Chronic kidney disease (CKD) induces secondary osteoporosis, characterized by an imbalance between bone formation and resorption due to kidney dysfunction; the result is a reduction in both bone mineral density and quality. This condition is compounded by disruption of bone metabolic turnover, abnormalities in bone microstructure and collagen cross-linking, and compromised bone quality, all of which contribute to increased bone fragility. Reduced kidney function is complicated by secondary hyperparathyroidism, which exacerbates bone fragility. Managing osteoporosis in patients with CKD is challenging because drugs may be contraindicated or require cautious administration, particularly those with high urinary excretion rates. In addition, severe hypercalcemia or hypocalcemia may develop in these patients following administration of active vitamin D or denosumab, respectively. The choice of pharmacotherapy depends on the stage of CKD; however, evidence for the safety and efficacy of osteoporosis drugs in moderate to severe cases of CKD, particularly stages G4, G5, and G5D (i.e., dialysis patients), is limited. This article focuses on the pathophysiology of CKD-associated osteoporosis, as well as the increased fracture risk, and provides a concise overview of safety considerations regarding administration of osteoporosis drugs in Japan. The data presented highlight the complexities associated with drug use in patients with CKD.

The parathyroid glands (PTGs) regulate calcium metabolism by secreting parathyroid hormone (PTH). Patients with hypoparathyroidism require lifelong replacement therapy, which is associated with risks of chronic kidney disease, bone fractures, and a reduced quality of life. Generating PTGs from pluripotent stem cells (PSCs) offers a potential regenerative therapy for this condition. This review first explains PTG organogenesis, followed by an overview of both in vitro and in vivo approaches to PTG generation. In vitro studies have successfully induced PTH-expressing parathyroid cells from human PSCs. However, challenges remain, particularly in achieving sufficient PTH secretion and functional efficacy in vivo. Meanwhile, an in vivo organ generation technique known as blastocyst complementation has successfully produced functional PTGs in rodents. However, whether this technology can be applied using human PSCs and animal embryos remains unclear. Pluripotent stem cell-derived PTGs hold promise for both clinical applications and basic research, but further advancements will be necessary to overcome existing challenges in this field.

To elucidate the clinicopathological features of follicular thyroid carcinoma (FTC) coexisting with papillary thyroid carcinoma (PTC) (FTC + PTC). We collected a total of 55 FTC + PTC patients (including 12 males [21.8%] and 43 females [78.2%]), with an average age of 47.6 years. In the FTC alone group, the average age was 52.3 years, and the proportion of females was 71.3%. The median age was 43.5 years, with an average age of 45 years in the PTC alone group. Compared with the tumors in the FTC alone group, FTC in the FTC + PTC group exhibited a smaller maximum diameter (49.1% measuring ≤2 cm), a younger patient age (70.9% younger than 55 years), an earlier tumor stage (94.5% in stages I–II), a lower incidence of recurrent cancer (n = 2, 3.6%), a lower frequency of distant metastasis (6.1%), and a lower proportion of “extensively invasive” subtype (12.7%) (all p < 0.05). Compared with the PTC alone group (n = 289), the FTC + PTC group had a higher proportion of PTC with a maximum diameter of ≤1 cm (72.5%), and the degree of invasion of thyroid extracellular tissue was less severe (all p < 0.05). No statistically significant differences were found in overall survival (OS), cancer-specific survival (CSS), and RFS between these two groups (the FTC or PTC alone group versus FTC + PTC group). In sum, FTC + PTC has some clinicopathological features.

Bilirubin is associated with vascular complications in diabetes. However, the correlation between bilirubin and sarcopenia or muscle strength has not been investigated. This study aimed to investigate the association between total bilirubin and skeletal muscle mass index (SMI), hand grip strength (HGS), and sarcopenia in patients with type 2 diabetes. This cross-sectional study included 1,108 patients with type 2 diabetes from three hospitals in Japan. Multiple and logistic regression analyses were used to examine the relationships between total bilirubin and SMI, HGS, and sarcopenia. Of the participants, 473 (43%) were women. The median (interquartile range) age, and glycated hemoglobin were 67 (59–73) years, and 7.4 (6.7–8.6) %, respectively. The median SMIs for women and men were 6.32 (5.73–7.04) kg/m² and 7.53 (7.02–8.19) kg/m², respectively. The median HGS for women and men were 21.5 (17.5–25.0) kg and 36.0 (30.0–41.5) kg, respectively. Sarcopenia was present in 11% and 12% of women and men, respectively. No correlation was observed between total bilirubin and SMI in both sexes. No significant association was observed between total bilirubin and HGS in men, whereas a positive correlation was observed in women (β = 0.18, p = 0.01). Total bilirubin was negatively associated with sarcopenia in women (odds ratio = 0.80, 95% confidence interval: 0.64–0.98, interaction p = 0.02). The total bilirubin was significantly associated with HGS and sarcopenia in women with type 2 diabetes. Total bilirubin may serve as a useful indicator of sarcopenia in Japanese women.

