Diets containing inorganic phosphate additives are unbalanced with respect to calcium and these diets have been linked to the development of altered bone metabolism. Using 2 randomized cross-over studies in healthy humans, we (1) characterized the hormonal and urinary response to 2 meals with the same reported phosphorus amount (562-572 mg), where one was manufactured with inorganic phosphate additives and a comparatively lower Ca:P molar ratio (0.26 vs 0.48), and (2) assessed how acute homeostatic mechanisms adapt following 5-d exposure to recommended dietary phosphorus amount (~700 mg P/d) compared to a diet enriched with inorganic phosphate additives (~1100 mg P/d). Participants were then challenged with 500 mg of oral phosphorus in the form of inorganic phosphate after an overnight fast following each diet condition. Measurements included serum calcium, phosphate, PTH, and fibroblast growth factor 23 , vitamin D metabolites, and urine calcium and phosphate excretion. Following the meal containing inorganic phosphate additives with a low Ca:P ratio, serum phosphate was higher and more phosphate was excreted in the urine compared to the low additive meal. Although the Ca:P and calcium content was lower in the high additive meal, the same amount of calcium was excreted into the urine. Subsequently, increasing only dietary phosphate through additives resulted in lower 24-h excretion of calcium. The oral phosphate challenge promoted urinary calcium excretion, despite no consumption of calcium, which was attenuated when pre-acclimated to a high phosphate diet. These data suggest that ingestion of inorganic phosphate promotes calcium excretion, but homeostatic mechanisms may exist to reduce calcium excretion that are responsive to dietary intake of phosphate. Future studies are required to evaluate potential implication of diets enriched with inorganic phosphate additives on bone health.

Primary hyperparathyroidism (PHPT), an endocrine disorder most commonly caused by parathyroid adenoma (PTA), manifests with a diverse array of symptoms, reflecting the multisystem impact of parathyroid hormone: nephrolithiasis, peptic ulcer disease, psychiatric disorders, muscle weakness, constipation, polyuria, pancreatitis, myalgia, and arthralgia. Rarely do these PTA attain a significant size. PHPT is usually diagnosed through biochemical tests, and radiological imaging characterizes the adenoma. Serum 25-hydroxyvitamin D levels are useful in explaining the large adenoma size. Here, we report a rare case of a 60-year-old female from Morocco who presented with marked dyspnea due to a giant PTA.

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

UNASSIGNED: The longitudinal changes in hip-bone microstructures and estimated bone strength in dialysis patients, and the impact of chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers on these changes, remain insufficiently explored.
UNASSIGNED: This retrospective study examined changes in cortical and trabecular bone compartments and estimated bone-strength indices, obtained by using 3D-SHAPER software, in the hip regions of 276 dialysis patients over up to 2.5 years. We used multivariate mixed models to investigate the associations between time-dependent CKD-MBD biomarkers and bone health metrics.
UNASSIGNED: There was a significant decrease in areal bone mineral density (aBMD), integral volumetric BMD (vBMD), trabecular vBMD, cortical thickness and cortical surface BMD (sBMD). Similar deteriorations were found in estimated bone-strength indices [cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (SM) and buckling ratio]. Neither serum calcium nor phosphate levels were significantly associated with changes in three-dimensional parameters or estimated bone-strength indices. In contrast, serum alkaline phosphatase levels showed a significant inverse correlation with aBMD and CSA. The intact-parathyroid hormone (i-PTH) was significantly inversely correlated with aBMD, integral vBMD, trabecular vBMD, cortical thickness, cortical vBMD, CSA, CSMI and SM. When applying the KDIGO criteria as a sensitivity analysis, the higher PTH group had significant negative associations with aBMD, integral vBMD, cortical vBMD, cortical thickness and cortical sBMD. Notably, the lower PTH group showed a positive significant correlation with integral vBMD and trabecular vBMD.
UNASSIGNED: Elevated PTH, not low PTH, was associated with deterioration of hip-bone microstructures. Better management of PTH levels may play a crucial role in the hip-bone microstructure in dialysis patients.

OBJECTIVE: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns.
METHODS: Crossover interventional study.
METHODS: We recruited 10 patients with postsurgical hypoparathyroidism with very low PTH levels on stable treatment with active vitamin D and calcium. Cortisol, cortisone, and aldosterone levels were measured in microdialysate from subcutaneous tissue over 24 h, before and during continuous subcutaneous PTH (1-34) infusion. Cortisol was also assayed in serum, saliva, and urine, and aldosterone and ACTH in serum and plasma, respectively. Ten patients with primary hyperparathyroidism and 10 healthy volunteers matched for sex and age served as controls.
RESULTS: Hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone, and aldosterone. Tissue aldosterone and cortisone levels were significantly lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. Treatment with PTH (1-34) increased tissue levels of aldosterone, cortisol, and cortisone and reduced the ratio of cortisol to cortisone.
CONCLUSIONS: Adrenocortical hormone levels are reduced in postsurgical hypoparathyroidism, and partly restored by short-term continuous subcutaneous PTH (1-34) therapy.
BACKGROUND: NCT02986607.

