Reduced PTH Levels Research Articles

Effect of cholecalciferol supplementation on PTH and increasing the glomerular filtration rate in kidney transplant patients at King Faisal Specialist Hospital and Research Center

The association between oral cholecalciferol and GFR has been identified in various renal transplant populations around the globe. This study aimed to evaluate the effect of oral cholecalciferol supplementation on the GFR and serum PTH levels, with other parameters in the Saudi kidney transplant population. A retrospective observational study was conducted on a cohort of 174 kidney recipients who underwent transplantation and had serum 25-Hydroxy VD level tests performed (2018-2022) at King Faisal Specialist Hospital and Research Center in Jeddah, KSA. Generalized and linear mixed effects regression models were conducted. The percentage of GFR >60 (25.86% vs 78.16%, P<.0001) and VD insufficiency (< 30 ng/mL) (36.21% vs 6.90%, P<.0001) were significantly different between pre-& post-transplant periods, respectively. After adjustment, significant changes were found in post-transplant GFR, hemoglobin levels, serum creatinine levels, blood urea nitrogen levels, hematocrit levels, PTH levels, and VD 25-Hydroxy from the baseline. Calciferol 1000/2000 IU and 50,000 IU (P<.0001) were significantly more effective in increasing the odds of having GFR >60 as compared to other supplements (P=0.75). VD supplementations may be particularly beneficial in improving kidney function in kidney transplant patients, as this contributes to normalizing GFR levels and creatinine levels and reducing PTH levels.

Rationale and Protocol of the ETERNITY-ITA Study: Use of Etelcalcetide for Preserving Vitamin K-Dependent Protein Activity—An Italian Study

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively.

Dependent and independent causes of hypercalcemia

Previous clinical studies show that the condition is significantly associated with mortality and increased cardiovascular morbidities. Accordingly, it is essential to conduct adequate diagnosis and evaluation to assess these cases properly. Studies show that different etiologies have been associated with hypercalcemia development with variable prevalence rates among different populations. Reduced PTH levels among patients with hypercalcemia indicate the presence of a non-PTH-dependant etiology for hypercalcemia. We have discussed various causes of hypercalcemia, including dependant and non-dependant causes. We found that malignancy-induced hypercalcemia is the commonest non-PTH-dependant etiology of hypercalcemia. Many malignancies were reported in the literature to attribute to the development of hypercalcemia. Vitamin D-mediated hypercalcemia was also reported as another common etiology for the condition. It might occur secondary to overdosing, immobilization, endocrine disorders, and granulomatous diseases. Other familial and congenital causes were also reported in the literature and discussed.

Safety and Efficacy of a 3-Year Therapy With Cinacalcet in Persistent Hyperparathyroidism After Renal Transplant

BackgroundPersistent post-transplant hyperparathyroidism (PPTHP) can occur in 20% to 50% of renal transplant recipients. The aim of this study was to analyze safety and efficacy of long-term cinacalcet therapy in a group of renal transplant recipients with PPTHP. MethodsA single center retrospective cohort study including renal transplant recipients, adults (>18 years old) with PPTHP and hypercalcemia. Inclusion criteria for cinacalcet therapy was increased parathormone levels (PTH > 65 pg/mL) associated with serum calcium >11.5 mg/dL any time after transplant or calcium >10.2 mg/dL within the first year after transplant. The follow-up period was 3 years. Demographic, laboratory data and adverse events were assessed. ResultsForty-six patients were included, mean age of 50 ± 11 years old, majority of white race (60%), male (58%), with a pretransplant length on dialysis of 67 ± 34 months. Cinacalcet therapy was started 37 ± 40 months after transplant, and normal calcium levels were achieved after 6 months of therapy. PTH levels presented a steady reduction over time, reaching levels near normal after 36 months (317 ± 242 vs 145 ± 72 pg/mL, baseline × month 36, P < .05). Renal function remained stable over time (GFR > 60 mL/min/1.73 m2) and no acute rejection episodes were observed. Most common adverse events were mild gastrointestinal symptoms. In 6 patients (12.5%) treatment was interrupted due to adverse events. Only 1 case (2%) was classified as treatment failure. ConclusionCinacalcet therapy proved to be efficient for PPTHP and safe for graft and patient. Long-term treatment reduced PTH levels to near normal range.

Potentielle application de l’axe fibroblast growth factor 23-Klotho dans la maladie rénale chronique

Membrane Alpha Klotho (α-klotho) is expressed in the kidney and functions as a co-receptor of FGF receptors (FGFRs) to activate specific fibroblast growth factor 23 (FGF23) signal pathway. FGF23 is produced in bones and participates in mineral homeostasis. The extracellular domain of transmembrane αklotho can be cleaved by proteases and released into the circulation as soluble α-klotho. Klotho deficiency is a pathogenic factor for chronic kidney disease progression and cardiovascular diseases. The FGF23 excess may also contribute to cardiovascular diseases where its pathogenic effect acts via the FGFR4 and independently of α-klotho. The decline in serum α-klotho followed by a rise in serum FGF23 at an early stage of chronic kidney disease can serve as a robust predictor for risk of cardiovascular diseases and mortality in both CKD patients and the general population. The first randomized trials suggest the possibility to reduce FGF23 excess in chronic kidney disease by controlling the phosphate serum using phosphate binders and reducing PTH levels with calcimimetic drug. New strategies emerge, including the administration of α-klotho recombinant and the use of epidrugs in order to correct the klotho deficiency. The FGR4 inhibitors are promising to limit the development of left ventricular hypertrophy linked to FGF23 excess. Finally, a better understanding of the molecular mechanisms of FGF23/α-klotho axis will allow us to find new strategic approaches and improve the CKD patient's management and their outcomes.

MON-534 Reduced PTH Levels in Adolescents with Anorexia Nervosa: Implication for Kidney and Bone

Background: Patients with anorexia nervosa (AN) experience bone as well as kidney complications including low bone mineral density (BMD), increased fracture rate, kidney stones, hypercalciuria and chronic renal failure. However, the mechanisms of those complications are not fully understood (1). The aim of this study is to investigate the interrelationship of central measures of calcium vitamin D metabolism and bone and kidney health in adolescents with newly diagnosed AN. Methods: This is a cross-sectional study that included newly diagnosed adolescents with AN referred to the Eating Disorder Program (EDP) at the Hospital for Sick Children over a two-year period. In addition to demographic and auxiological data, information on vitamin D and calcium intake was obtained. BMD and blood and urine samples for central measures of calcium vitamin D metabolism were investigated. In addition to descriptive statistics, multiple linear regression was performed to examine the association between PTH and various predictors. Results: A total of 61 patients (55 female, 6 male, mean age 15.2 ± 1.56 years) were included. Overall levels of serum calcium, phosphate, magnesium and 25-hydroxyvitamin D (25OHD) were normal and urinary calcium to creatinine ratio was increased (0.87 ± 0.47mmol/mmol, normal<0.7). However, a novel observation was made regarding low PTH levels in 35% of this cohort (<22ng/L, normal 22-88ng/l (2)). Low PTH levels did not appear to be a result of partial or complete hypoparathyroidism (normal calcium and phosphate levels), oral calcium intake (no significant correlation, p= 0.59) or magnesium deficiency (normal magnesium levels). As previously described, a significant negative correlation between PTH and 25OHD levels below 100 nmol/L was noted (p=0.007). However, 25OHD levels in the range of 100-200 nmol/L, did not contribute to the lower PTH levels (p= 0.39). Mean lumbar spine (L2-4) BMD Z-score was -0.69 ± 1.14. Conclusion: This study indicates reduced PTH levels in 1/3 of adolescents with AN at presentation to a tertiary care EDP. As in previous studies (1), this data suggests that the reduction in PTH may be due to a subtle increase in ionized serum calcium resulting from reduced bone formation and reduced mineralization with ongoing bone resorption. Reduced PTH levels in these patients may contribute to both the renal and bone complications in AN.

Treatment of secondary hyperparathyroidism: How do cinacalcet and etelcalcetide differ?

Secondary hyperparathyroidism (SHPT), commonly encountered in patients receiving maintenance dialysis, is associated with numerous adverse outcomes, including mortality. Calcimimetics, agents that act on the calcium sensing receptor (CaSR), were designed to overcome limitations in the use of vitamin D sterols to treat SHPT, and have demonstrated efficacy in reducing levels of PTH in randomized trials. Currently available calcimimetics include oral cinacalcet and the recently approved intravenously administered agent, etelcalcetide. While cinacalcet is an allosteric modulator of the CaSR, etelcalcetide acts as a direct CaSR agonist. Etelcalcetide's properties allow it to be administered intravenously thrice weekly at the end of a hemodialysis treatment session. Etelcalcetide has recently been shown to be more potent than cinacalcet in reducing PTH levels. However, etelcalcetide appears, like cinacalcet, to cause gastrointestinal intolerance. Additionally, etelcalcetide, which appears to reduce calcium substantially more than cinacalcet does, can prolong the QTc electrocardiographic interval. While etelcalcetide is very effective at reducing PTH levels, the current climate of dialysis cost containment in the United States may limit its widespread use. This review compares and contrasts the pharmacologic characteristics of cinacalcet and etelcalcetide, discusses the results of clinical trials involving these drugs, and posits implications for their use for clinical practice.

Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health.Four-week-old male Hyp mice received R568 in different doses, 1,25D or vehicle for 28days. Vehicle-treated wild-type mice served as controls. Both R568 and 1,25D reduced PTH levels, yet only 1,25D raised serum phosphate levels in Hyp mice. 1,25D increased calciuria and further enhanced FGF23 synthesis in bone and circulating FGF23 levels. By contrast, R568 reduced bone FGF23 expression and serum total but not intact FGF23 concentrations. Renal 1,25D metabolism was further impaired by 1,25D and improved although not normalized by R568. Hyp mice showed reduced renal Klotho levels, which were increased by 1,25D and high dose R568. 1,25D, but not R568, significantly improved femur growth, and weight gain, and partially restored growth plate morphology and bone mineralization. Although a significant improvement of trabecular bone was noted by μCT, compared to 1,25D the effects of R568 on bone histomophometric parameters were marginal.Our data indicate that monotherapy with R568 reduced PTH and FGF23 synthesis in bone, but failed to restore vitamin D and phosphate metabolism and skeletal abnormalities in Hyp mice. By contrast, 1,25D improved body growth, and defective mineralization despite further enhancement of skeletal FGF23 synthesis thereby highlighting the importance of vitamin D in bone mineralization in Hyp mice.

A novel surgical strategy for secondary hyperparathyroidism: Purge parathyroidectomy

ObjectiveThis study was intended to demonstrate the feasibility and efficacy of purge parathyroidectomy (PPTX) for patients with secondary hyperparathyroidism (SHPT). MethodsThe “seed, environment, and soil” medical hypothesis was first raised, following review of the literatures, to demonstrate the possible causes of persistence or recurrence of SHPT after parathyroidectomy. Subsequently, the novel surgical strategy of PPTX was proposed, which involves comprehensive resection of the fibro-fatty tissues, including visible or invisible parathyroid, within the region surrounded by the thyroid cartilage, bilateral carotid artery sheath, and the brachiocephalic artery. The perioperative information and clinical outcomes of patients who underwent PPTX from June 2016 to December 2016 were analyzed. ResultsIn total, PPTX was performed safely in nine patients with SHPT from June 2016 to December 2016. The operative time for PPTX ranged from 95 to 135 min, and blood loss ranged from 20 to 40 mL. No patients with perioperative death, bleeding, convulsions, or recurrent laryngeal nerve injury were reported. The preoperative concentration of PTH ranged from 1062 to 2879 pg/mL, and from 12.35 to 72.69 pg/mL on the first day after surgery. In total, 37 parathyroid glands were resected. The postoperative pathologic examination showed that supernumerary or ectopic parathyroid tissues were found within the “non-parathyroid” tissues in three patients. No cases encountered persistence or recurrence of SHPT, or severe hypocalcemia during the follow-up period. ConclusionPPTX involves comprehensive resection of supernumerary and ectopic parathyroid tissues, which may provide a more permanent means of reducing PTH levels.

Is there a role or target value for nutritional vitamin D in chronic kidney disease?

Vitamin D is important for bone health in the general population but the value of vitamin D supplementation, and the role of 25-hydroxyvitamin D independently of 1,25-dihydroxyvitmain D, in individuals with chronic kidney disease (CKD), particularly in those who require dialysis, remains uncertain. Supplementation may improve some biochemical parameters, such as reducing PTH levels in patients to CKD-stage 4 who have vitamin D deficiency; but it remains to be established whether the role of nutritional vitamin D in maintaining bone health in the general population can be extrapolated to the CKD population. There is currently insufficient evidence to recommend conclusively that nutritional vitamin D supplementation should be prescribed to individuals with CKD who have 25-hydroxyvitamin D deficiency, either for skeletal or non-skeletal health outcomes.

