BACKGROUND

Serum tartrate-resistant acid phosphatase 5b (TRACP) is a new marker of potential clinical use to monitor osteoclastic activity and bone resorption rate. The relationship between histomorphometric parameters of bone resorption and serum TRACP was evaluated in 14 chronically dialyzed patients and 6 healthy control subjects.

METHODS

All patients underwent bone biopsies and serum biochemical testing for TRACP, intact parathyroid hormone (iPTH), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), total calcium, phosphorus, and albumin, which were measured at the time of biopsy.

RESULTS

Bone histological examination showed predominant hyperparathyroid bone disease (HPT) in 6 patients, mixed uremic osteodystrophy in 3 patients, low-turnover osteomalacia in 1 patient, and adynamic bone disease in 4 patients. Mean TRACP activity was 3.25 +/- 0.59 U/L in control subjects. Median TRACP activity was significantly greater in patients with HPT (11.97 +/- 8.92 U/L) than those with other types of renal osteodystrophy (ROD; 2.17 +/- 0.61 U/L). Serum iPTH levels were greatest in all patients with HPT, but also were significantly elevated in 7 of 8 patients with other types of ROD. Serum ICTP levels also were significantly elevated in all patients with HPT and 6 of 8 patients with other types of ROD. Serum TRACP levels correlated more strongly with histological parameters of osteoclasts than those of erosion. Also, correlations between TRACP and histological parameters of osteoclasts were stronger than those of iPTH and ICTP levels.

CONCLUSIONS

These early results suggest that serum TRACP levels correlate well with histological indices of osteoclasts and may serve as a specific marker for osteoclastic activity in patients with renal bone disease.

Since no foods are vitamin D supplemented in Greece, vitamin D status was assessed in mothers at birth and their infants up to the first 6 months of life, while they were exclusively breast-fed. This was a prospective study. Full-terms (n =35) born during the summer-autumn months and their mothers were assigned to the summer group and the remainder (n =31) to the winter group. One week after birth, serum 25-hydroxyvitamin D (25OHD) was significantly lower in the winter-born than in the summer-born neonates (6.7+/-0.7 vs. 10.1+/-0.9 ng/ml, P <0.01). The respective levels of parathyroid hormone (iPTH) were 64.9+/-13.4 and 33.9+/-4.4 pg/ml (P <0.01). The mothers had serum 25OHD levels of 10.8+/-1.0 ng/ml and iPTH levels of 15.2+/-3.5 pg/ml in the winter and 12.9+/-1.3 ng/ml and 24.8+/-4.8 pg/ml in the summer. During the 6-month follow-up, a steady increase in circulating 25OHD (up to 19.4+/-2.8 ng/ml, P <0.0001) and a decrease in iPTH (to 26.8+/-3.5 pg/ml, P =0.10) were observed in the infants born in the winter. In the summer-born infants, serum 25OHD did not change but iPTH had increased significantly by the 3rd month (59.4+/-21.8, P <0.05). Serum calcium (Ca) increased within normal limits during the study period in both groups. Serum phosphorus (Pi) started higher in the winter group (7.43+/-0.38 vs. 6.27+/-0.23 mg/dl, P <0.01) but thereafter, it was similar in both groups. Total alkaline phosphatase (ALP) increased in both groups during the study (164+/-15 vs. 219+/-17 IU/l, P <0.05 and 189+/-14 vs. 288+/-35 IU/l, P <0.001, respectively). Serum osteocalcin (OC) decreased in the winter-born neonates (32.0+/-3.4 vs. 21.5+/-3.4 ng/ml, P <0.05) and did not change in the summer group (28.9+/-3.5 vs. 26.5+/-2.8 ng/ml).

CONCLUSIONS

Neonates who are breast-fed exclusively during the first 6 months of life are in need of vitamin D supplementation irrespective of the season even in a sunny country like Greece where foods are not supplemented.

