BACKGROUND

Although the variables that influence the development of post-thyroidectomy hypocalcaemia are now better understood, the risk factors and long-term outcome of persistent hypoparathyroidism (HPP) are poorly defined. A retrospective review of a prospective protocol for the management of post-thyroidectomy hypocalcaemia was performed.

METHODS

Patients with a serum calcium level below 8 mg/dl (2 mmol/l) 24 h after total thyroidectomy were prescribed oral calcium with or without calcitriol and followed for at least 1 year. Protracted HPP was defined as an intact parathyroid hormone (iPTH) level below 13 pg/ml and need for calcium medication at 1 month after thyroidectomy.

RESULTS

Of 442 patients (343 with goitre, 99 with carcinoma) undergoing total thyroidectomy, 222 (50.2 per cent) developed postoperative hypocalcaemia. Eleven patients were lost to follow-up. Parathyroid function recovered in 131 patients within 1 month and 80 developed protracted HPP, which was associated with lymphadenectomy, fewer than three glands left in situ and incidental parathyroidectomy. Parathyroid function recovered within 1 year in 78 per cent of patients with protracted HPP. Factors associated with late recovery of parathyroid function were higher serum calcium and low but detectable iPTH levels 1 month after surgery. These factors were associated with higher calcitriol and calcium dosages at hospital discharge. Parathyroid autotransplantation did not protect against permanent HPP.

CONCLUSIONS

Higher serum calcium levels at 1 month after total thyroidectomy are associated with recovery of parathyroid function. It is hypothesized that intensive medical treatment of hypocalcaemia-'parathyroid splinting'-may improve the outcome of patients with protracted HPP.

Bone disease is observed in 75-100% of patients with chronic renal failure as the glomerular filtration rate (GFR) falls below 60 ml/minute. Hyperparathyroid (high turnover) bone disease is found most frequently followed by mixed osteodystrophy, low-turnover bone disease, and osteomalacia. With advancing renal impairment, "skeletal resistance" to parathyroid hormone (PTH) occurs. To maintain bone turnover, intact PTH (iPTH) targets from two to four times the upper normal range have been suggested, but whole PTH(1-84) assays indicate that amino-terminally truncated fragments, which accumulate in end-stage renal disease (ESRD), account for up to one-half of the measured iPTH. PTH levels and bone-specific alkaline phosphatase (BSAP) provide some information on bone involvement but bone biopsy and histomorphometry remains the gold standard. Calcitriol and calcium salts can be used to suppress PTH and improve osteomalacia but there is growing concern that these agents predispose to the development of vascular calcification, cardiovascular morbidity, low-turnover bone disease and fracture. Newer therapeutic options include less calcemic vitamin D analogues, calcimimetics and bisphosphonates for hyperparathyroidism, and sevelamer for phosphate control. Calcitriol and hormone-replacement therapy (HRT) have been shown to maintain bone mineral density (BMD) in certain patients with end-stage renal disease (ESRD). After renal transplantation, renal osteodystrophy generally improves but BMD often worsens. Bisphosphonate therapy may be appropriate for some patients at risk of fracture. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and the careful use of an increasing number of effective therapies can reduce the morbidity associated with this common problem.

BACKGROUND

The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD.

METHODS

Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (< or = 1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline.

RESULTS

Two hundred twenty patients participated (n = 107, paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of placebo patients (P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and elevated calcium-phosphorus product levels were not significantly different between groups. Similarly, no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo.

CONCLUSIONS

Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD.

BACKGROUND

Vitamin D concentrations are linked to body composition indices, particularly body fat mass. Relationships between hypovitaminosis D and obesity, described by both BMI and waist circumference, have been mentioned. We have investigated the effect of a 12-week vitamin D3 supplementation on anthropometric indices in healthy overweight and obese women.

METHODS

In a double-blind, randomized, placebo-controlled, parallel-group trial, seventy-seven participants (age 38 ± 8.1 years, BMI 29.8 ± 4.1 kg/m²) were randomly allocated into two groups: vitamin D (25 μg per day as cholecalciferol) and placebo (25 μg per day as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D, iPTH, and dietary intakes were measured before and after the intervention.

