Continuous Subcutaneous Delivery of rhPTH(1-84) and rhPTH(1-34) by Pump in Adults With Hypoparathyroidism.

Context: Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited. Case Descriptions: We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: -130 ± 222 mg/24 hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction. Conclusion: In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.

Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone.

The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0 ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r = - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

EXPRESS: Relationship between Gut Microbiome and Bone Deficits in Primary Hyperparathyroidism: A Proof of Concept Pilot Study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and one month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversity were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p<0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, Ruminococcus and Alloprevotella increased (p<0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p<0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus, and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation.

OBJECTIVE: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.

Recombinant PTH Infusion in a Child With Sanjad-Sakati Syndrome Refractory to Conventional Therapy.

Hypoparathyroidism is the most common endocrinological feature in children with Sanjad-Sakati syndrome. Treatment includes active vitamin D and calcium supplementation. Here, we report a case of a newborn with Sanjad-Sakati syndrome who had severe hypocalcemia since birth who responded to PTH subcutaneous pump infusion. The child was born at 35 weeks with hypocalcemia since the first day of life. The standard medical treatment proved ineffective for the newborn, necessitating the administration of unusually high doses of oral and IV calcium and vitamin D analogue for a 2 months. As a result, intermittent subcutaneous injections of PTH were commenced, resulting in an initial improvement in calcium levels, although this proved to be short-lived. Subsequently, a switch to continuous infusion via a Medtronic Vio pump was made, which unfortunately resulted in iatrogenic hypercalcemia, requiring management of hypercalcemia. Later, calcium carbonate and alfacalcidol were resumed at a lower dosage and continued to have average requirements for patients with hypoparathyroidism. PTH subcutaneous infusion can be highly effective in refractory hypocalcemia cases and can significantly impact the treatment course and facilitate hospital discharge as seen in our case. Careful dosage and monitoring are required to avoid iatrogenic hypercalcemia.

Intraoperative parathyroid hormone measurement pitfalls: parathyroid hormone spikes with carboxyl-terminal parathyroid hormone fragments in primary hyperparathyroidism-a case report.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) monitoring is a critical surgical adjunct for determining the extent of surgery for primary hyperparathyroidism (PHPT), with reported false-positive and false-negative rates of up to 10%. Surgeons must understand the parathyroid hormone (PTH) dynamics and select the appropriate IOPTH protocol and interpretation criteria for curative surgery. CASE PRESENTATION: We present the case of a 64-year-old woman with a large cystic parathyroid tumor and PHPT who experienced a significant delay in IOPTH decrease but was cured without additional surgery. The patient's basal intact PTH was 96.2 pg/mL, which decreased to 93.3 pg/mL at 25 min and 72.4 pg/mL at 55 min after removal of the parathyroid tumor. In an attempt to elucidate its pathophysiology, 1-84 PTH levels were measured in stored serum. These results can also be attributed to the relatively low basal PTH levels, intact PTH spike, and high ratio of large carboxyl-terminal PTH fragments present. The patient had normal intact PTH and calcium levels at the 9-month postoperative visit. CONCLUSIONS: As detailed reports on these phenomena are scarce, we discuss the causes of false-negative IOPTH results in terms of PTH production, secretion, metabolism, and differences in measurement methods to avoid unnecessary surgery.

Beyond the Norm: Unusual Coexistence of Wilson's Disease and Hypoparathyroidism.

Wilson's disease (WD) encompasses diverse clinical symptoms involving the liver, nervous system, and kidneys. The fundamental cause of this condition is the build-up of copper in organs, mainly the hepatic and brain parenchyma. Here, we are reporting the hospital presentation of a male patient in his 20s who had been experiencing severe irritability, abdominal pain, distension, and yellowish discoloration of the skin for the previous 75 days. Upon examination of blood pressure, a refractory carpopedal spasm was found in him. In addition to Kayser-Fleischer (KF) rings in his cornea, he exhibited elevated 24-hour urine copper and serum ceruloplasmin (CP). He was diagnosed as a case of WD with a rare association of hypoparathyroidism.