Parathyroid function is described as normal in patients with phosphopenic rickets before initiation of therapy with phosphate salts; however, hyperparathyroidism is an occasional complication of treatment. We observed a higher than expected frequency of hyperparathyroidism in patients with phosphate-wasting rickets, present before treatment in some patients and, more frequently, after the onset of treatment. To better define parathyroid status in hypophosphatemic rickets, we sampled 12 affected children and 7 affected adults every 4 h for 1 day and measured PTH in assays detecting midmolecule fragments (cPTH) and intact hormone (iPTH). All children and 4 adults were receiving a vitamin D preparation and phosphate salts; 3 adults were untreated. Mean cPTH, iPTH, and nephrogenous cAMP excretions in each group of patients were greater than in controls. Exaggerated nocturnal rises in both cPTH and iPTH characterized the profile in patients. Seventeen patients demonstrated frankly elevated cPTH at night, with peak values at midnight, whereas no control individual did. Although mean iPTH values in patients increased at night, they did not exceed the upper limit of normal. Hyperparathyroidism in hypophosphatemic rickets occurs in both children and adults, may be present in untreated patients, is predominantly nocturnal, and is characterized by exaggerated secretion of midmolecule fragments. This manifestation of hypophosphatemic rickets is more widespread than currently recognized; we speculate that it may contribute to the pathogenesis of nephrocalcinosis and precede the development of tertiary hyperparathyroidism.

Lack of resolution of hyperparathyroidism after long-term renal transplantation is common. The relative roles of the graft function attained and the degree of pre-transplant hyperparathyroidism have not been established. Intact parathyroid hormone (iPTH) and several clinical parameters were studied before and 68.6+/-26.8 months (range: 30-124) after renal transplantation in 62 patients (20 females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal range, and values greater than twice the upper normal limit were not uncommon (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre-transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre-transplant PTH emerged as the more important predictor of post-transplant PTH (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism after renal transplantation is uncommon. In addition, the magnitude of pre-transplant hyperparathyroidism and the renal function determine the long-term post-transplant parathyroid function.

To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these two subgroups patients were randomly allocated to two therapeutics groups: 10 patients (group A) were dialyzed with the conventional amount of bicarbonate (33 +/- 2 mmol/liter) in the dialysate; the rest of the patients (group B, N = 11) had 7 to 15 mmol/liter sodium bicarbonate added to the dialysate to obtain 24 mEq predialysis bicarbonate plasma levels. An effective correction of acidosis was shown in group B by a higher predialysis plasma bicarbonate level (15.6 +/- 1 group A vs. 24.0 +/- 0.6 mEq/liter group B, P less than 0.005), which was reached three months after start of the study. Compared to the prestudy bone biopsy, osteoid and osteoblastic surfaces increased in group A but not in group B on the bone biopsies performed at the end of the study. Parathormone plasma level (iPTH), measured with an antiserum which cross reacts with the 44-68 region of PTH molecule, increased during the study in group A but not in group B. This finding suggested progression of secondary hyperparathyroidism (HPT) only in group A patients. Osteocalcin plasma values increased in both groups during the 18 months of the study. Consequently the two subgroups of patients formed on the basis of BFR level were evaluated separately.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

We aimed to determine the prevalence of 25(OH)D (D2 and D3 independently) inadequacy in healthy young/middle-aged men and to investigate its relationship with BMD, bone markers, demographic and lifestyle parameters such as age, BMI, smoking, alcohol consumption and dietary calcium intake.

METHODS

We determined 25(OH)D levels using LC-MS/MS, a robust method for measurement of both 25(OH)D3 and 25(OH)D2, iPTH, osteocalcin, beta C terminal cross-linked telopeptides of type I collagen (b-CTXs), procollagen type 1 amino-terminal propeptide (PINP), BMD at L2-L4 and proximal femur, smoking habits, daily dietary calcium intake and alcohol consumption in 181 randomly selected healthy men aged 20-50y.

