OBJECTIVE

Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed condition among adolescents and young adults. We review the clinical characteristics of these patients based on our institutional experience.

METHODS

Patients aged 12-28 years treated for PHPT at our institution from 1990 to 1996 were evaluated by a review of medical records and current follow-up data. This consisted of 22 patients (8M:14F), constituting approximately 3% of all patients operated for PHPT during this period.

METHODS

Serum and urinary calcium concentrations, renal function, and serum intact parathyroid hormone (IPTH) levels were measured in all patients. After biochemical confirmation of diagnosis, the patients completed a questionnaire to evaluate the presence of symptoms and/or conditions associated with PHPT. All the patients underwent parathyroidectomy and their tumour characteristics were evaluated. Surgical outcome was determined by measurements of serum calcium and IPTH levels postoperatively and during long-term follow-up.

RESULTS

A third of the patients were diagnosed by routine serum chemistry whereas two-thirds presented with symptoms or conditions associated with hypercalcaemia. Non-specific complaints such as fatigue or exhaustion, and weakness or lethargy constitute the most common findings on questionnaire review. A family history of PHPT was present in only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to 4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young adults (aged 19-28 years) revealed no differences in the clinical, pathological or laboratory profiles, except for a male predominance in adolescent patients. Fifteen patients had resection of one or more adenomas while 7 underwent subtotal parathyroidectomy. Six patients (27%) were reoperated cases, all received primary treatment elsewhere. All patients with benign PHPT were cured surgically, with a median follow-up of 47 months (range 3-77 months). One reoperated patient developed permanent hypocalcaemia. One patient with carcinoma underwent several operations for recurrence; he is now eucalcaemic despite persistent disease at 80 months from diagnosis.

CONCLUSIONS

We found a high incidence of multiglandular disease and relatively non-specific symptomatology in our adolescent and young adult patients with primary hyperparathyroidism. In view of the heterogeneous clinical expression noted in young patients, one should consider primary hyperparathyroidism in the differential diagnosis of unexplained non-specific complaints, and perform serum calcium estimations more readily in these subjects. Our experience suggests that primary hyperparathyroidism can be a serious disease with significant morbidity if left untreated, whereas parathyroidectomy provides successful results.

BACKGROUND

Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism.

METHODS

Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months.

RESULTS

During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P<0.001). iPTH decreased from 308.85+/-120.12 to 214.66+/-53.75 mg/dL (P<0.05). The mean serum creatinine decreased from 1.58+/-0.34 to 1.25+/-0.27 mg/dL (P=0.03) and the mean radial BMD increased from 0.881+/-0.155 to 0.965+/-0.123 gr/cm2 (P<0.05). There were no significant changes in the other parameters assessed. One patient was excluded for gastrointestinal intolerance.

CONCLUSIONS

In RT patients with hypercalcemia secondary to persistent SHP, cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.

BACKGROUND

Increased serum levels of bone-resorptive cytokines such as interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) have been implicated for changes in bone remodeling in hemodialysis patients. In this prospective randomized study, we aimed to compare the effect of oral and intravenous (IV) pulse calcitriol on serum levels of IL-1 beta and IL-6.

METHODS

Twenty-eight hemodialysis patients were included and consecutively randomized to receive either oral (n = 14, M/F = 7/7, mean age 42 +/- 15 years) or IV pulse (n = 14, M/F = 6/8, mean age 38 +/- 14 years) calcitriol treatment. No difference was found between groups for age, sex distribution, primary renal disease, mean time on hemodialysis and baseline biochemical parameters including serum levels of IL-1 beta and IL-6.

RESULTS

The percent fall of intact parathyroid hormone (iPTH) was significantly less with oral compared to IV calcitriol between 0 and the 3rd month (32 +/- 21 vs. 56 +/- 28%, p = 0.03). However, the percent fall in iPTH at the 6th month of the therapy was not different in the oral group compared to the IV group (57 +/- 22 vs. 73 +/- 24%, p = 0.12). The increase in bone mineral densities was higher in the IV group than the oral group. Oral and IV calcitriol caused a significant fall in IL-1 beta (p = 0.02 and p = 0.03, respectively) and IL-6 levels (p = 0.02 and p < 0.001, respectively) at the 6th month of treatment. The percent fall in serum IL-6 levels at the 6th month was significantly greater in the IV compared to the oral group (61 +/- 18 vs. 36 +/- 33%, p = 0.04), while the percent changes in serum IL-1 beta levels were similar.

CONCLUSIONS

IV calcitriol therapy has a greater suppression of PTH at the 3rd month of the therapy. Despite no difference in serum PTH levels at the 6th month, IV therapy has a greater increase in bone mineral densities and a greater decrease in serum IL-6 levels. These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group, beyond its suppressive effect on iPTH.

BACKGROUND

Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients.

METHODS

Double blind, placebo-controlled.

METHODS

Hemodialysis units and pediatric subjects receiving hemodialysis.

METHODS

After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level>> 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)).

METHODS

Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product.

RESULTS

60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group.

CONCLUSIONS

Low power to detect differences in safety between groups and a short-term study.

CONCLUSIONS

Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.

Bone mineral density was studied in 200 healthy Indian men above 50 years age, without fractures or osteoporosis. Mean vitamin D was 18.96 ng/ml; other biochemical evaluations were normal. Bone density (femur neck) decreased with age; there was osteoporosis in 8.5 %, osteopenia in 42 %, while 49.5 % were normal. Vitamin D deficiency may have caused osteoporosis.

OBJECTIVE

Osteoporosis is recognized as the disease of females; however, males are also affected and have serious consequences thereof. The present study aimed at studying the prevalence of osteoporosis in otherwise healthy Indian males aged 50 years or more and studying the factors affecting bone mineral density (BMD).

METHODS

With informed consent, 200 healthy males aged 50 years or more without the history of fractures or diseases affecting the BMD were evaluated clinically (including anthropometry) and biochemically (serum calcium, phosphate, alkaline phosphatase, creatinine, albumin, 25-OH Vitamin D, intact parathyroid hormone (iPTH), and testosterone). The BMD was measured by single observer on Lunar DPX-NT at right proximal femur for least effects of artifacts. Calculation of T score and categorization as osteoporosis, osteopenia, and normal BMD was done as per WHO classification.

RESULTS

The mean age was 62.61 ± 7.64 years, and BMI was 23.90 ± 3.73 kg/m(2). The testosterone levels were normal in 84 % subjects. The mean 25-OH vitamin D level was 18.96 ± 10.23 ng/ml; only 13.5 % subjects had normal levels. The mean iPTH level was 72.60 ± 43.77 pg/ml; 57 % subjects had normal iPTH (12-72 pg/ml). The other parameters studied were normal. The osteoporosis and osteopenia were more prevalent when BMD was evaluated at neck of femur (osteoporosis 8.5 vs 8 % at trochanter and 7.5 % at total right hip; osteopenia 42 vs 37 % at trochanter and 41 % at total right hip). The BMD deteriorated with age.

CONCLUSIONS

The osteoporosis affects 8.5 % of otherwise healthy males aged 50 years and above. Vitamin D deficiency is common in such group and maybe responsible for osteoporosis.

OBJECTIVE

Suboptimal levels of 25-hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease-5D: CKD-5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD-5D.

BACKGROUND

Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD-5D.

METHODS

This is a cross-sectional study of 25 CKD-5D patients with predialysis 25OHD, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen((c)) test (FST), Berg Balance Scale (BBS), timed 'up and go' (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES).