RESULTS

Serum 25(OH)D significantly increased in the vitamin D group compared to the placebo group (38.2 ± 32.7 nmol/L vs. 4.6 ± 14.8 nmol/L; P<0.001) and serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26 ± 0.57 pmol/L vs. 0.27 ± 0.56 pmol/L; P<0.001). Supplementation with vitamin D3 caused a statistically significant decrease in body fat mass in the vitamin D group compared to the placebo group (-2.7 ± 2.1 kg vs. -0.47 ± 2.1 kg; P<0.001). However, body weight and waist circumference did not change significantly in both groups. A significant reverse correlation between changes in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P = 0.005).

CONCLUSIONS

Among healthy overweight and obese women, increasing 25(OH) D concentrations by vitamin D3 supplementation led to body fat mass reduction.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

BACKGROUND

Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. We assessed whether bariatric surgery alters the 25-hydroxyvitamin D (calcidiol) and intact parathyroid hormone (iPTH) levels in patients presenting with morbid obesity.

METHODS

A cross-sectional survey was conducted on 144 patients of whom 80 had not undergone bariatric surgery, while 64 had bariatric surgery at a mean of 36 months previously. Calcidiol levels were defined as being normal (>50 nmol/L), insufficient (2550 nmol/L) and deficient (<25 nmol/L). Mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus.

RESULTS

80% of the patients presented low vitamin D levels and mild secondary hyperparathyroidism. Previous surgery or the presence of diabetes did not influence calcidiol levels. Corrected serum calcium, phosphorus, alkaline phosphatase, iPTH and Calcidiol were similar between subjects with and without surgery.

CONCLUSIONS

Vitamin D deficient states with secondary hyperparathyroidism in the morbidly obese precede and are not significantly affected by bariatric surgery. Hypovitaminosis D with secondary hyperparathyroidism due to low calcidiol bio-availability should be added to the crowded list of sequelae of morbid obesity. While further studies are warranted, it seems advisable to support vitamin D supplementation in the morbidly obese population.

BACKGROUND

End-stage renal disease is often associated with altered bone metabolism.

METHODS

In order to investigate the determinant factors of bone mineral density (BMD) and the risk factors of fractures, we studied 70 patients; 26 women (23 post-menopausal) and 44 men, (mean+/-SD) aged 60.5+/-14.3 years, treated by standard haemodialysis (HD) for 6.4+/-6.8 years. Main circulating bone biochemical markers were assessed and BMD was measured with a Lunar DPX densitometer at five sites. BMD results are expressed as a function of age and gender (Z-score).

RESULTS

Mean Z-score was markedly decreased at the mid-radius (-2.75+/-1.23) whereas it was normal at the femoral neck (-0.42+/-1.13) and lumbar spine (0.02+/-2.13), and total body (-0.62+/-1.53). Time on HD was negatively correlated to the Z-score at the mid-radius and total body but not at the other sites. Serum intact parathyroid hormone (iPTH), whole PTH or cyclase activating PTH (CAP) and bone-specific alkaline phosphatase concentrations were negatively correlated with Z-scores at all sites. Twenty-one out of 70 patients had sustained a total of 27 fractures since the beginning of dialysis therapy (seven ribs, seven ankles, six vertebrae, three humerus, two wrists and two hips). They had a total body Z-score significantly lower than that of patients without fractures, -1.34+/-1.54 vs -0.37+/-1.46, respectively (P<0.031); however, their Z-scores at the other sites were not different. They were on HD for longer time, 10.4+/-9.5 vs 5.0+/-5.1, respectively (P<0.003), and the relative risk of skeletal fractures was 6.4 times greater after 10 years of HD. The seven patients with rib fractures had a decreased Z-score at most of the sites but not at the mid-radius. Rib fractures but no other fractures were associated with markedly decreased body weight, fat mass and serum leptin levels.

