High Parathyroid Hormone Groups Research Articles

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.

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.

Metabolic bone changes after intradialytic resistive exercise in regular haemodialysis patients

IntroductionMineral bone disease is a crucial factor that contributes to mortality and morbidity in haemodialysis patients. Intradialytic resistance exercise training can be valuable in stimulating bone formation. The aim of this study was to evaluate the metabolic bone changes after intradialytic resistive exercise training in regular haemodialysis patients.MethodsThe study involved 60 patients on regular haemodialysis, aged 20–60 years. The patients were divided into 2 groups: a high parathyroid hormone group (parathyroid hormone over 800 pg/ml) and a low parathyroid hormone group (parathyroid hormone below 200 pg/ml), both groups randomly assigned into study and control groups. They received intradialytic resistive exercise 3 times per week for 3 months. Calcium, phosphorus, and parathyroid hormone were evaluated before and after the exercise period.ResultsThe training protocol proved to be effective in improving bone metabolism parameters, as there were statistically significant differences in the high parathyroid hormone exercise group. Parathyroid hormone and phosphorus decreased and calcium increased (&lt;i&gt;p&lt;/i&gt; = 0.001, &lt;i&gt;p&lt;/i&gt; = 0.012, and &lt;i&gt;p&lt;/i&gt; = 0.025, respectively). In the low parathyroid hormone exercise group, phosphorus decreased significantly (&lt;i&gt;p&lt;/i&gt; = 0.030) and calcium increased, although not significantly (&lt;i&gt;p&lt;/i&gt; = 0.111), while parathyroid hormone non-significantly increased in the exercise group (&lt;i&gt;p&lt;/i&gt; = 0.770), with a significant increase in the control group (&lt;i&gt;p&lt;/i&gt; = 0.007). These results supported the positive effects of intradialytic resistive exercise in improving bone metabolism.ConclusionsIntradialytic resistive exercise training improves bone metabolism in haemodialysis patients.

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.

Early persistent hyperparathyroidism post-renal transplantation as a predictor of worse graft function and mortality after transplantation.

Persistent hyperparathyroidism (pHPT) is frequently seen after transplantation contributing to post-transplant complications. We conducted a retrospective single center analysis to explore the relationship of early pHPT and long-term allograft outcome. Patients were divided into high (N=153) and low (N=252) PTH groups based on serum parathyroid hormone (PTH) level 3months post-transplant (PTH≥150 and<150pg/mL, respectively). High PTH was found to be an independent predictor for reduced kidney allograft function up to 3years post-transplant. eGFR decreased by 11.4mL/min (P<.001) and the odds of having an eGFR<60mL/min 3years post-transplant were sixfold higher (P<.01) in the high compared to the low PTH group. Subgroup analysis based on eGFR 1year post-transplant, presence of slow graft function (SGF), and transplant type revealed similar results. High PTH three months post-transplant was also independently associated with an increased risk for overall mortality and for death with a functioning graft (P<.05). pHPT three months post-renal transplantation is an independent predictor for a worse allograft function up to 3years post-transplant and a risk factor for mortality. This relationship remains statistically significant after accounting for baseline allograft function, presence of SGF and serum mineral levels abnormalities.

Mental Effects of Excess Parathyroid Hormone in Hemodialysis Patients: A Possible Role for Parathyroid 2 Hormone Receptor?