RESULTS

Mean age was 69.8 +/- 12.1 years, and median time on dialysis was 3.1 years. Median 25OHD level was 55.3 nmol/l (range 20.8-125.8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0.024) but not with 1,25(OH)(2)D (P = 0.477) or PTH (P = 0.461). Statistically significant correlation between 25OHD levels and FST (P = 0.028) plus MBI (P = 0.0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)(2)D or PTH.

CONCLUSIONS

Suboptimal levels of 25OHD in CKD-5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)(2)D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD-5D.

OBJECTIVE

To compare vitamin D status in an African population living at 10 degrees N with a Norwegian population living at 60 degrees N.

METHODS

Serum samples from 30 healthy young Ethiopians and 31 full term pregnant women from Addis Ababa were collected in September, and from 24 healthy Norwegians in March and 23 pregnant women from Oslo in February to June.

METHODS

Serum (s) levels of calcidiol and intact parathyroid hormone (iPTH) were measured.

RESULTS

The median values for s-calcidiol were significantly lower in Ethiopians compared with Norwegians (young Ethiopians 23.5nmol/l vs young Norwegians 81nmol/l, P<0.001; pregnant Ethiopians 25nmol/l vs pregnant Norwegians 36nmol/l, P<0.05) while those for s-iPTH were significantly higher (young Ethiopians 5.7pmol/l vs young Norwegians 2.4pmol/l, P<0.001; pregnant Ethiopians 4.8pmol/l vs pregnant Norwegians 2.8pmol/l, P<0.02).

CONCLUSIONS

In spite of abundant availability of ultraviolet radiation, the population from Addis Ababa had a high rate of biochemical vitamin D deficiency compared with the Norwegian group.

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

BACKGROUND

Patients with chronic kidney disease, especially those undergoing dialysis treatment and having secondary hyperparathyroidism, have a high risk of bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic bone resorption. We aimed to examine whether the use of RAS inhibitors reduces the incidence of fracture in hemodialysis patients.

RESULTS

This was a multicenter, 3-year, prospective, observational study. From 2008 to 2011, maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276) treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The association between the use of ACEI/ARB and hospitalization rate owing to fracture was examined by using Cox regression models. Effect modifications by the severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH] level), sex, and systolic blood pressure were also examined. The incidence proportion of fracture-related hospitalization was 5.42% throughout the observation period. ACEI/ARB use was associated with a lower rate of fracture-related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval [CI], 0.45-0.92). This association was not significantly affected by sex (P = 0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by iPTH levels were qualitatively different, but not statistically significant (P = 0.11): 0.77 (95% CI, 0.42-1.39), 0.38 (95% CI, 0.20-0.73), 0.59 (95% CI, 0.29-1.21), and 1.29 (95% CI, 0.58-2.42) for the first, second, third and fourth quartiles of iPTH, respectively.

CONCLUSIONS

Use of RAS inhibitors is associated with a lower rate of fracture-related hospitalization in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND

ClinicalTrials.gov NCT00995163.

OBJECTIVE

Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients.

METHODS

A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases.

RESULTS

Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH>>/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD.

CONCLUSIONS

These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.

OBJECTIVE

This study had 2 aims: (1) to assess the timing and magnitude of psychological and neurocognitive changes before and after parathyroidectomy and (2) to examine correlations between changes in serum biomarkers and psychological symptoms and neurocognitive performance.

BACKGROUND

Psychological and neurocognitive changes are common in patients with primary hyperparathyroidism (pHPT), but the associations of serum biomarkers and these changes have not been established.

METHODS

This prospective cohort study carried out at a large tertiary care referral center from 2004 to 2008 screened all adult patients with the biochemical diagnosis of pHPT who underwent first-time parathyroidectomy. Laboratory results, psychological symptom reports, and results of neurocognitive testing using validated instruments were obtained preoperatively and at 1, 3, and 6 months postoperatively. Outcomes measures included serum calcium, intact parathyroid hormone (iPTH), and thyroid stimulating hormone; psychological symptom inventories (Beck Depression Inventory-II, Brief Symptom Inventory-18, and Spielberger State-Trait Anxiety Inventory); and neurocognitive test scores (Rey Auditory Verbal Learning Test and Groton Maze Learning Test).

RESULTS

Two hundred twelve patients were enrolled; mean age was 60 years; 78% were female and had low comorbidity; 78% had parathyroidectomy under ambulatory, minimally invasive techniques; cure rate was 99%. Improvements in psychological and neurocognitive measures were observed at all postoperative follow-up visits. The most pronounced improvements were noted in depressive and anxiety symptoms, and visuospatial and verbal memory. Examination of change scores revealed that postoperative reduction in iPTH was associated with a decrease in state anxiety, which was also associated with improvement in visuospatial working memory.

CONCLUSIONS

Reduction in mood and anxiety symptoms is associated with reductions in both iPTH and spatial working memory in patients with pHPT who undergo successful parathyroidectomy.

Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m(2) after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced.

OBJECTIVE

Persons with ESRD identify non-disease-specific conditions as negatively affecting their quality of life. It is unknown how these non-ESRD-specific conditions correlate with each other and with ESRD-specific conditions such as anemia, renal osteodystrophy, dialysis access, and dialysis adequacy. The objectives of this study were to determine the prevalence and inter-relatedness of selected conditions among persons receiving hemodialysis and to analyze the relationship between non-ESRD-specific and ESRD-specific conditions.

METHODS

This was an observational cohort study of persons with ESRD that included standardized assessments for pain, fatigue, depression, cognitive impairment, and impaired physical performance. The study was conducted at three dialysis clinics in one urban geographic area. Of the 134 persons who met exclusion criteria, 25 declined participation, yielding a sample size of 109.

RESULTS

Pain was present in >81% of participants, fatigue and impaired physical performance in >60% participants, and cognitive impairment and depression in >25% of participants. Pain, fatigue, and depression were highly correlated, but had no correlation with use of a catheter for access, hemoglobin (Hgb), intact parathyroid hormone (iPTH), phosphorous, or Kt/V values outside of the range of guidelines. There was a modest correlation between cognitive function and both Hgb and iPTH.

CONCLUSIONS

Non-ESRD-specific conditions such as fatigue, pain, and depression are as prevalent as ESRD-specific conditions, and the magnitude of the correlations between the non-ESRD-specific conditions is greater than the correlations between non-ESRD-specific and ESRD-specific conditions. Current guidelines may be failing to address a substantial component of the disease burden for persons with ESRD.

Hemodialyzed patients have decreased bone strength not completely characterized. We evaluated bone microarchitecture in hemodialysis patients and compared it to that of subjects without renal disease by high-resolution peripheral quantitative computed tomography (HR-pQCT). Hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women.

BACKGROUND

Although fracture risk is greatly increased in dialysis patients, the corresponding decreased in bone strength has not been completely characterized.

METHODS

We evaluated volumetric bone mineral density (vBMD) and bone microstructure by HR-pQCT at the distal radius and tibia in 50 hemodialyzed (HD) patients (30 females, mean age 53.2 ± 6 years and 20 males, mean age 59.1 ± 11 years) and 50 sex- and age-matched controls.

RESULTS

At the distal radius HD, women showed a 29% reduction in total and trabecular density and trabecular bone volume fraction (p < 0.0001) compared to controls. Trabecular number was reduced by 25% (p < 0.0001), while trabecular separation was increased by 51%. Cortical thickness (-40%, p < 0.0001) and cortical area (-42%, p < 0.0001) were the parameters most reduced, while compact density was the parameter least reduced (-15%, p < 0.0001). Similar findings were found at the tibia. In HD men, HR-pQCT at the distal radius and tibia showed a reduction in volumetric density and microstructure parameters to a lesser extent than in women. In the hemodialyzed group, cortical thickness at the radius was negatively correlated with age both in women and men. At the distal radius and tibia, we found significant negative correlations between Log iPTH and total alkaline phosphatase with cortical vBMD(r = -0.48, p < 0.01; r = -0.69, p < 0.001), thickness (-0.37, p < 0.05; r = -0.60, p < 0.001), and area ((r = -0.43, p = 0.02; r = -0.65, p < 0.001) but only in women.

