Hereditary Vitamin-D Dependent Rickets Type II: A Case Report

Hereditary vitamin D dependent rickets type II is a rare genetic disorder in children characterized by early onset of rickets and deranged biochemical parameters. Low serum calcium level, high alkaline phosphatase, high parathyroid hormone, and high values of 1,25-dihydroxy vitamin D are characteristic biochemical findings. We are reporting a rare case of Vitamin D Dependent Rickets and subsequent improvement after addition of cinacalcet. This is a case report of a 2.5-year-child with Hereditary Vitamin D Dependent Rickets type II receiving cinacalcet as adjunct to oral calcium and calcitriol. Oral cinacalcet (0.25mg/kg/day) was added to the regimen as an adjunct after treatment failure with high dose of oral calcium and calcitriol. A significant improvement in radiological findings and normal homeostasis of calcium, phosphate and parathyroid hormone was achieved after initiation of cinacalcet.

Effects of 25-Hydroxyvitamin D3 and Oral Calcium Bolus on Lactation Performance, Ca Homeostasis, and Health of Multiparous Dairy Cows

Little information is available regarding the effect of supplementing 25-hydroxyvitamin D3 during the transition period combined with a postpartum oral calcium bolus on Ca homeostasis. The objectives of the current study were to evaluate the effects of 25-hydroxyvitamin D3 combined with postpartum oral calcium bolus on lactation performance, serum minerals and vitamin D3 metabolites, blood biochemistry, and antioxidant and immune function in multiparous dairy cows. To evaluate the effects of 25-hydroxyvitamin D3 combined with oral calcium, 48 multiparous Holstein cows were randomly assigned to one of four treatments: (1) supplementing 240 mg/day vitamin D3 without a postpartum oral Ca bolus (control), (2) supplementing 240 mg/day vitamin D3 with an oral Ca bolus containing 90 g of Ca immediately post-calving (Ca + VitD), (3) supplementing 6 g/day 25-hydroxyvitamin D3 without an oral Ca bolus (25D), and (4) supplementing 6 g/day 25-hydroxyvitamin D3 with an oral Ca bolus containing 90 g of Ca immediately post-calving (Ca + 25D). Lactation performance during the first 21 days was measured. Blood was collected at the initiation of calving and then 1, 2, 7, 14, and 21 days relative to the calving date. The yield of milk (0.05 < p < 0.10), energy-corrected milk (p < 0.05), 3.5% fat-corrected milk (p < 0.05), and milk protein (p < 0.05) were significantly higher in 25-hydroxyvitamin D3-treated groups within 3 weeks of lactation than in vitamin D3-treated cows. The iCa (p < 0.05) and tCa (p < 0.05) were higher in both Ca and 25D + Ca cows than in the control and 25D groups within 48 h. The concentrations of serum tCa (p < 0.05), tP (p < 0.05), and 25-hydroxyvitamin D3 (p < 0.05) in 25D and 25D + Ca cows were higher than those in control and Ca cows within 21 days postpartum. Feeding 25-hydroxyvitamin D3 also showed a lower concentration of malondialdehyde (p < 0.05), interleukin 6 (p < 0.05), and tumor necrosis factor-alpha (TNF-α) (p < 0.05), as well as a higher concentration of alkaline phosphatase (p < 0.05), total antioxidant capacity (p < 0.05), and immunoglobulin G (p < 0.05) than vitamin D3. Supplementing Ca bolus also showed lower concentrations of alanine transaminase (p < 0.05) and TNF-α (p < 0.05). In conclusion, supplementing 25-hydroxyvitamin D3 during the transition period combined with a postpartum oral calcium bolus improved lactation performance, Ca homeostasis, and antioxidant and immune function of medium-production dairy cows within 21 days postpartum.

Effect of Oral Calcium Supplementation on Insulin Sensitivity in Patients With Metabolic Syndrome

Background: Evidence from epidemiological research suggests that dietary calcium may protect against metabolic abnormality in populations at high risk. Observational studies show the relationship between dietary calcium intake and metabolic syndrome. However evidence for beneficial effect of elemental calcium supplementation on metabolic syndrome is limited. Aims: Present studydetermined whether oral calcium supplementation reduced insulin resistance in patients with metabolic syndrome or not. Methods; Hundred patients who have metabolic syndrome without diabetes mellitus, parathyroid disease, chronic renal failure, pregnancy and lactationwere randomly allocated to the group receiving 1500 mg/ day of elemental calcium as calcium carbonate for 8 weeks and the control group. The primary outcome was change in insulin resistance as measured by homeostasis model assessment of insulin resistance (HOMA-IR). Other outcomes were changes of serum free ionized calcium (FiCa) level with accompanying serum parathyroid hormone (PTH) level. Fasting serum glucose was measured by glucose oxidase method. Serum insulin and PTH level were measured by enzyme linked immunoassay. Total serum ionized calcium was analyzed by Atomic Absorption Spectrophotometry. Serum FiCa(mg/dl) level was calculated by using following formula = [6Ca-(K/3)]/(K+6). Results: Mean age of participants was 47.38±13.2 years in calcium supplement group (n = 50) and 49.46±12.9 years in control group (n=50). Mean body mass index was not significant different between two groups (30.91 ±4.23 vs 30.37 ± 4.62 kg/m2). More female were involved in both group, 72% vs 62% respectively. Baseline biochemical parameters of the participants between two groups were not significantly different. After 8 week intervention period, mean serum FiCa increased significantly from 2.64±1.19 mg/dl to 5.82± 5.59 mg/dl, p&lt;0.0001, serum PTH decreased significantly from 57.88 ±17.05 pg/ml to 35.7±23.12 pg/ml, p&lt;0.0001, HOMA-IR decreased significantly from 5.14 ± 3.71 to 2.94±1.51, p&lt;0.0001. None of these parameters were significantly affected in control group. By comparing biochemical changes of calcium supplement group to control group, Mean (SEM) of paired difference changes were observed in serum FiCa level [3.18(0.81) vs 0.81(0.25)mg/dl, p&lt;0.05], serum PTH level [22.18(3.24) vs 3.58(1.99)pg/ml, p&lt;0.0001] and HOMA-IR [2.19(0.45) vs 0.43(0.21), p&lt;0.05]. It indicated that elemental calcium supplementation not only reduced insulin resistance but also decompensated the higher level of PTH to normal range by replenishing FiCa significantly. Conclusion: Eight-week oral elemental calcium supplementation of 1500mg/day showed beneficial effect on insulin sensitivity in patients with metabolic syndrome.

MO796IMPACT OF ACTIVE VITAMIN D AND CALCIUM PREPARATION ON VASCULAR CALCIFICATION MARKERS IN HEMODIALYSIS PATIENTS WITH HYPOCALCEMIA INDUCED BY CALCIMIMETICS

Background and Aims Recently, we demonstrated the efficacy of etelcalcetide for control of secondary hyperparathyroidism (SHPT) in the DUET trial; a 12-week multicenter, open-label, randomized (1:1:1), parallel-group study treated with etelcalcetide + active vitamin D (Group E+D), etelcalcetide + oral calcium preparation (Group E+Ca), or control groups (Group C) in 124 subjects undergoing maintenance hemodialysis. Moreover, we also showed that active vitamin D was useful in correcting hypocalcemia induced by calcimimetics, but the oral calcium preparation was superior for suppression of hyperphosphatemia. In this post hoc analysis, we evaluated vascular calcification markers, fibroblast growth factor 23 (FGF23) and calciprotein particles (CPPs), in patients using etelcalcetide (n = 77) extracted from the registrants of the DUET trial. Method Serum levels of FGF23 and CPPs were measured at baseline, 6 weeks and 12 weeks after start of the trial. Skewed data (FGF23 and CPPs) were transformed to natural logarithm to achieve normal distribution prior to statistical analysis. The changes in log CPPs and log FGF23 were estimated in a linear mixed model with each treatment group, time point, and interaction of the treatment group and time point as the fixed effects. We compared these changes between treatment the groups using a linear mixed model and also the Tukey-Kramer method to correct for multiplicity. Additionally, we exploratory examined the correlations among changes of FGF23, CPPs and other biomarkers related to bone mineral metabolisms, iPTH, Ca, P, and calcium-phosphate product, tested by Spearman’s rank correlation coefficient. Results The decreases at the 12-week time point after the trial start in log FGF23 were estimated -1.13 pg/mL in Group E+Ca and -0.10 pg/mL in Group E+D in a linear mixed model, respectively. Similarly, the decreases in CPPs were estimated -1.60 AU in Group E+Ca and -0.82 AU in Group E+D, respectively. Changes of both FGF23 (P = 0.017) and CPPs (P &lt; 0.001) in Group E+Ca significantly decreased compared with those in in Group E+D by Tukey-Kramer multiple-comparison test at 12 weeks after the trial start, while both changes in CPPs and FGF23 could not reach the significant differences between two groups at 6 weeks after the trial start (Figure 1). Reductions in FGF23 positively correlated with reductions in calcium (ρ = 0.42, P &lt; 0.01) and phosphate (ρ = 0.48, P &lt; 0.01) at 6 weeks after the trial start, and in calcium (ρ = 0.30, P &lt; 0.01) and phosphate (ρ =0.70, P &lt; 0.01) at 12 weeks after 6 weeks of the trial start), but there was no correlation with reductions in iPTH at any time point. Reductions in CPPs positively correlated with reductions only in phosphate at 6 weeks after the trial start (ρ = 0.47, P &lt; 0.01) and at 12 weeks after 6 weeks of the trial start (ρ = 0.54, P &lt; 0.01). Conclusion In this analysis, vascular calcification markers were significantly decreased in Group E+Ca compared to those in Group E+D. Further studies should be needed, our study suggests that oral calcium preparation may have an advantage against vascular calcification rather than active vitamin D for the correction of hypocalcemia induced by etelcalcetide in hemodialysis patients with SHPT.

