maxacalcitol and Hyperparathyroidism

In conclusion, a number vitamin D analogues have been developed that have very low calcemic activity but retain several other properties of 1,25-(OH)2D3, including the ability to differentiate leukemia and skin cells, to enhance the immune response, and to suppress parathyroid hormone levels. Although the mechanism of this selective activity is not yet clear, these analogues may provide new insights into the differences in action of 1,25-(OH)2D3 in various target tissues. Most importantly, the selective action of these analogues may be exploited for the treatment of diseases such as leukemia, psoriasis and hyperparathyroidism.

Topics: Animals; Antineoplastic Agents; Calcitriol; Humans; Hyperparathyroidism; Leukemia; Psoriasis; Structure-Activity Relationship

The semi-quantitative method of bone scintigraphy [bone to soft tissue (B/ST) ratio] has been used in diagnosing and evaluating systemic metabolic bone diseases. The aim of this study is to evaluate of the therapeutic effect of secondary hyperparathyroidism (SHP).. The subjects were ten hemodialysis patients with SHP. Seven patients underwent parathyroidectomy (PTX), and 22-Oxacalcitoriol (derivative of 1,25-dihydroxyvitamin D3) (OCT) was given to three patients. Bone scintigraphy and blood tests [intact parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (Ca), phosphorus (P), bone alkaline phosphatase (BALP), and deoxypridinoline (DPYD)] were performed before and after treatment. Regions of interest were drown around cranium, lumbar vertebrae, femoral neck and soft tissue of left medial thigh to calculate the B/ST ratio.. The B/ST ratios of cranium, lumbar vertebrae, and femoral neck were reduced significantly after PTX (cranium, p = 0.0079, lumbar vertebrae, p = 0.0282, femoral neck, p = 0.0252). Intact PTH, ALP, Ca, P, BALP and DPYD levels were reduced significantly after PTX (intact PTH, p = 0.003, Ca, p = 0.0005, P, p = 0.0393, ALP, p = 0.0051, DPYD, p = 0.0232, BALP, p = 0.0324). After OCT administration, the B/ST ratio of each bony region showed tendency to diminish, although not significantly. Intact PTH levels were reduced significantly, although ALP, BALP, and DPYD levels were not. Ca and P levels were increased significantly because of the medicinal action of OCT.. The B/ST ratio of cranium may be non-invasive method and have potential in evaluating the therapeutic effect of SHP.

Topics: Adult; Aged; Bone and Bones; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Radionuclide Imaging; Thyroidectomy; Treatment Outcome

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

Maxacalcitol (22-oxacalcitriol [OCT]) is a newly developed vitamin D analogue in Japan. OCT has shown less calcemic action and a strong suppressive effect on parathyroid hormone (PTH) in uremic rats and dogs. In uremic patients with secondary hyperparathyroidism, OCT dose-dependently suppressed PTH secretion and increased serum calcium levels. However, more than 60% of patients achieved a greater than 30% decrease in intact PTH level from baseline with long-term OCT treatment up to 1 year without an unphysiological increase in mean serum calcium levels. Long-term treatment also brought about a reduction in bone metabolic markers, including bone alkaline phosphatase, tartrate-resistant acid phosphatase, and bone gra-protein. These results suggest that although careful attention should be paid to the onset of hypercalcemia and oversuppression of PTH, OCT is one of the effective tools for the treatment of secondary hyperparathyroidism.

Topics: Calcitriol; Calcium; Creatine Kinase; Dose-Response Relationship, Drug; Humans; Hypercalcemia; Hyperparathyroidism; Injections, Intravenous; Parathyroid Hormone; Pruritus; Renal Dialysis; Uremia