Depression as measured by the kidney disease quality of life (KDQOL) form is known to be an independent risk factor for mortality dialysis patients. Excess parathyroid hormone (PTH) has long been associated with neuropsychiatric disturbances. Those psychiatric complications are currently attributed to hypercalcemia with very little evidence; however, with the discovery of the parathyroid hormone 2 receptor (PTH2R) in the brain which can be activated by PTH, PTH2R might indicate a direct effect of PTH. As secondary and tertiary hyperparathyroidism is common in dialysis patients where the serum calcium is low or normal, we chose to investigate a possible relationship between PTH levels and depression in dialysis patients. This was a matched pair observational study with 10 patients with intact PTH values above 1000 pg/mL who were matched with 10 patients who had PTH values less than 400 pg/mL for the presence of diabetes, years on dialysis, duration of dialysis time, Kt/V, hemoglobin, and 25 OH vitamin D levels, as well as intravenous iron and erythropoietin administration. The Kidney Disease Quality of Life questionnaire (KDQOL-36) scores and patient Health Questionnaire scores were analyzed during that time. All variables underwent tests for normality and matched pair t-test. All subscales of the KDQOL-36 were worse in the high PTH group with the effect on daily life reaching P = 0.01 and the burden of disease and symptoms both reaching P = 0.02. PTH and PTH2R may be appropriate targets for investigations to improve the quality of life in hemodialysis patients.

Association of low serum parathyroid hormone with protein-energy wasting in maintenance hemodialysis patients

Objective: To examine the relationship between low serum parathyroid hormone (PTH) and protein-energy wasting (PEW) in patients who underwent maintenance hemodialysis (MHD) treatment. Methods: A cross-sectional study was conducted in MHD patients between June 2015 and August 2017 in 11 MHD centers from Guizhou province. Body composition and physical parameters were measured, clinical data and other related laboratory values were collected according to the medical record system. Participants were assigned to low serum PTH group (PTH<150 ng/L), target PTH group (150 ng/L≤ PTH ≤300 ng/L) and high serum PTH group (PTH>300 ng/L). Multivariate logistic regression analysis was used to analyze the relationship between low serum PTH and risk of PEW, which was diagnosed according to the diagnostic criteria recommened by the International Society of Renal Nutrition and Metabolism (ISRNM). Results: A total of 873 MHD patients (488 males and 385 females) were included in the final analysis, with a mean age of 55.0 (44.0, 67.0) years and a mean hemodialysis duration of 31.0(17.0, 54.0) months. In unadjusted model, low serum PTH group was associated with PEW (OR=2.12, 95% CI: 1.26-3.54, P=0.004), when compared with high serum PTH group. After adjustment for age and sex, low serum PTH group was still significantly associated with PEW (OR=2.09, 95% CI: 1.23-3.52, P=0.006). Further adjustment for diabetes and hypertension, the correlation between low serum PTH group and PEW was still significant (OR=2.02, 95% CI: 1.04-3.90, P=0.037). However, the correlation was not observed in target PTH group and high serum PTH group. Conclusion: Low serum PTH was associated with risk of PEW, regardless of age, sex, history of diabetes and hypertension, and thus it might be a promising indicator of PEW in MHD patients.

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.

Osteocytic perilacunar/canalicular turnover in hemodialysis patients with high and low serum PTH levels.

Osteocytic perilacunar/canalicular turnover in hemodialysis patients has not yet been reported. Osteocyte lacunae in lamellar bone and woven bone were classified as eroded surface-, osteoid surface-, and quiescent surface-predominant osteocyte lacunae (ES-Lc, OS-Lc, QS-Lc, respectively) in 55 hemodialysis patients with either high- (n = 45) or low- (n = 10) parathyroid hormone levels, and 19 control subjects without chronic kidney disease. We calculated the area and number of ES-Lc, OS-Lc, and QS-Lc. The mineralized surface on the osteocyte lacunar walls was measured in each group, and compared among the three groups. The shapes of the osteocyte lacunar walls were validated by backscattered electron microscopy. While the number of ES-Lc per bone area (N.ES-Lc/B.Ar) was higher than the number of OS-Lc per bone area (N.OS-Lc/B.Ar) in all groups, N.ES-Lc/B.Ar and N.OS-Lc/B.Ar were greater in high-parathyroid hormone group than in low-parathyroid hormone and control groups. The total volume of ES-Lc per bone area (ES-Lc.Ar/B.Ar) was greater than the total volume of OS-Lc per bone area (OS-Lc.Ar/B.Ar) in both parathyroid hormone groups. However, both lacunar erosion and lacunar formation increased proportionally, suggesting that global coupling between them was maintained. N.ES-Lc/B.Ar was higher in woven bone than in lamellar bone. The rate of OS-Lc stained by tetracycline hydrochloride, the mineralized lacunar surface and the mean area of OS-Lc with Tc obtained from both parathyroid hormone groups were greater than those in the control group. We conclude that osteocytic perilacunar/canalicular turnover is increased in hemodialysis patients with high parathyroid hormone levels. Osteocytic perilacunar/canalicular turnover depends, at least in part, on serum parathyroid hormone level. However, the ideal PTH level for osteocytic perilacunar/canalicular turnover could not be determined but osteocytic osteolysis was predominant in both the high- and low-PTH groups in this study. Thus, attention should be paid to bone loss from the viewpoint of osteocytic perilacunar/canalicular turnover in hemodialysis patients.