CONCLUSIONS

In conclusion, the Z-score at the mid-radius was decreased in HD patients and correlated with high serum PTH but not with fractures. Bone fractures were associated with the time passed on HD and with a low total body Z-score. Rib fractures were frequent and associated with a poor nutritional state.

Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk factor for osteoporosis and fracture. We determined serum levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X-ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency [25(OH)D < or = 15 ng/ml] was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 +/- 5.3 ng/ml vs. 21.8 +/- 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio [OR], 4.17, 1.83-9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.

To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001). They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score. Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.

BACKGROUND

Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial.

METHODS

Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment.

RESULTS

Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups.

CONCLUSIONS

Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4.

BACKGROUND

This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids.

METHODS

Phosphate binders were discontinued during a two-week washout period. Patients whose serum phosphorus was more than 6.0 mg/dl during washout were eligible for treatment. RenaGel(R), at starting doses of two, three, or four 440 mg capsules three times per day with meals, was administered to 172 hemodialysis patients for eight weeks. RenaGel(R) could be increased by one capsule per meal every two weeks as necessary to achieve serum phosphorus control. A second two-week washout period followed.

RESULTS

Mean serum phosphorus rose from 6.8 +/- 2.0 mg/dl at prewashout to 9.1 +/- 2.4 mg/dl at the end of the washout period. It then declined to 6.6 +/- 1.9 mg/dl by the end of the eight-week RenaGel(R) treatment period (P < 0. 0001). Serum phosphorus increased to 8.0 +/- 2.2 mg/dl at the end of the second washout period. The mean dose at the end of RenaGel(R) treatment was 5.4 g per day. Eighty-four percent of the patients previously used calcium-based phosphate binders. As expected, calcium declined during the initial washout period when calcium-based phosphate binders were discontinued. Mean serum calcium declined from 9.6 +/- 1.0 mg/dl at prewashout to 9.1 +/- 0.8 mg/dl after washout. It then increased to 9.4 +/- 0.9 mg/dl by the end of RenaGel(R) treatment. Median serum iPTH increased during the two-week washout from 208 pg/ml to 316 pg/ml and then declined to 224 pg/ml at the end of the eight-week treatment period (P < 0.0001 vs. end of initial washout). After eight weeks of treatment, RenaGel(R) reduced mean serum total cholesterol from 171.0 +/- 43.1 mg/dl to 145.0 +/- 38.7 mg/dl (P < 0.0001) and mean serum low-density lipoprotein cholesterol from 102.0 +/- 34.9 mg/dl to 75. 6 +/- 29.4 mg/dl (P < 0.0001). High-density lipoprotein cholesterol, triglycerides, and serum albumin did not change.

CONCLUSIONS

RenaGel(R), a novel and calcium- plus aluminum-free effective phosphate binder, can control serum phosphorus and reduce the levels of PTH and cholesterol without inducing hypercalcemia or other side effects. Thus, this new phosphate binder may be effective in the treatment of renal osteodystrophy in uremic patients.

OBJECTIVE

To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women.

METHODS

Randomized, double-blind, placebo-controlled intervention trial.

METHODS

Basel, Switzerland.

METHODS

Three hundred seventy-eight community-dwelling elderly (191 women/187 men).

METHODS

Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks.

METHODS

Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire.

RESULTS

At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed.

CONCLUSIONS

Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.

BACKGROUND

The use of calcium- or aluminum-based phosphate binders against hyperphosphatemia is limited by the adverse effects of hypercalcemia or aluminum toxicity in long-term hemodialysis. Because nicotinamide is an inhibitor of sodium-dependent phosphate cotransport in rat renal tubule and small intestine, we examined whether nicotinamide reduces serum levels of phosphorus and intact parathyroid hormone (iPTH) in patients undergoing hemodialysis.

METHODS

Sixty-five hemodialysis patients with a serum phosphorus level of more than 6.0 mg/dL after a 2-week washout of calcium carbonate were enrolled in this study. Nicotinamide was administered for 12 weeks. The starting dose was 500 mg/day, and the dose was increased by 250 mg/day every 2 weeks until serum phosphorus levels were well controlled at less than 6.0 mg/dL. A 2-week posttreatment washout period followed the cessation of nicotinamide. Blood samples were collected every week for measurement of serum calcium, phosphorus, lipids, iPTH, and blood nicotinamide adenine dinucleotide (NAD).

RESULTS

The mean dose of nicotinamide was 1080 mg/day. The mean blood NAD concentration increased from 9.3 +/- 1.9 nmol/105 erythrocytes before treatment to 13.2 +/- 5.3 nmol/105 erythrocytes after treatment (P < 0.01). The serum phosphorus concentration increased from 5.4 +/- 1.5 mg/dL to 6.9 +/- 1.5 mg/dL with the pretreatment washout, then decreased to 5.4 +/- 1.3 mg/dL after the 12-week nicotinamide treatment (P < 0.0001), and rose again to 6.7 +/- 1.6 mg/dL after the posttreatment washout. Serum calcium levels decreased during the pretreatment washout from 9.1 +/- 0.8 mg/dL to 8.7 +/- 0.7 mg/dL with the cessation of calcium carbonate. No significant changes in serum calcium levels were observed during nicotinamide treatment. Median serum iPTH levels increased with pretreatment washout from 130.0 (32.8 to 394.0) pg/mL to 200.0 (92.5 to 535.0) pg/mL and then decreased from the maximum 230.0 (90.8 to 582.0) pg/mL to 150.0 (57.6 to 518.0) pg/mL after the 12-week nicotinamide treatment (P < 0.05). With nicotinamide, serum high-density lipoprotein (HDL) cholesterol concentrations increased from 47.4 +/- 14.9 mg/dL to 67.2 +/- 22.3 mg/dL (P < 0.0001) and serum low-density lipoprotein (LDL) cholesterol concentrations decreased from 78.9 +/- 18.8 mg/dL to 70.1 +/- 25.3 mg/dL (P < 0.01); serum triglyceride levels did not change significantly.

CONCLUSIONS

Nicotinamide may provide an alternative for controlling hyperphosphatemia and hyperparathyroidism without inducing hypercalcemia in hemodialysis patients.

OBJECTIVE

Vitamin D deficiency is an important health problem in both developed and developing countries. Recent reports on the extraskeletal effects of vitamin D have led to increased interest in prevalence studies on states of deficiency/insufficiency of vitamin D. The aim of this study was to determine the frequency of vitamin D deficiency and insufficiency in children and adolescents residing in Ankara, Turkey and to investigate the factors associated with low vitamin D status.

METHODS

A total of 440 children and adolescents aged between 0 and 16 years were enrolled in this study. The subjects were divided into three groups according to their vitamin D status (deficiency ≤15 ng/mL; insufficiency: 15-20 ng/mL; sufficiency ≥20 ng/mL) and also according to their age (preschool<5 years; middle childhood: 5-10 years; adolescence: 11-16 years).

RESULTS

Overall, 40% of the subjects were found to have 25 hydroxy vitamin D [25(OH)D] levels of less than 20 ng/mL. The levels indicated a deficiency state in 110 subjects (25%) and insufficiency - in 66 (15%). The rate of vitamin D deficiency was higher in girls, regardless of age. 25(OH)D levels correlated negatively with age (r=-0.48, p<0.001), body mass index (BMI) (r=-0.20, p=0.001) and intact parathyroid hormone (iPTH) level (r=-0.31, p=0.001). A positive correlation was observed between 25(OH)D and serum ferritin levels (r=0.15, p=0.004).

CONCLUSIONS

The high frequency of vitamin D deficiency in childhood (especially among adolescent girls) indicates a need for supplementation and nutritional support.

ABSTRACT : BACKGROUND : The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS : Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS : Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 +/- 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION : High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.