This phase 1 dose-escalation study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of K1-70^TM, a TSH-receptor-specific monoclonal autoantibody that inhibits ligand binding and receptor activation, in Japanese Graves’ disease (GD) patients. Twelve patients were enrolled, divided into four dosage cohorts (5 mg, 25 mg, 75 mg, and 150 mg), and monitored for 100 days post-administration. The primary objective was to assess safety and tolerability, and the secondary objectives were evaluation of PK and thyroid function. Exploratory analyses focused on the dynamics of the anti-TSH receptor antibodies and Thyroid eye disease (TED). K1-70^TM demonstrated a favorable safety profile, with no reports of serious adverse events. Mild to moderate treatment-emergent adverse events, such as headache and fatigue, were observed in 83.3% of the participants, but none were deemed severe. PK analysis revealed a dose-dependent increase in half-life, suggesting prolonged systemic exposure at higher doses. Thyroid function remained stable at lower doses, but there were dose-dependent reductions at higher doses that were managed with adjunctive L-thyroxine therapy. Marked reductions in TSAb levels were observed across all cohorts, indicating effective suppression of TSH receptor activity. An improvement in proptosis was noted in 50% of the eyes, suggesting a potential therapeutic benefit against inactive-phase TED. These findings support K1-70^TM as a promising targeted therapy for GD and TED, and they warrant further studies involving larger patient populations and active disease phases to confirm its efficacy and safety (jRCT Registration Number: JRCT2080224902).

Levothyroxine (LT4) is the established treatment for hypothyroidism but some controversies, such as whether combining it with liothyronine (LT3) for hypothyroid patients and whether prescribing it to euthyroid patients, exist on its use. This survey was conducted to investigate current trends about thyroid hormone use in hypothyroid and euthyroid patients in Japan. Members of the Japan Thyroid Association (JTA) were invited to participate in an online questionnaire based on the THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) survey. Anonymous responses from 207 of 874 (23.7%) JTA-certified thyroid specialists were analyzed. LT4 was the first line treatment for hypothyroidism by all respondents. 18.8% and 28.0% would also use LT3 and LT3 + LT4 combination, respectively. LT3 + LT4 combination was preferred for patients on LT4 with residual symptoms or low serum T3 levels. Psychological factors and comorbidities were considered as the main contributors to residual symptoms. Respondents would prescribe thyroid hormones in euthyroid subjects for female infertility with positive anti-thyroid antibodies (46.9%), for Hashimoto’s disease with a huge goiter (29.0%), and for pregnant or infertile women with TSH between 2.5–4 mU/L irrespective of anti-thyroid antibody status (43.0 and 76.8%, and 46.9 and 77.3%, respectively). In conclusion, Japanese thyroid specialists chose LT4 as first line treatment for hypothyroidism in accordance with current guidelines. The use of LT3 + LT4 combination is less frequent in Japan than in other countries, whereas the use of thyroid hormones for non-hypothyroid indications is similarly high worldwide, which is not necessarily in accord with pertinent society guidelines.

Recombinant human growth hormone (GH; somatropin) treatment has beneficial effects on body composition in patients with Prader-Willi syndrome (PWS). However, this treatment option is limited to children in most countries and to children with short stature in countries such as the USA and Japan. The aim of this multicohort study was to evaluate the effect of somatropin on body composition and to assess its safety in Japanese pediatric and adult participants with PWS. GH-naïve pediatric participants (n = 6) received somatropin 0.245 mg/kg/week, GH-treated pediatric participants (n = 7) received somatropin 0.084 mg/kg/week, and adult participants (n = 20) received somatropin 0.042 mg/kg/week for 1 month, followed by 0.084 mg/kg/week. The study met its primary endpoint in the adult cohort because the least squares mean (95% CI) of the change from baseline to Month 12 in lean body mass (LBM) (%) was greater than the prespecified efficacy criterion of 0. LBM (%) was higher at 12 months in GH-naïve pediatric participants, while GH-treated pediatric participants showed little deterioration in LBM despite reduced GH dosage. Treatment-emergent adverse events (TEAEs) were experienced by five (83.3%), five (71.4%), and 19 (95.0%) participants in the GH-naïve pediatric cohort, GH-treated pediatric cohort, and adult cohort, respectively. Most TEAEs were mild or moderate in severity. Three participants reported four serious TEAEs, and none were treatment related. Somatropin improved body composition in adult participants, enabled maintenance of body composition in pediatric participants, and demonstrated a favorable safety and tolerability profile in all PWS cohorts. (ClinicalTrials.gov ID: NCT04697381)

