Beneficial role of intravenous calcitriol on bone mineral density in children with severe secondary hyperparathyroidism

OBJECTIVES: In this prospective study, the effect of calcitriol therapy on bone mineral density and osteopenia in patients with severe secondary hyperparathyroidism has been investigated. MATERIALS AND METHODS: The study was carried out on 24 chronic dialysis patients consisting of 13 boys and 11 girls, aged between 8-18 years. Patients were divided into 3 groups according to the severity of hyperparathyroidism and therapy regimens. Group I consisted of 5 patients with normal parathormon levels who did not receive calcitriol therapy. In group II and III, there were patients with secondary hyperparathyroidism. Group II consisted of 10 patients receiving oral calcitriol therapy. Group III consisted of 9 patients receiving intravenous (i.v.) calcitriol. Bone mineral density was measured by dual energy x-ray absorptiometry. Osteopenia was defined as a Z-score worse than -2. Bone mineral density was assessed as baseline and at the end of one year. RESULTS: A significant improvement was observed in Z-score in the group III whereas the mean value of Z-score tended to be worse in group I and it was not significantly different in group II from the initial values. The better Z-score in group III was associated with more effective stabilization of alkaline phosphatase level and bone specific alkaline phosphatases (BAP) concentrations. CONCLUSION: Significant improvement of Z-score in group III suggested the beneficial role in i.v. administration of calcitriol in chronic dialysis patients.     

Relations between calcidiol serum levels and bone mineral density in postmenopausal women with low bone density

The relationship between vitamin D and bone density was studied in 150 selected, mature (45–74), postmenopausal women with a lumbar spine Z score below 0. Vitamin D status was evaluated using calcidiol serum levels. Serum calcitriol and parathyroid hormone (PTH) values were also evaluated in some subjects. Bone mass was evaluated by ascertaining bone density and Z and T scores in the lumbar spine and femur region. The reference group consisted of 25 premenopausal women. The postmenopausal group was divided into subgroups according to age, i.e., under or over 60 years old. Additionally, the whole group was also subdivided according to their lumbar spine Z scores into group I (Z>-1), group II (Z<-1; >-2), and group III (Z<-2). Group III of postmenopausal women had higher PTH and lower calcitriol levels than premenopausal women. Calcidiol serum levels were lower in postmenopausal women groups II or III than in the group I and premenopausal women. Calcidiol serum levels and the bone mass values for the lumbar spine were correlated positively in all the postmenopausal women; in the women over 60 years of age, calcidiol levels also correlated with the bone mass values expressed as the bone density in three femur regions: femoral neck, trocanter, and Ward's triangle. In conclusion, mature postmenopausal woman showed high PTH levels and low calcidiol and calcitriol values. Calcidiol status is significantly related to bone mineral density in the lumbar spine and in women over 60 years, calcidiol levels also correlated with bone density in the femur regions.     

Direct injections of calcitriol into enlarged parathyroid glands in chronic dialysis patients with severe parathyroid hyperfunction

Summary: Severe secondary hyperparathyroidism in chronic dialysis patients has been recently treated by supraphysiological concentration of calcitriol achieved through pulse therapy. However, there are many patients resistant to this therapy, who usually have larger parathyroid gland(s). to overcome this resistance, calcitriol was injected directly into the enlarged glands under ultrasonographic guidance. We injected 70–90% of the calculated gland volume of calcitriol solution (1 μg/mL) into the glands of 7 patients three times per week for 2 weeks. the parathyroid hormone (PTH) levels decreased significantly after 2 weeks of direct injections of calcitriol. Following a further 4 weeks of calcitriol pulse therapy, PTH levels remained suppressed and serum alkaline phosphatase activity and the volume of parathyroid glands also decreased. During the long-term follow up, five patients remained well controlled with calcitriol pulse therapy, while two patients needed ethanol injections to control hyperparathyroidism. Although we could not completely rule out a toxic effect of the vehicle, direct injection of calcitriol into parathyroid glands may be another treatment option for chronic dialysis patients. Our data further support the important role of resistance of parathyroid cells to calcitriol in the pathogenesis of parathyroid hyper function in uraemic patients.     

Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism

Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing maintenance dialysis. The present review summarizes a prospective randomized study that evaluated the biochemical and skeletal responses to intermittent calcitriol therapy in 33 pediatric patients on peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of intermittent calcitriol therapy on linear growth was evaluated in 16 of 33 patients who had completed the clinical trial. Serum parathyroid hormone levels decreased by 62% from 648±125 pg/ml in patients treated with intermittent intraperitoneal (IP) calcitriol, and values remained unchanged from pre-treatment levels of 670±97 pg/ml with oral calcitriol therapy. Overall serum total and ionized calcium levels were higher in patients treated with IP calcitriol during the study. In contrast to these biochemical findings, the skeletal lesions of secondary hyperparathyroidism improved after 12 months of treatment in both groups and adynamic bone occurred in 33% of the patients. Z-scores for height decreased from –1.80±0.3 to –2.00±0.3, P<0.01, after 12 months of intermittent calcitriol therapy. Such findings suggest that an intermittent schedule of calcitriol administration adversely affects chondrocyte activity within epiphyseal cartilage in pre-pubertal children with end-stage renal disease. Received: 20 August 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000     

The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol

BACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx). METHODS: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy. CONCLUSIONS: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.     

Local Calcitriol Injections as a Suppressive Treatment of Secondary Hyperparathyroidism in Chronic Dialysis Patients

Aim. A prospective study was made of the effectiveness of repeatable local calcitriol injections therapy to suppress secondary hyperparathyroidism resistant to conventional therapy in chronic dialysis patients. Methods. Under ultrasonographic guidance, six injections at an interval of two days were performed in 14 chronic dialysis patients. The total amount of calcitriol to be injected each time was estimated as 100% of the calculated gland volume. Calcitriol was given in doses 1 μg of medicine per 1 cubic cm (as measured by USG) of parathyroid tissue. Parathormone concentration, total calcium, ionized calcium, phosphate, and alkaline phosphatase levels were assessed on the first and last day of the treatment period. Results. Prior to therapy, the mean gland volumes were 0.62 (0.15–3.0) ml, and they increased to 0.85 (0.2–3.9) after 14 days (NS). Seven patients were found to have decreased their PTH levels to 909 ± 387 pg/mL after 14 days of treatment when compared with the first day mean values of 1588 ± 440 pg/mL (p < 0.05). After completion of the therapy, four patients were reported to be free from any clinical symptoms of ostalgia or arthralgia. Others reported an alleviation of pain. Conclusions. Parathyroid adenoma injection is an alternative method of treatment for some patients resistant to treatment by means of vitamin D3 pulses or intravenous administration of calcitriol. The success of treatment is to a great extent determined by proper selection of patients and the taking of decisions when the period of secondary hyperparathyroidism is not very advanced.     

Bone mineral density may be related to atherosclerosis in hemodialysis patients

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated ( Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearman's rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearman's rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.     

Renoprotection following treatment of secondary hyperparathyroidism with percutaneous ethanol injection in pre-dialysis patients

What could be done for patients with chronic renal failure are marginally beneficial. Among 58 pre-dialysis patients, we found 24 of chronic glomerulonephritis (CGN) with serum creatinine >5 mg/dl and intact parathyroid hormone (i-PTH) >200 pg/ml. In this study, we determined if the residual renal function could be preserved when hyperparathyroidism was corrected by either low-dose calcitriol treatment or ethanol injection. The 58 CGN patients were divided into three groups. The first group, which comprised 11 cases with i-PTH >200 pg/ml and had parathyroid mass, were treated by ultrasonography-guided percutaneous ethanol injection therapy (PEIT). The second study group composed of 13 cases with i-PTH >200 pg/ml without parathyroid mass were treated by calcitriol 1 microg every other day. The third group made up of 34 cases with i-PTH <200 pg/ml, who did not receive calcitriol or ethanol therapy. All patients were followed up within 2 years or until dialysis. The average rate of decline in renal function (slope of reciprocal serum creatinine vs. time) was 0.0025 +/- 0.0026 dl/mg month in group 1, 0.0054 +/- 0.0024 in group 2, and 0.0067 +/- 0.0025 in group 3 (p = 0.018 in group 1 vs. group 2, p < 0.001 in group 1 vs. group 3). The declines of i-PTH, phosphorus, and alkaline phosphatase, and the increase of calcium were all significantly different between group 1 and group 3. Two cases of group 1, 6 cases of group 2, and 20 cases of group 3 entered into dialysis during this study. In conclusion, selective PEIT guided by color Doppler flow mapping is an effective therapy for treating hyperparathyroidism and protecting the residual renal function.     

