatment with antiresorptive agents (either bisphosphonates or denosumab), the risk for skeletal complications was lower compared with those who did not receive treatment (P =.04).
The researchers acknowledged several study limitations, including the retrospective design, heterogeneity in patient management, missing data, and lack of systematic follow-up.
“This study emphasises the importance of morphology of bone metastases in medullary thyroid carcinoma. Osteolytic bone metastases are associated with more skeletal related events and worse outcome. Anti-resorptive therapy may be more effective in osteolytic morphology to prevent skeletal related events,” concluded the researchers.
Vogel T, Wendler J, Frank-Raue K, et al. Bone metastases in medullary thyroid carcinoma: high morbidity and poor prognosis associated with osteolytic morphology [published online February 19, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa077