maxacalcitol and Hypocalcemia

Conventional calcitriol treatment can suppress parathyroid hormone (PTH) secretion in hemodialysis patients, although it can cause refractory hyperparathyroidism in some patients. We attempted to elucidate clinical outcomes of intravenous 22-oxa-1,25-dihydroxyvitamin D(3) (OCT) treatment and their determinants in a multicenter clinical trial.. One hundred one patients with serum PTH levels greater than 300 pg/mL (300 ng/L) and serum calcium levels less than 11 mg/dL (2.74 mmol/L) were recruited. OCT was administered intravenously at the end of each dialysis session. The dose was decreased by 5 microg when serum PTH level was less than 300 pg/mL or serum calcium level was greater than 11 mg/dL.. OCT was administered for 4.8 months to 101 patients (average age, 55.1 years) who were on dialysis therapy for 15.9 years. Percentages of decrease in PTH levels greater than 30% were obtained in 44 patients (43.5%). These patients were on dialysis therapy for a shorter duration than those who showed less than 30% decreases (13.0 +/- 3.3 versus 17.9 +/- 3.0 years). Multiple regression analysis of the final PTH level or percentage of decrease in PTH level with respect to initial PTH level, serum calcium level, serum phosphate level, age, and dialysis therapy duration showed that determinants of percentages of decrease in PTH levels were initial serum calcium and phosphate levels. Conversely, significant determinants of the final PTH level were initial PTH levels and initial calcium levels.. These results show that the decrease in PTH levels by OCT therapy could be predicted in patients with low calcium, PTH, and alkaline phosphatase levels; high phosphate levels; and short dialysis therapy duration before the start of OCT administration.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Calcitriol; Calcium; Drug Administration Schedule; Female; Humans; Hyperparathyroidism; Hypocalcemia; Infusions, Intravenous; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Vitamin D

A 41 year-old woman complained of general bone pain and polyuria. She did not have Albright hereditary osteodystrophy. Laboratory examination revealed hypokalemia, hypocalcemia, and an elevation of serum intact PTH concentration. The patient was polyuric and relatively hypercalciuric, though her glomerular filtration rate (GFR) was normal. Neither urinary Pi nor cAMP excretion was remarkably promoted by an exogenous PTH load. An iliac bone biopsy revealed osteopenia, active osteoclastic bone resorption, fibrous transformation in bone marrow tissue, and severely disturbed calcification. Although the oral administration of alfacalcidol showed no effects, 3 weeks of intermittent intravenous injection of maxacalcitol therapy decreased the serum intact PTH concentration from 597 pg/ml to 40 pg/ml, and the bone pain was greatly relieved. However, plasma Ca concentration also decreased and symptoms of tetany appeared. Pseudohypoparathyroidism type Ib was the most likely diagnosis in this patient. In conclusion, maxacalcitol therapy satisfactorily suppressed parathyroid function in a patient with secondary hyperparathyroidism without uremia. Appropriate Ca supplementation was required to perform it safely.

Topics: Adult; Bone Diseases; Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Injections, Intravenous; Parathyroid Hormone; Syndrome; Time Factors

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] is known to influence cell proliferation/maturation, whereas epidermal growth factor (EGF) is a potent stimulant of proliferation. Recently, hypocalcemia of vitamin D (D) deficiency was shown to significantly perturbe hepatic regeneration, which could be only partly restored by normalizing extracellular calcium, whereas normalization of 1,25-(OH)2D3 fully restored the process. To define the calcium- and/or D3-sensitive mechanisms associated with liver growth, a study of the initial events transduced by EGF was initiated by probing EGF receptor (EGFR) density and affinity, its subsequent autophosphorylation, and the level of its steady state transcript. Studies were carried out in D-depleted rats kept either untreated or supplemented with D3, 1,25-(OH)2D3, or calcium alone. The hepatic EGFR number (picomoles per mg microsomal protein) was significantly affected by hypocalcemic D-depleted (0.82 +/- 0.2), but responded with similar increases to calcium (1.7 +/- 0.09; P < 0.05), D3 (1.6 +/- 0.3; P < 0.05), and 1,25-(OH)2D3 (2.1 +/- 0.3; P < 0.01). The EGFR mRNA level revealed, however, no significant effect of the calcium or D3 status, indicating that posttranscriptional events were playing an important role. Phosphorylation studies showed that EGFR autophosphorylation and tyrosine protein kinase activity paralleled receptor density, with the lowest autophosphorylation values obtained in hypocalcemic D-depleted rats (D-depleted hypocalcemic vs. D3 repleted, P < 0.007). When normalized for receptor number, however, EGFR autophosphorylation increased in D-depleted hypocalcemic rats to a level comparable to that observed in all other groups. To dissociate the effect of the D3 hormone from that of calcium alone on EGFR, D-depleted rats were treated with the nonhypercalcemic 1,25-(OH)2D3 analog 22-OXA-1,25-(OH)2D3 (OCT), with or without calcium supplementation. Hypocalcemic OCT-treated rats did not exhibit any increase in EGFR number (0.6 +/- 0.1) compared to D-depleted hypocalcemic rats, but the addition of dietary calcium to OCT restored extracellular calcium concentrations and EGFR density (1.8 +/- 0.2; P < 0.002) to values comparable to those observed after D3 or 1,25-(OH)2D3 treatment. EGFR autophosphorylation was also decreased in hypocalcemic OCT-treated animals (P < 0.03), but after normalization for receptor density, full restoration of EGFR autophosphorylation was achieved. Our data demonstrate that in normal hepat

Topics: Animals; Calcitriol; Calcium; Cholecalciferol; Epidermal Growth Factor; ErbB Receptors; Female; Hypocalcemia; Liver; Male; Phosphorylation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor alpha; Vitamin D Deficiency