To examine the effectiveness of 22-oxacalcitriol (OCT) injection on the improvement of severe osteitis fibrosa, we studied 10 hemodialyzed patients (age, 59 +/- 12 years). The initial OCT dose was 5 microg and was administered three times weekly at the end of each hemodialysis session. OCT doses (1, 3, 5, 10, 15, and 20 microg) were changed in subsequent weeks to maintain serum calcium levels at less than 11.5 mg/dL. Administration of OCT significantly suppressed serum intact parathyroid hormone (PTH) from an initial level of 1,193 +/- 584 to 775 +/- 552 pg/mL in the 24th week (n = 10). OCT increased PTH levels again to 857 +/- 635 pg/mL in the 48th week (n = 7). Among the 10 patients, 5 patients (high responders) showed more than a 50% suppression of serum intact PTH levels at the end of the study. The rest of the patients had hypercalcemia and did not receive increased OCT doses (low responders). At the start of the treatment, the only difference between high and low responders was serum calcium level. Serum calcium levels (adjusted for serum albumin level) increased from 9.7 +/- 0.7 mg/dL (n = 10) at the beginning to 10.5 +/- 0.6 mg/dL (n = 10) in the 24th week and to 11. 1 +/- 0.7 mg/dL (n = 7) in the 48th week. Six patients (1 to 6) agreed to undergo a second bone biopsy in the 24th week of OCT administration. In bone histomorphometric measurements, OCT significantly changed bone marrow fibrosis, mineralization (labeled mineralizing surface and bone formation rate), and osteoid formation (osteoid volume and thickness). In conclusion, intravenous OCT effectively suppressed PTH secretion and improved the bone histological characteristics of severe osteitis fibrosa, especially in patients with initial serum calcium levels less than 10 mg/dL. With concerns about OCT causing adynamic bone, additional bone histological data are needed to ensure the long-term safety of OCT.

Topics: Adult; Aged; Calcitriol; Calcium Channel Agonists; Dose-Response Relationship, Drug; Female; Fibrous Dysplasia of Bone; Humans; Hyperparathyroidism; Infusions, Intravenous; Injections; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Treatment Outcome

In longitudinal data, a continuous response sometimes shows a profile approaching an asymptote. For such data, we propose a new class of models, autoregressive linear mixed effects models in which the current response is regressed on the previous response, fixed effects, and random effects. Asymptotes can shift depending on treatment groups, individuals, and so on, and can be modelled by fixed and random effects. We also propose error structures that are useful in practice. The estimation methods of linear mixed effects models can be used as long as there is no intermittent missing.

Topics: Azathioprine; Calcitriol; Computer Simulation; Drug Therapy, Combination; Humans; Hyperparathyroidism; Immunosuppressive Agents; Linear Models; Longitudinal Studies; Methylprednisolone; Multiple Sclerosis; Parathyroid Hormone; Randomized Controlled Trials as Topic; Receptors, Fc

Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size.. Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis.. Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05).. These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.

Topics: Antimetabolites; Body Weights and Measures; Calcitriol; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Glands; Ultrasonography

A synthetic analogue of calcitriol, 22-oxacalcitriol (OCT), strongly suppresses parathyroid hormone (PTH) secretion. This study investigated the influence of OCT on PTH secretion and bone metabolism in 12 hemodialysis patients with secondary hyperparathyroidism.. OCT was intravenously injected after every hemodialysis session (three times weekly) for 22 weeks. The levels of the following parameters were measured: intact PTH, whole PTH, whole PTH/7-84 PTH ratio, adjusted calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (OC), type I collagen carboxyterminal propeptide, tartrate-resistant acid phosphatase (TRAP), cross-linked C-terminal telopeptides of type I collagen, and interleukin-6.. The subjects were 12 hemodialysis patients (8 men and 4 women) with an intact PTH level of more than 460 pg/ml, a normal serum calcium level, and a serum phosphorus of less than 7 mg/dl.. The levels of intact PTH, whole PTH, whole PTH/7-84 PTH ratio, ALP, BAP, OC, and TRAP were significantly decreased after OCT administration, while adjusted calcium was significantly increased. Serum phosphorus and the other parameters showed no significant changes.. OCT effectively suppressed the PTH level and bone metabolism parameters in hemodialysis patients with secondary hyperparathyroidism.

Topics: Adult; Aged; Bone and Bones; Calcitriol; Calcium Channel Agonists; Female; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis