Role Of Parathyroid Hormone Research Articles

Machine learning classification models for fetal skeletal development performance prediction using maternal bone metabolic proteins in goats.

BackgroundIn developing countries, maternal undernutrition is the major intrauterine environmental factor contributing to fetal development and adverse pregnancy outcomes. Maternal nutrition restriction (MNR) in gestation has proven to impact overall growth, bone development, and proliferation and metabolism of mesenchymal stem cells in offspring. However, the efficient method for elucidation of fetal bone development performance through maternal bone metabolic biochemical markers remains elusive.MethodsWe adapted goats to elucidate fetal bone development state with maternal serum bone metabolic proteins under malnutrition conditions in mid- and late-gestation stages. We used the experimental data to create 72 datasets by mixing different input features such as one-hot encoding of experimental conditions, metabolic original data, experimental-centered features and experimental condition probabilities. Seven Machine Learning methods have been used to predict six fetal bone parameters (weight, length, and diameter of femur/humerus).ResultsThe results indicated that MNR influences fetal bone development (femur and humerus) and fetal bone metabolic protein levels (C-terminal telopeptides of collagen I, CTx, in middle-gestation and N-terminal telopeptides of collagen I, NTx, in late-gestation), and maternal bone metabolites (low bone alkaline phosphatase, BALP, in middle-gestation and high BALP in late-gestation). The results show the importance of experimental conditions (ECs) encoding by mixing the information with the serum metabolic data. The best classification models obtained for femur weight (Fw) and length (FI), and humerus weight (Hw) are Support Vector Machines classifiers with the leave-one-out cross-validation accuracy of 1. The rest of the accuracies are 0.98, 0.946 and 0.696 for the diameter of femur (Fd), diameter and length of humerus (Hd, Hl), respectively. With the feature importance analysis, the moving averages mixed ECs are generally more important for the majority of the models. The moving average of parathyroid hormone (PTH) within nutritional conditions (MA-PTH-experim) is important for Fd, Hd and Hl prediction models but its removal for enhancing the Fw, Fl and Hw model performance. Further, using one feature models, it is possible to obtain even more accurate models compared with the feature importance analysis models. In conclusion, the machine learning is an efficient method to confirm the important role of PTH and BALP mixed with nutritional conditions for fetal bone growth performance of goats. All the Python scripts including results and comments are available into an open repository at https://gitlab.com/muntisa/goat-bones-machine-learning.

Role of parathyroid hormone in anorexia on maintenance hemodialysis patients

Anorexia, which is a common condition in patients on hemodialysis (HD), is characterized by impaired appetite, a subjective condition that hinders anorexia diagnosis. Anorexia is frequently associated with protein energy wasting and inflammation, increasing morbidity and mortality risk. The aim of the study was to evaluate the association between appetite and nutritional, inflammatory, hormonal, and dietary intake parameters in patients on maintenance HD. Cross-sectional study with clinical, laboratory, and anthropometric parameters, body composition, muscle function, and dietary intake assessment. To evaluate appetite, a three simple questions questionnaire previously validated was used. After appetite classification, the sample was dichotomized in "normal appetite" and "impaired appetite" and compared. Multiple logistic regression was used to identify association between variables and outcome. 125 patients on HD were included, aged 60.6±14.12 years old, median HD vintage 35.5 months. In dichotomized sample, 78.4% patients showed "normal appetite", and 21.6% "impaired appetite". "Impaired appetite" was independently associated with increased serum PTH (OR 1.001; 95% CI 1.000-1.002; p=0.03), low zinc intake (OR 0.860; 95% CI 0.746-0.991; p=0.03) and lower urea serum (OR 0.982; 95% CI 0.965-0.999; p=0.04). Both groups showed insufficient dietary intake. Appetite was independently associated with increased serum of PTH, low serum concentration of urea, and low zinc intake which may infer association of appetite with mineral bone disease, protein intake and zinc deficiency.

An investigation into the role of parathyroid hormone in the regulation of aldosterone secretion in hypertensive cardiovascular patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The role of parathyroid hormone (PTH) and vitamin D in falls and hip fracture type.

Fragility fractures of the hip are associated with high morbidity and mortality, and represent a rather devastating consequence of osteoporosis. Hip fractures are traditionally investigated as a whole, although it has been recently implied that distinct pathogenic mechanisms may lead either to trochanteric or subcapital fractures. To investigate whether differences exist by hip fracture type with respect to serum 25(OH)D (vitamin D) and parathyroid hormone (PTH) levels, in addition to epidemiological and demographic data, including history of falls. The inclusion criteria were met by 116 patients [48 men and 68 women; mean age 80.8 ± 8.5 (range 62-94) years]. Patients were analyzed according to hip fracture type, history of falls, and vitamin D and PTH status. Older age, recurrent falls, serum levels of PTH > 65pg/ml, and severe vitamin D deficiency were found to be associated with trochanteric fractures. Additionally, older age, female gender, PTH > 65pg/ml, and severe vitamin D deficiency were related to recurrent falls. Meanwhile, patients with absence of PTH response to low vitamin D levels, were not repeated fallers and suffered mostly from subcapital fractures. Elevated PTH levels predispose both to falls and trochanteric fractures, while vitamin D-deficient patients with normal PTH levels are mostly related to subcapital fractures. It is thereby indicated that different pathophysiological processes lie behind subcapital and trochanteric fractures. A better understanding of these mechanisms may assist in the development of prevention strategies for individuals recognized at risk for falls and either type of hip fracture.

Resveratrol inhibits parathyroid hormone-induced apoptosis in human aortic smooth muscle cells by upregulating sirtuin 1

Background: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease, so there is an urgent need to identify therapeutic targets to control the progression of cardiovascular disease. Apoptosis of aortic smooth muscle cells can promote cardiovascular disease, but the role of parathyroid hormone (PTH) and sirtuin 1 in the pathophysiology of apoptosis is still unclear.Methods: Cultured human aortic smooth muscle cells (HASMCs) were stimulated with 10–6, 10–8, or 10–10 mol/L PTH for different days, apoptosis was measured by flow cytometry and sirtuin 1 and Bcl-2 protein levels in cell extracts were analyzed by western blotting. HASMCs were stimulated with PTH (10–8 mol/L) and 50 or 100 μmol/L RES for 3 d, apoptosis was measured by flow cytometry and sirtuin 1 and Bcl-2 protein levels in cell extracts were analyzed by western blotting.Results: We found that PTH decreased the expression of sirtuin 1 and Bcl-2, inducing apoptosis (p<.05). Resveratrol (RES), a sirtuin 1 agonist, inhibited PTH-induced apoptosis and restored Bcl-2 expression (p<.05).Conclusions: PTH induces apoptosis in HASMCs. Resveratrol inhibits PTH-induced apoptosis in HASMCs.

Vitamin D, Inflammation and Osteoporosis in Rheumatoid Arthritis

Patients with Rheumatoid Arthritis (RA) commonly develop osteoporosis and fragility fractures. This fact cannot be explained only with the use of glucocorticoids, known to be detrimental for bone health. RA is characterized by a chronic inflammation caused by the continuous activation of innate and adaptive immunity with proinflammatory cytokines overproduction. This process is detrimental for several organs and physiological processes, including the impairment of bone remodeling. We will briefly review the pathogenesis of inflammation-related bone loss in RA, describing well-known and new molecular pathways and focusing on vitamin D and Parathyroid Hormone role.

Corrigendum to "The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients with Cardiovascular Diseases".

[This corrects the article DOI: 10.1155/2018/5287573.].

Prospects of Parathyroid Hormone in Therapeutic Intervention

Biologically active peptides and proteins have wide applications as therapeutic agents as well as diagnostics. Parathyroid hormone (PTH), a polypeptide secreted by the parathyroid chief cells has been found to be an effective therapeutic protein for the treatment of osteoporosis. PTH as an anabolic agent and a potent regulator of ionized calcium and phosphate plays a pivotal role in maintaining active vitamin D metabolite levels in the circulating blood. Though licensed PTH is available in two forms as teriparatide having 1–34 amino acids and intact hormone having 1–84 aminoacids, due to short plasma half-life and low activity, their therapeutic purpose has been limited. Protein engineering approaches like PEGylation, conjugation with antibody complexes, and fusion proteins as well as amino terminal modification of intact or truncated PTH has helped to develop PTH and its modified analogs with improved therapeutic value and multitude functions in various fields of medicine. This review covers the significant role of PTH in osteoblast signaling mechanism, regulation of PTH secretion and its transcription, modifications in PTH along with its functional efficacy in different medical areas.

Association between High Levels of Parathyroid Hormone and Frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

Frailty is associated with poor outcomes hence identification of risks factors is pivotal. Since the independent role of parathyroid hormone (PTH) in frailty remains unexplored, we aimed to determine this in a population of older individuals with a history of falling. Cross-sectional study. Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia). 692 subjects (mean age=79, 65% women) assessed between 2009-2015. Assessment included clinical examination, mood, nutrition, grip strength, gait velocity, bone densitometry and posturography. Chemistry included serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic subjects were divided into 4 groups: (1) Normal: 25(OH)D3 >50nmol/L and PTH between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (<50nmol/L) and high PTH (>6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH (>6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried's criteria. Difference between the groups was assessed using one-way ANOVA and X2 analysis. Multinomial logistic regression evaluated the association between the groups and the number of Fried's criteria adjusted for age, BMI, renal function, 25(OH)D3 levels, and albumin. 22.6% subjects had high PTH levels (>6.8pmol/L). All subjects in the high PTH groups had significantly lower grip strength, gait velocity, limits of stability, and higher BMI. The PTH responsive group had a higher risk of pre-frailty (β=3.8, 95% CI = 3.42 - 5.22, p≷ 0.01) and frailty (β=8.26, 95% CI = 2.8-16.1, p<0.01). The risk of frailty was also higher in the Hyper PTH group (β=2.3, 95% CI = 1.74-4.32, p<0.01). We have reported an independent association of high PTH levels with high number of falls and with the clinical components of physical frailty in community dwelling older persons. Our results suggest a possible role of PTH in frailty that deserves further exploration.

Association of renal function with bone mineral density and fracture risk in the Longitudinal Aging Study Amsterdam

SummaryEarly renal dysfunction is associated with a 38% increased fracture risk in individuals aged 65 years and older. In men but not women, early renal dysfunction is associated with decreased femoral neck bone mineral density (BMD) which can be partially explained by increased parathyroid hormone (PTH) concentrations.IntroductionIt is uncertain whether early renal dysfunction is associated with osteoporosis and increased fracture risk. The aim of this study was to determine the relationship of decreased renal function with BMD and fracture risk and the role of PTH therein.MethodsWe analyzed data of participants aged 65 years and older from the Longitudinal Aging Study Amsterdam. A 6-year fracture follow-up was obtained in 1477 participants. BMD was measured by dual-energy x-ray absorptiometry (n = 535) and vertebral fractures by lateral spinal radiograph (n = 527) in a subsample at baseline. Glomerular filtration rate (eGFR) was estimated according to the modification of diet in renal disease equation and assessed by the five stages of chronic kidney disease (CKD).ResultsIn men and women, eGFR < 57 ml/min/1.73 m2 (lowest quartile) compared to eGFR > 74 ml/min/1.73 m2 (highest quartile) was associated with a 38% increase in fracture risk after adjustment for relevant confounders [hazard ratio (95%CI): 1.38 (1.17 to 1.61)]. Also, CKD stages 3a and 3b were associated to a 28 and 46% increase in fracture risk, respectively, as compared to CKD stages 1 and 2 together (eGFR > 60 ml/min/1.73 m2) after adjustment for confounders. Renal function was not associated with prevalent vertebral fractures. In men, but not women, lowest quartile of eGFR was related to lower femoral neck BMD as compared to the highest quartile eGFR [unstandardized B (95%CI) − 0.052 g/cm2 (− 0.098 to − 0.006)], after adjustment for relevant confounders. Further adjustment for PTH attenuated this relationship by 27%.ConclusionsIn men and women, early decreased renal function (eGFR < 60 ml/min/1.73 m2) was related to increased incident any fracture risk but not with increased prevalence of vertebral fractures. In men, but not women, early renal dysfunction was related to lower femoral neck BMD which could statistically be partially explained by increased PTH concentrations.

Role of Parathyroid Hormone in Regulating Transporter and Metabolizing Enzyme Function.

Recent studies demonstrate that parathyroid hormone (PTH) not only maintains mineral homeostasis through targeting the kidneys and bone, but also exerts its effects on other organs. For instance, PTH induces urate accumulation through inhibiting the expression of the ABCG2 in both the intestine and the kidney. In addition, PTH downregulates the expression of cytochrome P450 (CYP) 3A, a major enzyme for drug metabolism in both the intestine and liver, resulting in the increase of substrate drug exposure. These functions of PTH are mediated through the PTH receptor (PTHR) signaling. Since PTHR exists in various organs, PTH may regulate other, still unspecified transporters or enzymes in the organs that express PTHR.

The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients with Cardiovascular Diseases

25-hydroxyvitamin D (25(OH)D) plays a crucial role in human homeostasis. Its deficiency (vitamin D deficiency—VDD), being common in European population, combined with elevated concentration of parathyroid hormone (PTH), represents a vicious cycle of mechanisms leading to heart failure (HF). Despite several papers published in that field, the effect of VDD and PTH concentration on cardiovascular system remains unequivocal; thus, the aim of the study was to compare these data among HF and non-HF patients being prospectively enrolled into the study during hospital stay in the cardiology ward. Patients with HF had higher PTH concentration (85.0 ± 52.6 versus 64.5 ± 31.7, p ≤ 0.02) compared to non-HF patients. Mean PTH values were associated with the clinical status expressed by the New York Heart Association class (NYHA class) (“0”—66.04, “I”—56.57, “II”—72.30, “III”—85.59, and “IV”—144.37 pg/ml, p ≤ 0.00004). Interestingly, neither 25(OH)D (31.5 versus 29.7 ng/ml, p ≤ ns) nor phosphorus (P) (1.23 versus 1.18 mmol/l, p ≤ ns) nor total calcium (Ca2+) concentration (2.33 versus 2.37 mmol/l, p ≤ ns) differed among the groups. Reassuming PTH serum concentration in contrary to 25(OH)D, P and Ca2+ are significantly raised among the patients with HF and shows significant relationship with the clinical status expressed by the NYHA class.

ASSOCIATION BETWEEN HIGH LEVELS OF PARATHYROID HORMONE AND FRAILTY: THE NEPEAN OSTEOPOROSIS AND FRAILTY (NOF) STUDY

Background: Frailty is associated with poor outcomes hence identification of risks factors is pivotal. Since the independent role of parathyroid hormone (PTH) in frailty remains unexplored, we aimed to determine this in a population of older individuals with a history of falling. Design: Cross-sectional study. Setting: Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia). Participants: 692 subjects (mean age=79, 65% women) assessed between 2009-2015. Measurements: Assessment included clinical examination, mood, nutrition, grip strength, gait velocity, bone densitometry and posturography. Chemistry included serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic subjects were divided into 4 groups: (1) Normal: 25(OH)D3 &gt;50nmol/L and PTH between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (&lt;50nmol/L) and high PTH (&gt;6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH (&gt;6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried’s criteria. Difference between the groups was assessed using one-way ANOVA and X2 analysis. Multinomial logistic regression evaluated the association between the groups and the number of Fried’s criteria adjusted for age, BMI, renal function, 25(OH)D3 levels, and albumin. Results: 22.6% subjects had high PTH levels (&gt;6.8pmol/L). All subjects in the high PTH groups had significantly lower grip strength, gait velocity, limits of stability, and higher BMI. The PTH responsive group had a higher risk of pre-frailty (β=3.8, 95% CI = 3.42 – 5.22, p&lt; 0.01) and frailty (β=8.26, 95% CI = 2.8-16.1, p&lt;0.01). The risk of frailty was also higher in the Hyper PTH group (β=2.3, 95% CI = 1.74-4.32, p&lt;0.01). Conclusion: We have reported an independent association of high PTH levels with high number of falls and with the clinical components of physical frailty in community dwelling older persons. Our results suggest a possible role of PTH in frailty that deserves further exploration.

