Eldecalcitol is an active vitamin D3 derivative approved for the treatment of osteoporosis in Japan and postmenopausal osteoporosis in China. However, the impact of concomitant calcium supplementation on its safety profile is unclear. This was a prospective, observational, non-interventional post-marketing drug intensive monitoring study in Chinese postmenopausal women with osteoporosis (NCT05433207). Data were collected using an electronic case report form at baseline, before initial eldecalcitol dosing, and during routine clinical visits over a 1-year follow-up period. One thousand patients were enrolled from 29 Chinese clinical sites; 958 received eldecalcitol (853 without/105 with calcium supplementation). The mean age (standard deviation [SD]) of patients was 65.6 (9.0) years and mean (SD) time since osteoporosis diagnosis was 2.7 (3.8) years. Adverse drug reactions (ADRs) affected 39.2

The PaTHway clinical trial demonstrated sustained efficacy, safety, and tolerability of daily palopegteriparatide in the treatment of adults with hypoparathyroidism. Palopegteriparatide treatment was also associated with improvements in estimated glomerular filtration rate (eGFR) over 52 wk in a post hoc analysis, prompting further exploration of palopegteriparatide in the preservation of renal function. The current post hoc analysis evaluated the impact of palopegteriparatide treatment on renal function in adults with hypoparathyroidism through Week 104; as with prior analysis, changes in renal function were assessed using eGFR. At Week 104, 93% (76/82) of participants remained in the open-label extension. Of those, 82% had albumin-adjusted serum calcium levels in the normal range (8.3-10.6 mg/dL), 97% were independent from conventional therapy (≤600 mg/d of elemental calcium and no active vitamin D). Mean (SD) serum phosphate (3.5 (0.7) mg/dL) and albumin-adjusted calcium × phosphate product (30.7(5.1) mg2/dL2) levels were also within normal ranges. Palopegteriparatide treatment resulted in a mean (SD) increase in eGFR of 8.9 (11.0) mL/min/1.73m2 (p < .0001) from baseline to Week 52, which was sustained through Week 104, where it was 77.8 (14.8) mL/min/1.73 m2 with a mean (SD) change from baseline of 9.0 (10.3) mL/min/1.73 m2 (p < .0001). By Week 104, 45% and 34% of participants had an increase in eGFR of ≥5 mL/min/1.73 m2 and ≥10 mL/min/1.73 m2, respectively. Palopegteriparatide treatment normalized mean (SD) 24-h urine calcium within 26 wk and maintained levels below 250 mg/d through Week 104 (158.8 (90.5) mg/24 h). Most treatment-emergent adverse events were mild or moderate; no new safety signals or cases of treatment-related nephrolithiasis were reported. These findings demonstrate sustained renal safety of palopegteriparatide and suggest that PTH replacement therapy with palopegteriparatide preserves and may improve renal function in adults with chronic hypoparathyroidism after 104 wk of treatment.

Patient satisfaction with two teriparatide (TPTD) self-injection regimens [once-daily (1/D)-TPTD and twice-weekly (2/W)-TPTD] was compared in a randomized crossover study involving patients with osteoporosis at high fracture risk. Questionnaires evaluated overall satisfaction, satisfaction with treatment effectiveness, satisfaction with utility of the self-injection device, and preference for a particular injection regimen after crossover. Quality of life (QOL), visual analogue scale pain scores, and bone mineral density (BMD) were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs). The 1/D-TPTD and 2/W-TPTD groups comprised 180 (mean age: 75.9 ± 7.3 years) and 178 (75.4 ± 6.9 years) patients, respectively. After 26 weeks of treatment, the injection regimens were switched and treatment continued for another 26 weeks. Significantly higher persistence was observed in the 1/D-TPTD to 2/W-TPTD group (p = 0.032). No significant between-group differences in overall satisfaction scores or satisfaction with treatment were observed. Satisfaction with the utility of the injection device was significantly higher with the 2/W-TPTD regimen (p < 0.05); this regimen was preferred by 69.4

Although bone anabolic agents such as teriparatide are effective for osteoporosis, satisfaction and adherence may vary by regimen. This multicenter study assessed long-term satisfaction, persistence, efficacy, and safety in postmenopausal women with primary osteoporosis treated with alternating daily and twice-weekly teriparatide over 52 weeks, followed by a final free-choice treatment period. In a randomized, open-label, crossover study, 358 postmenopausal women at high risk for fracture were assigned to receive once-daily (20 µg) or twice-weekly (28.2 µg) subcutaneous teriparatide for 26 weeks, then crossed over to the alternative regimen for another 26 weeks. Afterwards, 233 patients entered a 52-week free-choice period under their preferred regimen. Among the 233 patients entering the free-choice period, 162 chose twice-weekly and 71 chose daily teriparatide. Persistence at 104 weeks was 90.1

Romosozumab is a potent pharmacological tool to prevent fractures in osteoporosis patients, and its mechanism of action is distinct from any other drugs. The efficacy of romosozumab to prevent osteoporotic fractures is remarkable. However, there remains a concern of increased cardiovascular adverse events. Further relevant investigations are essential to understand whether romosozumab is actually involved in the development of cardiovascular events or not. We need more robust evidence to establish an appropriate and reasonable guide to prescribe romosozumab in our clinical practice.

PaTHway Japan is an ongoing, phase 3, multicenter, single-arm, open-label trial comprised of a 26-week efficacy period with an extension period through week 182 designed to demonstrate the efficacy, safety, and tolerability of palopegteriparatide in Japanese individuals with hypoparathyroidism. Japanese men and women (≥18 years of age) with hypoparathyroidism of any etiology (≥26 weeks) taking stable doses of active vitamin D were enrolled across five sites in Japan. Once-daily palopegteriparatide was self-administered subcutaneously via a pre-filled pen injector. Titration of palopegteriparatide and conventional therapy was performed according to a protocol-specified algorithm. The main outcomes measures included the proportion of participants at week 26 who achieved albumin-adjusted serum calcium in the normal reference range, independence from active vitamin D, and independence from therapeutic doses of elemental calcium. Thirteen participants were enrolled. Hypoparathyroidism etiology was most commonly idiopathic, followed by postsurgical and genetic causes. After 26 weeks of treatment with palopegteriparatide, 92% (12/13) of participants achieved the primary multi-component endpoint. Of the participants who entered the extension period, 92% (11/12) met the multi-component endpoint at week 52. Adverse events were mild to moderate in severity; none led to discontinuation of palopegteriparatide treatment. These findings in Japanese adults are consistent with results of the pivotal phase 3 and phase 2 North American/European trials and demonstrate the reproducibility of the palopegteriparatide treatment benefit in diverse populations and geographies. Japan Registry of Clinical Trials ID: jRCT2051210058.

Pituitary neuroendocrine tumors (PitNETs) are generally benign, but a small subset may demonstrate aggressive behavior or undergo malignant transformation. Neuroendocrine carcinoma (NEC), defined as a high-grade, poorly differentiated neuroendocrine neoplasm, is extremely rare in the pituitary, and its existence as a primary entity remains controversial. We report two cases of corticotroph PitNETs in female patients with Cushing disease, in which NEC components emerged several years after radiotherapy. Case 1 presented as an invasive macroadenoma with cavernous sinus invasion, and Case 2 as a 5 mm microadenoma. In both cases, recurrent tumors developed following subsequent radiotherapy. NEC components exhibited marked nuclear pleomorphism, necrosis, elevated Ki-67 indices, diffuse p53 expression, and loss or reduction of ACTH and TPIT expression. In Case 2, faint TPIT expression and discontinuous tumor growth within the sella raised the possibility of a metastatic NEC to the pituitary could not be excluded. These cases highlight the emergence of NEC features in corticotroph PitNETs, most likely as a result of post-radiotherapy transformation. However, due to faint TPIT expression and an unusual tumor distribution in Case 2, the possibility of a primary NEC or metastatic neuroendocrine neoplasm from another organ cannot be definitively excluded.

