Parathyroid Hormone Group Research Articles

PET-TC [18F]F-Colina y PTH intraoperatoria en el tratamiento quirúrgico del hiperparatiroidismo primario sin localización preoperatoria

Background and objectivesTo assess the feasibility of performing selective parathyroidectomy without intraoperative parathyroid hormone (PTHio) determination when first-line preoperative localization tests (ultrasonography and [99mTc]Tc-MIBI) are negative and/or discordant, and second-line [18F]F-Colina PET-CT, is positive. Materials and methodsRetrospective cohort study, including patients with negative or discordant ultrasound and MIBI scans and positive [18F]F-Colina PET-CT, who underwent selective parathyroidectomy between 2019 and 2022. Groups were compared based on PTHio determination. Study variables were: gender, mean age, biochemical cure assessed by PTH value (pg/mL) and corrected calcium by albumin (mg/dL) at 6 months post-surgery follow-up, and histopathological analysis. ResultsThe final sample included 42 patients. At 6 months post-surgery, in the PTHio group (20 patients), PTH values were 64.50 pg/mL and calcium 9.30 pg/mL, with 19 adenomas and 1 hyperplasia found. In the non-PTHio group (22 patients), PTH values were 61 pg/mL and calcium 9.37 pg/mL, with 22 adenomas found. No statistically significant differences were found between both groups. ConclusionsBased on the results obtained in our patient cohort, selective parathyroidectomy could be considered with negative or discordant first-line tests and positive [18F]F-Colina PET-CT, without intraoperative PTH determination.

PET-TC [18F]F-choline and intraoperative PTH in the surgical treatment of the primary hyperparathyroidism without preoperative location

Background and objectivesTo assess the feasibility of performing selective parathyroidectomy without intraoperative parathyroid hormone (PTHio) determination when first-line preoperative localization tests (ultrasonography and [99mTc]Tc-MIBI) are negative and/or discordant, and second-line [18F]F-Colina PET-CT, is positive. Materials and methodsRetrospective cohort study, including patients with negative or discordant ultrasound and MIBI scans and positive [18F]F-Colina PET-CT, who underwent selective parathyroidectomy between 2019 and 2022. Groups were compared based on PTHio determination. Study variables were: gender, mean age, biochemical cure assessed by PTH value (pg/mL) and corrected calcium by albumin (mg/dL) at 6 months post-surgery follow-up, and histopathological analysis. ResultsThe final sample included 42 patients. At 6 months post-surgery, in the PTHio group (20 patients), PTH values were 64.50 pg/mL and calcium 9.30 pg/mL, with 19 adenomas and 1 hyperplasia found. In the non-PTHio group (22 patients), PTH values were 61 pg/mL and calcium 9.37 pg/mL, with 22 adenomas found. No statistically significant differences were found between both groups. ConclusionsBased on the results obtained in our patient cohort, selective parathyroidectomy could be considered with negative or discordant first-line tests and positive [18F]F-Colina PET-CT, without intraoperative PTH determination.

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis.

Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

Exploring the Interactive Role of Parathyroid Hormone and Sodium Intake in Inducing Cardiac Hypertrophy in Rats: A Novel Study.

Background and objectives Previous research has suggested that hyperparathyroidism and excessive salt intake may contribute to the development of cardiac hypertrophy. This study aimed to investigate the relationship and underlying mechanisms between parathyroid hormone (PTH) and salt intake in the development of left ventricular hypertrophy (LVH). Additionally, the study sought to determine whether captopril intervention could reduce the impact of sustained PTH stimulation and excessive salt intake on LVH. Methodology We employed 40 eight-week-old male Sprague-Dawley rats, which were randomly assigned to eight groups: a sham group, a PTH group, a low-salt group (0.6% NaCl), a high-salt group (8% NaCl), a PTH + low-salt group, a PTH + high-salt group, a PTH + low salt + captopril group, and a PTH + high salt + captopril group. The rats were continuously infused with recombinant PTH (1-34) (2 pmol/kg per hour) via an osmotic pump for two weeks and were administered varying concentrations of saline for gavage over two weeks, according to their group. We monitored changes in blood pressure, measured heart weight, left ventricular wall thickness, and myocardial histological morphology, and assessed the relative expression of type III collagen. Results The PTH + high-salt group displayed a significant increase in blood pressure, heart weight, and left ventricular posterior wall thickness (P＜0.05), in addition to myocardial cell hypertrophy and increased Col III expression (P＜0.05), compared to other groups. Captopril intervention significantly reduced blood pressure (P＜0.05), ameliorated myocardial tissue morphology changes, and significantly decreased Col III expression (P＜0.05) but did not entirely reverse the increase in heart weight and left ventricular posterior wall thickness (P＞0.05). Conclusions Our findings suggest that the co-intervention of PTH and high salt can lead to an increase in blood pressure, heart weight, myocardial cell hypertrophy, LVH, and myocardial fibrosis levels in Sprague-Dawley rats. Captopril intervention can lower blood pressure and alleviate pathological myocardial tissue changes and myocardial fibrosis but cannot completely reverse LVH.

