OBJECTIVE: The research aimed to determine the importance of vitamin D and markers of bone metabolism in the overall assessment of bone mineralization during a child\'s first year of life.
METHODS: The 198 children were selected by screening all infants seen at our pediatric clinic over a 2-year period from 2020-2022 and including those who met the eligibility criteria of being aged 0 to 1 year, healthy with no chronic conditions, and not on vitamin D supplementation. Children were divided into 3 groups depending on the content of vitamin D in the blood serum: sufficient, insufficient, and deficient. The markers of bone tissue status included: markers of mineral metabolism (calcium, phosphorus, parathyroid hormone, calcitonin), a marker of bone formation (osteocalcin), resorption marker (deoxypyridinoline). Laboratory values were obtained at the time of study enrollment during the initial study visit. Labs were not repeated during the course of the study.
RESULTS: A quarter of the infants exhibited vitamin D deficiency at enrollment with serum 25OHD concentrations below 20 ng/mL, which showed a positive correlation with serum calcium and phosphorus -concentrations and a negative correlation with PTH, while osteocalcin and deoxypyridinoline concentrations remained consistent regardless of vitamin D status.
CONCLUSIONS: The study\'s practical significance allows for the recommendation of using vitamin D -concentrations as a marker to detect bone formation and mineral metabolism disorders in children during their first year of life. By identifying and addressing these issues early on, the health care system aims to ensure better musculoskeletal health for children.

UNASSIGNED: Lung adenocarcinoma with parathyroid hormone (PTH)-related hypercalcemia is uncommon.
UNASSIGNED: A 69-year-old man was admitted to our hospital due to anorexia and fatigue. Serum calcium (15.0 mg/dL) and carcinoembryonic antigen (361.7 ng/mL) were extremely high, and PTH-related protein (PTH-rP) also elevated (16.7 pmol/L). Systemic computed tomography revealed multiple enlarged lymph nodes and disseminated peritoneal nodules, with irregularly shaped nodules in the upper lobe in the left lung. Ultrasound-guided biopsy from the axillary lymph node revealed adenocarcinoma. Immunohistological staining showed the tumor cells to be positive for cytokeratin 7 and PTH-rP and negative for cytokeratin 20 and thyroid transcription factor-1. Although the primary origin remains undetermined despite detailed examinations, possible primary tumor was considered to be lung adenocarcinoma in the present case. The serum calcium level was reduced by denosumab, but the patient died 20 days after admission.
UNASSIGNED: The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma.

BACKGROUND: Hypoparathyroidism is a rare endocrine disease frequently associated with serious physical and cognitive symptoms. This study\'s purpose was to understand the impacts of the phase 3 PaTHway clinical trial treatment, TransCon PTH, on patients\' overall, physical, and cognitive hypoparathyroidism signs/symptoms and what patients consider meaningful improvement.
METHODS: Individual telephone exit interviews were conducted with patients who recently completed the PaTHway trial blinded period. Using a semi-structured interview guide, interviews focused on trial treatment impact on hypoparathyroidism symptoms following the symptom list in the Hypoparathyroidism Patient Experience Scale-Symptom (HPES-Symptom). Meaningful changes in hypoparathyroidism symptoms were assessed with the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) measures. Interviewees were probed on the meaningfulness of reported changes in symptoms from prior to starting trial treatment to the past 2 weeks/current time. Interviews were audiotaped and transcribed. Transcripts were coded for emerging concepts and themes/subthemes covered in the interview guide based on an adapted grounded theory approach.
RESULTS: Nineteen adults with hypoparathyroidism participated in interviews in the United States (n = 13, 68.4%) and Canada (n = 6, 31.6%). Marked improvements in physical and cognitive symptoms were described among trial treatment group respondents. The majority of participants who reported experiencing hypoparathyroidism physical symptoms pre-trial indicated symptom improvement with treatment, including muscle twitching (100%, n = 15), low energy (92.9%, n = 13), feeling tired (92.3%, n = 12), muscle weakness (92.9%, n = 13), tingling without numbness (84.6%, n = 11), trouble sleeping (92.3%, n = 12), muscle cramping (92.3%, n = 12), tingling with numbness (92.3%, n = 12), muscle spasms (100%, n = 12), and pain (90.9%, n = 10). Most participants who reported experiencing cognitive symptoms pre-trial reported symptom improvement with treatment, including difficulty finding the right words (86.7%, n = 13), difficulty concentrating (93.3%, n = 14), trouble remembering (92.9%, n = 13), trouble thinking clearly (85.7%, n = 12), and difficulty understanding information (83.3%, n = 10). Those in the placebo group reported limited or no improvement. The vast majority of participants affirmed that the improvements they experienced in symptom frequency on the PGIS/PGIC and HPES-Symptom were meaningful.
CONCLUSIONS: Findings indicate that TransCon PTH treatment improved participants\' physical and cognitive hypoparathyroidism symptoms in meaningful ways, while reducing the daily burden associated with conventional therapy.
BACKGROUND: NCT04701203 Registered: 06 January 2021. https://clinicaltrials.gov/study/NCT04701203?term=NCT04701203&rank=1 .

OBJECTIVE: The aim of this study was to determine the disturbances in the concentration of parathyroid hormone (PTH) and 25-hydroxyvitamin D (vitamin D) in patients with stable chronic obstructive pulmonary disease (COPD) and its correlation with airflow obstruction.
METHODS: A prospective study included 200 patients with a confirmed diagnosis of COPD in the Department of Lung Diseases and Tuberculosis and Pulmonology Polyclinic of University Clinical Hospital Mostar in the period of three years, between May 2021 and May 2024. Inclusion criteria were a stable phase of COPD, hemodynamically stable patients older than 40 years, forced vital capacities in the first second (FEV1)/forced vital capacities (FVC) <0.7, and patients with PTH, vitamin D, calcium, and phosphate measurements. Exclusion criteria were acute exacerbation of COPD in the last month; current treatment with nutritional supplements, vitamins, and statins; lack of availability of lung function data; use of systemic corticosteroids in the previous three months; chronic renal insufficiency, respiratory diseases other than COPD (asthma, pneumonia, tuberculosis, and bronchiectasis), and other diseases (cancer and parathyroid disease). Medical records about demographic data (age and gender), pulmonary function test (FVC, FEV1, FEV1%FVC, mean expiratory flow (MEF)50), body mass index (BMI), COPD assessment test (CAT), Modified Medical Research Council (mMRC) Dyspnea Scale, and serum PTH, vitamin D, calcium, and phosphate levels were obtained.
RESULTS:  Patients with higher COPD stage had lower spirometry values, most significantly MEF50. The higher the COPD group (Global Initiative for Chronic Obstructive Lung Disease (GOLD) D), the lower vitamin D ​​and the higher PTH levels were. Calcium and phosphate values ​​were the same for all groups. Vitamin D and PTH levels significantly ​​correlated with MEF50 values. The lower MEF50 level, the higher PTH levels, ​​and lower vitamin D levels were found (P<0.05).
CONCLUSIONS: Our study showed that the patients in the higher COPD group have lower vitamin D levels ​​and higher PTH levels, indicating that they developed secondary hyperparathyroidism. The levels of vitamin D and PTH correlated the most with MEF50 values while other spirometry parameters did not significantly correlate with vitamin D and PTH levels.

BACKGROUND: Chronic kidney disease (CKD) and its associated complications, such as anemia and secondary hyperparathyroidism (SHPT), pose significant challenges to global healthcare systems. This study explores the demographic and clinical characteristics of 284 kidney failure (KF) patients undergoing hemodialysis, in an effort to shed light on the possible association between anemia and SHPT. A proven connection between the two could theoretically influence the management plans for CKD patients, with the hopes of achieving lower morbidity and/or mortality in this patient group.
METHODS: A retrospective, cross-sectional, real-world data analytical study was conducted at a hemodialysis center in Tbilisi, Georgia, encompassing a sample size of n = 284 patients on maintenance hemodialysis. The data analyzed was extracted from patients\' medical records.
RESULTS: According to our results, the prevalence of anemia was strikingly high at 82.04%, underlining its substantial burden within this patient population. Our analysis revealed a notable systemic association between anemia and SHPT, particularly when considering hemodialysis vintage. However, our final analysis model revealed no statistically significant association between anemia and intact parathyroid hormone (iPTH) levels.  Conclusion: Our study revealed a significant systemic relationship between anemia and SHPT when hemodialysis duration was considered, despite initial analyses showing no direct association. Future research should focus on longitudinal and multi-center studies to better understand this relationship, aiming to enhance the care and management of CKD patients on hemodialysis.