Calcimimetics treatment strategy for serum calcium and phosphate management in patients with secondary hyperparathyroidism undergoing dialysis: A systematic review and meta-analysis of randomized studies.

INTRODUCTION: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis. METHODS: A systematic literature search through October 2023 and a meta-analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included. RESULTS: Participants treated with calcimimetics had lower serum calcium and phosphate levels than placebo. CONCLUSION: Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment.

International variations in serum PTH and calcium levels and their mortality associations in peritoneal dialysis patients: Results from PDOPPS.

BACKGROUND: Mineral bone disorder (MBD) in chronic kidney disease (CKD) is associated with high symptom burden, fractures, vascular calcification, cardiovascular disease and increased morbidity and mortality. CKD-MBD studies have been limited in peritoneal dialysis (PD) patients. Here, we describe calcium and parathyroid hormone (PTH) control, related treatments and mortality associations in PD patients. METHODS: We used data from eight countries (Australia and New Zealand (A/NZ), Canada, Japan, Thailand, South Korea, United Kingdom, United States (US)) participating in the prospective cohort Peritoneal Dialysis Outcomes and Practice Patterns Study (2014-2022) among patients receiving PD for >3 months. We analysed the association of baseline PTH and albumin-adjusted calcium (calciumAlb) with all-cause mortality using Cox regression, adjusted for potential confounders, including serum phosphorus and alkaline phosphatase. RESULTS: Mean age ranged from 54.6 years in South Korea to 63.5 years in Japan. PTH and serum calciumAlb were measured at baseline in 12,642 and 14,244 patients, respectively. Median PTH ranged from 161 (Japan) to 363 pg/mL (US); mean calciumAlb ranged from 9.1 (South Korea, US) to 9.8 mg/dL (A/NZ). The PTH/mortality relationship was U-shaped, with the lowest risk at PTH 300-599 pg/mL. Mortality was nearly 20% higher at serum calciumAlb 9.6+ mg/dL versus 8.4-<9.6 mg/dL. MBD therapy prescriptions varied substantially across countries. CONCLUSIONS: A large proportion of PD patients in this multi-national study have calcium and/or PTH levels in ranges associated with substantially higher mortality. These observations point to the need to substantially improve MBD management in PD to optimise patient outcomes. LAY SUMMARY: Chronic kidney disease-mineral bone disorder (MBD) is a systemic condition, common in dialysis patients, that results in abnormalities in parathyroid hormone (PTH), calcium, phosphorus and vitamin D metabolism. A large proportion of peritoneal dialysis (PD) patients in this current multi-national study had calcium and/or PTH levels in ranges associated with substantially higher risks of death. Our observational study design limits our ability to determine whether these abnormal calcium and PTH levels cause more death due to possible confounding that was not accounted for in our analysis. However, our findings, along with other recent work showing 48-75% higher risk of death for the one-third of PD patients having high phosphorus levels (>5.5 mg/dL), should raise strong concerns for a greater focus on improving MBD management in PD patients.

Effectiveness of calcimimetics on fractures in dialysis patients with secondary hyperparathyroidism: meta-analysis of randomized trials.

INTRODUCTION: This study aimed to assess the effectiveness of calcimimetics in reducing the risk of fractures in dialysis patients with secondary hyperparathyroidism (SHPT). MATERIAL AND METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Library for articles published through December 9, 2023. The quality of each trial was evaluated using the Cochrane Collaboration tool. Meta-analysis was performed using a random-effects model, and effect measures across studies were synthesized. The risk ratio (RR) and 95% confidence interval (CI) were used to quantify the risk of fracture. RESULTS: We identified seven studies involving 6481 dialysis patients with SHPT. The administration of calcimimetics reduced fracture incidence compared to placebo or conventional treatment (RR: 0.50, 95% CI 0.29-0.88, p = 0.02). Calcimimetics demonstrated a low number needed to treat (NNT) to prevent an incident fracture (NNT: 47). CONCLUSION: The use of calcimimetics offers a significant benefit in reducing the risk of fractures in patients undergoing dialysis with SHPT.