CONCLUSIONS

We conclude that hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women.

The relationship between serum 25(OH)D and intact parathyroid hormone (iPTH) was evaluated in the Multicenter Osteoarthritis Study (MOST). No further change in iPTH was observed for African Americans with 25(OH)D levels above 20 ng/ml, suggesting that compared to Caucasians, lower vitamin D targets for sufficiency may be appropriate for African Americans.

BACKGROUND

Vitamin D levels ≥30 ng/ml are commonly considered "normal" based upon maximal suppression of iPTH; however, this has recently been challenged and the optimal 25(OH)D level among non-Caucasians is unclear. We evaluated the cross-sectional relationship between serum 25(OH)D and iPTH in a sample of Caucasian and African American adults.

METHODS

We used baseline serum samples of participants from the Multicenter Osteoarthritis Study (MOST) for this analysis and used three methods to model the relationship between 25(OH)D and iPTH: ordinary least squares regression (OLS), segmented regression and Helmert contrasts.

RESULTS

Among Caucasians (n = 1,258), 25(OH)D and iPTH ranged from 4 to 51 ng/ml and 2 to 120 pg/ml and from 3 to 32 ng/ml and 3 to 119 pg/ml in African Americans (n = 423). We observed different thresholds between African Americans and Caucasians using each analytic technique. Using 25(OH)D as a categorical variable in OLS, iPTH was statistically higher at lower 25(OH)D categories than the 24-32 ng/ml referent group among Caucasians. However, in African Americans, the mean iPTH was only significantly higher at 25(OH)D levels below 15 ng/ml. Using segmented regression, iPTH appeared to stabilize at a lower 25(OH)D level in African Americans (19-23 ng/ml) compared to in Caucasians (>32 ng/ml). Helmert contrasts also revealed a lower threshold in African Americans than Caucasians.

CONCLUSIONS

Among MOST participants, the 25(OH)D thresholds at which no further change in iPTH was observed was approximately 20 ng/ml in African Americans versus approximately 30 ng/ml in Caucasians, suggesting optimal vitamin D levels in Caucasians may not be applicable to African Americans.

Serum immunoreactive parathyroid hormone(IPTH) is normal in patients with X-linked hypophosphatemic rickets who are not treated with phosphate salts. Phosphate raises IPTH in these patients. Endogenous IPTH does not influence the existing defect in tubular reabsorption of phosphate in male patients.

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.