RESULTS

The prevalence of vitamin D deficiency (25(OH)D < 20 ng/ml) was 50.3%. Only 8.8% of the participants had vitamin D sufficiency (25(OH)D ≥ 30 ng/ml). We found a strong correlation between 25(OH)D and smoking in the totality of participants (p<0.001). 25(OH)D level was lower by approximately 4.3 ng/dl (p<0.001) in a smoker compared to a non-smoker among the totality of participants, while this value increased to 9.2 ng/ml in the 40-50y subgroup (p=0.003). A multinomial logistic regression model demonstrated that a young smoker (20-29y) had 58% increased likelihood of having vitamin D deficiency compared to a non-smoker of the same age group (p=0.041).

CONCLUSIONS

A high prevalence of vitamin D deficiency was identified in a young and middle-aged male population. Smoking is a significant determinant of serum 25(OH)D, while it increases significantly the likelihood of having vitamin D deficiency. In our hands, vitamin D levels are not a determinant of bone turnover and BMD in this population.

OBJECTIVE

Biochemical markers of bone turnover exhibit circadian rhythms with the peak during the night/early morning and the nadir in the late afternoon. The nocturnal increase in bone resorption could theoretically be caused by the absence of food consumption which brings about a decrease in net calcium absorption and an increase in parathyroid hormone (PTH), followed by increased bone resorption in response to the body's demand for calcium. The aim of the present study was to assess the influence of a 33-h fast on the circadian variation in biochemical markers of bone turnover.

METHODS

Eleven healthy premenopausal women (age: 24+/-5 years) participated in a randomised, cross-over study consisting of two periods: either 33h of fasting (fasting) followed 1 week later by a 33-h period with regular meals eaten at 0800-0830h, 1130-1230h and 1800-1900h (control) or vice versa.

METHODS

Urinary CrossLaps (U-CL/Cr) corrected with creatinine, as a marker of bone resorption; serum osteocalcin (sOC) as a marker of bone formation; serum intact PTH (iPTH); serum phosphate; and serum calcium corrected with albumin.

RESULTS

Both the fasting and the control periods showed a significant circadian rhythm in U-CL/Cr (P<0.001), but the decrease was significantly less pronounced in the morning hours during the fasting period. Fasting resulted in a significant decrease in serum iPTH (throughout the study period) as compared with the control period (P<0.05-0.001). No change was observed in sOC by fasting.

CONCLUSIONS

Food consumption has a small influence on the circadian variation in bone resorption, independent of PTH. The fall in iPTH during fasting may be secondary to an increased bone resorption produced by fasting.

OBJECTIVE

To assess the effect of smoking and smoking cessation on bone density, bone remodeling markers, sex hormones, and vitamin D-PTH axis in healthy young subjects.

METHODS

We studied 74 healthy people (31 men, 43 women; mean age 32.2 (7) years) divided into 52 never smokers and 22 smokers, 15 of which stopped smoking for one month.

RESULTS

Male smokers compared with never smokers showed lower BMD (0.971 (0.11) g/cm(2) vs. 1.069 (0.09) g/cm(2), P=0.042); higher plasma estrone levels (32.37 (10.13) pg/mL vs. 20.91 (5.46) pg/mL, P=0.001); and lower serum iPTH levels (16.2 (3.5) pg/mL vs. 28.8 (2.0) pg/mL, P=0.008). In women, BMD values were similar in smokers than in never smokers, but 25-hydroxyvitamin D levels were lower in smokers (31.9 (15.1) ng/mL vs. 16.8 (9.9) ng/mL, P=0.002). After adjusting by age and coffee consumption, female smokers had higher urinary-NTX levels than never smokers. After smoking cessation, statistically significant decreases of 25-hydroxyvitamin D and SHBG plasma levels were observed in men and women, respectively.

CONCLUSIONS

Tobacco increases bone resorption and affects bone mass by some alterations in sex hormone metabolism, but also importantly by alterations on the vitamin D-PTH axis.

OBJECTIVE

Hyperparathyroidism is a risk factor for bone loss. An age-related increase in parathyroid hormone (PTH) level has been demonstrated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D deficiency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects.

METHODS

Twelve young women with mean age +/- SD of 26.4 +/- 1.6 years, 12 young men with mean age of 26.6 +/- 1.3 years, 12 older women with mean age of 68.6 +/- 1.3 years and 12 older men with mean age of 67.2 +/- 1.6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Cai) were characterized by maximal and minimal iPTH levels, the set-points (levels of Cai causing half-maximal suppression of iPTH), and the slopes of the curves at the set-points.

RESULTS

Baseline serum Ca, Cai, 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels, as well as the set-points, slopes and minimal values of the sigmoidal curves relating Cai to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not significantly higher in the older age groups (P = 0.18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not significant (P = 0.29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were significantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels.

CONCLUSIONS

In both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in integrated PTH secretory response to changes in serum calcium. No alterations in the Cai/iPTH set-point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain.

BACKGROUND

The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 (25[OH]D) levels<30ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol.

METHODS

2-center, double-blind, randomized, 13-week, controlled trial followed by a 26-week open-label study.

METHODS

55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009.

METHODS

Cholecalciferol, 25,000IU, per week orally versus placebo for 13 weeks, then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines.

RESULTS

Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D.

METHODS

Blood calcium and phosphate were measured weekly; iPTH, 25(OH)D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39.

RESULTS

The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P<0.001), as well as 1,25(OH)2D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10-15]pg/mL; P<0.001) and the proportion of patients achieving the target calcium level (76.9% vs 48.2%; P=0.03). Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group.

CONCLUSIONS

Small size of the study population.

CONCLUSIONS

Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients. Further evaluation of clinical end points is suggested.

Serum immunoreactive parathyroid hormone (iPTH) and indices of mineral and glucose metabolism were determined in 58 insulin treated diabetic patients (duration of disease 1-11 years). The mean serum iPTH level in all diabetic patients, measured simultaneously with sera from normal subjects, was 55% of normal mean (P < 0.01). The diabetic patients had hypomagnesaemia (P < 0.001), hypercalciuria (P < 0.001) and a 9.6% decrease in bone mass (P < 0.001). Low serum iPTH values were correlated with high glycosuria (R = -0.28, P < 0.05) and with long duration of diabetes (R = -0.31, P < 0.02). Patients with both high glycosuria and long diabetes duration had especially low iPTH values (mean 16 ng/l, n = 16) compared with patients with both low glycosuria and short diabetes duration (mean 32 ng/l, n = 15, P < 0.005) and with normal subjects (mean 37 ng/l, n = 28, P < 0.001). The 16 patients with low serum iPTH values also had higher urinary calcium excretion rate (P < 0.05) than the 15 patients with low glycosuria and short duration of diabetes. The diabetic hypoparathyroidism may be secondary to a primary disturbance of bone metabolism, with a negative net calcium balance.

OBJECTIVE

To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease.

BACKGROUND

Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery.

METHODS

A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy.

RESULTS

Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery.

CONCLUSIONS

Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.

OBJECTIVE

Secondary hyperparathyroidism decreases renal clearance of parathyroid hormone (PTH).

OBJECTIVE

To determine whether rapid PTH assays can be used to predict the success of a total parathyroidectomy to treat symptomatic secondary hyperparathyroidism.

METHODS

Case series from August 1 to December 31, 2000.

METHODS

Tertiary referral center.

METHODS

Patients with symptomatic secondary hyperparathyroidism (n = 24) who underwent total parathyroidectomy and autotransplantation were included in the study.

METHODS

Blood samples for rapid PTH analyses were drawn from an indwelling catheter at the induction of anesthesia (baseline) and before (0 minutes), 10 minutes, and 30 minutes after the removal of the last parathyroid gland. Regular intact PTH (iPTH) assays were conducted later.

METHODS

If a patient's regular iPTH levels were below 65 pg/mL at 1 week or 3 months postoperatively, the operation was considered successful.

RESULTS

All 24 patients had successful operations. Rapid PTH and regular iPTH correlated significantly at 0, 10, and 30 minutes. Rapid PTH levels decreased significantly at each time period and were 176 +/- 40.9 pg/mL (mean +/- SE) at 10 minutes. The percentage decrease in rapid PTH levels was 39.5% +/- 12.7% at 0 minutes, 75.1% +/- 6.2% at 10 minutes, and 91.0% +/- 0.1% at 30 minutes (mean +/- SE). A decrease of 60% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 30 minutes predicted the successful removal of all parathyroid glands.