Severe Hypocalcemia and Vitamin D Deficiency in Adolescence - A Case Series

Background: Hypocalcemia due to vitamin D (vit D) deficiency is uncommon among adolescents in the US. Only 3% to 6% of those ages 12- to 19-years-old have a vit D level &lt;12 ng/ml.1 We present three cases of severe hypocalcemia secondary to vit D deficiency in non-obese adolescents with restricted diets and limited sun exposure. Clinical Cases: A 14-year-old Ethiopian male with history of absence seizures presented with bloody stool. Incidentally, labs revealed: Ca 5.6 (8.4–10.2) mg/dL, iCal 0.71 (1.2–1.38) mmol/L, PTH 295.1 (10.0–65.0) pg/mL, 25(OH)D &lt;4 (20–100) ng/mL, Mg 1.9 (1.7–2.2) mg/dL, PO4 3.8 (2.5–4.5) mg/dL. He endorsed weight loss and knee pain, but denied paresthesias, tetany and seizures. He was a vegetarian and had minimal sun exposure. EKG and femur X-ray were unremarkable. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days three and four. He was discharged on day ten with iCal 0.84 on oral calcium carbonate and calcitriol. A 16-year-old male with history of autism, ADHD and bipolar disorder presented with a seizure. Labs revealed: Ca 5.7, iCal 0.62, PTH 372, 25(OH)D &lt;4, Mg 1.9, PO4 3.5. Exam showed tetany, carpopedal spasms and positive Trousseau and Chvostek signs. EKG revealed prolonged QTc of 480 (&lt;450) ms. He had a restricted diet and minimal sun exposure. His mother described his gait as “waddling” for the past two years. X-ray revealed bilateral femoral head fractures and evidence of rickets. He underwent bilateral surgical repair. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days two and four. He was discharged on day 14 with iCal 1.01 on oral calcium carbonate and cholecalciferol. A 16-year-old male with history of severe food allergies and restricted diet presented with a seizure. He visited urgent care three months prior for perioral tingling, muscle cramps and chest pain. He started a multivitamin for “low Ca” and “prolonged QTc.” The ED labs revealed: Ca 4.8, PTH 414.8, 25(OH)D 11, Mg 1.9, PO4 5.0, Alk Phos 539 (44–147) IU/L. Exam showed upper extremity twitching and QTc was 543 ms. He received 2 g calcium gluconate IV, then began oral calcium carbonate and cholecalciferol and continued supplementation following discharge on day six. Conclusions: Vit D deficiency among adolescents is re-emerging, likely due to decreasing sun exposure, unbalanced diets and increasing obesity.2 Adolescents with restricted diets due to allergy or behavioral disorders may be at higher risk of vit D deficiency. Increased screening of high-risk adolescents may lead to early identification of cases. References: 1) Palacios, C., et al. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2013;144PA;138-145 2) Antonucci, R., et al. Vitamin D deficiency in childhood: old lessons and current challenges. J Pediatr Endocrinol Metab. 2018;31(3);247–260.