Obese pregnant women are more likely to develop hypertensive disorders of pregnancy (HDP), which puts them at risk for future cardiovascular events and type 2 diabetes. This study aimed to investigate the relationship between body weight and HDP in nondiabetic singleton-pregnant women. We examined the KODMO database, which included 5,120 pregnant women who gave birth at NHO Kokura Medical Center between January 2009 and December 2019, excluding those with pre-existing diabetes mellitus, hypertension, or multiple pregnancies. A multivariate logistic regression analysis of potential HDP risk factors revealed that both pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were independent risk factors. The estimated impact was considerably greater in women with higher pre-pregnancy BMI, with odds ratios of 1.60 (95% CI: 1.18–2.18, p = 0.0025) for obesity degree 1 (25 ≤ BMI < 30 kg/m²) and 3.42 (95% CI: 2.35–5.01, p < 0.0001) for obesity degree ≥2 (BMI ≥ 30 kg/m²) (reference: normal weight [18.5 ≤ BMI < 25 kg/m²]). GWG was further investigated by stratifying BMI categories, which revealed that obese pregnant women have a risk of developing HDP even with the normal GWG defined by current guidelines. The odds ratio of HDP in pregnant women with normal GWG was 1.79 (95% CI: 1.02–3.41, p = 0.0436) in obesity degree 1 and 3.25 (95% CI: 1.57–6.74, p < 0.0001) in obesity degree ≥2. The impact of GWG as a modifiable factor of HDP varies with pre-pregnancy BMI, highlighting the importance of weight management before and during pregnancy.

Esaxerenone, a nonsteroidal mineralocorticoid receptor blocker, may be an effective treatment for diabetes-associated mineralocorticoid receptor-related hypertension, but there have been few studies of its use in clinical practice. We aimed to determine the effects of esaxerenone on blood pressure (BP) and metabolic parameters of hypertensive subjects with diabetes in a clinical practice setting. We performed a retrospective multicenter observational study of hypertensive subjects with type 2 diabetes/prediabetes. We first compared the values of parameters at baseline and after 6 months of esaxerenone administration, then compared the changes in the parameters in propensity score-matched subjects who initiated esaxerenone or amlodipine administration. Correlation analysis was performed to identify factors associated with these changes. The single-arm analysis showed that esaxerenone caused significant reductions in systolic and diastolic BP from 155.2 ± 17.7 and 83.3 ± 12.3 mmHg at baseline to 132.9 ± 15.5 and 72.3 ± 12.9 mmHg, respectively, after 6 months of treatment (p < 0.01). In addition, body mass index (BMI), glycated hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, estimated glomerular filtration rate, and urine albumin/creatinine ratio (UACR) significantly decreased (p < 0.05). The esaxerenone group showed significantly larger reductions in systolic BP, AST, ALT, and UACR than the amlodipine group (p < 0.05). Furthermore, there was a negative correlation between the change in ALT and baseline BMI (p < 0.05). Esaxerenone has an antihypertensive effect, reduces the albuminuria, and reduces the activities of liver enzymes in hypertensive subjects with type 2 diabetes/prediabetes. The present findings suggest that esaxerenone has pleiotropic effects in such subjects.

This study aimed to confirm the applicability of the product of depth and width of the right thyroid lobe measured by ultrasonography, as an index of estimated thyroid volume in patients with Hashimoto thyroiditis. This study included 118 patients with Hashimoto thyroiditis and 163 patients with Graves’ disease. The product of depth and width of the right thyroid lobe ranged from 1.7 to 10.2 (median, 4.4) cm² for Hashimoto thyroiditis and 2.6 to 10.8 (median, 5.8) cm² for Graves’ disease. The estimated volume obtained by ellipsoidal approximation correlated well with the product of depth and width of the right thyroid lobe in Hashimoto thyroiditis (ρ = 0.820, p < 0.0001) and Graves’ disease (ρ = 0.928, p < 0.0001), respectively. However, the correlations were not identical. The comparison of 72 patients with Hashimoto thyroiditis and 72 patients with Graves’ disease who were matched for the product of depth and width revealed no significant difference in the estimated thyroid volume. These results show that the product of depth and width of the right thyroid lobe can be applied to indicate thyroid volume instead of the estimated volume obtained from ellipsoidal approximation in both Hashimoto thyroiditis and Graves’ disease within the range of volumes investigated in this study.