CONCLUSIONS

A drop in PTH levels is delayed until 30 minutes after total parathyroidectomy; however, a rapid PTH assay 10 minutes after the removal of the last parathyroid gland is as accurate as an assay performed at 30 minutes postoperatively. Intraoperative PTH monitoring demonstrates relevant decreases in rapid PTH levels after parathyroidectomy that are similar to those previously documented in patients with primary hyperparathyroidism.

OBJECTIVE

Because impaired renal function is detrimental for the conversion of calcidiol to calcitriol (D-hormone) and since D-hormone analogues have been shown to decrease the risk of falls, we investigated whether creatinine clearance (CrCl) is associated with the number of fallers and falls in elderly men and women.

METHODS

Within a randomized controlled study, we observed for 36 weeks 186 placebo-treated community-dwelling elderly men and women over 70, in an attempt to determine the influence of baseline CrCl on calcitropic hormone serum levels, as well as the influence of baseline CrCl on the number of fallers and falls over time. With the help of questionnaires, we regularly assessed fall incidence and frequency. The risk of falls and the risk of becoming a faller were assessed in multivariate-controlled logistic regression models according to a cutoff value of the CrCl set at 65 ml/min.

RESULTS

At baseline, serum levels of 1.25(OH)(2)D(3) and iPTH were, in multivariate-controlled analyses, significantly associated with CrCl (p<0.0001, p=0.001, respectively), whereas serum levels of 25(OH)D(3) were not associated with CrCl. Below a CrCl of 65 ml/min, 1.25(OH)(2)D(3) serum levels steadily declined. We therefore chose a CrCl of 65 ml/min as cutoff for further analyses. During the 36 weeks of observation, elderly people with a CrCl of < 65 ml/min had, in multivariate controlled analyses, compared with elderly with a CrCl of>> or =65 ml/min, a significantly higher incidence of number of fallers (25/70 vs 21/116; OR=4.01; 95% CI, 1.48-10.98; p=0.006), and a significantly higher incidence of falls (28/70 vs 23/116; OR=3.68; 95% CI, 1.38-9.82; p=0.009).

CONCLUSIONS

For the first time we showed that in a community-dwelling population of elderly men and women, a CrCl of less than 65 ml/min is a significant and independent risk factor for fallers and falls.

BACKGROUND

In pediatric chronic renal failure (CRF) optimal parathyroid hormone (PTH) concentrations that minimize renal osteodystrophy and maximize growth are unknown. The search for optimum concentrations has been complicated as currently used "intact" PTH (iPTH) assays cross-react with long carboxyl-terminal PTH fragments (C-PTH), which antagonize the biologic actions of 1-84 PTH. The purpose of this study was to investigate the relationship between PTH, the 1-84 PTH:C-PTH ratio and growth rate in children with CRF.

METHODS

A total of 162 patients, median (range) age 9.9 years (0.3 to 17.1 years), were recruited: 136 with a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)[96 managed conservatively (CRF group) and 40 transplanted patients], and 26 dialysis patients. Over a median (range) period of 1.1 years (0.5 to 1.7 years), children attended five (three to 15) clinics at which iPTH, cyclase-activating PTH (CAP-PTH), and height were measured.

RESULTS

Mean PTH concentrations were within the normal range for both assays for the CRF group and up to twice the upper limit of normal for the dialysis group; CAP-PTH 24.8 pg/mL and 59.9 pg/mL (normal range 5 to 39 pg/mL), iPTH 37.1 pg/mL, and 102.6 pg/mL, respectively (normal range 14 to 66 pg/mL). The patients grew normally (change in height standard deviation score per year (DeltaHtSDS) =-0.01). There was no relationship between PTH concentrations and DeltaHtSDS in any patient group. The 1-84 PTH:C-PTH ratio was lower in dialyzed patients (P= 0.003), with worsening renal function (P= 0.047) and with PTH concentrations outside the normal range (P= 0.01). There was a weak correlation between the 1-84 PTH:C-PTH ratio and the DeltaHtSDS (r= 0.2, P= 0.01).

