Decreased Serum Parathyroid Hormone Research Articles

Cholecalciferol

The primary source of exposure to cholecalciferol in dogs and cats is ingestion of rodenticide baits with vitamin D3 as the active ingredient. Other sources of this toxin are human medications and rarely, contaminated pet food. Although the reported lethal dose 50% for cholecalciferol is 88mg/kg, deaths have been seen with an individual exposure of 2mcg/kg in dogs. Clinical signs are induced by profound hypercalcemia affecting multiple body systems. Clinical presentations may include anorexia, depression, muscle weakness, vomiting, polyuria, polydipsia, dehydration, abdominal pain, hematemesis, melena, and bradycardia. Tissue mineralization may develop if calcium × phosphorous product is greater than 60. Serum testing for hypercalcemia, hyperphosphatemia, and decreased serum parathyroid hormone are confirmatory. Initial treatment relies upon decontamination with emesis induction followed by administration of pulse-dose activated charcoal designed to interfere with the extensive enterohepatic recirculation of toxin. Medical management is designed to decrease serum calcium levels by use of intravenous fluid diuresis with administration of furosemide and prednisolone. Biphosphate pamidronate is used to inhibit calcium release from the bone. Phosphate binders aid in decreasing phosphate availability to interact with calcium. The prognosis is better if treatment is instituted early before development of hypercalcemia and hyperphosphatemia enables tissue mineralization to progress.

CaSR-mediated interactions between calcium and magnesium homeostasis in mice.

Calcium (Ca) and magnesium (Mg) homeostasis are interrelated and share common regulatory hormones, including parathyroid hormone (PTH) and vitamin D. However, the role of the calcium-sensing receptor (CaSR) in Mg homeostasis in vivo is not well understood. We sought to investigate the interactions between Mg and Ca homeostasis using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR) (double knockout, DKO). Serum Mg is lower in PTH KO and DKO mice than in WT mice on standard chow, whereas supplemental dietary Ca leads to equivalent Mg levels for all three genotypes. Mg loading increases serum Mg in all genotypes; however, the increase in serum Mg is most pronounced in the DKO mice. Serum Ca is increased with Mg loading in the PTH KO and DKO mice but not in the WT mice. Here, too, the hypercalcemia is much greater in the DKO mice. Serum and especially urinary phosphate are reduced during Mg loading, which is likely due to intestinal chelation of phosphate by Mg. Mg loading decreases serum PTH in WT mice and increases serum calcitonin in both WT and PTH KO mice but not DKO mice. Furthermore, Mg loading elevates serum 1,25-dihydroxyvitamin D in all genotypes, with greater effects in PTH KO and DKO mice, possibly due to reduced levels of serum phosphorus and FGF23. These hormonal responses to Mg loading and the CaSR's role in regulating renal function may help to explain changes in serum Mg and Ca found during Mg loading.

Early changes in 25-hydroxyvitamin D levelsand bone markers after monthly risedronatewith cholecalciferol in Korean patients with osteoporosis

PurposeThis study investigated the efficacy and safety of monthly risedronate, with and without cholecalciferol, on 25-hydroxyvitamin D (25[OH]D) levels and bone markers in Korean patients with osteoporosis.MethodsA randomized, double-blinded, prospective, 16-week clinical trial was conducted in ten hospitals. A total of 150 subjects with osteoporosis were randomized to one of the two treatment groups: RSDM+ (monthly risedronate 150 mg and cholecalciferol 30,000 IU combined in a single pill, n = 74) or RSDM (monthly risedronate 150 mg alone, n = 76). We measured serum levels of 25-hydroxyvitamin D (25[OH]D), parathyroid hormone (PTH), and bone markers, as well as performing muscle-function tests at baseline and after 16 weeks of treatment.ResultsAfter 16 weeks, serum 25(OH)D levels significantly increased from 17.8 to 26.8 ng/mL in the RSDM+ group, but did not change in the RSDM group. The RSDM+ group exhibited significantly decreased serum PTH from 46 to 36.7 pg/mL, while the RSDM group showed a tendency for PTH to increase from 38 to 40.6 pg/mL. In both groups, serum bone-specific alkaline phosphatase and C-terminal telopeptide rapidly declined, with significance at 16 weeks; there were no significant differences between the groups.ConclusionA once-monthly pill of risedronate and cholecalciferol provided equivalent antiresorptive efficacy to risedronate alone in terms of bone turnover and improved 25(OH)D levels over the 16-week treatment period without significant adverse events in Korean patients with osteoporosis.

Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes

BackgroundSuboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial. The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus (DM). MethodsIn a double-blind, placebo-controlled trial, we randomized 100 type 2 DM patients to vitamin D supplement (5000 IU/day, n = 50) or placebo (controls, n = 50) for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilatation (FMD), circulating levels of endothelial progenitor cells (EPCs) and brachial-ankle pulse wave velocity, and metabolic parameter, high-sensitivity C-reactive protein (hsCRP) and oxidative stress markers were performed before and after the supplementation. ResultsAfter 12 weeks, vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [25(OH)D] concentration (treatment effect 34.7 ng/mL, 95% CI 26.4–42.9, P < 0.001) and serum ionized calcium (treatment effect 0.037 mmol/L, 95% CI 0.007–0.067, P = 0.018); decreased serum parathyroid hormone concentration (treatment effect −0.55 pmol/L, 95% CI −1.08 to −0.02, P = 0.042) compared to patients who received placebo. Nevertheless, vitamin D supplementation did not improve vascular function as determined by FMD, circulating EPC count or baPWV (all P > 0.05). Furthermore, hsCRP, oxidative stress markers, low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups (all P > 0.05). ConclusionIn patients with type 2 DM, 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress. Clinical trial numberHKCTR-867, www.hkclinicaltrials.com.

Treatment of Calcium and Vitamin D Deficiency in HIV-Positive Men on Tenofovir-Containing Antiretrovial Therapy

Background: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate–containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. Objective: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. Methods: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. Results: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. Conclusion: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.

Secondary hyperparathyroidism in HIV‐infected patients: relationship with bone remodeling and response to vitamin D supplementation

Purpose of the studySecondary hyperparathyroidism (SH) is frequent in HIV‐infected patients. However, the causes and consequences are not well established. The aim of our study was to determine the relationship between parathyroid hormone (PTH), vitamin D and bone mineral density (BMD) in HIV‐infected patients, and the effect of vitamin D replacement on PTH levels.MethodsProspective study of 506 patients with at least two sequential serum determinations of PTH and 25‐hydroxyvitamin D levels. In all cases, a bone dual X‐ray absorptiometry (DEXA) was performed at inclusion. Hyperparathyroidism was defined as a PTH level above 65 pg/ml.Summary of resultsMean age was 44 yrs (24–78), and 75% were male. Mean BMI was 23.7 (17.97–33.11), and only 3% were of black race. Median nadir CD4+ was 200 cells/µL (9–499), and median time of HIV infection was 15.3 yrs (1.7–25.2). At inclusion, 488 patients (86%) were on HAART (31% TDF+PI, 44% TDF+NNRTI, 25% non‐TDF based regimen) for a median of 929.5 days (154–1969), and 40% were HCV‐coinfected. Median eGFR was 97.9 ml/min (62.14–134.08). Overall, mean serum PTH was 56.3 pg/mL (27.2–95.07). SH was observed in 27% of cases, with a marked influence of seasonality (from 44% in January to 10% in August). Mean levels of vitamin D were 17.45 ng/mL (7.6–40.78), with 16% below 10 ng/ml, 59%&lt;20 ng/ml (deficiency), 85%&lt;30 ng/ml (insufficiency). SH was related to vitamin D deficiency (relative risk, RR, 2.44), age (RR 1.04 per year), and a higher decrease in eGFR (RR 1.03 per ml/min), after adjustment by season, antiretroviral therapy, GFR at baseline, and HCV coinfection. DEXA scan showed 18% osteoporosis and 54% osteopenia, and there was an inverse correlation between PTH levels and T and Z score in femoral neck (r=−0.14, p&lt;0.01), higher in those patients below 40 yrs. Vitamin D supplementation in 181 patients produced a significant decrease in serum PTH (57.2 if not treated vs 50.5 pg/ml, p=0.02, 23% continues with SH) and the only factor associated with lack of response was persistent vitamin D deficiency.ConclusionSH is relatively frequent in HIV patients, in close relation with vitamin D deficiency. It is associated with bone resorption, especially in the femoral neck. The use of vitamin D supplementation improves SH when levels above 20 ng/ml are achieved.

The Short-Term Effects of Vitamin D Repletion on Cholesterol

Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile. One hundred fifty-one vitamin D-deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other nuclear magnetic resonance-based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [-80 to +116 nmol/L]; P=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [-1.4 to +13.0 mg/dL], P=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [-2.5 to +10.2 mg/dL], P=0.13); high-density lipoprotein cholesterol (+0.4 mg/dL 95% CI [-1.6 to +2.6 mg/dL], P=0.71); and triglycerides (+7.9 mg/dL 95% CI [-6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (P<0.001) and inversely with the changes in serum parathyroid hormone (P=0.02). In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01008384.

High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial

Vitamin D deficiency contributes to secondary hyperparathyroidism, which occurs early in chronic kidney disease (CKD). We aimed to determine whether high-dose cholecalciferol supplementation for 1 y in early CKD is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration ≥30 ng/mL) and decrease serum parathyroid hormone (PTH). A secondary aim was to determine the effect of cholecalciferol on blood pressure and serum fibroblast growth factor-23 (FGF23). This was a double-blind, randomized, placebo-controlled trial. Forty-six subjects with early CKD (stages 2-3) were supplemented with oral cholecalciferol (vitamin D group; 50,000 IU/wk for 12 wk followed by 50,000 IU every other week for 40 wk) or a matching placebo for 1 y. By 12 wk, serum 25(OH)D increased in the vitamin D group only [baseline (mean ± SD): 26.7 ± 6.8 to 42.8 ± 16.9 ng/mL; P < 0.05] and remained elevated at 1 y (group-by-time interaction: P < 0.001). PTH decreased from baseline only in the vitamin D group (baseline: 89.1 ± 49.3 to 70.1 ± 24.8 pg/mL; P = 0.01) at 12 wk, but values were not significantly different from baseline at 1 y (75.4 ± 29.5 pg/mL; P = 0.16; group-by-time interaction: P = 0.09). Group differences were more pronounced in participants with secondary hyperparathyroidism (group-by-time interaction: P = 0.004). Blood pressure and FGF23 did not change in either group. After 1 y, this oral cholecalciferol regimen was safe and sufficient to maintain serum 25(OH)D concentrations and prevent vitamin D insufficiency in early CKD. Furthermore, serum PTH improved after cholecalciferol treatment, particularly in patients who had secondary hyperparathyroidism.

Phosphate Binders in CKD

Hyperphosphatemia has long been considered an important contributor to the mineral and bone disorder associated with CKD (CKD-MBD).[1][1] Already 50 years ago, Slatopolsky et al. [2][2] showed that as GFR decreased, fractional phosphate excretion rose because of inhibition of tubular phosphate

Effects of Cinacalcet in Renal Transplant Patients with Hyperparathyroidism

Background: Cinacalcet decreases serum parathyroid hormone (PTH) and calcium concentrations in kidney transplant recipients with autonomous hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary calcium excretion and the risk of renal calcium deposits and may alter renal graft function. Methods: We studied 71 renal recipients with hypercalcemic hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3 and month 12 after renal transplantation. We compared phosphate calcium balance, measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet-treated and non-cinacalcet-treated patients. Measurements were performed before initiating cinacalcet treatment (month 3) and at month 12. Results: Patients treated with cinacalcet had more severe hyperparathyroidism. Serum PTH concentration decreased in both groups between months 3 and 12, but the decrease was much more important in cinacalcet-treated patients. Urinary calcium excretion significantly increased under cinacalcet treatment and was more than twice as high at month 12 as in patients who did not receive cinacalcet treatment. However, the hypercalciuria was not associated with an increase in calcium deposits on renal biopsies or an alteration of measured GFR. Conclusions: Despite sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet does not have adverse effects on GFR or on renal graft calcium deposits in the first year following renal transplantation.

Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

Background.Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT.Methods.We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT.Results.Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium.Conclusions.The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH.

Regulation of serum 1,25(OH)2 vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosphatemic disorders. FGF23 causes hypophosphatemia by decreasing the expression of sodium phosphate cotransporters (NaPi-2a and NaPi-2c) and decreasing serum 1,25(OH)(2)Vitamin D(3) levels. We previously showed that FGFR1 is the predominant receptor for the hypophosphatemic actions of FGF23 by decreasing renal NaPi-2a and 2c expression while the receptors regulating 1,25(OH)(2)Vitamin D(3) levels remained elusive. To determine the FGFRs regulating 1,25(OH)(2)Vitamin D(3) levels, we studied FGFR3(-/-)FGFR4(-/-) mice as these mice have shortened life span and are growth retarded similar to FGF23(-/-) and Klotho(-/-) mice. Baseline serum 1,25(OH)(2)Vitamin D(3) levels were elevated in the FGFR3(-/-)FGFR4(-/-) mice compared with wild-type mice (102.2 ± 14.8 vs. 266.0 ± 34.0 pmol/l; P = 0.001) as were the serum levels of FGF23. Administration of recombinant FGF23 had no effect on serum 1,25(OH)(2)Vitamin D(3) in the FGFR3(-/-)FGFR4(-/-) mice (173.4 ± 32.7 vs. 219.7 ± 56.5 pmol/l; vehicle vs. FGF23) while it reduced serum 1,25(OH)(2)Vitamin D(3) levels in wild-type mice. Administration of FGF23 to FGFR3(-/-)FGFR4(-/-) mice resulted in a decrease in serum parathyroid hormone (PTH) levels and an increase in serum phosphorus levels mediated by increased renal phosphate reabsorption. These data indicate that FGFR3 and 4 are the receptors that regulate serum 1,25(OH)(2)Vitamin D(3) levels in response to FGF23. In addition, when 1,25(OH)(2)Vitamin D(3) levels are not affected by FGF23, as in FGFR3(-/-)FGFR4(-/-) mice, a reduction in PTH can override the effects of FGF23 on renal phosphate transport.

Effect of Alfacalcidol on Anemia in Renal Failure Patients

Background: Anemia is a major feature of chronic kidney disease (CKD). Additionally, secondary hyperparathyroidism (SHPT) has been associated with anemia in uremic patients. Administration of active vitamin D metabolites like alfacalcidol is established for PTH suppression and may also play a role in hematopoiesis. Aim:To investigate the effect of alfacalcidol on anemia and SHPT with end stage renal failure patients underwent hemodialysis. Subjects and Methods: In the present study 17 anemic patients over 15years, with serum level of PTH greater than 500pg/ml. The study was carried out by means of data collection and analysis of serum parathyroid hormone (PTH) and hemoglobin (Hb) levels in these patients. Results: Low serum PTH levels were detected in uremic patients treated with alfacalcidol. Also, in these patients, Hb levels increased. Serum PTH and Hb levels were inversely correlated. Conclusions: High-dose alfacalcidol can decrease serum PTH levels and elevate Hb level in uremic patients showing considerable resistance to Epoetin.

