Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy — a nationwide cohort study

ObjectivesLevothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer.MethodsWe enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation.ResultsWe evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771–0.932), 0.703 (0.591–0.836), and 0.405 (0.224–0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648–0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients.ConclusionWe suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy

Effect of Denosumab on Bone Mineral Density of Hematopoietic Stem Cell Transplantation Recipients

Purpose. Denosumab is a monoclonal antibody that prevents the development of osteoclasts. The effect of denosumab in solid organ transplant recipients has been elucidated, but its effect in haematopoietic stem cell transplantation recipients has not been studied yet. The aim of this study was to determine the effectiveness and safety of denosumab in haematopoietic stem cell transplantation recipients. Methods. We retrospectively evaluated 33 female patients with osteoporosis (mean age 52.6 ± 9.8 years) following allogeneic haematopoietic stem cell transplantation. Patients were treated with denosumab every 6 months for 12 months. Changes in bone mineral density were evaluated for denosumab-treated patients in a 12-month interval after the first administration of denosumab. Results. Significant increases in bone mineral density were observed in all measured skeletal sites including 4.39 ± 6.63% in the lumbar spine (p=0.014), 3.11 ± 7.69% in the femoral neck (p=0.048), and 1.97 ± 6.01% in the total hip (p=0.138). The bone turnover marker serum cross-linked C-terminal telopeptide of type 1 collagen was decreased at 18 months (−51.6 ± 17.6%, p<0.001). No serious symptomatic hypocalcaemia was observed. Serious adverse drug reactions requiring drug discontinuation were not observed. Conclusion. Denosumab improved bone mineral density in haematopoietic stem cell transplantation recipients. The use of denosumab could be a good therapeutic option without causing severe adverse effects in recipients of haematopoietic transplantation

Gut microbiome in the Graves' disease: Comparison before and after anti-thyroid drug treatment.

While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment

Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis

Background: Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis. Methods: We analyzed the serum Cyfra 21.1 level in 51 consecutive patients with thyroid cancer manifesting distant metastasis treated with prior total thyroidectomy. Serum Cyfra 21.1 levels of 26 thyroid cancer patients without metastasis and 50 healthy individuals were used for comparison. Results: Higher serum Cyfra 21.1 levels were detected in thyroid cancer patients with distant metastasis compared with healthy subjects and thyroid cancer patients without metastasis (p = 0.012). Serum Cyfra 21.1 levels were significantly increased in patients with positive BRAF V600E mutation (p = 0.019), undergoing Tyrosine Kinase Inhibitor (TKI) therapy (p = 0.008), with radioiodine-refractory status (p = 0.047), and in disease progression compared with those manifesting stable disease (p = 0.007). In progressive disease with undetectable or unmonitored thyroglobulin because of thyroglobulin antibody, serum Cyfra 21.1 was useful as a biomarker for follow-up of disease course. Conclusion: Serum Cyfra 21.1 in thyroid cancer patients might represent an alternative biomarker predicting tumor progression, especially in cases not associated with serum Tg levels

Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study

Background Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures. Methods We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment. Results Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures. Conclusion Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment

Table_1_Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy — a nationwide cohort study.docx

ObjectivesLevothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer.MethodsWe enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation.ResultsWe evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771–0.932), 0.703 (0.591–0.836), and 0.405 (0.224–0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648–0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients.ConclusionWe suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy.</p