CONCLUSIONS

Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.

Hyperfunctioning parathyroid carcinoma is a relatively rare endocrine tumor, accounting for approximately 1% of all cases of primary hyperparathyroidism. The diagnosis is suspected when the tumor is large, parathyroid hormone (iPTH) levels are high, and a palpable tumor is present in the neck. Patients who have recurrence of hyperparathyroidism several months after surgical treatment should be suspected of having a recurrent or persistent parathyroid carcinoma. At operation, a large invasive tumor is usually found. The fibrous, inflammatory-like reaction is the most characteristic indication of malignancy. Even in tumors with minimal invasiveness, the possibility of a carcinoma should be considered if the tumor has mitotic activity and a monotonous instead of a pleomorphic cellular population. If the surgeon can recognize the possibility of parathyroid malignancy and adequately treat the patient during the initial operation, more gratifying results should be obtained.

This study was designed to assess whether reliability of quick intraoperative assay of intact (1-84) immunoreactive parathyroid hormone (iPTH) could allow us to quit after removing one (or several) enlarged parathyroid gland(s) and obtaining a normal iPTH level. Intact iPTH was assayed during surgery before removal of enlarged parathyroid gland(s) and 5, 10, and 20 minutes afterward. Forty-seven patients entered the study: 40 with primary hyperparathyroidism (32 with uniglandular disease and eight with multiglandular disease) and seven with secondary hyperparathyroidism; all underwent bilateral neck exploration. Among 32 patients with uniglandular disease, five had normal basal intraoperative levels, 25 demonstrated a clear-cut drop from supranormal to normal levels, and two had elevated levels. Among the eight patients with multiglandular disease, two had undetectable levels and two had normal levels after removal of the first enlarged gland. The seven patients with secondary hyperparathyroidism demonstrated a decline in PTH levels, suggesting hormone clearance similar to that of patients with primary hyperparathyroidism. In conclusion, quick intraoperative assay with intact (1-84) iPTH (1) is not hampered by renal insufficiency, (2) may overlook a second enlarged gland after removal of a first adenoma and obtaining normal iPTH levels, and (3) should not be used as a substitute for bilateral neck exploration.

Turkey, especially its eastern part, has been accepted as endemic for vitamin D deficiency rickets (VDDR). In a study performed by our team in the region in 1998, the incidence of VDDR was 6.09% in children aged between 0-3 years. In 2005, the Ministry of Health initiated a free vitamin D supplementation campaign nationwide for every infant to eradicate VDDR. In this study, we aimed to investigate the prevalence of VDDR in children aged between 0-3 years in order to evaluate the effectiveness of this campaign. Between March 2007 and February 2008, 39,133 children aged between 0-3 years who were brought to different pediatric outpatient clinics in Erzurum, Turkey, were examined for VDDR. VDDR diagnosis was made by radiological and biochemical findings in the cases who were initially suspected of having clinical VDDR. During a one-year period, 39 (0.099%) of the 39,133 patients were diagnosed with VDDR. None of the cases with rickets was taking vitamin D supplementation. The most frequent physical findings were rachitic rosary, enlargement of the wrists, and craniotabes. The laboratory findings of the cases were compatible with VDDR; serum calcium (Ca) 7.5 +/- 1.9 mg/dL, PO4 4.4 +/- 1.3 mg/dL, alkaline phosphatase (ALP) 1,341 +/- 823, 25-hydroxyvitamin D (25 (OH) D) 5.8 +/- 2.9 ng/mL, intact parathyroid hormone (iPTH) 240 +/- 106 pg/mL. It was concluded that, although VDDR has been a continuing childhood health problem, a nationwide free vitamin D supplementation campaign initiated by the government appeared to be effective in eliminating VDDR.