Role of dehydroepiandrosterone in management of glucocorticoid-induced secondary osteoporosis in female rats

The current study aimed to evaluate the potential role of dehydroepiandrosterone (DHEA) in the protection and intervention of glucocorticoid-induced secondary osteoporosis in female rats. For this purpose this study was conducted on five groups of female Sprague Dawley rats which were classified into: (1) negative control group received saline as vehicle, (2) osteoporotic group orally administered with prednisolone (5 mg/kg b.wt.) daily for six months, (3) positive control group orally administered with DHEA (250 mg/kg b.wt.) three times weekly for six months, (4) protective group orally administered with prednisolone daily with simultaneous oral administration of DHEA three times weekly for six months and (5) therapeutic group orally administered with prednisolone daily for six months then orally administered with DHEA three times weekly for other six months. The obtained data revealed that prednisolone administration resulted in significant decrease in serum osteocalcin (OC), 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3)) and osteoprotegerin (OPG) levels accompanied with significant increase in serum parathyroid hormone (PTH) and receptor activator nuclear factor kappa B ligand (RANKL) levels. Histopathological investigation of left femur bone showed that prednisolone administration produced compression of the reduced articular surface and atrophy of the epiphyseal bone. On the other hand, DHEA supplementation to osteoporotic rats increased serum OC, 1,25-(OH)(2) D(3) and OPG levels while decreased serum PTH and RANKL levels. Moreover, DHEA administration resulted in restoration of intact epiphyseal bony structure and articular surface. In conclusion, DHEA via its control on glucocorticoid activity and androgenic action provided potent effect on bone.

Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease

Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with early chronic kidney disease (CKD) and are postulated to cause low blood levels of 1,25-dihydroxyvitamin D, as well as normal phosphate levels. In order to provide more direct evidence for the pathophysiological role of FGF23 in the settings of mineral ion homeostasis typically seen in early CKD, we studied rats with progressive CKD treated with anti-FGF23 neutralizing antibody. Without antibody treatment, rats with CKD exhibited high circulating levels of FGF23 and parathyroid hormone, low 1,25-dihydroxyvitamin D, and normal serum phosphate levels, accompanied by increased fractional excretion of phosphate. Antibody treatment, however, lessened fractional excretion of phosphate, thus increasing serum phosphate levels, and normalized serum 1,25-dihydroxyvitamin D by increased 1α-OHase and decreased 24-OHase expressions in the kidney. These antibody-induced changes were followed by increased serum calcium levels, leading to decreased serum parathyroid hormone. Hence, our study shows that FGF23 normalizes serum phosphate and decreases 1,25-dihydroxyvitamin D levels in early-stage CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by increased FGF23, followed by a reduction of 1,25-dihydroxyvitamin D and calcium levels, thereby increasing parathyroid hormone secretion.

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls. Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm(3) (group S) and 25 had at least one enlarged gland larger than 500 mm(3) (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia.

Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia

We describe a child with familial hypocalciuric hypercalcemia (FHH) in whom the hypercalcemia seemed to interfere with tissue healing after tympanoplasty. Consequently, he was placed on cinacalcet (30 mg/day), changed after 2 weeks to 60 mg/day. The treatment resulted in a decrease in serum parathyroid hormone (PTH) from 148 to 32 pg/mL (normal 7-75) and ionized calcium from 1.48 to 1.23 mmol/L (1.13-1.34), as well as successful healing of the revised surgical scar. Over the 12-month treatment period no complications were noted. We conclude that cinacalcet may be considered a new, and currently the only, tool in treating children with symptomatic FHH.

Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease

Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro.

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases

Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D(3). This study therefore aimed to assess the effect of this dose of vitamin D(3) in patients with bone metastases from breast cancer. Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D(3) and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity. Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption.

Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women

Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.