BACKGROUND

Although the incidence of sudden cardiac death (SCD) is high among haemodialysis (HD) patients, there are few papers available on this topic. The aim of this study on a single-centre HD population observed over a 10 year period was to identify patient- and HD-related specific factors that might be associated with a higher risk of SCD.

METHODS

The study included 123 patients (76 men; age 29-79 years) undergoing renal replacement therapy at our dialysis unit for at least 6 months. For each patient, routine laboratory tests were performed monthly, blood pressure was measured both at the start and the end of each dialysis session, haemoglobin and pre-dialysis serum K(+) were determined weekly, serum iPTH was assessed thrice yearly, and an echocardiographic study was performed annually to determine the left ventricular mass index (LVMi). The prevalence of cardiovascular (CV) co-morbidities, and the incidence of new events were also recorded.

RESULTS

During the 10 years, 85 patients died-16 from SCD, 30 from cardiac causes (CC) other than SCD, and 39 from other causes (OC); 38 patients were still alive (AL) at the end of the observation period. Comparative analysis of SCD, CC, OC and AL, reveals that the male prevalence (13/3) was higher in SCD than in AL, while AL were younger than the deceased patients regardless of the cause of death (P<0.0001; ANOVA), the duration of arterial hypertension was higher in SCD (129+/-104 months; P = 0.0005; ANOVA), despite similar antihypertensive therapies, and the difference between LVMi at end-point and at inception (deltaLVMi) was significantly higher in SCD [+56+/-38 g/m(2) body surface area] compared with OC (-5+/-35), AL (-17+/-25) and even CC (7+/-30) (P<0.0001; ANOVA); finally, the prevalence of patients with ischaemic heart disease (IHD) was higher in the SCD group (11/5; P<0.0001, chi(2)). Univariate Cox regression analysis demonstrated that the factors increasing the risk of SCD were IHD (P = 0.002), the worsening of left ventricular hypertrophy (LVH) (P<0.0001), and the presence of long-lasting arterial hypertension (P = 0.001). An increase in LVH was the sole risk factor for SCD when comparing SCD with CC patients (P = 0.003). By multivariate Cox regression analysis deltaLVMi was identified as the strongest predictor of SCD (P<0.0001).

CONCLUSIONS

While confirming the role of common CV risk factors for SCD in dialysis patients such as IHD and arterial hypertension, this study is the first to demonstrate that the worsening of LVH is the strongest predictor of sudden death.

BACKGROUND

Vitamin D deficiency is frequently observed in end-stage renal disease (ESRD) patients; however, the effects of vitamin D supplementation have rarely been reported. We aimed to assess the effects of daily 25(OH)D(3) supplementation on mineral metabolism, bone markers and Kidney Disease Outcomes Quality Initiative (KDOQI) targets in haemodialysis (HD) patients for a period of 6 months.

METHODS

HD patients were included in this study if their serum 25(OH)D level was <75 mmol/L. Oral 25(OH)D(3) was administered daily at 10-30 microg/day based on the severity of the deficiency. Characteristics of the patients were compared from the baseline to 6 months on the basis of their response to 25(OH)D(3) administration and the patients were divided into three groups. Patients who showed partial response [serum 25(OH)D <75 nmol/L] were placed in group 1, those who showed normal response [serum 25(OH)D ranging from 75 to 150 nmol/L] were placed in group 2 and those who showed excessive response [serum 25(OH)D >150 nmol/L] were placed in group 3.

RESULTS

Of the 253 HD patients, 225 (89%) showed vitamin D insufficiency or deficiency, 172 were included in the study and 149 patients completed the study. After 6 months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], the serum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P < 0.001), with 13% of patients in group 1, 57% in group 2 and 30% in group 3. The serum intact parathyroid hormone (iPTH) level decreased (235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bone alkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16 to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease in alfacalcidol administration from 66% to 43% (P < 0.05), except in group 1. The KDOQI targets achieved increased significantly for serum calcium (76% to 85%) and phosphate levels (66% to 77%) in all patients. The serum albumin level increased in all groups (34.6 +/- 4 to 36.8 +/- 4 g/L, P < 0.05), without any significant improvement in normalized protein catabolic rate (nPCR) or C-reactive proteins (CRP).

CONCLUSIONS

With a daily dose ranging from 10 to 30 microg, daily oral 25(OH)D(3) supplementation corrects most vitamin D deficiencies or insufficiencies in HD patients, without any evident toxicity. The main effects observed included correction of excessive bone turnover, despite less alfacalcidol administration, increase in serum albumin level and increase in the percentage of patients with serum calcium and phosphorus levels within the recommendation of the KDOQI guidelines.

Little is known about the prevalence of actual vitamin D deficiency in healthy school-aged adolescents, particularly in China. The aim of this study was to examine the prevalence of hypovitaminosis D and to identify whether there was any association between vitamin D status, body composition and physical exercise in 323 Chinese adolescent girls in Beijing, China (40 degrees N).

BACKGROUND

It is well recognized that persistent severe vitamin D deficiency is associated with the bone abnormalities of rickets and osteomalacia. However, there is now evidence suggesting that low vitamin D status, not previously considered to be a state of deficiency is associated with secondary hyperparathyroidism, increased bone remodelling and other clinical signs thought only to be found in severe vitamin D deficiency. Hypovitaminosis D in healthy children and adolescents has been reported frequently in many countries, especially in winter.

METHODS

We performed a cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter. Mean age of the subjects was 15.0 (+/-0.4) years. About 32.8%, 68.4% and 89.2% of the subjects were at risk of vitamin D deficiency when defined as plasma concentrations of 25OHD of 25, 37.5 or 50 nmol/L, respectively.

RESULTS

This cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter showed that hypovitaminosis D was common in these subjects. In addition, body mass index, milk intake, participation in organized sports and total physical activity were all significant independent determinants of vitamin D status. An inverse association was found between plasma 25OHD and intact-parathyroid hormone (iPTH) concentration. Body mass index (BMI), milk intake, participation in organized sports and total physical activity all emerged as major independent determinants of vitamin D status as assessed by plasma 25OHD concentration. Vitamin D status was positively associated with lean body mass (LBM), but there was no association with the degree of body adiposity. Regardless of the concentration of 25OHD in blood used to define vitamin D deficiency, hypovitaminosis D was common in these subjects.

CONCLUSIONS

It is recommended that policies be developed to prevent vitamin D deficiency in adolescent girls. Further studies are needed to identify the mechanisms whereby vitamin D status is related to exercise and to body composition during growth.

BACKGROUND

A variety of minimally invasive parathyroidectomy (MIP) techniques have been currently introduced to surgical management of primary hyperparathyroidism (pHPT) caused by a solitary parathyroid adenoma. This study aimed at comparing the video-assisted MIP (MIVAP) and open MIP (OMIP) in a prospective, randomized, blinded trial.

METHODS

Among 84 consecutive pHPT patients referred for surgery, 60 individuals with concordant localization of parathyroid adenoma on ultrasound and subtraction Tc99m-MIBI scintigraphy were found eligible for MIP under general anesthesia and were randomized to two groups (n = 30 each): MIVAP and OMIP. An intraoperative intact parathyroid hormone (iPTH) assay was routinely used in both groups to determine the cure. Primary end-points were the success rate in achieving the cure from hyperparathyroid state and hypocalcemia rate. Secondary end-points were operating time, scar length, pain intensity assessed by the visual-analogue scale, analgesia request rate, analgesic consumption, quality of life within 7 postoperative days (SF-36), cosmetic satisfaction, duration of postoperative hospitalization, and cost-effectiveness analysis.

RESULTS

All patients were cured. In 2 patients, an intraoperative iPTH assay revealed a need for further exploration: in one MIVAP patient, subtotal parathyroidectomy for parathyroid hyperplasia was performed with the video-assisted approach, and in an OMIP patient, the approach was converted to unilateral neck exploration with the final diagnosis of double adenoma. MIVAP versus OMIP patients were characterized by similar operative time (44.2 +/- 18.9 vs. 49.7 +/- 15.9 minutes; P = 0.22), transient hypocalcemia rate (3 vs. 3 individuals; P = 1.0), lower pain intensity at 4, 8, 12, and 24 hours after surgery (24.9 +/- 6.1 vs. 32.2 +/- 4.6; 26.4 +/- 4.5 vs. 32.0 +/- 4.0; 19.6 +/- 4.9 vs. 25.4 +/- 3.8; 15.5 +/- 5.5 vs. 20.4 +/- 4.7 points, respectively; P < 0.001), lower analgesia request rate (63.3% vs. 90%; P = 0.01), lower analgesic consumption (51.6 +/- 46.4 mg vs. 121.6 +/- 50.3 mg of ketoprofen; P < 0.001), better physical functioning aspect and bodily pain aspect of the quality of life on early recovery (88.4 +/- 6.9 vs. 84.6 +/- 4.7 and 90.3 +/- 4.7 vs. 87.5 +/- 5.8; P = 0.02 and P = 0.003, respectively), shorter scar length (17.2 +/- 2.2 mm vs. 30.8 +/- 4.0 mm; P < 0.001), and higher cosmetic satisfaction rate at 1 month after surgery (85.4 +/- 12.4% vs. 77.4 +/- 9.7%; P = 0.006). Cosmetic satisfaction was increasing with time, and there were no significant differences at 6 months postoperatively. MIVAP was more expensive (US$1,150 +/- 63.4 vs. 1,015 +/- 61.8; P < 0.001) while the mean hospital stay was similar (28 +/- 10.1 vs. 31.1 +/- 9.7 hours; P = 0.22). Differences in serum calcium values and iPTH during 6 months of follow-up were nonsignificant. Transient laryngeal nerve palsy appeared in one OMIP patient (P = 0.31). There was no other morbidity or mortality.

CONCLUSIONS

Both MIVAP and OMIP offer a valuable approach for solitary parathyroid adenoma with a similar excellent success rate and a minimal morbidity rate. Routine use of the intraoperative iPTH assay is essential in both approaches to avoid surgical failures of overlooked multiglandular disease. The advantages of MIVAP include easier recognition of recurrent laryngeal nerve (RLN), lower pain intensity within 24 hours following surgery, lower analgesia request rate, lower analgesic consumption, shorter scar length, better physical functioning and bodily pain aspects of the quality of life on early recovery, and higher early cosmetic satisfaction rate. However, these advantages are achieved at higher costs because of endoscopic tool involvement.

Serum bone Gla protein (BGP) was measured by radioimmunoassay in 166 healthy men and women aged 30-90 years. Serum BGP levels increased with age in both sexes and were higher in women than in men at all ages. The most striking rise occurred in women after age 40-49. BGP was significantly correlated positively with serum alkaline phosphatase and negatively with midshaft and distal bone mass in both sexes. In women only, BGP levels were significantly positively related to levels of immunoreactive parathyroid hormone (iPTH). When age was included in the multiple regression analysis BGP was still correlated with alkaline phosphatase in both sexes and iPTH in women only. Serum BGP levels were significantly higher in 13 osteoporotic patients than in age-matched controls. It is postulated that with increasing age 1,25-dihydroxyvitamin D levels fall, causing a rise in iPTH and thus in bone turnover, which is reflected by a rise in BGP levels.

BACKGROUND

The predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.

METHODS

Dialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.

RESULTS

Sixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the <em>iPTH</em> levels, calcium x phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, <em>iPTH</em>, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment <em>iPTH</em> and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 </=9860 ng/L and <em>iPTH</em> </=591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and <em>iPTH</em> >591 pg/mL.

CONCLUSIONS

Pretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism.