OBJECTIVE

Osteoporosis is a common complication of Crohn's disease (CD). Glucocorticoid use and detrimental effects of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) can lead to osteoporosis. The aim of this study was to assess the ability of treatment with the TNF-alpha antagonist infliximab to increase bone formation as measured by surrogate markers of bone turnover in patients with active CD.

METHODS

Sera from 38 prospectively enrolled CD patients were examined for levels of bone alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), immunoreactive parathyroid hormone (iPTH), calcium, and pro-inflammatory cytokines at baseline and 4 weeks following infliximab infusion. Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and glucocorticoid dose also were collected.

RESULTS

In this cohort, CDAI and IBDQ scores were significantly improved at week 4 (P<0.001). Infliximab therapy was associated with an increase in BAP, a marker of bone formation (P=0.010), whereas NTX, a marker of bone resorption, was not increased (P=0.801). Among 22 patients who were taking glucocorticoids, mean glucocorticoid dose decreased 36% (P<0.001; -7.9 mg).

CONCLUSIONS

Treatment with infliximab was associated with increased markers of bone formation (BAP) without increasing bone resorption (NTX). This effect may be due to a beneficial effect of TNF-alpha blockade on bone turnover, a beneficial effect on CD activity resulting in decreased glucocorticoid dose, or both. Studies of longer duration are needed to assess the effect of infliximab on bone mineral density.

OBJECTIVE

Parathyroid hormone increases the differentiation of osteoblast precursors through canonical wingless (Wnt) signalling, resulting in an osteoanabolic effect. We aimed to evaluate serum levels of the Wnt-inhibitor Dickkopf-1 (Dkk-1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD - human recombinant PTH 1-34).

METHODS

A total of 31 postmenopausal Caucasian women with established osteoporosis (mean age 66.3 +/- 1.4 years) received daily injections of 20 microg TPTD for 18 months. Follow-up was continued for another 6 months after treatment discontinuation (total duration of treatment 24 months).

METHODS

Serum samples for total calcium (Ca), intact PTH (iPTH), bone-specific alkaline phosphatase, C-terminal cross-linking telopeptide of type 1 collagen (CTx) and Dkk-1 were obtained at baseline, and at 6, 18 and 24 months after TPTD initiation. Lumbar spine bone mineral density (BMD) was measured before and after 18 months of TPTD treatment. A total of 16 age- and gender-matched healthy controls were also analysed at baseline.

RESULTS

Serum Dkk-1 levels at baseline were significantly higher in osteoporotic women compared with that in controls (P < 0.002). Dkk-1 increased significantly during TPTD administration (P < 0.044) and decreased to baseline 6 months after TPTD discontinuation. Dkk-1 change was positively correlated to Ca (r = 0.530, P = 0.004) and negatively correlated to iPTH change (r = -0.398, P = 0.040). There was no correlation between Dkk-1 and BMD changes.

CONCLUSIONS

Our data suggest that Dkk-1 levels are increased in women with postmenopausal osteoporosis. TPTD therapy results in further increase of Dkk-1 that may be compensative to TPTD-induced enhanced Wnt signalling.

BACKGROUND

Vitamin D is important for bone health. An inadequate supply of vitamin D to the body is associated with a higher fracture risk in the elderly. Young adults with type 1 diabetes are reported to have a lower peak bone mass than healthy individuals, which could possibly lead to an increased fracture risk in the future. The prevalence of vitamin D deficiency in healthy young people is high. Thus, optimal supply of vitamin D may be of particular importance for bone health in children with type 1 diabetes.

METHODS

In this prospective cross-sectional study we measured serum 25-hydroxy-vitamin D, iPTH, total and ionised calcium, phosphate, and alkaline phosphatase in 129 Swiss children and adolescents with type 1 diabetes.

RESULTS

Of the 129 subjects 78 (60.5%) were vitamin D deficient, defined as a 25-hydroxy-vitamin-D level below 50 nmol/L. During the winter this number rose to 84.1%. 25-hydroxy-vitamin-D levels showed marked seasonal fluctuations, whereas there was no correlation with diabetes control. Despite the high prevalence of vitamin D deficiency, we found a low prevalence of secondary hyperparathyroidism in vitamin D deficient diabetic children and adolescents.