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.

The study on the inhibitive effects of recombinant parathyroid hormone (1-34) on osteolysis in a murine calvarial model induced by wear particles

Objective: To investigate the effect of different doses of recombinant parathyroid hormone (PTH) (1-34) on osteolysis in a murine calvarial model. Methods: In total, 48 adult male C57BL/J6 mice were randomly divided into four groups: the sham group, the vehicle group, the low dose-, and high dose PTH group (n=12 each group). Mice in the PTH groups were treated with local injection of recombinant PTH at 30 or 60 μg·kg-1·d-1, intermittent injection 3 times per week for two weeks. Mice in the sham and vehicle groups received local injection of saline daily. Two weeks after surgery, calvarial tissue and peripheral blood were harvested for further analysis. Osteolysis was assessed by micro-computed tomography. The mRNA and protein expression of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB Ligand (RANKL) of calvarial tissue and peripheral blood were tested by real-time PCR and ELISA, respectively. Results: Compared with the vehicle group, PTH treatment significantly inhibited the severity of osteolysis and improved the bone volume. Real time-PCR and ELISA showed that PTH significantly increased the mRNA and protein expression of OPG and reduced the RANKL/OPG ratio. Conclusion: These findings suggest that local application of PTH could effectively inhibit wear-particle-induced-osteolysis in a murine calvarial model.

Elevated Parathyroid Hormone is Associated with Left Ventricular Remodeling in Elderly Patients with Mild to Moderate Chronic Kidney Disease

Background Parathyroid hormone (PTH) plays an important role in bone metabolism. Aging and chronic kidney disease is recognized as an important factor associated with elevation in PTH. Although elevated PTH was associated with cardiovascular mortality, the association of PTH and left ventricular remodeling in elderly patients with mild to moderate kidney disease has not been elucidated. Methods and results238 patients over 65 years with CKD stage 2 or 3 were examined (101 male, 75 years). Subjects with LV dysfunction (LVEF < 50%), atrial fibrillation and advanced chronic kidney disease (eGFR < 15 ml/min/1.73 m2) were excluded. Patients were divided into two groups according to intact PTH level: below 65 pg/ml (normal PTH, n = 201) and above 65 pg/ml (high PTH, n = 37). High PTH groups had lower creatinine-based estimated GFR (57 ± 15 vs 63 ± 13 ml/min/1.73 m2, (ex.)P < .05) and higher cystatin C level (1.21 ± 0.44 vs 1.01 ± 0.30 mg/L, (ex.)P < .01). In echocardiography, high PTH group had lower e (5.3 ± 1.6 vs 5.9 ± 1.7 cm/sec, (ex.)P < .05), higher E/e (16.1 ± 21.9 vs 11.5 ± 3.6, (ex.)P < .01) and higher LVMI (119 ± 28 vs 107 ± 30g/m2, (ex.)P < .05). The intact PTH was significantly associated with LVMI, even after adjustment for confounding factors. Also, high PTH group had high prevalence of LVH in multivariable logistic regression analysis. Conclusion In elderly patients with mild to moderate CKD, higher level of parathyroid hormone is associated with left ventricular remodeling, which may cause cardiovascular event in these patients.

Low parathyroid hormone levels after parathyroidectomy reduce cardiovascular mortality in chronic hemodialysis patients.

The aim of the study is to elucidate whether parathyroid hormone (PTH) levels after parathyroidectomy affect the prognosis of patients with secondary hyperparathyroidism. Two hundred and ninety-five patients, who underwent PTx without autotransplantation from July 1998 to December 2011, were divided into the low (n=148) and high (n=147) PTH groups, using the median value of each mean value of intact PTH after surgery (16.6pg/mL). After observation for 5.00years, we evaluated demographic factors, influences of postoperative mineral metabolism, magnitude of uremia, and vitamin D receptor activators on their prognosis, with the multivariate Cox proportional hazard model. While overall survival rates in the high and low PTH groups were 54.9 and 74.2%, respectively (P=0.1500), cardiovascular survival rates were 71.6 and 94.4%, respectively (P=0.0256). The hazard ratio for cardiovascular mortality in the high PTH group (≥16.6pg/mL) was 3.132 (P=0.0470), and those in groups with the median age more than 59years and with cardiovascular disease were 2.654 (P=0.0589) and 3.377 (P=0.0317), respectively. The intact PTH level 6days after surgery and the mean postoperative intact PTH value showed a strong correlation (Spearman ρ=0.9007, P<0.0001, y=0.4725x+30.395, R 2=0.51798). The present study suggests that maintaining low PTH levels after parathyroidectomy reduces cardiovascular mortality and improves the prognosis. Total parathyroidectomy (more than 4 glands) without autotransplantation seems to be one of the treatment options for managing severe secondary hyperparathyroidism.

Anti-sclerostin antibody treatment in a rat model of progressive renal osteodystrophy.

Chronic kidney disease (CKD) is associated with abnormalities in bone quantity and quality, leading to increased fractures. Recent studies suggest abnormalities of Wnt signaling in animal models of CKD and elevated sclerostin levels in patients with CKD. The goal of this study was to evaluate the effectiveness of anti-sclerostin antibody treatment in an animal model of progressive CKD with low and high parathyroid hormone (PTH) levels. Cy/+ male rats (CKD) were treated without or with calcium in the drinking water at 25 weeks of age to stratify the animals into high PTH and low PTH groups, respectively, by 30 weeks. Animals were then treated with anti-sclerostin antibody at 100 mg/kg i.v. weekly for 5 doses, a single 20-µg/kg subcutaneous dose of zoledronic acid, or no treatment, and were then euthanized at 35 weeks. As a positive control, the efficacy of anti-sclerostin antibody treatment was also evaluated in normal littermates. The results demonstrated that the CKD animals with high PTH had lower calcium, higher phosphorus, and lower FGF23 compared to the CKD animals with low PTH. Treatment with anti-sclerostin antibody had no effect on any of the biochemistries, whereas zoledronic acid lowered dkk-1 levels. The anti-sclerostin antibody increased trabecular bone volume/total volume (BV/TV) and trabecular mineralization surface in animals with low PTH, but not in animals with high PTH. Neither anti-sclerostin antibody nor zoledronic acid improved biomechanical properties in the animals. Cortical porosity was severe in high-PTH animals and was unaffected by either treatment. In contrast, in normal animals treated with anti-sclerostin antibody, there was an improvement in bone volume, cortical geometry, and biomechanical properties. In summary, this is the first study to test the efficacy of anti-sclerostin antibody treatment on animals with advanced CKD. We found efficacy in improving bone properties only when the PTH levels were low.

