Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients

Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3–5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87?±?3.48 vs. 3.97?±?0.34 in CKD vs. control, respectively, p?p?p?p?p?p?p?相似文献   

Bone mineral density and parathyroid function in patients on maintenance hemodialysis

Background

The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details.

Methods

In a cross-sectional design, data from 270 patients (age 55 ± 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D.

Results

Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the ??low PTH?? group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the ??target range?? (100?C300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = ?0.255, ?0.278 and ?0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the ??low PTH?? group.

Conclusions

Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.     

Effect of Depot Oral Cholecalciferol Treatment on Secondary Hyperparathyroidism in Stage 3 and Stage 4 Chronic Kidney Diseases Patients

By the time patients require dialysis replacement therapy, nearly all chronic kidney diseases (CKD) patients are affected with uremic bone diseases. High-turnover osteodystrophy can be prevented; patients with CKD should be monitored for imbalances in calcidiol (25 OH vitamin D), calcium, and phosphate homeostasis. We aimed to determine the effect of a monthly oral 300,000 IU vitamin D₃ (cholecalciferol) supplementation on the uremic bone diseases (UBD) markers such as iPTH and alkaline phosphatase in CKD patients. Among a total of 70 patients under treatment in the nephrology unit, 40 predialysis CKD patients (mean age of 49 ± 14, male/female 20/20) were included the study. The patients were randomly divided into two groups. Treatment group included 20 patients (mean age of 51 ± 14, male/female 9/11), and the control group comprised 20 patients (mean age of 47 ± 14, male/female 9/11). Treatment group patients were given a single dose of Devit3 ampoule (300,000 U cholecalciferol) per month orally way. Patients in the control group did not take any vitamin D for a month. The level of calcidiol was lower than normal range in two groups. After a month, treatment group patient's calcidiol increased statistically significant (6.8 ± 3.5 to 17.8 ± 21.4 ng/mL, p < 0.001). After a month, iPTH level decreased in the treatment group statistically significantly (368 ± 274 to 279 ± 179 pg/ml, p < 0.001). At the 30^th day of the treatment, in 9/20 of the treatment group patients (45%), the iPTH value decreased at least 30% (p < 0.001). We suggest that oral depot cholecalciferol treatment causes a statistically significant decrease of serum iPTH level but does not cause a statistically significant change in Ca, P, ratio of Ca?×?P, or urinary calcium creatinine rate in UBD predialysis CKD. This treatment can be used safely for the predialysis CKD patients, along with the cautious control of serum calcium and phosphor.     

Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease

Background

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Recent data implicate disordered bone and mineral metabolism, including changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and fetuin A, as novel risk factors for arterial calcification. The potential role of calcitonin, another hormonal regulator of mineral and bone metabolism, has not been studied in detail.

Materials and methods

We investigated the link between serum calcitonin and the total burden of coronary artery disease (CAD) using the validated Gensini score, in a cross-sectional study of 88 patients with estimated GFR (eGFR) between 46 and 87?ml/min/1.73?m2 who underwent coronary angiography. We evaluated the associations between serum calcitonin, minerals (calcium, phosphate), calcium?×?phosphate product, and other factors that regulate mineral metabolism (intact PTH, 25-OH-vitamin D, FGF-23, and fetuin A) and the severity of CAD.

Results

The mean serum calcitonin was 11.5?±?7.8?pg/ml. In univariate analysis, the Gensini CAD severity score correlated significantly with male gender, eGFR, and serum levels of 25-OH-vitamin D, iPTH, FGF-23, fetuin A, and calcitonin (R?=?0.474, P?=?0.001 for the latter). In multivariate analysis adjusted for calcium, phosphate, 25-OH-vitamin D, iPTH, FGF 23, fetuin A, and calcitonin, only calcitonin (???=?0.20; P?=?0.03), FGF-23, fetuin A, and 25-OH-vitamin D emerged as independent predictors of Gensini score. In the second step, we adjusted for the presence of traditional risk factors, proteinuria, and GFR. After these adjustments, the FGF-23 and fetuin A remained statistically significant predictors of the Gensini score, while calcitonin did not.

Conclusions

Our study suggests that, in addition to other well-known components of mineral metabolism, increased calcitonin levels are associated with greater severity of CAD. However, this relation was not independent of traditional and nontraditional cardiovascular risk factors. Longitudinal studies in larger populations including patients with more advanced CKD are needed.     

Intensified treatment of hyperphosphatemia associated with reduction in parathyroid hormone in patients on maintenance hemodialysis

Background: This study investigated the therapeutic effect of intensive phosphorus-lowering therapy on intact-parathyroid hormone (iPTH) levels in hemodialysis patients.

Methods: Ninety-five hemodialysis patients with serum phosphorus ≥1.78?mmol/L and iPTH ≥300?pg/dL were apportioned to either the treatment or control group (n?=?43 and 52, respectively) based on patient commitment to treatment. The treatment group was given phosphorus-lowering therapies with phosphate binders (lanthanum, sevelamer or/and calcium reagent) combined with dietary phosphate restriction and intensified hemodialysis. The control individuals were given low doses of calcium agents, if serum calcium was <2.54?mmol/L. Percent changes in serum phosphorus and iPTH levels were compared between the two groups. In addition, based on the time required to achieve >20% decrease in serum phosphorus, the patients in the treatment group were further stratified as rapid responders (≤2?months; 27 patients) or slow responders (>2?months; 16 patients) and percent changes in iPTH were compared.

Results: Serum phosphorus and iPTH levels decreased from baseline in the treatment group (?24.08?±?1.93% and ?9.92?±?3.70%, respectively) but increased in the control group (22.00?±?3.63% and 104.21?±?23.89%; both p?p?Conclusions: For these patients on maintenance hemodialysis, intensive treatment of hyperphosphatemia was associated with a decrease in iPTH levels, especially for those who had achieved substantial reduction in serum phosphorus within 2?months.     

Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old

Introduction

It is known that chronic kidney disease (CKD) and senescence bring about a progressive reduction in glomerular filtration rate (GFR) and that in the former this is usually associated with an increase in the fractional excretion of calcium, phosphorus, magnesium, and uric acid. However, it has not yet been explained how these substances are excreted in the healthy oldest old. Thus, in the present study, we examined the renal handling of these substances in very aged people in comparison with CKD patients with similar GFR levels (stage III??CKD).

Materials and methods

Twenty volunteers were studied; 10 of them were healthy very old (VO) (??75?years old) individuals and 10 were stage III CKD patients. Exclusion criteria were as follows: presence of altered (abnormally high or low) plasma calcium, phosphorus, magnesium and uric acid, as well as previous diagnoses of diabetes mellitus and obstructive uropathy and use of drugs that could alter plasma levels of the studied substances. All volunteers were on a diet with the same content of these elements (3-day dietary register). We measured calcium, phosphorus, magnesium, uric acid, creatinine in serum plasma and morning urine, as well as serum parathyroid hormone level, in each volunteer. From these data, fractional excretion (FE) of these substances was obtained. A statistical analysis was carried out using the Wilcoxon test.

Results

Serum creatinine: 1.8?±?0.4?mg/dl (CKD) versus 0.8?±?0.2?mg/dl (VO), p?=?0.0002; serum calcium: 9.1?±?0.3?mg/dl (CKD) versus 8.7?±?0.4 (VO), p?=?0.022; serum magnesium: 2.3?±?0.2?mg/dl (CKD) versus 2.0?±?0.1 (VO), p?=?0.05; serum phosphorus: 3.9?±?0.5?mg/dl (CKD) versus 3.0?±?0.4?mg/dl (VO), p?=?0.002; serum uric acid: 6.6?±?1.5 (CKD) versus 5.2?±?1.4?mg/dl (VO), p?=?0.04; FE of calcium: 2.5?±?1?% (CKD) versus 0.8?±?0.3?% (VO), p?=?0.04; FE of magnesium: 7.2?±?4.1?% (CKD) versus 2.9?±?0.9?% (VO), p?=?0.02; FE of phosphorus: 25?±?9?% (CKD) versus 9.1?±?5.7(VO), p?=?0.001; FE of uric acid: 10?±?3?% (CKD) versus 8?±?5?% (VO), p?=?0.05.

Conclusion

Serum levels and FE of calcium, phosphorus, magnesium and uric acid were significantly higher in CKD patients compared to healthy very old people with similar GFR, except for serum magnesium and FE of uric acid, which were similar in both groups.     

Urinary biomarkers in assessing the nephrotoxic potential of gentamicin in solitary kidney patients after 7 days of therapy