The Calcium-sensing receptor (CaSR) has only a PTH-dependent role in the acute response of renal phosphatetransporters to phosphate intake.

The kidney controls systemic inorganic phosphate (Pi) levels by adapting reabsorption to Pi intake. Renal Pi reabsorption is mostly mediated by sodium-phosphate cotransporters NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) which are tightly controlled by various hormones including parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH and FGF23 rise in response to Pi intake and decrease NaPi-IIa and NaPi-IIc brush border membrane abundance enhancing phosphaturia. Phosphaturia and transporter regulation occur even in the absence of PTH and FGF23 signalling. The calcium-sensing receptor (CaSR) regulates PTH and FGF23 secretion, and may also directly affect renal Pi handling. Here, we combined pharmacological and genetic approaches to examine the role of the CaSR in the acute phosphaturic response to Pi-loading. Animals pretreated with the calcimimetic cinacalcet were hyperphosphatemic, had blunted PTH levels upon Pi administration, a reduced Pi-induced phosphaturia and no Pi-induced NaPi-IIa downregulation. The calcilytic NPS-2143 exaggerated the PTH response to Pi-loading but did not abolish Pi-induced downregulation of NaPi-IIa. In mice with a dominant inactivating mutation in the Casr (CasrBCH002), baseline NaPi-IIa expression was higher, whereas downregulation of transporter expression was blunted in double CasrBCH002/PTH KO transgenic animals. Thus, in response to an acute Pi load, acute modulation of the CaSR affects the endocrine and renal response, while chronic genetic inactivation, displays only subtle differences in the downregulation of NaPi-IIa and NaPi-IIc renal expression. We did not find evidence that the CaSR impacts on the acute renal response to oral Pi-loading beyond its role in regulating PTH secretion.

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.

Background: Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses. Methods: We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis. Results: The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations. Conclusion: Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

Early hospital discharge through prediction of post-thyroidectomy hypoparathyroidism.

INTRODUCTION: Hypoparathyroidism is the most common postsurgical complication of total thyroidectomy. Furthermore, it is the main cause of prolonged hospitalisation after this procedure. OBJECTIVE: To predict the probability of post-thyroidectomy hypocalcaemia according to the levels of intact parathyroid hormone (iPTH), as well as to determine the needs for treatment with exogenous calcium according to the levels of serum calcium (Ca). MATERIALS AND METHODS: Retrospective study was carried out on patients who underwent total thyroidectomy between January 2017 and January 2020 at Los Arcos del Mar Menor University Hospital (HULAMM). iPTH and Ca levels ​​were measured at 4, 24 and 48 h after the surgery. Follow-up was 6 months. RESULTS: Ninety-four patients were operated on. Temporary and permanent postoperative hypoparathyroidism percentages were, respectively, 51.06% and 6.38%. iPTH level 24 h after the procedure was the most reliable predictor of post-thyroidectomy temporary hypoparathyroidism (Area Under the ROC Curve (AUC) = 0.933, p < .001). iPTH levels ​​≥29 pg/mL predicted normal parathyroid metabolism. CONCLUSIONS: The combined values of iPTH and Ca levels 24 h after thyroidectomy seems to be a reliable, safe and efficient method to control the post-thyroidectomy hypoparathyroidism. Our protocol could reduce the hospital stay of patients at low risk of hypocalcaemia, allowing them to be discharged from the hospital on the first postoperative morning and identifying patients at high risk of hypocalcaemia early.

Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition.

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D-binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. METHODS: A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. RESULTS: Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. DISCUSSION: While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.