UNASSIGNED: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications.
UNASSIGNED: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p < 0.05.
UNASSIGNED: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%.
UNASSIGNED: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by hypercalcemia due to inappropriately high parathyroid hormone secretion. While in the typical, symptomatic form of the disease diagnosis is set easily and standard management is surgical removal of the hyperfunctioning parathyroid (HP), this may not be the case in more subtle forms of PHPT, such as the asymptomatic and the normocalcemic PHPT. Localization of the HP could also be challenging, especially in small-sized adenomas, ectopic lesions or multiglandular disease. An experienced surgical team is essential to achieve curative parathyroidectomy. In this article, we used illustrative clinical vignettes to dissect the approach to the patient with PHPT, from the diagnosis establishment to the suggested investigation to identify classical and non-classical PHPT features and the methodology to locate the abnormal tissue. Accordingly, we elaborated on appropriate management, both surgical and conservative.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are often complicated by high-turnover renal osteodystrophy (HTRO) and secondary hyperparathyroidism (SHPT), characterized by disturbances in mineral metabolism and skeletal abnormalities. Genetic variations within the vitamin D receptor (VDR) gene, known as VDR gene polymorphisms, have been implicated in modulating the susceptibility to HTRO and SHPT. This systematic review aims to evaluate the existing literature on the association between VDR gene polymorphisms and the development of these complications in ESRD and hemodialysis patients. A comprehensive literature search across multiple databases was conducted, and studies investigating VDR gene polymorphisms and HTRO or SHPT in ESRD or hemodialysis patients were included. The included studies examined various VDR gene polymorphisms, such as BsmI, ApaI, TaqI, and FokI, and their associations with clinical outcomes like parathyroid hormone (PTH) levels, bone mineral density, and the development of SHPT or HTRO. The findings suggest that certain VDR gene polymorphisms, notably the ApaI \"aa\" genotype, BsmI \"bb\" genotype, TaqI \"tt\" genotype, and FokI variant, may contribute to the pathogenesis of SHPT and HTRO by affecting PTH levels, bone turnover markers, and vitamin D sensitivity. However, the studies had relatively small sample sizes and were conducted in different populations, limiting generalizability. Further larger-scale studies, functional investigations, and exploration of gene-environment interactions are warranted to elucidate the underlying mechanisms and facilitate personalized treatment approaches for CKD and ESRD patients with mineral and bone disorders.

OBJECTIVE: There is limited information on population-specific norms of trabecular-bone-score (TBS) and its associated factors. Here, we provide norms of TBS in Asian-Indians and its relationship with serum 25-hydroxyvitamin D [25(OH)D] and intact-parathyroid hormone (iPTH).
METHODS: TBS, bone-mineral-density (BMD), and vertebral-fractures (VFs) were assessed using dual-energy X-ray absorptiometry in 923 healthy Asian-Indians (aged 20-60 years). Serum 25(OH)D, iPTH, T4/TSH,, glycosylated-haemoglobin (HbA1c) were measured and associations with TBS assessed using multivariable linear regression. Subjects with BMD Z-score ≤ -2.0 or ≥2.0 at any sites, VFs, TSH > 10.0 or <0.05 µIU/ml, blood-glucose >11.1 mmol/L or HbA1c > 8.0% were excluded for generating Asian-Indian norms.
RESULTS: TBS norms were generated in 744 healthy Asian-Indians (M:F,389:385). The cut-offs generated for \'normal\', \'partially-degraded\', and \'degraded\' TBS were >1.305, 1.204-1.305 and <1.204, respectively. Mean TBS was lower in females than males (p < .001). There was 75% congruency in TBS categories between Asian-Indian and existing norms. Specificity (97.8 vs. 77.9%, p < .001) and diagnostic-accuracy (97.8% vs. 78.4%, p < .001) of TBS to detect osteoporosis were higher with Asian-Indian norms. The sensitivity of \'partially-degraded\' TBS to diagnose osteopenia was also higher with Asian-Indian norms. In multivariable regression, gender, body-mass-index (BMI), BMD-L1-L4, serum PTH, daily dietary-calorie intake and calcium intake were associated with TBS. Though 25(OH)D inversely correlated with PTH, 25(OH)D was not associated with TBS.
CONCLUSIONS: This study provides norms for TBS in Asian-Indians with gender-specific differences. Increasing age and higher BMI were associated with lower TBS. Associations of TBS with circulating PTH and/or 25(OH)D need confirmation in further studies.