Calcitriol pulse therapy is not more effective than daily calcitriol therapy in controlling secondary hyperparathyroidism in children with chronic renal failure

Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean age 8.4±4.7 years) with chronic renal insufficiency (mean C_cr 22.4±11.6 ml/min per 1.73 m²) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485 pg/ml (range 83–2032) in the daily group (n=29) and 315 pg/ml (range 93–1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63–1614) and 218 pg/ml (range 2–1785) (ns). The mean iPTH decrease from baseline was 19.2±57.8% and 13.7±46.7% respectively (not significant). Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis. Received: 29 September 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000     

Comparison of the efficacy of an oral calcitriol pulse or intravenous 22-oxacalcitriol therapies in chronic hemodialysis patients

Background 1,25-dihydroxy-22-ovavitamin D₃ (22-oxacalcitriol, OCT) was recently introduced commercially as an analogue of 1,25 (OH)₂ vitamin D₃, but one which has less pronounced calcemic activity. Methods To examine the efficacy and tolerability of OCT, 46 hemodialysis patients with secondary hyperparathyroidism were randomly assigned to receive either intravenous OCT or oral calcitriol pulse therapies. The patients were monitored for serum calcium, phosphate, intact parathyroid hormone (PTH), and bone alkaline phosphatase (BAP) for 24 weeks. The efficacy of intravenous OCT was also examined in 24 additional patients who were refractory to oral calcitriol pulse therapy. Results In the randomized trial, intact PTH levels were significantly suppressed within 4 weeks after the initiation of each therapy, and this effect was well maintained thereafter in both treatment groups. While intact PTH was significantly lower at 4 weeks in the calcitriol pulse group than in the OCT group (P = 0.02), no statistical differences were observed during later treatment periods. BAP was reduced equally by each treatment. At 4 weeks (P = 0.02) and thereafter (P = 0.06), serum calcium was higher among calcitriol-treated patients than among those who received OCT treatment. Eight of 24 patients who were refractory to oral calcitriol pulse therapy responded to intravenous OCT. The patients who responded tended to have lower serum intact PTH and phosphorus levels and smaller parathyroid glands at the start of OCT treatment than nonresponders. Conclusions OCT is as effective as oral calcitriol pulse therapy in suppressing intact PTH and BAP in chronic hemodialysis patients. It was confirmed that OCT exhibits less calcemic activity than calcitriol. Moreover, under certain conditions, switching to OCT may help in the treatment of hyperparathyroidism, which is refractory to conventional oral calcitriol pulse therapy.     

Local calcitriol injections as a suppressive treatment of secondary hyperparathyroidism in chronic dialysis patients

AIM: A prospective study was made of the effectiveness of repeatable local calcitriol injections therapy to suppress secondary hyperparathyroidism resistant to conventional therapy in chronic dialysis patients. METHODS: Under ultrasonographic guidance, six injections at an interval of two days were performed in 14 chronic dialysis patients. The total amount of calcitriol to be injected each time was estimated as 100% of the calculated gland volume. Calcitriol was given in doses 1 mug of medicine per 1 cubic cm (as measured by USG) of parathyroid tissue. Parathormone concentration, total calcium, ionized calcium, phosphate, and alkaline phosphatase levels were assessed on the first and last day of the treatment period. RESULTS: Prior to therapy, the mean gland volumes were 0.62 (0.15-3.0) ml, and they increased to 0.85 (0.2-3.9) after 14 days (NS). Seven patients were found to have decreased their PTH levels to 909 +/- 387 pg/mL after 14 days of treatment when compared with the first day mean values of 1588 +/- 440 pg/mL (p < 0.05). After completion of the therapy, four patients were reported to be free from any clinical symptoms of ostalgia or arthralgia. Others reported an alleviation of pain. CONCLUSIONS: Parathyroid adenoma injection is an alternative method of treatment for some patients resistant to treatment by means of vitamin D3 pulses or intravenous administration of calcitriol. The success of treatment is to a great extent determined by proper selection of patients and the taking of decisions when the period of secondary hyperparathyroidism is not very advanced.     