A 16-year-old girl presented with a high fever that had persisted for more than 4 weeks. Computed tomography (CT) revealed a 4-cm mass in the left adrenal gland. Clinically, there were no obvious symptoms of adrenal hormone excess; however, serum interleukin-6 (IL-6) and C-reactive protein levels were significantly elevated. After laparoscopic left adrenalectomy, the fever subsided, and her IL-6 level normalized. The tumor was pathologically diagnosed as adrenocortical carcinoma (ACC), with a Weiss score of 5/9. The tumor cells were immunoreactive for IL-6. To our knowledge, this is the first case report of symptomatic IL-6-producing ACC that initially presented with a persistent fever.

Several osteoanabolic agents have been developed to build new bone more efficiently than anti-resorptive drugs. Among them, romosozumab, an anti-sclerostin antibody, is a potent pharmacological tool to prevent fractures in osteoporosis patients. The efficacy of romosozumab in preventing osteoporotic fractures is robust. However, there remains a concern about increased cardiovascular (CV) adverse events related to romosozumab. Available data have been reviewed to address this concern. Published articles on romosozumab of which pivotal randomized controlled trials (RCTs), meta-analyses of RCTs, pharmacovigilance investigations, and retrospective observational clinical studies using real-world data were collected through PubMed and other available tools. Meta-analyses of RCTs of romosozumab compared to placebo and other anti-osteoporosis drugs have left room for controversy in the CV safety of romosozumab. Investigations of the real-world data also provide no conclusive evidence in this issue. We need more robust evidence to establish an appropriate and reasonable guide to prescribe romosozumab in our clinical practice.

Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m2. At week 52, over 95

Fracture prevention in the elderly is an urgent issue at all levels: individual, family, and societal. Osteoporosis is the underlying cause of fractures in the elderly, and it is important to understand its pathogenesis and treatment. Diet, exercise, and pharmacotherapy are all important for fracture prevention. Particularly with regard to pharmacotherapy, it is important to understand the mechanism of action of each drug and its characteristics and problems from a clinical point of view. Appropriate treatment of osteoporosis has been proven to reduce fractures in the elderly, and its widespread implementation is desirable.

CONTEXT:Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE:To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS:This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS:The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION:To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

This post hoc analysis examines the impact of palopegteriparatide on renal function in adults with chronic hypoparathyroidism through week 104 of PaTHway, a phase 3 trial with a randomized, double-blind, placebo-controlled 26-week period and ongoing 156-week open-label extension. Changes in renal function were assessed using eGFR. At week 104, 76 of 82 participants remained in the trial. Of those, 82% had normal albumin-adjusted serum calcium levels (2.07–2.64mmol/L), 97% were independent from conventional therapy, and none required active vitamin D. Mean (SD) serum phosphate (1.1 (0.2) mmol/L) and albumin-adjusted calcium x phosphate product (2.5 (0.4) mmol2/L2) were normal. At week 104, mean (SD) eGFR was 77.8 (14.8) mL/min/1.73m2. With palopegteriparatide treatment mean eGFR increased 8.9 (11.0) mL/min/1.73m2 (P<.0001) from baseline to week 52, which was sustained through week 104 (mean (SD) change from baseline 9.0 (10.3) mL/min/1.73 m2 (P<0.0001)). By week 104, 61% and 44% of participants had an increase in eGFR of ≥ 5mL/min/1.73 m2 and ≥ 10mL/min/1.73 m2, respectively. Palopegteriparatide normalized mean 24-hour urine calcium within 26 weeks, maintaining levels below 6.2mmol/day through week 104 (4.0 (2.3) mmol/day). No cases of nephrolithiasis were reported with palopegteriparatide. Most TEAEs were mild or moderate; no new safety signals reported. These findings show sustained renal safety of palopegteriparatide and suggest that PTH replacement with palopegteriparatide and independence from conventional therapy may not only preserve but improve renal function in adults with chronic hypoparathyroidism.