Catabolic Effects of Human PTH (1\u201334) on Bone: Requirement of Monocyte Chemoattractant Protein-1 in Murine Model of Hyperparathyroidism

The bone catabolic actions of parathyroid hormone (PTH) are seen in patients with hyperparathyroidism, or with infusion of PTH in rodents. We have previously shown that the chemokine, monocyte chemoattractant protein-1 (MCP-1), is a mediator of PTH’s anabolic effects on bone. To determine its role in PTH’s catabolic effects, we continuously infused female wild-type (WT) and MCP-1−/− mice with hPTH or vehicle. Microcomputed tomography (µCT) analysis of cortical bone showed that hPTH-infusion induced significant bone loss in WT mice. Further, μCT analysis of trabecular bone revealed that, compared with the vehicle-treated group, the PTH-treated WT mice had reduced trabecular thickness and trabecular number. Notably, MCP-1−/− mice were protected against PTH-induced cortical and trabecular bone loss as well as from increases in serum CTX (C-terminal crosslinking telopeptide of type I collagen) and TRACP-5b (tartrate-resistant acid phosphatase 5b). In vitro, bone marrow macrophages (BMMs) from MCP-1−/− and WT mice were cultured with M-CSF, RANKL and/or MCP-1. BMMs from MCP-1−/− mice showed decreased multinucleated osteoclast formation compared with WT mice. Taken together, our work demonstrates that MCP-1 has a role in PTH’s catabolic effects on bone including monocyte and macrophage recruitment, osteoclast formation, bone resorption, and cortical and trabecular bone loss.

Parathyroid hormone contributes to the down-regulation of cytochrome P450 3A through the cAMP/PI3K/PKC/PKA/NF-κB signaling pathway in secondary hyperparathyroidism

Chronic kidney disease (CKD), which affects, not only renal clearance, but also non-renal clearance, is accompanied by a decline in renal function. Although it has been suggested that humoral factors, such as uremic toxins that accumulate in the body under CKD conditions, could be involved in the changes associated with non-renal drug clearance, the overall process is not completely understood. In this study, we report on the role of parathyroid hormone (PTH), a middle molecule uremic toxin, on the expression of drug metabolizing or transporting proteins using rats with secondary hyperparathyroidism (SHPT) as models. In SHPT rats, hepatic and intestinal CYP3A expression was suppressed, but the changes were recovered by the administration of the calcimimetic cinacalcet, a PTH suppressor. Under the same experimental conditions, a pharmacokinetic study using orally administered midazolam, a substrate for CYP3A, showed that the AUC was increased by 5 times in SHPT rats, but that was partially recovered by a cinacalcet treatment. This was directly tested in rat primary hepatocytes and intestinal Caco-2 cells where the expression of the CYP3A protein was down-regulated by PTH (1–34). In Caco-2 cells, PTH (1–34) down-regulated the expression of CYP3A mRNA, but an inactive PTH derivative (13–34) had no effect. 8-Bromo-cyclic adenosine monophosphate, a membrane-permeable cAMP analog, reduced mRNA expression of CYP3A whereas the inhibitors of PI3K, NF-κB, PKC and PKA reversed the PTH-induced CYP3A down-regulation. These results suggest that PTH down-regulates CYP3A through multiple signaling pathways, including the PI3K/PKC/PKA/NF-κB pathway after the elevation of intracellular cAMP, and the effect of PTH can be prevented by cinacalcet treatment.

