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 (IV) 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 IV administration of calcitriol in chronic dialysis patients. This revised version was published online in August 2006 with corrections to the Cover Date.     

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.     

Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism

To evaluate the response of circulating intact parathyroid hormone (iPTH) on myocardial hypertrophy in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), echocardiographic and neurohormonal assessments were performed over a 15-week period in 15 HD patients with SHPT before and after calcitriol treatment and 10 HD control patients with SHPT not receiving calcitriol therapy. We prospectively studied a group of 15 patients with significantly elevated iPTH levels (iPTH >450 pg/mL) receiving calcitriol (2 microg after dialysis twice weekly). Clinical assessment, medication status, and biochemical and hematological measurements were performed once a month. Throughout the study, calcium carbonate levels were modified to maintain serum phosphate levels at less than 6 mg/dL, but body weight, antihypertensive medication, and ultrafiltration dose remained constant. In patients treated with calcitriol, an adequate reduction of iPTH levels was found (1,112 +/- 694 v 741 +/- 644 pg/mL; P < 0.05) without changes in values of serum ionized calcium (iCa++), phosphate, or hematocrit. Blood pressure (BP), cardiac output (CO), and total peripheral resistance (TPR) did not significantly change. After 15 weeks of treatment with calcitriol, M-mode echocardiograms showed pronounced reductions in interventricular wall thickness (13.9 +/- 3.6 v 12.8 +/- 3.10 mm; P = 0.01), left ventricular posterior wall thickness (12.5 +/- 2.4 v 11.3 +/- 1.8 mm; P < 0.05), and left ventricle mass index (LVMi; 178 +/- 73 v 155 +/- 61 g/m2; P < 0.01). However, in control patients, these changes were not found after the treatment period. In addition, sequential measurements of neurohormonal mediator levels in patients receiving calcitriol showed that plasma renin (18.5 +/- 12.7 v 12.3 +/- 11.0 pg/mL; P = 0.007), angiotensin II (AT II; 79.7 +/- 48.6 v 47.2 +/- 45.7 pg/mL; P = 0.001), and atrial natriuretic peptide (ANP; 16.6 +/- 9.7 v 12.2 +/- 4.4 pg/mL; P = 0.03) levels significantly decreased, whereas antidiuretic hormone (ADH), epinephrine, and norepinephrine levels did not change significantly. The percent change in LVMi associated with calcitriol therapy had a strong correlation with the percent change in iPTH (r = 0.52; P < 0.05) and AT II (r = 0.47; P < 0.05) levels. We conclude that the partial correction of SHPT with intravenous calcitriol causes a regression in myocardial hypertrophy without biochemical or hemodynamic changes, such as heart rate, BP, and TPR. The changes in plasma levels of iPTH and, secondarily, plasma levels of neurohormones (especially AT II) after calcitriol therapy may have a key role in attenuating ventricular hypertrophy in SHPT.     

Cardiac surgery with cardiopulmonary bypass in patients with chronic renal failure.

OBJECTIVE: Renal failure is known to increase the morbidity and mortality in patients undergoing cardiac surgery. The results of heart surgery in patients with non-dialysis-dependent, mild renal insufficiency are not clear. METHODS: One hundred nineteen adult patients with chronic renal failure underwent cardiac surgery. Group I consisted of 93 patients who had creatinine levels between 1.6 and 2.5 mg/dL but who were not supported by dialysis. Group II consisted of 18 patients with creatinine levels higher than 2.5 mg/dL who were not supported by dialysis. Group III consisted of 8 patients with end-stage renal disease who were receiving hemodialysis. RESULTS: The hospital mortality rates were 11.8%, 33.0%, and 12.5%, respectively. Morbidity was 21.5%, 44.4%, and 75.0%, respectively, in groups I, II, and III. Postoperative hemodialysis was needed in 2 (2.15%) patients from group I and 6 (33%) patients from group II. On multivariable logistic regression analysis, risk factors for mortality were preoperative creatinine level more than 2.5 mg/dL, angina class III-IV, emergency operation, excessive mediastinal hemorrhage, postoperative pulmonary insufficiency, low cardiac output, and rhythm disturbances. Risk factors for morbidity were preoperative creatinine level more than 2.5 mg/dL and postoperative dialysis. CONCLUSIONS: Chronic renal failure increases the mortality and morbidity in patients undergoing cardiac surgery. Renal insufficiency with creatinine levels higher than 2.5 mg/dL increases the risk of postoperative dialysis and prolongs the length of hospital stay. Careful preoperative management and intraoperative techniques, such as avoiding low perfusion pressure and using low-dose dopamine, may be useful for a good operative outcome.     