High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

The elevated serum Monocyte Chemoattractant Protein‐1 (MCP‐1) in obesity is influenced by parathyroid hormone (PTH) and not body mass index (BMI)

Monocyte chemoattractant protein‐1 is an inflammatory cytokine that is produced predominantly by macrophages, endothelial cells and is expressed in adipose tissue, and also by the mature osteoblast. PTH administration increases gene expression and serum MCP‐1 in rodents, yet both MCP‐1 and PTH are elevated in obesity. The goal in this study was to determine whether the higher MCP‐1 in obesity is influenced by PTH. We recruited 84 women aged 51 ± 10 years, who were either normal‐weight (NL‐wt, n = 38, BMI = 22 ± 2 kg/m2) or obese (Ob, n = 46, BMI = 44 ± 7 kg/m2) and further separated them into 2 categories based on median of PTH. BMI, fat mass, lean mass and calcium intake did not differ in the two PTH groups in NL‐wt and Ob women. PTH was inversely associated with serum 25 hydroxy vitamin D levels in the entire population (r = −0.31, p&lt;0.01). Ob and NL‐wt women in the high PTH groups had higher MCP‐1 (p&lt;0.05) and no difference in control adipokines [C‐reactive protein (CRP) and adiponectin]. As expected, CRP was higher and adiponectin was lower (p&lt;0.05) in Ob than NL‐wt women, whereas MCP‐1 did not differ due to weight category. We found that the positive association between MCP‐1 and BMI was only present when PTH was &lt;40 pg/mL (normal = 10–55 pg/mL). Together, these data suggest that when serum PTH is in the high‐normal range, it has a greater influence on MCP‐1 than BMI, as observed in both NL‐wt and Ob women.Grant Funding Source: CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCES (CCTS)‐ UMDNJ

The whole-PTH/intact-PTH ratio is a useful predictor of severity of secondary hyperparathyroidism.

Background. The newer parathyroid hormone (PTH) assay, whole-PTH, uses an antibody that binds the region harbouring the first amino acid, making it specific for the complete molecule, 1–84-PTH. Especially among dialysis patients, it has been reported that the level of whole-PTH can be calculated as ∼60% of their intact-PTH value. In addition, since 1–84-PTH is part of intact-PTH, the whole-PTH/intact-PTH ratio should not theoretically exceed 1. However, an abnormally high 1–84-PTH/intact-PTH ratio is reported in a few patients with parathyroid carcinoma, primary hyperparathyroidism and secondary hyperparathyroidism. In this study, we examined the correlation between the 1–84-PTH/intact-PTH ratio and the severity of hyperparathyroidism in patients on haemodialysis (HD).Patients and methods. The study population comprised 196 HD patients (males 113, females 83, age 67.4 ± 13.6 years, HD period 8.1 ± 7.3 years; mean ± SD). The whole-PTH/intact-PTH ratio was compared in patients with high PTH levels (intact-PTH ≥300 pg/ ml; high PTH group, n = 32), moderate PTH levels (intact-PTH >150–<300 pg/ml; moderate PTH group, n = 50) and low PTH levels (intact-PTH <150 pg/ml; low PTH group, n = 114). The ratio was also compared in 25 patients with at least one enlarged gland >0.5 cm3 suggesting nodular hyperplasia, as determined by power Doppler ultrasonography (hyperplasia group) with seven patients without enlarged gland (non-hyperplasia group) and six patients who had undergone total parathyroidectomy (post-PTx group).Results. The whole-PTH/intact-PTH ratio of the high PTH group (0.68 ± 0.1) was significantly higher than those of the moderate (0.61 ± 0.1, P < 0.001) and low (0.52 ± 0.1, P < 0.001) groups. Moreover, the ratio was significantly higher in the hyperplasia group (0.70 ± 0.1) than those in the non-hyperplasia group (0.59 ± 0.1, P < 0.05) and post-PTx group (0.456 ± 0.12, P < 0.001).Conclusions. The whole-PTH/intact-PTH ratio correlated with the severity of hyperparathyroidism. Our results suggest that the ratio might be a useful predictor of severity of secondary hyperparathyroidism in HD patients.