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Osteoporosis International : a Journal... Jun 2024Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is...
PURPOSE
Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases.
CASE PRESENTATION
A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden.
CONCLUSION
Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.
PubMed: 38847810
DOI: 10.1007/s00198-024-07137-x -
FASEB Journal : Official Publication of... Jun 2024Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in... (Comparative Study)
Comparative Study
Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.
Topics: Animals; Calcitriol; Rats; Calcimimetic Agents; Parathyroid Hormone; Male; Osteoblasts; Hyperparathyroidism, Secondary; Bone and Bones; Rats, Wistar; Renal Insufficiency; Osteogenesis; Renal Insufficiency, Chronic; Cell Differentiation; Calcium
PubMed: 38847773
DOI: 10.1096/fj.202302704R -
Frontiers in Endocrinology 2024Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of...
Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was Tc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal Tc-sestamibi uptake in the neck region.
Topics: Humans; Female; Technetium Tc 99m Sestamibi; Parathyroid Neoplasms; Adult; Neurilemmoma; Diagnosis, Differential; Adenoma; Esophageal Neoplasms; Single Photon Emission Computed Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38841301
DOI: 10.3389/fendo.2024.1258233 -
Journal of Nuclear Medicine Technology Jun 2024Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to... (Review)
Review
Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT. Using the input from radiologists, endocrinologists, and surgeons, we apply patient criteria such as large body habitus, concomitant multiglandular disease, multinodular thyroid disease, confusing previous imaging, and unsuccessful previous surgery to create an imaging paradigm that uses 4D SPECT/CT yet is cost-effective, accurate, and limits extraneous radiation exposure. 4D SPECT/CT capitalizes on the strengths of SPECT and 4D CT and addresses limitations that exist when these modalities are used in isolation. In select patients with complicated clinical parameters, preoperative imaging with 4D SPECT/CT can improve accuracy yet remain cost-effective.
Topics: Humans; Hyperparathyroidism, Primary; Single Photon Emission Computed Tomography Computed Tomography; Four-Dimensional Computed Tomography
PubMed: 38839121
DOI: 10.2967/jnmt.123.266990 -
La Revue Du Praticien May 2024
Topics: Humans; Parathyroid Neoplasms; Adenoma; Female; Middle Aged; Male
PubMed: 38833234
DOI: No ID Found -
Calcified Tissue International Jun 2024Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to... (Review)
Review
Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.
PubMed: 38833001
DOI: 10.1007/s00223-024-01227-y -
Journal of Lipid and Atherosclerosis May 2024This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease...
OBJECTIVE
This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD).
METHODS
The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques.
RESULTS
CAC patients had considerably higher levels of TNF-α (<0.001), IL-6 (<0.001), hs-CRP (=0.006), TC, TG, parathyroid hormone (PTH) (<0.001) and phosphorus (<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (=0.046), age (=0.009), TNF-α (=0.027), IL-6 (=0.005), TG (=0.002), PTH (=0.002), and phosphorus (=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (=0.045).
CONCLUSION
Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.
PubMed: 38826181
DOI: 10.12997/jla.2024.13.2.194 -
Archives of Medical Research Jun 2024Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions...
BACKGROUND
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up.
OBJECTIVE
To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors.
METHODS
Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons.
RESULTS
Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine.
CONCLUSIONS
More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.
Topics: Humans; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Phenotype; Parathyroid Hormone; Phosphorus; Vitamin D; Renal Dialysis; Renal Insufficiency, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder; Calcium
PubMed: 38824883
DOI: 10.1016/j.arcmed.2024.103008 -
Nature Communications Jun 2024Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological...
Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling ("biased agonism") with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present an approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Topics: Ligands; Humans; Receptor, Parathyroid Hormone, Type 1; Single-Domain Antibodies; HEK293 Cells; Signal Transduction; Receptors, G-Protein-Coupled; Protein Binding; Animals; Peptides
PubMed: 38824166
DOI: 10.1038/s41467-024-49068-5 -
Journal of Clinical Pathology May 2024This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and...
AIMS
This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and calcium levels.
METHODS
A historical cohort study was conducted on adult patients with solitary PTA removed in the Gold Coast Health Precinct, Australia, between 2017 and 2022.
RESULTS
PTA weight is correlated with the change in day 1 PTH level (r=0.26, p=0.036), the change in day 1 corrected calcium level (r=0.20, p=0.033), and the change in follow-up corrected calcium level (r=0.47, p<0.001). The largest dimension (size) of PTA is also correlated with the change in day 1 PTH (r=0.30, p=0.011) and the change in follow-up corrected calcium level (r=0.40, p<0.001). Adjusted for age and gender, a statistically significant negative correlation was found between day 1 PTH level and adenoma size, resulting in a 0.5% change in size for every percentage change in PTH level (equating to a 5.0% increase in variance explained, p=0.038). Similarly, a negative correlation was identified in day 1 corrected calcium levels and weight, with a 4.7% change in weight for every percentage of change in day 1 corrected calcium level (an increase of 5.6% variance explained, p=0.010). In addition, a negative correlation was identified, where every 3.1% change in size (an increase of 17.4% variance explained, p<0.001) and 7.6% change in weight (an increase of 22.7% variance explained, p<0.001) was seen with every percentage change in follow-up corrected calcium levels. Clear-cell PTA had the most significant percentage fall in day 1 corrected calcium levels compared with other PTA subtypes (p=0.007).
CONCLUSIONS
Preoperative calcium and PTH levels correlate with PTA weight and size. The degree of change in postoperative corrected calcium levels behaved differently in the clear-cell subtype.
PubMed: 38821854
DOI: 10.1136/jcp-2023-209340