Antibodies to a urea-trichloroacetic acid extract [hPTH-(TCA)] of human parathyroid tumors and to the synthetic NH(2)-terminal fragments of human parathyroid hormone hPTH-(1-12) and -(1-34) were developed in goats to characterize immunochemically various PTH preparations and to estimate immunoreactive PTH (iPTH) in human sera. They were quantitated on the basis of their capacity to bind [(131)I]-hPTH-(1-12), [(131)I]hPTH-(1-34) or [(131)I]bovine PTH (bPTH-(1-84)). The quality of the antibodies was assessed by reference to inhibition of their interaction with labeled peptides by synthetic hPTH comprising 34 NH(2)-terminal amino acid residues or fragments thereof [hPTH-(1-12), -(13-34), -(18-34), -(25-34), -(18-24)] or by the Sephadex G-100-purified full-length peptide hPTH-(1-84) [hPTH-(1-84)G-100]. The synthetic peptides used in this work correspond in their structure to the NH(2)-terminal amino acid sequence 1-34, as elucidated by Brewer and collaborators (1972. Proc. Natl. Acad. Sci. U. S. A.69: 3583-3588). Inhibition studies were also carried out with bPTH-(1-34) and bPTH-(1-84). Anti-hPTH-(TCA) exhibited specificities directed to determinants in the COOH-terminal and NH(2)-terminal part of hPTH-(1-84) and exhibited cross-reactivity with bPTH-(1-84). Anti-hPTH-(1-34), on the other hand, showed immunological specificities mainly directed to antigenic determinants located in the COOH-terminal half of hPTH-(1-34). In addition, some reactivity with the NH(2)-terminal hPTH-(1-12) and with the extractive full-length peptides of human and bovine origin was observed. Antibodies to hPTH-(1-12) cross-reacted with hPTH-(1-34) and -(1-84)G-100.IPTH WAS RADIOIMMUNOLOGICALLY DETERMINED IN HUMAN SERA BY THE FOLLOWING SYSTEMS: (a) [(131)I]bPTH-(1-84), anti-hPTH-(TCA) and hPTH-(1-84)G-100 as standard; (b) [(131)I]hPTH-(1-34), anti-hPTH-(1-34) and hPTH-(1-34) as standard. With system (a), COOH-terminal fragments of hPTH-(1-84) having a molecular weight of approximately 7,000 were detected, and there was an almost total discrimination of serum iPTH levels in normal and in hyperparathyroid subjects. With system (b), on the other hand, several molecular species of iPTH were detected, including a component larger than hPTH-(1-84) and others similar to hPTH-(1-84) and to a fragment co-eluting with the NH(2)-terminal fragment hPTH-(1-34). When serum iPTH was assayed in system (b), there was a large overlap of iPTH levels in control subjects and in patients with primary hyperparathyroidism.

BACKGROUND

Under physiological conditions kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialyzed only 12-15 h/ week. This unphysiological dialysis dose, even if considered adequate by current Kt/V-based dose estimates, is just capable to maintain the alterations of multiple metabolic parameters at a level that permits an unacceptable annual mortality rate of 10-20%, mainly due to cardiovascular events, protein energy wasting and infections.

METHODS

Thirteen haemodialysis patients were converted from conventional (3 x 4 h/week) to an intensified nocturnal (3 x 8 h/week) dialysis and were longitudinally followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during the follow-up period [i.e. dialysis efficacy (eKt/V), mean arterial pressure (MAP), antihypertensive drug score, extra-cellular volume (ECV), haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight (BW), albumin, protein, normalized protein catabolic rate (nPCR), bioelectrical impedance analysis (BIA)), C-reactive protein, calcium-phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy].

RESULTS

The calculated dialysis efficacy rose after switching the treatment mode (eKt/V 1.87 versus 2.7, P < 0.0001). Further, a significantly decreased MAP in the pre- (100 versus 89 mmHg) and postdialytic period (97 versus 83 mmHg), and a decreased ECV (13.8 versus 13.2 L; P = 0.03) even though antihypertensive pharmacotherapy could be substantially reduced (P < 0.0001), was found. Concomitant with a reduction of ESA (66.5 versus 45.2 IU/ kg/week; P = 0.006), the haemoglobin level rose significantly (11.4 versus 12.5 g/dL, P = 0.01). Nutritional status assessed by BW (70.9 +/- 20.2 versus 72.1 +/- 19.8 kg, P = 0.02), nPCR (1.39 versus 2.25 g/kg/day, P = 0.02) and BIA (phase angle: 6.2 versus 6.9 degrees, P < 0.001) improved. The calcium-phosphate product slightly declined, without changes in the dose of any phosphate binders. Surprisingly, iPTH of those patients with intact parathyroid glands (n = 7) increased approximately 3-fold (27.9 versus 59.35 pmol/L, P = 0.009), while the AP was found stable.

CONCLUSIONS

This study demonstrates improvements in numerous dialysis-associated metabolic variables after intensification of HD time. Of note, an increase of iPTH was detected in those patients with intact parathyroid glands.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level>> 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.

Plasma concentration of immunoreactive parathyroid hormone (IPTH) was measured in 18 patients who had been on a hemodialysis program for longer than 6 months. A negative correlation was found between the predialysis plasma concentration of IPTH and the mean concentration of calcium in the dialysate previously used: plasma concentrations of IPTH were higher in patients dialyzed against a calcium concentration between 4.9 and 5.6 mg/100 ml than in patients dialyzed against a calcium concentration of 6.0 mg/100 ml or more. Plasma concentrations of IPTH also were higher in patients with bone disease than in patients without bone disease. Furthermore, a positive correlation was found between predialysis plasma concentrations of IPTH and calcium, and between mean predialysis concentration of IPTH and phosphate. To obviate the possibility that individual differences in susceptibility could have accounted for the observed effects of plasma phosphate and of dialysate calcium, a 2 x 2 factorial study was conducted in seven of these patients to examine the independent effects of perturbation of each of these factors. It was observed that plasma concentration of IPTH was lowest with the combination of high dialysate calcium and low plasma phosphate, highest with the combination of low dialysate calcium and high plasma phosphate, and intermediate with the two other combinations. It is concluded that both dialysate calcium and plasma phosphate are important determinants of parathyroid function in these patients.

Secondary hyperparathyroidism (high-turnover bone disease, or HTBD) is manifested by elevated parathyroid hormone (PTH) levels. Control of HTBD may be achieved by maintaining low serum phosphorous levels and administering vitamin D therapy, although some patients continue to exhibit high PTH levels. We report the results of the efficacy of the calcimimetic cinacalcet in six hemodialysis (HD) and three peritoneal dialysis (PD) pediatric patients with HTBD, age 14.5 +/- 1.0 (range 7.5-17.5) years. Six patients received 30 mg/day, one required 60 mg/day, and two received 120 mg/day. Treatment with cinacalcet resulted in a 61% decline in intact PTH (iPTH) levels (1,070 +/- 171.5 pretreatment to 417.6 +/- 97.8 posttreatment pg/ml, p = 0.005). Serum alkaline phosphatase also declined (561.8 +/- 169.6 U/L pretreatment to 390.3 +/- 110.3 U/L posttreatment pg/ml). During therapy, serum calcium (p = 0.9) and phosphorous (p = 0.9) levels, calcium-phosphorous product (p = 0.8), systolic blood pressure (BP) (p = 1.0), diastolic BP (p = 0.8), and hemoglobin (p = 0.9) remained unchanged. The dose of oral calcitriol for the three patients on PD while receiving cinacalcet trended downward (0.8 +/- 0.2 pretreatment vs. 0.5 +/- 0.0 microg/day posttreatment pg/ml), as did the dose of paracalcitol for those receiving HD (6.6 +/- 2.3 pretreatment vs. 4.3 +/- 1.7 micrograms/day posttreatment pg/ml). We conclude that short-term treatment with the calcimimetic cinacalcet is efficacious in adolescent dialysis patients.

The aim of the study was to evaluate the prevalence of renal osteodystrophy types in children undergoing haemodialysis and continuous ambulatory peritoneal dialysis and to assess the usefulness of biochemical parameters in diagnosis of renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH) level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and phosphorus levels were performed in 51 children aged 11.5 +/- 2.9 y with end-stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows: adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%), osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and hyperparathyroidism (HP) in 12 (24%) children. There was no difference in prevalence of ROD types between children on CAPD and HD. We found significant differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%) were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between BFR and iPTH, BFR and OC, AP levels was found.

CONCLUSIONS

The biochemical markers of bone turnover have only limited value in the differentiation of renal osteodystrophy types.

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5+/-5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228+/-496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26+/-8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (-60.4+/-34% versus -65.4+/-28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium x phosphorus product (CaxP>> or =70 mg(2)/dl(2) occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.