Double treatment with paricalcitol-associated calcifediol and cardiovascular risk biomarkers in haemodialysis.

The deficit of 25-hydroxyvitamin D (25OHD) associated with secondary hyperparathyroidism (SHPT) is a frequent finding in chronic kidney disease (CKD) patients on haemodialysis (HD). These events are associated with increased morbidity and mortality rates of cardiovascular (CV) origin. Adequate 25OHD serum levels as well as the use of selective vitamin D receptor activators (VDRA) have been shown to have beneficial and independent effects on bone mineral metabolism and cardiovascular risk. Currently, there is still controversy regarding the type of supplementation needed by CKD patients on HD. The aim of our study was to evaluate whether there is a benefit of combination therapy with 25OHD, calcifediol and a VDRA, oral paricalcitol, on bone-mineral metabolism and inflammatory markers, compared to single treatment with each of these in a group of patients on HD. We performed a prospective study of 6 months, involving 26 patients in our HD unit. We randomised patients into two groups: group 1 (G1) received oral paricalcitol treatment at doses of 1 mcg/day. Group 2 (G2) was treated with 1 ampoule calcifediol/wk (0.266 mg/wk=16 000U) orally. After 3 months of treatment, calcifediol and paricalcitol were added to the G1 and G2 respectively at the same doses, keeping these treatments together for 3 months to complete the 6 months of follow-up. Laboratory tests were performed at months 0, 3 and 6, measuring in all patients serum markers of 25OHD, calcium (Ca), phosphorus (P) and PTH. Bone turnover markers measured were: alkaline phosphatase (AP), aminoterminal propeptide of procollagen type 1 (Pinp1) and carboxyl-terminal telopeptide of type I collagen (CrossLaps), and inflammatory markers: IL-8. We also collected data on levels of insulin, glucose, haemoglobin, erythropoiesis-stimulating agents (ESAs) and rates of resistance to EPO and HOMA (homeostasis model assessment). We detected a deficit of 25-hydroxyvitamin D in all patients studied, with a mean of 13.67 ± 4.81 ng/ml. Supplementation with oral calcifediol significantly corrects this deficit without evidence of toxicity (35.36 ± 33.68 ng/ml in G1 at 6 months and 59.21 ± 26.50 ng/ml in G2 at 3 months). Paricalcitol treatment significantly reduces PTH levels in G1 at 3 months (P<.039). We also noted a decrease in bone marker Pinp1 with paricalcitol, pointing to a possible direct effect on bone cells (P<.001). Both treatment with paricalcitol and with calcifediol produced a significant decrease in levels of IL-8 (P<.001), a known inflammatory marker, drawing attention to a trend towards better response to erythropoiesis-stimulating agents (ESAs), possibly related to the decrease in inflammation. The HOMA index did not change significantly. Based on our results, we cannot conclude that the association of calcifediol and paricalcitol produces advantages over the effect of each drug separately. In addition, Paricalcitol by itself appears to have a direct effect on cellular bone remodelling.

Effects of Paricalcitol in Calcium-Phosphorus Metabolism, Renal Function and Proteinuria in Kidney Transplantation

Introduction: Paricalcitol, a selective activator of the vitamin D receptor, is a viable alternative to treat secondary hyperparathyroidism in transplantation. In addition, studies have shown that combined treatment with paricalcitol and ACEI / ARA II improves proteinuria in patients with chronic renal disease, peritoneal dialysis and hemodialysis, but there are no studies in renal transplant population. Objectives: To study the effects of paricalcitol in the calcium-phosphorus metabolism, renal function and proteinuria in a renal transplant population. Materials: Retrospective cohort study. We evaluated medical records of 66 outpatient renal transplant recipients with a median time post transplantation of 88.4 months P25-75 (36.6 to 160.9). They were treated with paricalcitol (1mcg / 3 times per week) for a minimum period of 3 months. The following variables were analyzed before and after initiation of treatment: MDRD estimated glomerular filtration rate, Proteinuria (g/24hrs), Protein/creatinine ratio, serum creatinine, calcium, phosphorus, PTH and 25-OH-Vitamin D. Results: The mean values of calcium, phosphorus, vitamin D, creatinine, PTH and Protein/creatinine ratio before and after treatment with paricalcitol are described in the attached table. Paricalcitol treatment was able to reduce PTH without increasing serum calcium. There was no beneficial effect on proteinuria. 17 patients (25.75%) were not able to reduce PTH levels. This effect was observed in patients with higher baseline calcium levels and lower baseline PTH levels. Only 7 patients developed hypercalcemia.[Table 1]Conclusions: In our study, Paricalcitol reduced PTH levels during the monitoring period but there was no beneficial effect on proteinuria.

