Role Of Parathyroid Hormone Research Articles

Clinical Utility of Bone Turnover Markers in Chronic Kidney Disease

Chronic kidney disease (CKD) often leads to mineral and bone disorders (CKD-MBDs), which are nearly universal in patients undergoing dialysis. CKD-MBD includes abnormal calcium-phosphate metabolism, vascular and soft tissue calcification, and bone abnormalities (renal osteodystrophy [ROD]). Bone fragility in CKD occurs due to low bone mass and poor bone quality, and patients with CKD have higher fracture and mortality rates. Bone histomorphometry is the gold standard for ROD diagnosis; however, it is labor-intensive and expensive. The Kidney Disease Improving Global Outcomes clinical practice guidelines on CKD-MBD suggest serum parathyroid hormone (PTH) and bone-specific alkaline phosphatase (bone ALP) for predicting bone turnover in ROD. In this review, we focus on the role of PTH and bone turnover markers, intact procollagen type N-terminal propeptide of type I collagen, bone ALP, and tartrate-resistant acid phosphatase 5b in diagnosing ROD, predicting fractures, and guiding treatment in patients with CKD.

Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease.

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

#1736 Correlation between chronic kidney disease-mineral and bone disorder parameters and clinical events in hemodialysis patients

Abstract Background and Aims Patients with chronic kidney disease experience mineral and bone metabolism alterations, collectively known as Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), linked to elevated cardiovascular mortality. A significant biochemical change is the development of secondary hyperparathyroidism—an adaptive response to uremic conditions that, when surpassing critical thresholds, becomes maladaptive, heightening clinical risk. Presently, optimal parathyroid hormone (PTH) values for hemodialysis (HD) patients lack a clear definition, with recent evidence challenging international guideline limits. This study aimed to evaluate the impact of PTH values on mortality in a population of patients in HD. Method A prospective observational study involving chronic hemodialysis patients commenced in January 2020, with a 40-month follow-up for mortality recording. Exclusion criteria comprised parathyroidectomy, primary hyperparathyroidism evidence, prior kidney transplant, or transplant plans within three months. Clinical and biochemical data, aligned with the 2017 KDIGO guidelines for PTH, calcium (Ca), and phosphorus (Ps) target values, were recorded. Our laboratory PTH values ranged from 25 to 88 pg/ml, and stable PTH values within 180 to 700 pg/ml were deemed adequate in HD patients. Patients were categorized based on the average of three values over 12 months for PTH, Ca, and Ps parameters. Results One hundred patients (average age: 71 ± 13.59) were enrolled. Seventy-seven percent achieved PTH targets (180-700 pg/ml), 73% for Ca, and 19% for phosphorus (Table 1). During follow-up, 36 deaths (36%) occurred. While percentages of target achievement were similar between survivor and non-survivor groups, non-survivor patients exhibited higher PTH values (423.08 ± 277 vs. 360.44 ± 214.92; p = 0.05) without differences in Ca and Ps levels between the two groups (Table 2). Stratifying based on the median PTH value (330 pg/ml) revealed higher mortality in patients with PTH > 330 pg/ml (Log-rank test p = 0.05) (Fig. 1). Conclusion Despite comparable target achievements for PTH, Ca, and Ps, deceased patients had elevated average PTH values, especially those exceeding 330 pg/ml, indicating a higher risk of death during our follow-up. In line with recent literature, these findings underscore PTH's role as a uremic toxin, suggesting a revaluation of current PTH targets for hemodialysis patients

PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche.

Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH's role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH-catabolic and anabolic-on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH's multifaceted influence on bone health.

Pth1r in Neural Crest Cells Regulates Nasal Cartilage Differentiation

Neural crest cells (NCC) arise from the dorsal margin of the neural plate border and comprise a unique cell population that migrates to and creates the craniofacial region. Although factors including Shh, Fgf8, and bone morphogenetic proteins have been shown to regulate these biological events, the role of parathyroid hormone 1 receptor (Pth1r) has been less studied. We generated an NCC-specific mouse model for Pth1r and researched gene expression, function, and interaction focusing on nasal cartilage framework and midfacial development. Wnt1-Cre;Pth1rfl/fl;Tomatofl/+ mice had perinatal lethality, but we observed short snout and jaws, tongue protrusion, reduced NCC-derived cranial length, increased mineralization in nasal septum and hyoid bones, and less bone mineralization at interfrontal suture in mutants at E18.5. Importantly, the mutant nasal septum and turbinate cartilage histologically revealed gradual, premature accelerated hypertrophic differentiation. We then studied the underlying molecular mechanisms by performing RNA seq analysis and unexpectedly found that expression of Ihh and related signaling molecules was enhanced in mutant nasomaxillary tissues. To see if Pth1r and Ihh signaling are associated, we generated a Wnt1-Cre; Ihh fl/fl; Pth1r fl/fl;Tomatofl/+ (DKO) mouse and compared the phenotypes to those of each single knockout mouse: Wnt1-Cre; Ihh fl/fl;Pth1rfl/+;Tomatofl/+ (Ihh-CKO) and Wnt1-Cre;Ihhfl/+; Pth1r fl/fl;Tomatofl/+ (Pth1r-CKO). Ihh-CKO mice displayed a milder effect. Of note, the excessive hypertrophic conversion of the nasal cartilage framework observed in Pth1r-CKO was somewhat rescued DKO embryos. Further, a half cAMP responsive element and the 4 similar sequences containing 2 mismatches were identified from the promoter to the first intron in Ihh gene. Gli1-Cre ERT2 ;Pth1rfl/fl;Tomatofl/+, a Pth1r-deficient model targeted in hedgehog responsive cells, demonstrated the enlarged hypertrophic layer and significantly more Tomato-positive chondrocytes accumulated in the nasal septum and ethmoidal endochondral ossification. Collectively, the data suggest a relevant Pth1r/Ihh interaction. Our findings obtained from novel mouse models for Pth1r signaling illuminate previously unknown aspects in craniofacial biology and development.

Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition.

Parathyroid hormone (PTH) is an endocrine peptide found exclusively in the parathyroid glands, whereas parathyroid hormone-related protein (PTHrP) is expressed in a wide range of tissues and organs and exerts endocrine, paracrine, and autocrine actions. PTH and PTHrP have a similar homology, sharing the initial 13 amino acid residues at the N-terminus and binding to the same type 1 PTH receptor (PTH1R), which regulates calcium homeostasis. An abnormal increase in PTH production can occur in primary and secondary hyperparathyroidism, whereas PTHrP can be produced in large quantities by malignant cancer cells from solid organs. In addition to increased bone resorption and hypercalcemia, recent evidence suggests that excess PTH and PTHrP can result in protein-energy wasting, malnutrition, and cachexia. Through binding to PTH1R and activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A in white adipose tissue, PTH and PTHrP can stimulate the expression of thermogenic genes causing adipose tissue browning. This change results in an increase in resting energy expenditure, loss of muscle and fat mass, and weight loss. These findings provide a mechanistic link for the long-established relationship between hyperparathyroidism and myopathy, as well as cancer and cachexia. The purpose of this review is to provide a summary of the emerging evidence from both experimental and clinical studies on the role of PTH and PTHrP in protein-energy malnutrition.

Association of vitamin D deficiency and insulin resistance in nondiabetic obese women: role of parathyroid hormone

Association of vitamin D deficiency and insulin resistance in nondiabetic obese women: role of parathyroid hormone

Parathyroid Hormone in the Regulation of Bone Growth and Resorption in Health and Disease

Parathyroid hormone (PTH) is a key hormone responsible for regulation of calcium homeostasis in the body. Since the main body calcium depot is bone tissue, PTH has a decisive effect on its homeostasis. In this case, the hormone can activate both bone formation and resorption. Thus, PTH can ensure the conjugation of anabolic and catabolic processes, which is necessary for the renewal of bone tissue, which is had to function under constant mechanical stress. At the same time, the use of PTH in medical practice is rather small, despite its high potential as a basis for the treatment of various pathologies associated with impaired bone homeostasis. Presented review, describes the intracellular signaling cascades and molecular mechanisms that underlie the action of PTH on bone tissue cells, and intracellular signaling cascades are described. A separate section examines the cellular mechanisms of the action of PTH on bone homeostasis, discusses how the effect of the hormone on different types of cells provides an interface between the processes of synthesis and resorption. In addition, the review examines diseases associated with impaired bone homeostasis, as well as the role of PTH and impaired signaling in their etiology.

Abstract 11631: A Critical Role of Parathyroid Hormone in the Development of Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is characterized by increased pulmonary artery pressure and develops right heart failure. Parathyroid hormone (PTH) is secreted from parathyroid gland and play a critical role in calcium homeostasis. Recent studies have suggested that PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We hypothesized that PTH would play a role in the pathogenesis of PH. Object: This study aimed to investigate the effect of PTH on pulmonary hemodynamics. Method: We measured serum PTH levels in patients who were suspected of PH and underwent right heart catheter examination. We used two types of PH animal models, hypoxia (Hx)-induced PH mouse model and Sugen/hypoxia (SuHx)-induced PH rat model. Hx mice were administered PTH daily for 3 weeks. SuHx rats underwent parathyroidectomy, after which they received SuHx treatment for 10weeks. We measured physical data and right ventricular systolic pressure (RVSP) in these models. We cultured pulmonary artery smooth muscle cell (PASMC) treated with PTH to analyze cell signaling, proliferation and migration. Result: We enrolled 20 participants. PTH concentration was significantly correlated with mean pulmonary artery pressure and pulmonary vascular resistance. PTH treatment exacerbated right ventricular hypertrophy and increased RVSP (33.6mmHg vs. 48.2mmHg) in Hx mice compared with non-treated Hx mice(Figure). Conversely, parathyroidectomy significantly attenuated right ventricular hypertrophy and reduced RVSP (54.2mmHg vs. 29.3mmHg) in SuHx rats compared with sham-operated SuHx rats. PTH promoted migration and proliferation through ERK signaling in PASMC. Conclusion: Our clinical and experimental data demonstrated a critical role of PTH in the development of PH and suggested that PTH would be a novel therapeutic target for PH treatment.

The Association between Parathyroid Hormone (PTH) Level and Hemoglobin and Hematocrit Level in Chronic Kidney Disease (CKD) Patients with Regular Hemodialysis

Introduction: Chronic Kidney Disease (CKD) is a pathophysiological process with various etiology that causes a progressive decline in kidney function and ends in kidney failure. [1] CKD is a health problem that occurs in the community and has covered globally. The 2010 Global Burden of Disease stated that CKD was the 27th leading cause of death in the world in 1990. This has increased to 18th in 2010. Parathyroid hormone is a potential factor in the incidence of anemia in CKD patients. In CKD patients, there is an increase in levels of parathyroid hormone which is a uremic toxin that inhibits erythropoietin by increasing fibrosis in the bone marrow (myelofibrosis). The role of PTH in cases of renal anemia has been extensively investigated by various clinical observational studies. This study aimed to determine the association between parathyroid hormone (PTH) levels and hemoglobin and hematocrit levels in chronic kidney disease (CKD) patients with regular hemodialysis in Haji Adam Malik Central General Hospital. Methods: This is an analytical study with a cross-sectional design. A total of 45 study subjects met the inclusion criteria and exclusion criteria, underwent history taking, physical examination, anthropometry, and laboratory examination to measure parathyroid hormone, hemoglobin, hematocrit, and albumin levels. Data analysis was performed using SPSS. Results: The measured PTH level had a minimum value of 113 pg/ml and a maximum of 595 pg/ml with an average of 431.4. The minimum hemoglobin value is 6.3 g/dl and a maximum of 11.5 g/dl with an average of 7.9, while for the hematocrit the minimum value is 19% and the maximum is 35% and the average is 24.7. The Mann-Whitney U test showed that there is a significant relationship between PTH levels and hemoglobin, indicated by a significant p value of 0.001 (p value < 0.05). A significant relationship was also found between PTH levels and hematocrit (p value = 0.039). Conclusion: Parathyroid hormone has a statistically significant relationship with haemoglobin and haematocrit levels in CKD patients with regular hemodialysis. Keywords: Chronic kidney disease; haemoglobin; haematocrit; parathyroid hormone; anemia; hemodialysis.

The Association between Parathyroid Hormone (PTH) Level and Hemoglobin and Hematocrit Level in Chronic Kidney Disease (CKD) Patients with Regular Hemodialysis

Introduction: Chronic Kidney Disease (CKD) is a pathophysiological process with various etiology that causes a progressive decline in kidney function and ends in kidney failure. [1] CKD is a health problem that occurs in the community and has covered globally. The 2010 Global Burden of Disease stated that CKD was the 27th leading cause of death in the world in 1990. This has increased to 18th in 2010. Parathyroid hormone is a potential factor in the incidence of anemia in CKD patients. In CKD patients, there is an increase in levels of parathyroid hormone which is a uremic toxin that inhibits erythropoietin by increasing fibrosis in the bone marrow (myelofibrosis). The role of PTH in cases of renal anemia has been extensively investigated by various clinical observational studies. This study aimed to determine the association between parathyroid hormone (PTH) levels and hemoglobin and hematocrit levels in chronic kidney disease (CKD) patients with regular hemodialysis in Haji Adam Malik Central General Hospital. Methods: This is an analytical study with a cross-sectional design. A total of 45 study subjects met the inclusion criteria and exclusion criteria, underwent history taking, physical examination, anthropometry, and laboratory examination to measure parathyroid hormone, hemoglobin, hematocrit, and albumin levels. Data analysis was performed using SPSS. Results: The measured PTH level had a minimum value of 113 pg/ml and a maximum of 595 pg/ml with an average of 431.4. The minimum hemoglobin value is 6.3 g/dl and a maximum of 11.5 g/dl with an average of 7.9, while for the hematocrit the minimum value is 19% and the maximum is 35% and the average is 24.7. The Mann-Whitney U test showed that there is a significant relationship between PTH levels and hemoglobin, indicated by a significant p value of 0.001 (p value < 0.05). A significant relationship was also found between PTH levels and hematocrit (p value = 0.039). Conclusion: Parathyroid hormone has a statistically significant relationship with haemoglobin and haematocrit levels in CKD patients with regular hemodialysis.

Beyond Bone: Infectious Diseases and Immunity in Parathyroid Disorders.

Parathyroid disorders are characterized by alterations in calcium and phosphate homeostasis due to inappropriately high or low levels of parathyroid hormone (PTH). Despite PTH receptor type 1 has been described in almost all immune lineages and calcium signalling has been confirmed as a crucial mediator for immune response, in vitro studies on the physiological interactions between PTH and immunity are conflicting and not representative of the clinical scenarios seen in patients with parathyroid disorders. Infectious diseases are among the main causes of increased morbidity and mortality in patients with secondary hyperparathyroidism and chronic kidney disease. More, immune alterations have been described in primary hyperparathyroidism. Recent studies have unveiled an increased risk of infections also in hypoparathyroidism, suggesting that not only calcium, but also physiological levels of PTH may be necessary for a proper immune response. Finally, calcium/phosphate imbalance could affect negatively the prognosis of infectious diseases. Our review aimed to collect available data on infectious disease prevalence in patients with parathyroid disorders and new evidence on the role of PTH and calcium in determining the increased risk of infections observed in these patients.

Parathyroid hormone levels and aging: Effect on balance.

Falls result in multiple adverse health outcomes including mortality in older persons. Impaired balance is known to increase the risk of falls. Numerous factors play a role in the etiology of balance disturbance. Among the calciotropic hormones, the role of vitamin D in falls risk has been extensively studied. There is evolving interest in the role of parathyroid hormone (PTH) in this area. Elevated PTH hormone levels have been associated with age-related syndromes such as frailty, osteoporosis, and sarcopenia. Among the existing studies, most have focused on muscle strength with few studies evaluating its role in balance disturbances. In this chapter, we will summarize the aspects of PTH and aging, its biological effects on muscle, and the known associations between PTH and balance.

Intermittent parathyroid hormone (1\u201334) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis

BackgroundBone marrow stromal cells (BMSC) have promise in cartilage tissue engineering, but for their potential to be fully realised, the propensity to undergo hypertrophy must be mitigated. The literature contains diverging reports on the effect of parathyroid hormone (PTH) on BMSC differentiation. Cartilage tissue models can be heterogeneous, confounding efforts to improve media formulations.MethodsHerein, we use a novel microwell platform (the Microwell-mesh) to manufacture hundreds of small-diameter homogeneous micro-pellets and use this high-resolution assay to quantify the influence of constant or intermittent PTH(1–34) medium supplementation on BMSC chondrogenesis and hypertrophy. Micro-pellets were manufactured from 5000 BMSC each and cultured in standard chondrogenic media supplemented with (1) no PTH, (2) intermittent PTH, or (3) constant PTH.ResultsRelative to control chondrogenic cultures, BMSC micro-pellets exposed to intermittent PTH had reduced hypertrophic gene expression following 1 week of culture, but this was accompanied by a loss in chondrogenesis by the second week of culture. Constant PTH treatment was detrimental to chondrogenic culture.ConclusionsThis study provides further clarity on the role of PTH on chondrogenic differentiation in vitro and suggests that while PTH may mitigate BMSC hypertrophy, it does so at the expense of chondrogenesis.

Effects of parathyroid hormone and vitamin D supplementation on stroke among patients receiving peritoneal dialysis

BackgroundContinuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients.MethodsThis study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up.ResultsA total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7–22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort.ConclusionsCAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.

The Role of Parathyroid Hormone in Alveolar Bone Resorption on Postmenopausal Women

Background: Postmenopausal women exhibit reduced bone mineralization, which causes bone resorption, including that of alveolar bone. Parathyroid hormone has been shown to play a role in alveolar bone resorption. Objective: This study aims to analyze relationships between parathyroid hormone and other factors that may contribute to alveolar bone resorption in postmenopausal women. Methods: This cross-sectional study included 82 postmenopausal women aged 50–74 years, who resided in Central and East Jakarta, Indonesia. Subjects' data were obtained through questionnaires, dental examinations, and blood collection for the examination of parathyroid hormone levels by enzyme-linked immunosorbent assay and using panoramic radiography to measure bone resorption. Results: Spearman correlation analysis showed a significant correlation between parathyroid hormone level (p = 0.005) and extent of alveolar bone resorption, but age (p = 0.292), menopausal duration (p = 0.244), and number of missing teeth (p = 0.517) were not significantly correlated with the extent of alveolar bone resorption. Conclusion: Various factors play a role in the mechanism of bone resorption, so knowing the role of each factor is expected to reduce the effects of alveolar bone resorption that occurs in postmenopause. Among the factors investigated in this study, the parathyroid hormone was the sole factor correlated with postmenopausal alveolar bone resorption.

Effect of fluoride on osteocyte-driven osteoclastic differentiation

Excessive systemic uptake of inorganic fluorides causes disturbances of bone homeostasis. The mechanism of skeletal fluorosis is still uncertain. This study aimed to study the effect of fluoride on osteocyte-driven osteoclastogenesis and probe into the role of PTH in this process. IDG-SW3 cells seeded in collagen–coated constructs were developed into osteocyte-like cells through induction of mineral agents. Then, osteocyte-like cells were exposed to fluoride in the presence or absence of parathyroid hormone (PTH). Cell viability and their capacity to produce receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and sclerostin (SOST) were detected by MTT and Western blot assays, respectively. Finally, a transwell coculture system using osteocyte-like cells seeded in the low compartment, and osteoclast precursors added in the inserts was developed to observe the osteocyte-driven osteoclasogenesis response to fluoride with or without PTH, and the expression of molecules involved in this mechanism were measure by real time RT-PCR. Results showed that osteocytes withstood a toxic dose of fluoride, and yet PTH administration significantly reduced osteocytes viability. PTH amplified the effect of fluoride on the expression of osteoclastogenesis-related molecules in osteocyte, but did not enlarged the stimulating effect of fluoride on osteoclastogenesis drove by osteocyte coculture. Gene expression levels of TRAP, RANK, JNK and NFAtc1 significantly increased in fluoride affected osteoclast precursor cocultured with osteocyte-like cells. The impact of fluoride on osteocyte-driven osteoclast differentiation was stronger than that of PTH. In conclusion, osteocyte played a pivotal role on the mechanism underlying fluoride-affected osteoclastogenesis in which RANK-JNK-NFATc1 signaling pathway was involved, and PTH had a significant impact in this process.

The role of parathyroid hormone and cardiac output in pulmonary hypertension in hemodialysis patients

Introduction: High prevalence of pulmonary hypertension has been reported in patients with chronic renal failure, especially those undergoing hemodialysis. Objectives: Considering the high prevalence of pulmonary hypertension in hemodialysis patients and uncertainty about the causes, the present study planned to investigate the role of parathyroid hormone (PTH) and cardiac ejection fraction (EF %) in development of pulmonary hypertension. Patients and Methods: By simple census sampling, all patients on hemodialysis in the hemodialysis center of Birjand University of Medical Sciences were enrolled. After obtaining written consent, the EF% and systolic pulmonary artery pressure (sPAP) were determined using echocardiography (MEDISON V10 model, Korea). The cut-point of less than 35 mm Hg was considered for normal sPAP. The blood sample was prepared to assay PTH using COBAS411 and ROCH kit. Independent t test or Man-Whitney test were used to compare means. P value &lt;0.05 was considered significant. Results: A totsl of 114 patients were enrolled in the study. Finally 89 patients, including 49 (55.1%) male and 40 (44.9%) female completed the study. The mean age and mean sPAP of the studied patients were 55.14 ± 15.68 years and 30.65 ± 12.10 mm Hg respectively. Among the studied patients, normal and high sPAP were reported in 60 (67.4%) and 29 (32.6%) cases respectively. Cardiac EF% in patients with normal and high sPAP was 59.08 ± 2.83 versus 56.37 ± 4.79 respectively (P = 0.01). PTH was determined 275.12 ± 218.44 versus 395.67 ± 332.05(pg/mL) (P = 0.03), in patients with normal and high sPAP respectively. Conclusion: The prevalence of pulmonary hypertension in the studied patients was 32.6%. Patients in the pulmonary hypertension group had higher levels of PTH and lower cardiac EF%.

The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone

SummaryThe risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk.IntroductionVertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture.MethodsIn 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture.ResultsMean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13–55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders.ConclusionsThe prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.