UNASSIGNED: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD.
UNASSIGNED: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH.
UNASSIGNED: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients.
UNASSIGNED: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients.

Glucocorticoids (GC) and parathyroid hormone (PTH) are widely used therapeutic endocrine hormones where their effects on bone and joint arise from actions on multiple skeletal cell types. In osteocytes, GC and PTH exert opposing effects on perilacunar canalicular remodeling (PLR). Suppressed PLR can impair bone quality and joint homeostasis, including in GC-induced osteonecrosis. However, combined effects of GC and PTH on PLR are unknown. Given the untapped potential to target osteocytes to improve skeletal health, this study sought to test the feasibility of therapeutically mitigating PLR suppression. Focusing on subchondral bone and joint homeostasis, we hypothesize that PTH(1-34), a PLR agonist, could rescue GC-suppressed PLR. The skeletal effects of GC and PTH(1-34), alone or combined, were examined in male and female mice by micro-computed tomography, mechanical testing, histology, and gene expression analysis. For each outcome, females were more responsive to GC and PTH(1-34) than males. GC and PTH(1-34) exerted regional differences, with GC increasing trabecular bone volume but reducing cortical bone thickness, stiffness, and ultimate force. Despite PTH(1-34)\'s anabolic effects on trabecular bone, it did not rescue GC\'s catabolic effects on cortical bone. Likewise, cartilage integrity and subchondral bone apoptosis, tartrate-resistant acid phosphatase (TRAP) activity, and osteocyte lacunocanalicular networks showed no evidence that PTH(1-34) could offset GC-dependent effects. Rather, GC and PTH(1-34) each increased cortical bone gene expression implicated in bone resorption by osteoclasts and osteocytes, including Acp5, Mmp13, Atp6v0d2, Ctsk, differences maintained when GC and PTH(1-34) were combined. Since PTH(1-34) is insufficient to rescue GC\'s effects on young female mouse bone, future studies are needed to determine if osteocyte PLR suppression, due to GC, aging, or other factors, can be offset by a PLR agonist.

In this study, we used a bioinformatic approach to construct a miRNA-target gene interaction network potentially involved in the anabolic effect of parathyroid hormone analogue teriparatide [PTH (1-34)] on osteoblasts. We extracted a dataset of 26 microRNAs (miRNAs) from previously published studies and predicted miRNA target interactions (MTIs) using four software tools: DIANA, miRWalk, miRDB, and TargetScan. By constructing an interactome of PTH-regulated miRNAs and their predicted target genes, we elucidated signaling pathways regulating pluripotency of stem cells, the Hippo signaling pathway, and the TGF-beta signaling pathway as the most significant pathways in the effects of PTH on osteoblasts. Furthermore, we constructed intersection of MTI networks for these three pathways and added validated interactions. There are 8 genes present in all three selected pathways and a set of 18 miRNAs are predicted to target these genes, according to literature data. The most important genes in all three pathways were BMPR1A, BMPR2 and SMAD2 having the most interactions with miRNAs. Among these miRNAs, only miR-146a-5p and miR-346 have validated interactions in these pathways and were shown to be important regulators of these pathways. In addition, we also propose miR-551b-5p and miR-338-5p for further experimental validation, as they have been predicted to target important genes in these pathways but none of their target interactions have yet been verified. Our wet-lab experiment on miRNAs differentially expressed between PTH (1-34) treated and untreated mesenchymal stem cells supports miR-186-5p from the literature obtained data as another prominent miRNA. The meticulous selection of miRNAs outlined will significantly support and guide future research aimed at discovering and understanding the crucial pathways of osteoanabolic PTH-epigenetic effects on osteoblasts. Additionally, they hold potential for the discovery of new PTH target genes, innovative biomarkers for the effectiveness and safety of osteoporosis-affected treatment, as well as novel therapeutic targets.

OBJECTIVE: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture.
METHODS: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray.
RESULTS: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures.
CONCLUSIONS: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.

BACKGROUND: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.
METHODS: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).
RESULTS: During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (β = .33, P = .001), and absolutely lower, serum calcium levels (β = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L.
CONCLUSIONS: SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.