BACKGROUND

Sudden cardiac death is common in patients on hemodialysis (HD), and its rate is as high as 25% of all cardiac deaths associated with left ventricular hypertrophy (LVH) and secondary hyperparathyroidism. A prolonged QT interval on standard electrocardiography is related to an increase in sudden death in various patient groups. It is also well known that LVH has been noted in uremic patients with high parathyroid hormone levels.

METHODS

To evaluate the response of intravenous calcitriol treatment on the QT interval and LVH in HD patients with secondary hyperparathyroidism (intact parathyroid hormone, iPTH,>> 450 ng/ml), echocardiographic, electrocardiographic (ECG), and biochemical assessments were performed over a 15-week period in 25 HD patients before and after intravenous calcitriol treatment. We also evaluated 25 age-, sex-, HD duration-, and BMI-matched HD control patients with secondary hyperparathyroidism.

RESULTS

In patients receiving intravenous calcitriol, a significant reduction in iPTH levels (p < 0.05) and alkaline phosphatase levels (p < 0.01) was found without changes in values of serum calcium and ionized Ca2+, phosphorus, Na+, K+, Mg2+, hematocrit, blood pressure, or other hemodynamic changes. Echocardiograms showed significant decreases in the thickness of the interventricular septum (p < 0.05), left posterior wall thickness (p < 0.05), and left ventricle mass index (LVMi, p < 0.01). In addition, sequential ECG measurement in patients with calcitriol treatment showed significant reductions in QTcmax (QTmax interval corrected for heart rates, p < 0.01) and QTc dispersion (QT dispersion corrected for heart rates, p < 0.01). However, in the control patients, biochemical, hemodynamic, and ECG changes, as well as myocardial structural and functional changes were not seen. Multiple regression analysis in all patients indicated that iPTH and LVMi levels were independent predictors of QTcmax while the LVMi level was the only independent predictor of QTc dispersion (p < 0.05).

CONCLUSIONS

Our study showed a significant correlation between LVMi and QT dispersion in HD patients with secondary hyperparathyroidism. Intravenous calcitriol treatment, to be used for the control of secondary hyperparathyroidism, was found to cause regression of myocardial hypertrophy and a reduction in the QTc interval and dispersion, without biochemical and hemodynamic changes. These findings suggest that an active vitamin D metabolite has a cardioprotective action in HD patients.

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

BACKGROUND

Sclerostin is a soluble inhibitor of osteoblast function. Sclerostin is downregulated by the parathyroid hormone (PTH). Here, it was investigated whether sclerostin levels are influenced by intact (i) PTH and whether sclerostin is associated with bone turnover, microarchitecture and mass in dialysis patients.

METHODS

Seventy-six haemodialysis patients and 45 healthy controls were included in this cross-sectional study. Sclerostin, Dickkopf-1 (DKK-1), intact parathyroid hormone (iPTH), vitamin D and markers of bone turnover were analysed. A subset of 37 dialysis patients had measurements of bone mineral density (BMD) using dual-energy X-ray absorptiometry and bone microarchitecture using high-resolution peripheral quantitative computed tomography.

RESULTS

Dialysis patients had significantly higher sclerostin levels than controls (1257 pg/mL versus 415 pg/mL, P < 0.001). Significant correlations were found between sclerostin and gender (R = 0.41), iPTH (R = -0.28), 25-hydroxy-cholecalciferol (R = 0.27) and calcium (R = 0.25). Gender and iPTH remained significantly associated with sclerostin in a multivariate analysis. Sclerostin serum levels were positively associated with BMD at the lumbar spine (R = 0.46), femoral neck (R = 0.36) and distal radius (R = 0.42) and correlated positively mainly with trabecular structures such as trabecular density and number at the radius and tibia in dialysis patients. DKK-1 was related neither to bone measures nor to serologic parameters.

CONCLUSIONS

Considering that sclerostin is an inhibitor of bone formation, the observed positive correlations of serum sclerostin with BMD and bone volume were unexpected. Whether its increase in dialysis patients has direct pathogenetic relevance or is only a secondary phenomenon remains to be seen.