Role of PTH in Bone Marrow Niche and HSC Regulation

The bone marrow microenvironment hosts a multicellular complex that is extraordinary in its interdependence and function. The composite machinery within the axial and long bones is involved in the homing, maintenance, differentiation, and egress of hematopoietic/progenitors stem cells (HSCS) as well as mesenchymal/stromal stem cells (MSCs) that dwell in specific anatomical areas inside the marrow space, described as niches. The need for more efficient hematopoietic stem cell transplantation protocols and bone marrow manipulation techniques has motivated scientists to identify effective niche regulators such as the parathyroid hormone (PTH). PTH treatment is increasingly used with promising outcomes in autologous and allogeneic transplantation of HSCs, because PTH operates as a significant mediator in HSC engraftment, expansion, and mobilization. In addition to the well-established anti-osteoporotic effect of PTH, there is evidence that it may also coordinate hematopoietic stem cell activities. This report provides up-to-date information about PTH action within marrow niches and highlights the importance of this hormone in the behavior of hematopoietic elements in the bone marrow.

Interspecies differences in PTH-mediated PKA phosphorylation of the epithelial calcium channel TRPV5

The epithelial calcium (Ca2+) channel TRPV5 (transient receptor potential vanilloid 5) is expressed in the distal convoluted tubule of the kidney and facilitates active Ca2+ reabsorption. This process is instrumental for the maintenance of Ca2+ homeostasis. Therefore, all aspects of TRPV5 function are tightly regulated by the calciotropic parathyroid hormone (PTH). Rabbit (rb)TRPV5 channel activity was shown to be stimulated upon PTH-mediated protein kinase A (PKA) phosphorylation. Since there is incomplete conservation of the PKA consensus motif (RR/QxT) across species, the aim of this study was to extend these findings to humans and characterize the expression and function of human (h)TRPV5. Functional differences between rbTRPV5 and hTRPV5 upon PTH stimulation were investigated using 45Ca2+ uptake assays, Fura-2 Ca2+ imaging, and cell surface biotinylation. While PTH treatment enhanced rbTRPV5 channel activity, it did not stimulate hTRPV5 activity. Mutation of the human RQxT motif into rabbit RRxT (hTRPV5 Q706R) partially restored the sensitivity to PTH. An ancestral sequence reconstruction of TRPV5 orthologues demonstrated that the change in the RRxT motif coincides with the creation of another putative PKA motif (RGAS to RRAS) in the amino terminus of hTRPV5. Interestingly, a constitutively phosphorylated hTRPV5 mutant (hTRPV5 S141D) displayed significantly decreased channel function, while its plasma membrane abundance was increased. Taken together, PTH-mediated stimulation of TRPV5, via PKA, is not conserved in humans. Our data suggest that PTH regulation of TRPV5 is altered in humans, an important observation for future studies that may add to new concepts on the role of PTH in renal Ca2+ handling.

Parathyroid Hormone Levels Predict Long-Term Outcome After Operative Management of Parathyroid Cancer.

The role of parathyroid hormone (PTH) serum levels for prediction of outcome is ill defined for parathyroid cancer, which is a very rare disease. This investigation of 17 consecutive patients with parathyroid cancer, (re-)operated on at a tertiary referral center between 1994 and July 2016, with a mean follow-up of 179.6 months (15 years) aimed to clarify the suitability of PTH serum levels for prediction of clinical outcome after comprehensive operative management of parathyroid cancer. Cancer-specific mortality occurred significantly more often with the performance of sternotomy before or at first operation at this institution (80 vs. 0%; p=0.002); mean PTH serum levels before first operation (1 105 vs. 357 pg/ml; p=0.008; r=0.77) and at most recent follow-up (3 167 vs. 101 pg/ml; p=0.019; r=0.60); and normalization of PTH serum levels at most recent follow-up (0 vs. 64%; p=0.034). For cancer-specific survival, receiver-operating characteristics analysis identified as optimum cut-off point an initial PTH serum level of 700 pg/ml. For local recurrence, no significant associations were found. Kaplan-Meier analysis confirmed that the patients with initial PTH serum levels >700 pg/ml (plog-rank=0.011) and sternotomy (plog-rank<0.001), but not node or lung metastases, had worse cancer-specific survival. Parathyroid cancer is much more an endocrine disease with oncological features than an oncological disease with endocrine features. Operative intervention(s) should be comprehensive and directed at clearing all metabolically active parathyroid tumor deposits early. If surgical cure cannot be reached, it is pivotal to achieve metabolic control, obviating the need for, or facilitating, medical therapy of hypercalcemia, and preserve renal function.

Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts

BackgroundExternal root resorption, commonly starting from cementum, is a severe side effect of orthodontic treatment. In this pathological process and repairing course followed, cementoblasts play a significant role. Previous studies implicated that parathyroid hormone (PTH) could act on committed osteoblast precursors to promote differentiation, and inhibit apoptosis. But little was known about the role of PTH in cementoblasts. The purpose of this study was to investigate the effects of intermittent PTH on cementoblasts and its influence after mechanical strain treatment.ResultsHigher levels of cementogenesis- and differentiation-related biomarkers (bone sialoprotein (BSP), osteocalcin (OCN), Collagen type I (COL1) and Osterix (Osx)) were shown in 1–3 cycles of intermittent PTH treated groups than the control group. Additionally, intermittent PTH increased alkaline phosphatase (ALP) activity and mineralized nodules formation, as measured by ALP staining, quantitative ALP assay, Alizarin red S staining and quantitative calcium assay. The morphology of OCCM-30 cells changed after mechanical strain exertion. Expression of BSP, ALP, OCN, osteopontin (OPN) and Osx was restrained after 18 h mechanical strain. Furthermore, intermittent PTH significantly increased the expression of cementogenesis- and differentiation-related biomarkers in mechanical strain treated OCCM-30 cells.ConclusionsTaken together, these data suggested that intermittent PTH promoted cementum formation through activating cementogenesis- and differentiation-related biomarkers, and attenuated the catabolic effects of mechanical strain in immortalized cementoblasts OCCM-30.

Abstract P217: Parathyroid Hormone is Not Independently Associated With Cognitive Decline: 20 Year Follow-up From the Atherosclerosis Risk in Communities (ARIC) Study

Background: Little is known about the role of parathyroid hormone (PTH) in cognitive decline. Elevated PTH may contribute to cognitive impairment and dementia by mechanisms of endothelial dysfunction, increased vascular stiffness, hypertension, and atherosclerosis, as well as via small vessel cerebral disease. We hypothesized that elevated PTH levels will be independently associated with 20-year cognitive decline in a large population-based cohort study. Methods: We studied 12,964 middle-aged white and black ARIC participants without history of prior stroke who had serum PTH levels and cognitive function testing measured in 1990-92 (baseline) and repeat cognitive testing at up to 2 follow-up visits in 1996-98 and 2011-13. The cognitive tests included the Delayed Word Recall, Digit Symbol Substitution, and Word Fluency tests, which were summed as a global z score. Using mixed-effects models, we compared the relative decline in global cognitive score between each of the top three quartiles of PTH levels to the reference bottom quartile. Time since baseline was modeled by using a linear spline with a knot at 6 years. We adjusted for demographic variables, education, vascular risk factors, and calcium, phosphorous, and vitamin D levels. We imputed missing covariates and follow-up cognitive data using multiple imputation by chained equations (MICE) methods to account for attrition during study follow-up. Results: The mean (SD) age of our cohort was 57(6) years, 57% were women, and 24% black race. There was no cross-sectional association of elevated PTH with cognitive global Z score at baseline (all p&gt;0.05). Over a median of 20.7 years, participants in each PTH quartile showed decline in cognitive function ( Table Part A ). However, cognitive decline was not steeper in participants with PTH levels in the higher quartiles than participants with the lowest PTH levels (all p&gt;0.05). [ Table Part B ]. Conclusions: Our work does not support an independent influence of PTH on cognitive decline in this biracial population-based cohort study.