Bone mineral density in patients with predialysis chronic kidney disease

Abstract

Background: There is limited data available especially in Indian Population about prevalence of reduced bone mineral density (BMD) and various factors associated with it in CKD patients not on dialysis. Material: This study included 75 adult patients. Patients were divided into three groups depending upon GFR. Serum creatinine, albumin, calcium, phosphate (PO4), alkaline phosphatase, iPTH and Vitamin D were measured at baseline. BMD was measured by dual energy X-ray absorptiometry. Results: There were 51 male and 24 female patients. The mean serum phosphate, alkaline phosphatase and iPTH levels increased steadily as CKD progressed. On the other hand, mean corrected serum calcium and Vitamin D levels decreased progressively in group A, B and C. The mean serum PTH values in group A, B and C were 137.16?±?109.85, 265.02?±?132.03 and 328.14?±?119.23?pg/mL, respectively and there was significant increase in mean PTH level from group A to group C (p?<?0.05). The mean level of vitamin D showed a trend of declination from group A to C (p?<?0.05). Z-score for group A, group B and group C was 1.11?±?2.39, 0.87?±?2.66 and ?0.92?±?1.59, respectively. Similarly, T score for the three groups were 0.47?±?2.34, ?0.4?±?2.00 and ?1.524?±?1.42. Both T-score and Z-score positively correlated with GFR. There was negative correlation between Z-score and iPTH, and positive correlation with Vitamin D. Conclusion: Reduced bone density was seen early in the course of CKD as estimated from reduced BMD levels, increased prevalence of osteoporosis and increased fracture risk and it worsened with the progression of CKD.     

1.25 (OH)2 cholecalciferol pulse therapy and the effects of different dialysis membranes on serum PTH levels of haemodialysis patients

Either oral, intravenous or subcutaneous 1.25 (OH)₂ cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis. We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types of dialysis membranes used. In the poly sulfone group, mean age was 43.7±0.97 years and the average dialysis period lasted 29.9±1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2±1.31 years and the average dialysis period lasted 16.2±0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l. According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently. After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered. Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63 pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy protocol applied. PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used. PTH and phosphorus clearances were 15.2±3 ml/min and 239.1±19.2 ml/min, respectively, in the polysulfone membrane group, and 1.1±0.3 ml/min and 112.8±9.88 ml/min, respectively, in the cuprophane membrane group (p<0.05).     

2型糖尿病患者微血管病变与骨密度相关性研究

目的探讨2型糖尿病患者微血管病变与骨密度的相关性。方法本横断面研究共纳入2 170例2型糖尿病患者(包括1 188名绝经后女性和982名50岁男性)。根据24 h尿蛋白水平对这些受试者进行分组:一组(30 mg)、二组(30～299mg)和三组(300 mg)。通过双能X射线吸收测定法评估其腰椎、髋部和股骨颈的骨密度。视网膜病的眼底照相和24 h尿蛋白作为2型糖尿病中微血管病的标志物。比较受试者的特征和骨密度。多变量分析用于研究骨密度与微血管病之间的关联。结果第三组在两种性别中具有最低的骨密度水平。在调整年龄、体重指数、高血压、高脂血症、糖尿病状态、肝功能、肾功能、性激素和25(OH)维生素D后,多变量分析显示,微血管病变与女性骨密度呈负相关(腰椎:r=-0. 522,P0. 001;髋关节:r=-0. 301,P=0. 010;股骨颈:r=-0. 314,P=0. 009),男性未发现相关性。结论绝经后女性2型糖尿病患者的微血管病变与骨密度之间呈负相关。     

Usefulness of pamidronate in severe secondary hyperparathyroidism in patients undergoing hemodialysis