Introduction: The solitary kidney (SK) may present increased vulnerability to nephrotoxicity because of adaptive phenomena. Aims: Assessing the vulnerability of the SK with urinary tract infections (UTI) to gentamicin by means of urinary biomarkers (N-acetyl-beta-D-glucosaminidase (NAG) and urinary alpha-1-microglobulin), as well as glomerular filtration rate (GFR). Methods: We studied 14 patients with SK with UTI (group A) (mean age 58.07?±?13.61 years, mean duration of SK 13.55?±?12.33 years) who were administered gentamicin for 7 days. Group B consisted by 17 patients with SK without any other associated renal pathology (average age 51.17?±?9.39 years, average existence period of a single kidney 33.23?±?21.73 years). We also included a third group (group C) represented by nine healthy individuals, with two kidneys. Results: Increased values of urinary NAG were found in group B as compared to group C and alpha-1 microglobulin in group A as compared to group B. During treatment with gentamicin, increased values of both NAG and alpha-1-microglobulin in group A were found on day 7 as compared to values before treatment (day 7 NAG?=?18.99?±?14.07?U/g creat versus day 0, NAG?=?5.15?±?6.54?U/g creat, p?=?0.004; day 7 alpha-1-microglobulin?=?20.88?±?18.84?mg/g creat versus day 0, urinary alpha-1-microglobulin?=?4.96?±?6.57?mg/g creat, p?=?0.003). No statistically significant alterations of GFR were noticed after 7 days of treatment. Conclusions: We found the nephrotoxic effects of gentamicin at tubular level, but not at glomerular level. The nephrotoxic potential of gentamicin in patients with a SK can be monitored by assessing urinary biomarkers during treatment of UTI.     

Wintertime Vitamin D Supplementation Inhibits Seasonal Variation of Calcitropic Hormones and Maintains Bone Turnover in Healthy Men

Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21–49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 ± 5.1 (SD) μg/d. This was a 6‐mo double‐blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 μg (800 IU), 10 μg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S‐)25(OH)D, iPTH, bone‐specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S‐25(OH)D, S‐PTH, and S‐TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S‐BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S‐BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5–20 μg (700–800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.     

Changes in Bone Mineral Density After Sleeve Gastrectomy or Gastric Bypass: Relationships with Variations in Vitamin D,Ghrelin, and Adiponectin Levels

Background

A major long-term concern after gastric bypass (GBP) is the risk of osteoporosis; however, little is known about this complication in patients undergoing sleeve gastrectomy (SG).

Objective

To evaluate changes in bone mineral density (BMD) after GBP and SG, and its relationship with changes in vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin.

Methods

Twenty-three women undergoing GBP (BMI 42.0?±?4.2 kg/m²; 37.3?±?8.1 years) and 20 undergoing SG (BMI 37.3?±?3.2 kg/m²; 34.2?±?10.2 years) were studied before and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and adiponectin concentrations were determined. Food as well as calcium and vitamin D supplement intake was recorded.

Results

Excess weight loss (mean?±?SE), adjusted by baseline excess weight, was 79.1±3.8 % and 74.9?±?4.1 % 1 year after GBP and SG, respectively (p?=?0.481). Significant reduction in BMD for total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP. In the SG group, reduction in BMD was significant only for TB. Adjusted by baseline BMD, the difference between change in BMD for GBP vs. SG was not significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG groups).

Conclusions

One year after gastric bypass, bone mineral density was significantly affected, mainly at the femoral neck. Decreases in bone mineral density were more dramatic among patients who had greater baseline BMD and greater reduction in ghrelin concentrations.     

High serum chemerin level in CKD patients is related to kidney function,but not to its adipose tissue overproduction

Abstract

Chemerin is an adipokine modulating inflammatory response and affecting glucose and lipid metabolism. These disturbances are common in CKD. The aim of the study was: (a) to evaluate circulating chemerin level at different stages of CKD; (b) to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate the efficiency of renal replacement therapy in serum chemerin removal. 187 patients were included into the study: a) 58 patients with CKD; (b) 29 patients on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects constituted control group. Serum chemerin concentration was estimated by ELISA. The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum chemerin concentration in CKD patients was 70% higher than in the control group (122.9?±?33.7 vs. 72.6?±?20.7?ng/mL; p?<?0.001) and it negatively correlated with eGFR (r?=??0.71, p?<?0.001). The equally high plasma chemerin level was found in HD patients and a HD session decreased it markedly (115.7?±?17.6 vs. 101.5?±?16.4?ng/mL; p?<?0.001). Only successful kidney transplantation allowed it to get down to the values noted in controls (74.8?±?16.0 vs. 72.6?±?20.7?ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD patients was not different than in patients of the control group. The study demonstrates that elevated serum chemerin concentration in CKD patients: (a) is related to kidney function, but not to increased chemerin production by subcutaneous adipose tissue, and (b) it can be efficiently corrected by hemodialysis treatment and normalized by kidney transplantation.     