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.     

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.     

The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients.

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.     

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.     

A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients

BACKGROUND: Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors. SUBJECTS AND METHODS: We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia. RESULTS: In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic. CONCLUSION: Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in 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     

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.     

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.     

Tacrolimus and low-dose steroid immunosuppression preserves bone mass after renal transplantation

Bone loss, a recognized complication of renal transplantation (TP), is mainly attributed to steroids. The effect of other immunosuppressive agents on patients' bone mass is difficult to distinguish from that of steroids. In this study, we evaluate the evolution of bone mass density over the first 12 months following renal TP in two groups of patients given either low-dose steroids with tacrolimus ( n=7) or normal-dose steroids and cyclosporine ( n=19). Bone mineral density (BMD) of the lumbar spine, total hip, and hip subregions and total-body bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry within the first 15 days, and 1 year after TP. Biological markers of bone turnover (serum calcium, phosphate, total alkaline phosphatase activity, intact parathyroid hormone, bone-specific alkaline phosphatase, calcitriol, and urinary pyridinolines) were regularly measured during follow-up. After TP, renal function improved rapidly in all patients. One year after TP, bone mass had decreased significantly in the cyclosporine group in all investigated sites. By contrast it had increased in the tacrolimus group. In order to compare the evolution of bone mass in patients given similar amounts of steroids, the cyclosporine group was subdivided in tertiles according to the 1-year cumulative oral intake of prednisolone. A significant bone loss was still observed in the low-steroid cyclosporine subgroup but not in the tacrolimus group, despite the similar steroids intake (3.5+/-0.5 g and 2.7+/-1 g, respectively). Bone gain in the tacrolimus group occurred despite a previous longer dialysis duration and a higher number of postmenopausal women who were not receiving hormone substitutes. Long-term evaluation of bone density (3-5 years post-TP) confirmed the bone gain in the tacrolimus patients. Interestingly, the profile of the biological markers of bone turnover appeared better in patients prescribed tacrolimus than in those given cyclosporine, though the differences did not reach statistical significance. Weconclude that tacrolimus associated with low-dose steroids might better preserve bone mass after renal TP than cyclosporine and normal doses of steroids.     

Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:   Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO₄) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO₄ product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Methods:   This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.
Results:   Twenty-five patients were enrolled into the study – 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced ( P  = 0.003) only in the paricalcitol group but not in the calcitriol group ( P  = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group ( P  = 0.004 vs P  = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO₄ product were not different.
Conclusion:   Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.     

High doses of intravenous calcitriol in the treatment of severe secondary hyperparathyroidism

BACKGROUND: In hemodialysis (HD) patients, secondary hyperparathyroidism (HPTH) is a severe common disease. Calcitriol administration has been demonstrated as an effective therapy. In this prospective study, our aim was to determine the necessary calcitriol dose required to control severe HPTH preventing hypercalcemia or hyperphosphatemia and avoiding parathyroidectomy. METHODS: Eighteen dialysis patients suffering from severe HPTH during a 12-month period received intravenous (i.v.) calcitriol pulse doses (2-8 mcg/3x/week). Multislice helical computed tomography (CT) cardiac imaging was performed to measure coronary artery calcifications. RESULTS: Fourteen patients showed an improvement (parathyroid hormone (PTH) level < 400 pcg/mL), one patient an incomplete reduction, and three patients starting from PTH levels between 1100 and 2386 pcg/mL did not appear to benefit from the therapy. After a 6-month therapy in 15/18 patients PTH levels were significantly lower (p<0.05). In a large portion of the group, as well as in the control group, coronary calcification values were high when compared to the normal range. CONCLUSIONS: According to our data, we concluded that severe HPTH could be treated successfully by i.v. calcitriol pulse doses reaching high doses (up to 8 mcg/3x/week) and for a prolonged period of time (6 months). In such cases, close monitoring is necessary to prevent hyperphosphatemia and hypercalcemia episodes.     

Does L-thyroxine administration in a dose to suppress TSH secretion induce metabolic bone disturbance in patients with thyroid carcinoma?]

We investigated whether L-thyroxine for TSH suppression may induce metabolic bone disturbance, especially in trabecular bone. Subjects were 75 premenopausal women (mean age: 37.7) who underwent surgery at Ito Hospital or Yokohama City University Hospital from 1972 to 1988 for differentiated thyroid carcinoma. All of them received L-thyroxine for the purpose of TSH suppression. According to the duration of the drug therapy after surgery, they were divided into 3 groups: Group I patients were treated for more than 10 years after surgery (17 cases), Group II from 5 to 10 years (28 cases), and Group III less than 5 years (30 cases). The control group was consisted of 15 premenopausal women (mean age: 37.0). There was no significant difference in age among these 4 groups. Quantitative CT was used for evaluation of trabecular bone mineral content. Mean bone mineral contents determined in Group I, Group III, Group II and control group patients were 204.7, 213.1, 207.6, 222.6 mg/cm3, respectively. There was no significant difference among them. It is concluded that L-thyroxine can be administered safely without metabolic disturbance in trabecular bone.     

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).     

Effective treatment of secondary hyperparathyroidism in hemodialysis patients by titration of intravenous calcitriol dosage.

AIM: Effective treatment of secondary hyperparathyroidism (HPTH) with intravenous (i.v.) administration of calcitriol in hemodialysis patients. PATIENTS AND METHODS: The current study evaluates the use of i.v. calcitriol dosing in relation to the severity of the HPTH in 35 hemodialysis patients with serum phosphate < 6.5 mg/dl. Arbitrarily, patients with plasma IPTH levels (intact PTH) between 288 and 576 pg/ml (288 pg/ml = four-fold the upper normal limit) were given initially 1 microg i.v. calcitriol at the end of each dialysis (group A, n = 15). Patients with IPTH between 577 and 864 pg/ml received 2 microg i.v. calcitriol (group B, n = 10) and patients with IPTH more than 865 pg/ml were given 3 - 4 microg i.v. calcitriol (group C, n = 10). As IPTH levels decreased, the dose of i.v. calcitriol was also decreased gradually. Patients were followed-up for 4 months after the end of calcitriol treatment. RESULTS: During the i.v. calcitriol treatment period, the observed plasma IPTH concentrations compared with the baseline values were significantly lower (p < 0.01 for A and B group and p < 0.05 for C group) from the sixth month onwards in group A and C and from the third month onwards in group B. At the 12th month of follow-up, all patients being off i.v. calcitriol treatment for four months, a sharp and significant increase (p < 0.01 for group A and B and p < 0.05 for group C) of plasma IPTH was recorded in all three groups of patients. Alkaline phosphatase was also gradually decreased in all studied groups. Serum Ca and P remained unchanged in most patients. CONCLUSION: In conclusion, the study presented here demonstrates that the titration of i.v. calcitriol dosage according to the severity of HPTH is an effective and safe treatment of HPTH in chronic hemodialysis patients. It also shows that parathyroidectomy could be avoided in the majority of patients with severe HPTH, if an appropriate dose of calcitriol not aggravating hyperphosphatemia is administered.     

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。