Denosumab Induced Severe Prolonged Hypocalcemia in Metastatic Prostate Cancer

Background: Denosumab is a RANK-l inhibitor that, in addition to the treatment of osteoporosis, is used in patients with advanced cancer and metastatic bone disease to prevent skeletal-related events. Although denosumab is generally safe and effective, it can cause hypocalcemia which in some patients can be severe and life threatening. We present a case of severe prolonged hypocalcemia after a single dose of denosumab in a patient with metastatic prostate cancer. Case: A 78-year-old male with a past medical history of stage 4 prostate cancer on antiandrogen treatment with GnRH antagonist presented with severe hypocalcemia. Physical exam revealed a blood pressure 125/80 mm Hg, pulse 115 per min and weight 135 lb with negative Chvostek’s and Trousseau’s signs. The electrocardiogram showed supraventricular tachycardia with prolonged QTc interval of 503 ms (&lt;430 ms). Labs showed serum calcium 4.9mg/dL (8.5–10.5), albumin 2.5g/dL (3.6–5.1), corrected calcium 5.7 mg/dL, ionized serum calcium 0.64mmol/L (1.05–1.3), creatinine 1.10mg/dL (0.7–1.2), eGFR &gt;60, phosphorus 2.0mg/dL (2.5–4.5), magnesium 1.9 mg/dL (1.6–2.6), 25-OH vitamin D 29.7 ng/mL (30–100), 1,25 dihydroxy vitamin D 174 pg/mL (18–64), iPTH 244.0 pg/mL (11–68) and PSA 1860 ng/mL. Three weeks prior to presentation, the patient received 120 mg of subcutaneous denosumab. Pre-treatment serum calcium was 9.2 mg/dL (8.5–10.5), and Tc-99m bone scan showed multiple osteoblastic osseous metastatic lesions involving both axial and appendicular skeleton. The patient was diagnosed with denosumab-induced severe hypocalcemia and started on intravenous (IV) calcium gluconate infusion, oral phosphate 250 mg twice daily, and ergocalciferol 50,000 IU twice weekly. He required IV calcium gluconate up to 10 g per day in addition to oral calcium carbonate 2 g t.i.d. for 2 weeks to resolve hypocalcemia and normalize QTc interval. Patient was discharged to nursing home on calcium carbonate 2 g q.i.d. with IV calcium gluconate as needed to keep corrected calcium &gt;8.0 mg/dL. After discharge he required up to 4 g of IV calcium and 8 g of oral calcium per day. Unfortunately, he presented again with severe hypocalcemia 5 weeks after discharge. In addition to current regimen of oral and IV calcium boluses, low dose calcitriol was started. We were only able to maintain his serum calcium&gt;8.0 mg/dL by administering high daily dose of oral calcium carbonate 8 g /day and calcitriol 2 mcg daily. Due to poor prognosis, he was transitioned to hospice care and died 2 weeks later. Discussion: There are not many case reports on severe prolonged hypocalcemia secondary to denosumab in cancer patients but normal kidney function. Our patient remained on high dose of calcium even 101 days after denosumab administration. Reference: 1. Milat F et al. Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone. 2013 Aug 1;55(2):305–8.

Effect of oral calcium administration on metabolic status and uterine health of dairy cows with reduced postpartum rumination and eating time

Background Hypocalcemia has detrimental effects on health and performance of dairy cows. As hypocalcemic cows show reduced feed intake, we hypothesized that cows with reduced combined rumination and eating time (CRET) may benefit from Ca supplementation. The objective was to evaluate the effect of postpartum oral Ca administration on metabolic status (Calcium [Ca], fatty acids [FA], and β-Hydroxybutyrate [BHB] serum concentrations) and incidence of puerperal metritis (PM) in dairy cows with reduced postpartum CRET. Cows in an organic-certified dairy, diagnosed with reduced CRET (< 489 min/d; n = 88) during the first day postpartum were assigned into 1 of 2 treatments: i) Calcium administration (CA; n = 45) that received 1 Ca oral capsule (Bovikalc bolus, Boehringer Ingelheim, St. Joseph, MO) containing CaCl2 and CaSO4 (43 g of Ca) once per day, for 3 consecutive days, starting at d 1 postpartum; and ii) Control (CON; n = 43) that did not receive oral Ca. A convenience group consisting of cows with CRET ≥489 min/d was used for comparison and did not receive oral Ca (NOR; n = 96). Results At day 1 postpartum cows with reduced CRET had lower Ca serum concentrations (CA = 2.08 mmol/L; CON = 2.06 mmol/L) compared with NOR cows (2.17 mmol/L). Calcium concentrations at d 3, 5, and 12 postpartum were not different among the three groups. Serum FA concentrations at d 1, 3 and 5 postpartum were higher in both CA and CON cows compared with NOR. At d 12, only CA cows had higher FA concentrations than NOR cows. Serum BHB concentrations at d 3 were highest in CA, with no difference between CON and NOR. At d 5, BHB concentrations were higher in CA, followed by CON, and NOR. No effect was observed for Ca administration on incidence of PM and reproductive performance. CON cows had lower survival at 30 DIM (86.5%) than NOR cows (97.9%). Conclusions The use of remote sensor technology identified cows with reduced rumination and eating time that had lower postpartum serum concentrations of calcium and altered metabolic status. However, oral calcium administration to cows with reduced CRET did not affect incidence of metabolic disorders nor reproductive health and subsequent pregnancy. Although survival at 30 days postpartum was lower for non-Ca supplemented cows, the identification of effective interventions in cows with reduced CRET requires further consideration.