CONCLUSIONS

Prevalence of vitamin D deficiency in diabetic children and adolescents is high. Therefore, screening for vitamin D deficiency and supplementation in children with low vitamin D levels may be considered.

We conducted an observational study in order to assess the prevalence of hypovitaminosis D and its seasonal changes, in the Tokai area (N35.3 E137.0), in 197 normal subjects in Japan. The mean serum 25-hydroxyvitamin D (25-OHD) level measured by direct radioimmunoassay (RIA) was lowest at the end of winter, and highest at the end of summer (15.1+/-7.1 ng/ml in March; 21.5+/-5.5 ng/ml in June; 31.6+/-5.6 ng/ml in September; 23.1+/-5.3 ng/ml in December; mean+/-SD). The prevalence of hypovitaminosis D (<20 ng/ml) was 86.7%, 33.4%, 1.0%, and 26.0% in March, June, September, and December, respectively. Mean plasma intact parathyroid hormone (iPTH) concentration was lowest at the end of summer and highest at the end of winter (28.2+/-9.3 pg/ml in March; 21.7+/-7.0 pg/ml in June; 19.8+/-6.9 pg/ml in September; and 25.7+/-9.2 pg/ml in December; mean+/-SD). Serum 25-OHD was inversely associated with iPTH (coefficient, -0.223; r=0.251; P<0.001). Serum 25-OHD levels were higher in men than in women. The serum 25-OHD level was positively associated with age, body weight, and body mass index, but not with body fat content. These results suggest a high prevalence of hypovitaminosis D associated with elevation of iPTH in Japan, in winter, even in a sunny area.

The objective of this study was to determine the effect of age on the blood levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive parathyroid hormone (iPTH) in normal, healthy males and females. A total of 855 normal subjects (361 males and 494 females) were studied. The results show that for healthy males, blood concentrations of 1,25(OH)2D remained essentially constant with increasing age up to age 65, and then the concentrations decreased significantly. For healthy females, 1,25(OH)2D increased up to age 65, and then decreased at a significant rate. Serum iPTH in males increased with advancing age, but the rate of increase was greater after age 65. In females a significant increase in iPTH concentrations did not occur until after age 65. Serum creatinine increased in both males and females with advancing age.

BACKGROUND

Abnormalities in bone mineral metabolism parameters are common in patients with end-stage kidney disease on dialysis therapy. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines propose targets for calcium, phosphate, and intact parathyroid hormone (iPTH) levels in patients undergoing dialysis. However, whether achievement of these targets improves survival is unknown.

METHODS

Retrospective cohort study.

METHODS

Incident patients on hemodialysis or peritoneal dialysis therapy in the United Kingdom from 2000-2004 who survived at least 12 months.

METHODS

Achievement of KDOQI calcium, phosphate, and iPTH guideline targets during the first year of dialysis therapy.

RESULTS

All-cause mortality in the subsequent 2 years.

METHODS

Calcium, phosphate, and iPTH at quarterly intervals, demographic and comorbid condition data at baseline.

RESULTS

We included 7,076 incident patients (4,947 hemodialysis, 2,129 peritoneal dialysis) in our analysis. Approximately two thirds of patients were men and 21% had diabetes as the cause of kidney failure. Guideline target achievement for each quarter varied from 23%-26% for iPTH level, 43%-47% for calcium level, and 54%-62% for phosphate level targets. In adjusted Cox proportional hazards models, patients who achieved guideline targets in all 4 quarters did not have a survival advantage over patients who never achieved target (P>> 0.1 for calcium, phosphate, and iPTH).

CONCLUSIONS

Missing information about medication use, vitamin D and alkaline phosphatase levels, and dialysate calcium content.

CONCLUSIONS

Our findings do not support the use of KDOQI bone mineral guideline achievement as a quality measure for dialysis care. Prospective studies with longer term follow-up are needed to define the optimal cutoff values for calcium, phosphate, and iPTH and assess the effect of guideline implementation on patient survival.