Update on the use of cinacalcet in the management of primary hyperparathyroidism.

Cinacalcet is an allosteric modulator of the calcium sensing receptor acting to sensitize this receptor to the extracellular calcium. Cinacalcet has been shown to be effective in reducing or normalizing serum calcium levels in several groups of patients with primary hyperparathyroidism (PHPT), including patients with mild to moderate PHPT, intractable PHPT, and parathyroid carcinoma, and in PHPT as a part of multiple endocrine neoplasia type 1. Cinacalcet slightly reduces PTH levels and has no effects on bone mineral density. Cinacalcet at low doses is well tolerated, but side effects are more frequent and severe when relatively high doses are needed to control hypercalcemia. Cinacalcet may be of benefit in a wide spectrum of PHPT severity, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. To what extent the reduction of serum calcium particularly in patients with mild to moderate hypercalcemia, translates into a clinical benefit is currently unknown. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT. Finally, more data are needed on the long-term safety of cinacalcet, particularly at the renal level.

Moderate Strontium Loading Induces Rickets in Rats with Mild Chronic Renal Failure

Background/Aims: Renal osteodystrophy and eventually osteoporosis are serious long-term complications in children with end-stage renal disease before and after renal transplantation. Strontium (Sr) salts are used for treatment of osteoporosis in adults. Methods: To evaluate the time-dependent effects of Sr on growth plate morphology and their reversibility, chronic renal failure (CRF) rats received either normal or Sr-loaded drinking water (2 g/l; ±200 mg/kg/day) for periods of 2, 6 and 12 weeks with or without subsequent washout periods of 0, 2, 4 or 8 weeks. Results: While weight gain was not affected by Sr loading, a significant enlargement of the entire growth plate, mainly due to expansion of the hypertrophic zone, was already present after 2 weeks. Sr-loaded animals showed increased osteoid areas and reduced bone formation rates at 2, 6 and 12 weeks compared to controls. This was accompanied by reduced PTH levels and increased serum bone alkaline phosphatase activity. After the washout periods these effects were reversed. In general, the height of the hypertrophic zone was positively correlated with osteoid area and negatively correlated with bone formation rate. Conclusion: Moderate Sr loading in CRF rats results in rapid development of rickets, which is reversible after washout.

Effectiveness of treatment with oral paricalcitol in patients with pre-dialysis chronic kidney disease.

Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease. Treatment with paricalcitol, a selective vitamin D receptor (VDR) activator, has shown benefits in these patients by adequately reducing PTH levels with minimal changes in serum calcium and phosphorus. The aim of this study was to assess the effectiveness and safety of paricalcitol in chronic renal disease patients (CKD grades 3 and 4). A study of our experience with paricalcitol was conducted in normal clinical practice in patients over 18 years diagnosed with grade 3 or 4 chronic kidney disease. Patients were periodically evaluated every 3 months. The primary endpoint of effectiveness was to obtain two consecutive decreases of ≥30% in iPTH with respect to baseline values. The secondary endpoints were fulfilment of the objectives in accordance with the Spanish Society of Nephrology (SEN) and Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines, as well as the relationship between the effectiveness of the treatment and different patient variables. Safety was studied by means of hypercalcaemia events. The primary study endpoint was achieved in 54.3% of patients. In addition, another 16.3% of patients had reduced iPTH by more than 30% at the 3rd visit. Therefore, 70.6% of patients reduced their iPTH levels by more than 30% in 6 months. The relationship between treatment success and both glomerular filtration rate and body mass index was significant. There were few adverse events, although hypercalcaemia was found in 5.4% of patients. Treatment with paricalcitol is effective in controlling secondary hyperparathyroidism in non-dialysed patients with a wide safety margin.