This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture. In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs). The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4

The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92

Hypoparathyroidism is a rare endocrine disorder characterized by low serum calcium and elevated serum phosphorus levels. Patients who do not recover parathyroid function after surgeries or have nonsurgical causes involving congenital and metabolic diseases, require long-term use of active vitamin D and calcium supplementation as conventional therapy in Japan. This study aimed to estimate prevalence of chronic hypoparathyroidism and investigate its disease etiology, patient characteristics, and treatment in Japan, using a health insurance claim database. Individuals who were available in the 4-yr observation period spanning 2015-2018 (2015-2017 for look-back and 2018 for prevalence estimation) were eligible for the denominator. Chronic hypoparathyroidism was defined as individuals who had both a record of prescription of conventional therapy for hypoparathyroidism in 2018 and a record of relevant surgery, radiotherapy, or disease at least 6 mo apart. Among the denominator (N = 2 241 717), 509 patients with chronic hypoparathyroidism were identified (mean age of 49 yr). The standardized prevalence of chronic hypoparathyroidism in 2018 was 38.3 (95% CI: 33.4-43.6) per 100 000 individuals, with 37.0 (32.2-42.3) and 1.2 (0.8-2.0) per 100 000 for postoperative and nonoperative causes, respectively. Six percent of the patients had chronic kidney disease as a comorbidity. Chronic hypoparathyroidism had heterogenous causes, with thyroid malignancy and 22q11.2 deletion syndrome being the most common postoperative and nonoperative causes, respectively. The mean duration of prescribed vitamin D and calcium was 963 and 629 d, respectively, during the 4-yr period. The prevalence of chronic hypoparathyroidism was similar but slightly higher than estimates reported for the United States and Europe, which may be due to the differences in study designs and high healthcare accessibility in Japan. Our study suggests that there is a nonnegligible number of patients, similar to 48 500 patients, with chronic hypoparathyroidism in Japan.

The association of renal function with fracture incidence during teriparatide or alendronate treatment in elderly Japanese women was examined. Fracture incidence differed by fracture type, renal function, and treatment protocol. The results provide important information on pharmacotherapy in clinical practice for osteoporosis. Incidence rate of morphometric vertebral fracture was lower under treatment with once-weekly teriparatide (TPTD) followed by alendronate (ALN) than under treatment with ALN throughout the study among elderly Japanese women at high fracture risk in JOINT-05. This is an exploratory subgroup analysis according to chronic kidney disease (CKD) status at baseline. Participants received sequential therapy with TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group, N = 483) or ALN monotherapy for 120 weeks (ALN group, N = 496). Baseline CKD status was classified by the estimated glomerular filtration rate (eGFR) and categorized as: CKD 1/2 (eGFR ≥ 60 mL/min/1.73 m2), CKD 3a (eGFR 45–59 mL/min/1.73 m2), or CKD 3b/4 (eGFR < 45 mL/min/1.73 m2). Incidences of vertebral fractures including morphometric fractures, non-vertebral fractures, and all fractures were evaluated during follow-up. Baseline characteristics were not different between treatment groups. Higher stages of CKD were associated with age and number of prevalent vertebral fracture. In CKD 1/2 patients (N = 556 with 90 incidents of morphometric vertebral fracture), the incidence of vertebral fractures was lower in the TPTD-ALN group than in the ALN group (p = 0.01). In CKD 3b/4 patients (N = 112 with 10 incidents of non-vertebral fracture), the incidence of non-vertebral fractures was lower in the ALN group than in the TPTD-ALN group, although the number of fractures was small. In the ALN group, the incidences of vertebral fractures, non-vertebral fractures, and all fractures remained constant across CKD stages. This exploratory analysis showed that fracture incidence on ALN was constant regardless of renal function. It also suggested that the incidence of vertebral fractures on TPTD-ALN was lower than ALN monotherapy in CKD 1/2 patients. These results provide important information for drug selection in the clinical practice of osteoporosis.