BACKGROUND: Although bisphosphonates have been widely used to treat bone diseases characterized by increased bone resorption, there are limited data showing their possible usefulness in patients on hemodialysis (HD) with secondary hyperparathyroidism. METHODS: The aim of this study was to evaluate the efficacy and safety of pamidronate in HD patients affected by severe secondary hyperparathyroidism and moderate hypercalcemia who were receiving intravenous calcitriol (Calcijex). RESULTS: In this prospective one-year, open-labeled study, 13 patients (9 women/4 men) with a mean age of 64 +/- 9 years and a mean time on dialysis of 94 +/- 61 months were evaluated. The inclusion criteria were: iPTH>500 pg/mL, Ca>11 mg/dL, P <6 mg/dL, and osteopenia (T-score <-1 SD). Blood levels of Ca, P, alkaline phosphatase (AP), and iPTH were assessed at the beginning of the study and every month. Radiographs of the vertebral spine and bone mineral density (BMD) (lumbar spine and femoral neck) were assessed basal and every 6 months. All patients received 60 mg of pamidronate intravenously every two months throughout the study period. Calcitriol and phosphate binders were adjusted according to iPTH, Ca, and P blood levels. BMD increased in both the lumbar and femoral neck scans (mean increase of 33%) at 6 and 12 months. iPTH increased at 3 months in all patients, and decreased more than 50% in 10 patients after increasing the calcitriol doses. Three patients had no response. A slight decrease in Ca and P was observed in all patients with no significant changes in AP. There were no adverse events. CONCLUSION: Pamidronate is effective in controlling hypercalcemia in patients on HD with secondary hyperparathyroidism and allows for a more aggressive use of intravenous calcitriol.     

Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx. METHODS: Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy. CONCLUSIONS: Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.     

Improved anemia and reduced erythropoietin need by medical or surgical intervention of secondary hyperparathyroidism in hemodialysis patients

BACKGROUND: The available literature is still controversial and shows that surgical (parathyroidectomy, PTX) or medical (calcitriol) treatment actually improved or even corrected the rhEPO-resistant anemia of ESRD patients with severe SHP. The aims of this study were to 1) assess the influence of SHP on hematological parameters in ESRD patients, 2) evaluate whether or not calcitriol could improve anemia and reduce the need of erythropoietin in dialysis patients, and 3) investigate the longitudinal effect of a parathyroidectomy for 6 months on regarding any improvements in calcitriol-refractory ESRD patients. METHODS: 37 chronic hemodialysis patients in Chang Gung Memorial Hospital Dialysis Unit were divided into two groups: patients with SHP (iPTH>300 pg/mL) and patients without SHP (ipTH<300 pg/mL) before calcitriol therapy was applied. Sixteen patients remain with a status of hyperparathyroidism and were considered candidates for calcitriol therapy. Furthermore, we divided the patients according to the response of HPT to calcitriol into responding patients and nonresponding patients. Among nonresponder groups, three patients agreed to accept surgical intervention to treat their hyperparathyroidism status. RESULTS: The phosphate levels and serum alkaline phosphatase levels in patients with SHP were significantly higher when compared with those without SHP (P<0.05). As for the hematological data, hematocrit for patients with SHP was significantly higher than those without SHP (10.5 +/- 0.6 vs. 8.9 +/- 0.8, p<0.05). Other hematological parameters such as transferrin saturation and serum ferritin were not significantly different. We found a significant difference in alkaline phosphate levels in responding and nonresponding patients at 6 months on calcitriol therapy. Concomitantly, the hematocrit level is significantly higher in responding group when compared to those in nonresponding group (10.63 +/- 0.72 vs. 8.96 +/- 1.21, p<0.01). As for the dose of EPO requirement, significant difference between groups was also found after 6-month treatment (3617 +/- 2011 vs. 5416 +/- 1947, p<0.05). As for rhEPO dose requirement, positive effects of PTX were significantly found. The rhEPO doses needed to maintain patients in the hematocrit target range of 30-33% decreased gradually by 29% from 5323 +/- 1326 micro to 3774 +/- 2145 micro per week. The hematocrit level showed a significant increase at 3 months after PTX (p<0.05). This effect lasted until 6 months after PTX. The serum ferritin level was constantly around 350 to 400 pg/mL. While the transferrin saturation decreased 3 months after PTX (p<0.05) and recovered at 6 months. CONCLUSION: ESRD patients with SHP, usually associated with more severe anemia show resistance to rhEPO. In this case, investigation of SHP is strongly recommended with measurement of serum PTH, phosphate and alkaline phosphatase level. Treatment of calcitriol has a beneficial effect on renal anemia in ESRD patients with SHP. In addition, PTX could also provide another choosing therapy in improving renal anemia when medical treatment fails.     

Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial

Introduction Oral glucocorticoid therapy reduces bone mineral density (BMD) and increases fracture risk. It is uncertain whether inhaled glucocorticoids, the most commonly used long-term therapy for asthma, have a similar effect. If bone loss does occur, it is unclear whether this is preventable by calcitriol. Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone, and treatment with 0.5 μg/day of calcitriol will prevent bone loss.Methods A 2-year randomized double-blind placebo-controlled trial. One hundred eight patients with asthma were stratified by gender, age, and inhaled glucocorticoid dose and treated with calcitriol (n=55) or placebo (n=53). There were 41 men (mean age 53.2±1.7 years) and 67 women (mean age 49.1±1 years) with moderate to severe asthma (requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy). BMD values at the lumbar spine (LS) and femoral neck (FN) were measured at baseline and at 6, 12, and 24 months using dual x-ray absorptiometry.Results Changes in LS and FN BMD. Bone loss occurred in both groups at the FN (both p<0.03) and at the LS in the calcitriol (p<0.001), but not the control, group. Bone loss was not less in the calcitriol group at either site.Conclusion Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone. Calcitriol is unlikely to be appropriate therapy against this bone loss.     

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

Background: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. Methods: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 &mgr;g twice a week, n=10) or daily (0.75 &mgr;g a day, n=8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. Results: Pharmacokinetic analysis after a single dose of 3.0 &mgr;g (pulse) vs 0.75 &mgr;g (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse=562±291 vs daily=454±113 pg/ml), calcium (pulse=2.32±0.20 vs daily=2.32±0.12 mmol/l) and phosphorus (pulse=1.32±0.52 vs daily=1.35±0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and rate of decline in PTH were similar (time: pulse=14.2±6.8 weeks, daily=12.2±7 weeks; rate: pulse=7.4±4.2 vs daily=8.4±4.2% PTH/week; P=NS). The serum calcium increased similarly in both groups. Hypercalcaemia (>2.9 mmol/l) was rare (pulse=3, daily=2 episodes). Conclusions: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy. Key words: calcitriol; calcium balance; CAPD; dialysis; hyperparathyroidism; renal osteodystrophy      

Vitamin D levels, bone turnover and bone mineral density show seasonal variation in patients with chronic kidney disease stage 5

AIM: Many patients with chronic kidney disease (CKD) have reduced levels of 25-hydroxyvitamin D (25(OH)D). Although renal conversion of 25(OH)D to calcitriol is reduced or absent in CKD stage 5 (GFR < 15 mL/min per 1.73 m(2) or on dialysis), 25(OH)D may have direct skeletal and non-skeletal paracrine actions. The aim of this study was to assess seasonal variation in levels of 25(OH)D, bone turnover markers and bone mineral density, which would support a direct physiological role for 25(OH)D. METHODS: Vitamin D levels, bone turnover markers and bone mineral density were measured and assessed for seasonal variation in 257 patients about to undergo kidney or kidney pancreas transplantation. RESULTS: The mean age was 43 +/- 11 years; 62% were on haemodialysis, 24% on peritoneal dialysis and 34% had type 1 diabetes. Serum 25(OH)D was less than 50 nmol/L in 39% and lower levels were associated with female sex, diabetes and peritoneal dialysis (P < 0.0001 for each). Levels of 25(OH)D varied by season (P = 0.018; anova) peaking in autumn with a nadir in spring and calcitriol levels followed a similar seasonal trend. Bone mineral denisty Z-scores differed between summer and winter at the lumbar spine (P = 0.009) with a similar trend at the hip. Osteocalcin levels also showed seasonal periodicity (P = 0.0142) and together with alkaline phosphatase were higher in summer than winter. CONCLUSION: In summary, these data suggest direct effects of 25(OH)D on bone parameters in CKD stage 5 and support the need for prospective studies to establish the effect of treatments that increase 25(OH)D levels in all stages of CKD.