Diagnostic Value of Four-Dimensional Dynamic Computed Tomography for Primary Hyperparathyroidism in Patients with Low Baseline Parathyroid Hormone Levels.

Low baseline levels of parathyroid hormone (PTH) are associated with a higher rate of multiglandular disease, lower localization rates of preoperative imaging modalities, and a higher rate of unsuccessful minimally invasive parathyroidectomies. The objective of this study is to assess the diagnostic value of four-dimensional dynamic computed tomography (4D-CT) in localizing primary hyperparathyroidism (pHPT) in patients with low baseline PTH levels, compared to patients with high baseline PTH levels. Patients with pHPT who received a 4D-CT scan as part of their standard diagnostic evaluation were divided into two groups based on the following criteria: (1) preoperative PTH levels less than 100 pg/mL and (2) patients with preoperative PTH levels greater than 100 pg/mL. All patients underwent parathyroidectomy based on 4D-CT findings, with intraoperative parathyroid hormone monitoring. The lesion-based sensitivity of 4D-CT was 88% in patients with low baseline PTH levels and 94.7% in patients with high baseline PTH levels (p = 0.33). However, the success rate of image-guided resection based on 4D-CT findings was 71.4% in the low baseline PTH group compared to 90.6% in the high baseline PTH group (p = 0.06). Our study demonstrated that 4D-CT has a high lesion-based sensitivity in patients with pHPT and low baseline PTH levels but led to a relatively low rate of successful image-guided resection in patients with low baseline PTH levels. Therefore, it is important to exercise increased caution during 4D-CT-guided surgical exploration of patients with low baseline PTH levels to ensure successful surgical resection of all parathyroid lesions.

Low-intensity pulsed ultrasound and parathyroid hormone improve muscle atrophy in estrogen deficiency mice

Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality. Low-intensity pulsed ultrasound (LIPUS) is an acoustic wave inducing biological effects mainly by the mechanical stimulation and used as a non-invasive physical therapy for muscle repair. Parathyroid hormone (PTH) is an 84-amino-acid polypeptide, and its bioactive fragment [PTH (1–34)] has potential application in the treatment of MA. We speculate that the combination of physical therapy (i.e., the LIPUS) and regulatory hormone (i.e., the PTH) would be more effective in the treatment of MA. The objective of this study was to evaluate the individual and combined effects of LIPUS and PTH therapy on MA in estrogen deficiency mice. Seventy 8-week-old female C57BL/6J mice were used in this study and the MA model was induced by an intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD) for 20 consecutive days. The VCD-induced MA mice were randomly divided into MA, LIPUS, PTH and LIPUS + PTH (Combined) groups (n = 10/group). In the LIPUS group, the mice were treated by LIPUS in bilateral quadriceps muscles for 20 min, five times a week for 6 weeks. In the PTH group, the mice received subcutaneous injection of PTH (1–34) (80 ug/kg/d) five times a week, for 6 weeks. In the Combined group, the PTH was administrated 30 min before each LIPUS session. Hematoxylin-eosin (H&E) staining, serum biochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to evaluate the therapeutic effects of related treatments. The results showed that the MA mice had a disordered estrus cycle, significantly decreased muscle mass and myofibers cross-sectional area (CSA). After treatments, LIPUS, PTH and Combined groups had a significantly increased CSA, compared with the MA mice without treatment. In addition, Combined group had a significantly increased mRNA expression of Pax7, MyoD and MyoG, compared with LIPUS and PTH monotherapy groups. Our findings indicated that the combination of LIPUS and PTH treatment improves muscle regeneration ability, which might have potential for treating MA in postmenopausal women.

Parathyroid hormone-induced vascular smooth muscle cells calcification by endoplasmic reticulum stress.

Vascular smooth muscle cells (VSMCs) play a key role in vascular calcification, which is associated with enhanced mortality in chronic kidney disease. To ascertain the concentration of parathyroid hormone (PTH) that induces apoptosis of VSMCs and to explore whether the mechanism of endoplasmic reticulum (ER) stress is involved in PTH-induced calcification of VSMCs. The appropriate concentration and intervention time of PTH-inducing apoptosis of VSMCs were screened by flow cytometry. To investigate the effects of PTH on ER stress-related and apoptotic proteins in VSMCs, they were divided into four groups. These were the control group, the PTH group, the siC/EBP homologous protein (CHOP) + PTH group (in which siCHOP was used to knockdown the expression of CHOP at first), and the sp600125 + PTH group (in which the cells were pretreated with sp600125 at a concentration of 10 ng/ml for 24 h at first). Then, all groups except the control group were given 1x10-6 mol/L PTH to stimulate VSMCs. The changes in ER stress and apoptosis-related proteins in each group were detected, and the cell calcification was tested by Alizarin Red staining. Flow cytometry showed that the concentration of 1x10-6 mol/L PTH induced apoptosis most significantly. The apoptosis rate of the cells increased with the extension of stimulation time. The apoptosis of VSMCs pretreated with the Jun-N-terminal kinase (JNK) antagonist sp600125 was significantly reduced. The expression of cleaved caspase-3, PERK, IRE1, and CHOP was detected by Western blot analysis when cells were stimulated with 10-6 mol/L PTH for 14 days. After the knockdown of the CHOP expression by siCHOP, cleaved caspase-3 expression was significantly reduced. Alizarin Red staining showed siCHOP and sp600125 inhibits the VSMCs' calcification induced by PTH. In conclusion: the ER stress mechanism is involved in VSMCs' calcification induced by PTH.

Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats.

ObjectiveTo investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.MethodsThirty female Sprague–Dawley rats were divided into three groups: sham‐operation (SHAM) group, OVX group and PTH treatment group. After 3 months of treatment, the femurs, serum and feces were acquired for micro‐CT, biochemical analysis and 16S rRNA sequencing, respectively. For 16S rRNA sequencing, after raw reads filtrated and chimera sequences removed, the clean reads were obtained. According to these clean reads, the operational taxonomic units (OTUs) were clustered. Venn diagram analysis was conducted to explore common and unique GM among the three groups. The α‐diversity analysis including Shannon and Simpson indexes were used to evaluate the richness and diversity of the GM. The β‐diversity analysis was performed to estimate the structure of GM. The metabolic function was predicted by Tax4Fun analysis.ResultsWith micro‐CT and biochemical analysis, significant improvements were found in the PTH group compared with the OVX group. In Venn diagram analysis, more unique OTUs were found in the SHAM and PTH groups than the OVX group. According to the rank abundance curve, the SHAM and PTH groups had similar richness and evenness, which were higher than the OVX group. Simpson and Shannon indexes were higher in the SHAM and PTH groups compared with the OVX group, indicating that the SHAM and PTH groups had higher microbiota complexity than the OVX group. In β‐diversity analysis, apparent separation was found in the OVX group from the PTH and SHAM groups, which suggested that osteoporosis is the critical factor influencing the GM composition and PTH treatment and can restore the structure of GM. Compared with the OVX group, treatment with PTH increased the abundances of GM which were reported to increase bone mass, such as Lactobacillus_reuteri, Muribaculaceae, Ruminococcaceae, and Clostridia, and inhibited the relative abundance of Rikenellaceae, which was reported to be potentially related to osteoporosis. GM function analysis showed that PTH could promote butyrate synthesis. In Tax4Fun analysis, the function of butanoate metabolism is more vital in the PTH group than the OVX and SHAM groups, suggesting PTH treatment could regulate microbial metabolic function, including butanoate metabolism.ConclusionIntermittent PTH can interact with GM through increasing the abundance of probiotics and reducing the abundance of the pathogenic bacteria to enhance the bone mass.

Supplementation of articular cartilage-derived chondroprogenitors with bone morphogenic protein-9 enhances chondrogenesis without affecting hypertrophy.

Chondroprogenitors (CPCs) have emerged as a promising cellular therapy for cartilage-related pathologies due to their inherent primed chondrogenic potential. Studies report that the addition of growth factors such as parathyroid hormone (PTH) and Bone Morphogenic Protein (BMP) enhance the chondroinducive potential in chondrocytes and mesenchymal stem cells. This study evaluated if supplementation of the standard culture medium for cell expansion with 1-34 PTH and BMP-9 would enhance the chondrogenic potential of CPCs and reduce their hypertrophic tendency. Human chondrocytes were isolated from patients undergoing total knee replacement for osteoarthritis (n = 3). Following fibronectin adhesion assay, passage 1 CPCs were divided and further expanded under three culture conditions (a) control, i.e., cells continued under standard culture conditions, (b) 1-34 PTH group, additional intermittent 6h exposure with 1-34 PTH and (c) BMP-9 group, additional BMP-9 during culture expansion. All the groups were evaluated for population-doubling, cell cycle analysis, surface marker and gene expression for chondrogenesis, hypertrophy, multilineage differentiation and GAG (glycosaminoglycan)/DNA following chondrogenic differentiation. Concerning growth kinetics, the BMP-9 group exhibited a significantly lower S-phase and population-doubling when compared to the other two groups. Qualitative analysis for chondrogenic potential (Alcian blue, Safranin O staining and Toluidine blue for GAG) revealed that the BMP-9 group exhibited the highest uptake. The BMP-9 group also showed significantly higher COL2A1 expression than the control group, with no change in the hypertrophy marker expression. BMP-9 can potentially be used as an additive for CPCs expansion, to enhance their chondrogenic potential without affecting their low hypertrophic tendency. The mitigating effects of 1-34PTH on hypertrophy would benefit further investigation when used in combination with BMP-9 to enhance chondrogenesis whilst reducing hypertrophy.

Transplantation of Parathyroid Hormone–Treated Achilles Tendon Promotes Meniscal Regeneration in a Rat Meniscal Defect Model

Background: Autologous tendon grafts are used for meniscal reconstruction of surgically removed knee joint meniscus. However, as meniscal reconstruction cannot prevent the progression of cartilage degeneration, additional procedures that confer meniscus-like histological properties to the transplanted tendon are required for improved outcomes. Hypotheses: Parathyroid hormone (PTH)(1-34) induces cartilage formation in the rat tendon, and transplantation of PTH-treated tendon promotes meniscal regeneration. Study Design: Controlled laboratory study. Methods: Rat Achilles tendon–derived cells were cultured with or without PTH for 28 days and stained with Alcian blue to determine chondrogenic differentiation. After 14 and 28 days of incubation, gene expression was assessed using quantitative real-time polymerase chain reaction. In an in vivo study, rat Achilles tendon was injected with PTH and then transplanted onto a medial meniscal defect. Macroscopic and histological assessments of the regenerated meniscus and of cartilage degeneration in the tibial plateau were performed at 4 and 8 weeks after surgery. Results: In vitro, PTH-treated cells showed better staining with Alcian blue than the control (normal medium) group. PTH1R, Col2a1, Sox9, and RUNX2 were significantly upregulated in PTH-treated cells (P < .05). Macroscopically, the in vivo results revealed more prominent meniscal coverage and lesser progression of articular cartilage degeneration in the PTH group than in the phosphate-buffered saline–injected group. Histologically, toluidine blue staining revealed metachromasia in the PTH-injected tissue at 4 and 8 weeks. The PTH-treated regenerated meniscus showed positive immunostaining for type II collagen in the area exhibiting metachromasia. Moreover, PTH-treated tendon had an enhanced histological score compared with the untreated group at 4 and 8 weeks (P < .05). Conclusion: PTH(1-34) induced cartilage formation in the rat tendon. Transplantation of PTH(1-34)–treated Achilles tendon in a rat meniscal defect model induced meniscal regeneration and preserved knee articular cartilage. Macroscopically, PTH groups showed a greater coverage of the regenerated meniscus. Histologically, the regenerated meniscus had higher cartilaginous matrix content in rats transplanted with PTH-treated tendons. PTH(1-34) stimulated tendon-derived cells to promote chondrogenic differentiation. Clinical Relevance: Meniscal transplantation using PTH-injected autologous tendon grafts might promote meniscal regeneration and prevent progression of cartilage degeneration by stimulating chondrogenic differentiation of tendon-derived cells.

Low Parathyroid Hormone Versus Secondary Hyperparathyroidism and Survival in Patients Undergoing Hemodialysis: A Propensity-Matched Analysis.

IntroductionLow serum parathyroid hormone (PTH) and secondary hyperparathyroidism (SHPT) are very common in patients undergoing hemodialysis. However, it remains unclear which of these has a lower mortality.ObjectiveIn this study, we compared outcomes between hemodialysis patients with low PTH and those with SHPT.MethodsThis was a multi-center, retrospective, matched cohort study. Median intact PTH (iPTH) was used as the cutoff for allocating participants to low PTH (iPTH<100 pg/mL) and SHPT groups (iPTH ≥600 pg/mL). Sex, diabetes, age, and dialysis vintage were matched between the groups. The primary outcome was all-cause death at 72 months.ResultsThe study cohort comprised 2282 patients (1166 in each study group). Prior to matching, the primary outcome occurred in 429/1166 patients (36.79%) in the low PTH group and in 284/1116 (25.45%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.423). The hazard ratio for low PTH versus SHPT was 1.08 (95% confidence interval, 0.90–1.30). Propensity matching created 619 pairs of patients. Baseline characteristics, including age, sex, diabetes, and dialysis vintage were comparable between the groups. The primary outcome occurred in 195/619 patients (31.50%) in the low PTH group and in 193/619 (31.18%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.43). The adjusted hazard ratio for low PTH versus SHPT was 1.10 (95% confidence interval, 0.87–1.39).ConclusionsHemodialysis patients with low PTH have similar all-cause death rates to the rates for those with SHPT.

MO541: Secondary Hyperparathyroidism Influence on Parathyroid Hormone Levels After Kidney Transplantation

Abstract BACKGROUND AND AIMS Optimal parathyroid hormone (PTH) control in patients before kidney transplantation (KT) might decrease the subsequent risk of parathyroid hyperplasia and hyperparathyroidism (HPT) after surgery. We evaluated the patient characteristics and HPT markers control before and over the first post-transplant year. METHOD We studied 210 patients (107 women, 103 men and age 45 ± 9 years) with end-stage renal failure (ESRF). All patients underwent primary KT. The duration of the pre-transplant period ranged from 0 to 158 months (median 19). The determination of HPT markers was carried out before 3 and 12 months after KT. The target PTH after KT was considered to be 130 pg/mL. Serum concentrations of PTH, calcium, phosphorus, total alkaline phosphatase activity, albumin and creatinine were determined using standard methods, estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula and stratification of chronic kidney disease stages was carried out according to the eGFR. RESULTS Patients were divided into two groups based on PTH before KT. In the first group were 63 patients with PTH &amp;gt; 585 pg/mL (median 866, Q1–Q3: 667; 1078), in the second group there were 147 patients with PTH 130–585 pg/mL (median 300, Q1–Q3: 225; 400). Patients with secondary HPT versus target PTH group had long duration of dialysis therapy (27 months versus 15 months; P = 0.005), frequency of hyperphosphatemia (87% versus 57%; P &amp;lt; 0.001) and increased activity of blood alkaline phosphatase (21% versus 4%; P &amp;lt; 0.001). Initial renal transplant function was the same in both groups: acute tubular necrosis amounted to 57% and 46% respectively (P = 0.07), duration of acute tubular necrosis 2 and 0 days respectively (P = 0.087). Three months after kidney transplantation in the first group median blood PTH decreased to 247 pg/mL (Q1–Q3: 163; 452), the prevalence of PTH &amp;gt; 130 pg/mL had 88% patients, in the second group median blood PTH decreased to 150 pg/mL (Q1–Q3: 120; 210), the prevalence of PTH &amp;gt; 130 pg/mL had 59% patients (P &amp;lt; 0.001). Hypercalcemia was in 13% patients of first group and 0 in second group (P &amp;lt; 0.001). Serum creatinine and eGFR did not differ and amounted respectively to 114 (Q1–Q3: 86; 150) and 110 (Q1–Q3: 80; 136) μmol/L (ns), 60 (Q1–Q3: 45; 80) and 60 (Q1–Q3: 49; 80) mL/min (ns). The ratio of stages of chronic kidney disease was the same (Figure 1). A total of 12 months after KT the blood level PTH was 180 (Q1–Q3: 95; 247) and 106 (Q1–Q3: 88; 125) pg/mL (P = 0.004), the prevalence of PTH &amp;gt; 130 pg/mL had 54% and 15% (P &amp;lt; 0.001) patients respectively. Kidney transplant function did not differ as well as after 3 months (median serum creatinine 120–121 μmol/L, eGFR 55 and 55 mL/min). In the post-transplant period, patients of the first group were more often prescribed vitamin D preparations and its analogues, five were treated with cinacalcet due to hypercalcemia and seven underwent parathyroidectomy after 1.5–2.5 years. CONCLUSION Secondary HPT before KT predicted a higher PTH level in the first year after surgery. Patients with ESRF who are on the waiting list for KT need careful monitoring of blood PTH and adequate treatment of secondary HPT.