P‐109: Subclinical hyperparathyroidism, an age dependent phenomena, is an antecedent of both osteoporosis and dementia

Parathyroid glands cause bones to release calcium, over time this weakens bone density and leads to osteoporosis (OP). Hyperparathyroidism is blood level of PTH above 70 pg/ml. Kidney disease studies suggest that PTH levels should be kept around 35 pg/ml and vitamin D and calcium have been shown to lower PTH. Age-induced enhanced PTH plasma levels are associated with prolonged P300 latency and cognition decline. P300 latency is a better predictor of preclinical dementia than memory or mental status tests. We determined if PTH levels correlate to brain speed and/or bone density. In this study, patients (n=92, age-matched, age 12–90 years, mean=58.85, SD=15.47) had PTH levels tested compared to brain speed (P300). The study groups were: PTH levels <30 (n=30, mean = 22.7±5.6 SD) and PTH levels >30 (n=62, mean = 62.4±28.3 SD, p≤.02). Groups were compared for age, bone density and P300 latency. One-tailed tests were used to ascertain the statistical significance of the correlations. Patients with PTH levels <30 showed statistically significantly less P300 latency (P300= 332.7 ± 4.8 SE) relative to those with high PTH levels >30, which demonstrated greater P300 latency (P300=345.7 ± 3.6 SE, p=.02). Participants with PTH values <30 (n=26) were found to have statistically significantly higher bone density (M=-1.25 ± .31 SE) than those with PTH values >30 (n= 48, M= -1.85 ± .19 SE, p=.04). In order to test the hypothesis of reduced PTH levels following a pulsed administration of PTH, like calcium and vitamin D, we found a significant difference between pre and post injection PTH levels, Pre-PTH injection n=12, M=43.67, SD = 25.35, post-PTH injection n=12, M=23.30, SD=20.31, P<. 01). Our findings of a statistically lower bone density and prolonged P300 in patients with high PTH levels may suggest that PTH levels coupled with delayed P300 latency may become putative biological markers of not only dementia but OP. Additionally, PTH injection may be a useful treatment in lowering PTH levels. This study provides the first potential indirect evidence that may highlight the importance of brain processing speed as an OP early electrophysiological marker, which warrants intensive investigation.

Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis

This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.

A calcium homeostasis model: orchestration of fast acting PTH and calcitonin with slow calcitriol

Calcitriol is in plasma bound to transcalciferin and this results in a long calcitriol half-life in plasma (5–12 h). Abundance of bound calcitriol molecules prevents the exact and quick control of its effects and makes it an inert regulator with a time lag between the changes of calcitriol synthesis and its effect on peripheral tissues. The added regulatory inertia is here defined as: calcitriol bound/calcitriol free and it approaches value of 99. Estrogens increase transcalciferin levels. It is possible that the estrogen-induced increase in the total calcitriol plasma pool makes calcitriol effects even more inert, augmenting and prolonging the calcitriol effects and thus improving calcium balance in women. Since calcitriol synthesis in kidneys depends on the PTH level, it can be assumed that the size of the total calcitriol pool in plasma reflects more the average PTH secretion during previous hours, than the high or low peaks of PTH secretion in the same period. In other words, one or more PTH tides of short duration are followed with a late calcitriol tide that lasts for hours, and even longer lasting rise in calcitriol effects. Bone integrity depends also on the cortisol level. A possible speculation is that the main result of all profound bone effect of hypecortisolemia, might be reduction of the bone amino acids uptake, thus allowing redistribution of available proteins. Both PTH and calcitriol prevent dangerous hypocalcemia. PTH is quick in mobilizing bone calcium, while calcitriol tends to increase absorption of dietary calcium. In case of low or no dietary calcium, calcitriol mobilizes bone calcium and thus increase PTH initiated demineralization. In the case of calcium abundance, increased plasma calcium reduces PTH levels. Calcitriol plasma level (reflecting previous PTH surges) can induce both calcium absorption and bone demineralization. This two-blade action is tuned by calcitonin that reduces osteoclastic bone resorption, allowing bone deposition of abundant calcium. An overnight fast with a reduced absorption of dietary calcium, might decrease plasma calcium below the regulatory set point, inducing an increase in PTH secretion. Increased average nighttime PTH secretion induces more calcitriol to be synthesized in kidneys. The resultant late calcitriol morning and daytime tide would stimulate calcium absorption from gut, or from bone, depending on the availability of dietary calcium. Due to the described time lag in calcitriol effects, increased calcium absorption might continue during daytime, regardless of the plasma calcium level. If plasma calcium is above the set point, calcitonin will allow excess calcium to deposit in bones. A speculation based on this model is that it might be more efficient to avoid calcium rich food for dinner or supper, and to administer calcium supplementation in the morning, during the calcitriol tide.