Intermittent parathyroid hormone treatment affects the bone structural parameters and mechanical strength of the femoral neck after ovariectomy-induced osteoporosis in rats

BackgroundMenopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force.MethodsFifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX + PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system.ResultsCompared with the control and OVX + PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX + PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX + PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p = 0.005) and 0.700 (p = 0.004).ConclusionIntermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (= vBMD × CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.

Parathyroid hormone promotes maxillary expansion and reduces relapse in the repeated activation maxillary expansion rat model by regulating Wnt/\u03b2-catenin pathway

BackgroundConstricted maxillary bone is a common skeletal deformity, which may lead to crowding and posterior crossbite. Mid-palatal suture expansion is often used to increase the maxillary width, but its skeletal effects are limited and tend to relapse, even with prolonged retention. We hypothesized that parathyroid hormone (PTH) may reduce the relapse of maxillary expansion.MethodsWe established a novel rat maxillary expansion model using palatal tubes with an insertable “W”-shaped spring which can be repeatedly activated. A total of 32 male healthy Wistar rats were randomly divided into six groups: the control group, the PTH group, the expansion group, the expansion + PTH group, the expansion + relapse group and the expansion + PTH + relapse group. All animals in the first 4 groups were killed after 10 days and the 2 relapse groups were killed after 15 days. The maxillary arch widths and histological staining were used to assess the expansion and relapse effects. The immunohistochemical staining, micro-CT, RT-qPCR and Western blot were used to evaluate the bone remodeling during expansion.ResultsThe suture width was increased by the expansion device, and the repeated activation maxillary expansion rat model showed better expansion effects than the conventional model. PTH significantly promoted the expansion width and reduced the relapse ratio. Meanwhile, in the expansion + PTH group, histological and immunohistochemical staining showed that osteoblasts, osteoclasts, new cartilage and osteoid were significantly increased, micro-CT showed increased bone mass, and PCR and Western blot results confirmed up-regulation of RANKL, β-catenin, type II collagen and OCN.ConclusionThe novel repeated activation maxillary expansion rat model has better effects than the conventional model. PTH enhances the maxillary expansion and reduces its relapse by regulating Wnt/β-catenin and RANKL pathways. PTH administration may serve as an adjunctive therapy in addition to mechanical expansion for treatment of maxillary constriction.

Analysis of the cause and management of persistent laboratory abnormalities occurring after the surgical treatment of primary hyperparathyroidism.

PurposeThe surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%–98%. However, 3%–24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This single-center retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH.MethodsThe normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group.ResultsThere were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency.ConclusionPreoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults

ObjectiveTo examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults. MethodsThis study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels. ResultsDuring a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group. ConclusionHigher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.

High parathyroid hormone levels after parathyroidectomy for parathyroid adenoma are not related to the cellularity of the remaining glands.

BackgroundPatients with primary hyperparathyroidism (PHPT) treated surgically occasionally have normalized calcium, but persistently high parathyroid hormone (PTH). We hypothesized that a possible explanation for this phenomenon is an underlying hyperplasia rather than adenoma.MethodsRetrospective cohort of patients who underwent parathyroidectomy for PHPT with biopsy of a normal‐appearing parathyroid gland were included. Cellularity level of each biopsy and of the adenoma's rim was determined.ResultsForty‐seven patients were included. Of them, 19 (40%) had postoperative normocalcemia but elevated PTH. There was no correlation between cellularity either in the rim or of the normal‐appearing parathyroid gland and postoperative PTH. The postoperative high PTH group had higher preoperative PTH (P = 0.001) and larger adenomas (P = 0.025).ConclusionsHigh PTH levels after successful parathyroidectomy in patients with primary hyperparathyroidism do not appear to result from underlying hyperplasia. A possible alternative explanation is that these patients have a higher preoperative burden of disease.

PTH/PTHrP in controlled release hydrogel enhances orthodontic tooth movement by regulating periodontal bone remodaling.

This study aimed to evaluate the effects of local application of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) on osteogenesis and osteoclastogenesis during orthodontic tooth movement (OTM). Periodontal bone remodeling is the crucial biological process in the OTM that involves both bone resorption and formation, with the former more important as the initiator. PTH or PTHrP both play dual roles in bone remodeling regulation, and the balance may shift to the bone resorption side when they are given continuously, suggesting them as potential candidate medicine for OTM acceleration. A total of 40 rats underwent orthodontic mesialization of the maxillary first molars and received no micro-perforation (MOP), or MOP followed by injection of temperature-sensitive hydrogel containing PTH, PTHrP, or normal saline. The rats were sacrificed after 2-week OTM, except for the relapse groups, which had one more week of observation after removal of the force appliances. The amount of tooth movement, rate of relapse after OTM, and effects on the bone remodeling were assessed through micro-computed tomography (μCT) analysis, alkaline phosphatase (ALP) assay, alizarin red staining, tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) analysis, Western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of PTHrP on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) were explored in vitro. The cumulative release of PTH or PTHrP from PECE hydrogels was beyond 75% at 14days in a sustained manner. After the intervention in vivo, the distance of OTM in the PTH (0.78±0.06mm) or PTHrP (0.81±0.04mm) group was significantly larger than that of the MOP only (0.51±0.04mm) or the no MOP (0.46±0.05mm) group. Moreover, PTH injection significantly reduced the rate of relapse after OTM (25.7±4.3%) compared to the control (69.6±6.1%). μCT analysis showed decreased BV/TV, BS/BV, and Tb.N, while increased Tb.Sp of alveolar bone in the PTH or PTHrP group. There were also more TRAP-positive osteoclasts in the PTH or PTHrP group with a significantly enhanced ratio of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG). The protein expressions of PTH/PTHrP type 1 receptor (PTHR1), alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and β-catenin were significantly increased in the PTH or PTHrP group, as well as the gene expressions of Pth1r, Bglap, and Alpl. There was no significant difference between the effects of PTH and PTHrP. Nevertheless, inhibition of PTHrP on the osteogenic differentiation of hPDLCs was detected in vitro with decreased expression of OCN, RUNX2, COL-1, and ALP. Local injection of either PTH or PTHrP carried by controlled release PECE hydrogel similarly enhances OTM in rats through regulating periodontal bone remodeling, which deserves further study for potential clinical application.

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.

Effect of PTH and corticotomy on implant movement under mechanical force

BackgroundOsseointegrated implants are considered as clinically non-movable. Parathyroid hormone (PTH) is known to play a significant role in the regulation of bone remodeling and in intermittent, low doses, result in osteoanabolic effects. This study aimed to investigate the effects of PTH and corticotomy, both under traction force, on osseointegrated implants.MethodsFour implants—two in each hemimandible—were placed in each of the three study mongrels. Each mongrels were designated as control, normal dose PTH (PTH-1), and high dose PTH (PTH-2) groups, with each groups further subdivided into non-surgery implant and surgery implant. After osseointegration, mechanical force with NiTi closed coil springs (500 g) was applied around each implants. Corticotomy was performed around one of four implants in each mongrels. Parathyroid hormone was administered locally on a weekly basis for 20 weeks. Clinical movement of the implants were evaluated with the superimposed 3D- scanned data, bone- microarchitectural and histologic examinations.ResultsSuperimposition analysis showed continuous movement of the non-surgery implant of PTH-1 group. Movement was further justified with lowest bone implant contact (adjusted BIC; 44.77%) in histomorphometric analysis. Upregulation of bone remodeling around the implant was observed in the normal dose PTH group. In the surgery implants, the remarkably higher adjusted BIC compared to the non-surgery implants indicated increased bone formation around the implant surface.ConclusionThe results indicate that the catabolic and anabolic balance of osseointegrated implants in terms of bone remodeling can be shifted via various interventions including pharmacological, surgical and mechanical force.Clinical relevanceUpregulated bone remodeling by PTH and corticotomy under continuous mechanical force showed the possible implications for the movement of osseointegrated dental implant.