Volumetric bone mineral density and bone structure in childhood chronic kidney disease

Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex‐, race‐, and age‐ or tibia length–specific Z‐scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z‐score in younger participants (p < .001) compared with healthy children; this association was attenuated in older participants (interaction p < .001). Mean CortArea Z‐score was lower (p < .01) in CKD 4–5 [?0.49, 95% confidence interval (CI) ?0.80, ?0.18)] and CKD 5D (?0.49, 95% CI ?0.83, ?0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z‐score (p < .01), and this association was significantly attenuated in older participants (interaction p < .05). Higher levels of PTH and biomarkers of bone formation (bone‐specific alkaline phosphatase) and resorption (serum C‐terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z‐scores and greater EndoC Z‐score (r = 0.18–0.36, all p ≤ .02). CortBMD Z‐score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage‐specific target range: ?0.46 ± 1.29 versus 0.12 ± 1.14 (p < .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible. © 2011 American Society for Bone and Mineral Research     

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2–4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2-–5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2–4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.     

Does neutrophil to lymphocyte ratio demonstrate deterioration in renal function?

Introduction: Chronic kidney disease (CKD) is a major health issue worldwide, which leads to end-stage renal failure and cardiovascular events. Neutrophil to lymphocyte ratio (NLR) is a surrogate marker of inflammation and has been widely studied in malignancies, hypertension, heart diseases, and vascular diseases. In this study, we aimed to investigate if NLR represents renal reserve and function after partial or radical nephrectomy.

Methods: We conducted a retrospective study consists of patients who had undergone radical/partial nephrectomy in our hospital and/or who admitted to urology and nephrology clinics as an outpatient. Patients were divided into four groups: Group 1 (n?= 46): Healthy controls; Group 2 (n?= 50): Patients who had undergone unilateral partial nephrectomy; Group 3 (n?= 46): Patients who had gone unilateral nephrectomy; Group 4 (n?= 82): Patients who had CKD.

Results: The mean NLR of each group was as follows: Group 1: 2.14?±?0.73; Group 2: 3.52?±?3.74; Group 3: 3.64?±?3.52, and Group 4: 3.53?±?2.30. NLR was lower in Group 1 compared to other groups but statistically significant difference was observed only between Group 1 (control) and Group 4 (CKD), 2.14?±?0.73 versus 3.53?±?2.30 (p?=?.005). In non-parametric correlation analysis NLR was found negatively correlated with GFR and positively correlated CKD stage (p?=?.028 for both correlations).

Conclusions: The NLR may constitute a practical predictor of CKD besides Cr in patients who had undergone partial or radical nephrectomy.     

Early impairment of trabecular microarchitecture assessed with HR‐pQCT in patients with stage II‐IV chronic kidney disease

Bone fragility is a complication of chronic kidney disease (CKD). The aim of this study was to assess whether volumetric bone mineral density (vBMD) and microarchitecture could be impaired early in the course of CKD. Bone microarchitecture was examined with a noninvasive 3D imaging technique [high‐resolution peripheral quantitative computed tomography (HR‐pQCT)] at the tibia and radius in 70 stage II‐IV CKD patients older than 50 years of age; controls belonged to two cohorts of healthy subjects comparable for age and gender (OFELY cohort in women and STRAMBO cohort in men). We examined 46 men and 24 women; 19 patients were diabetic. Mean age was 70.8 ± 8.5 years, mean glomerular filtration rate (GFR) was 34 ± 12 mL/min per 1.73 m², and mean serum parathyroid hormone (PTH) level was 87 ± 59 pg/mL. Both CKD men and women experienced a moderate but significant trabecular (Tb) impairment, positioning CKD patient values between those of normal and osteopenic controls (e.g., CKD men versus healthy controls: Tb vBMD 172 ± 35 versus 188 ± 34 mg HA/cm³; Tb number 1.75 ± 0.27 versus 1.86 ± 0.26 mm^?1, and Tb separation 503 ± 94 versus 465 ± 78 µm; p < .05). Cortical thickness (Ct.Th) in men also was significantly decreased compared with healthy controls (e.g., CKD men versus healthy controls: tibial Ct.Th 1171 ± 331 versus 1288 ± 283 µm; p < .05). In conclusion, this study, using a noninvasive bone‐imaging device, shows for the first time an early impairment of trabecular microarchitecture in stage II‐IV CKD patients. Further longitudinal studies should be performed to validate HR‐pQCT as a tool for predicting the fracture risk in CKD. © 2010 American Society for Bone and Mineral Research.     

Tuberculin Skin Test Results and the Booster Phenomenon in Two-Step Tuberculin Skin Testing in Hemodialysis Patients

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty‐eight end‐stage renal disease patients (28 male, 20 female mean age 42 ± 13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than ? 1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92 ± 0.17 g/cm² and ? 1.36 ± 1.50, respectively. Twenty‐one patients (43,7%) were osteopenic (T score worse than ? 1.5) and mean T score of osteopenic patients was ? 2.72 ± 0.72. T score of nonosteopenic group was ? 0.29 ± 0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre‐ and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p < 0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R = 0.48 p < 0.05). Serum ACE activity was positively correlated with serum iPTH (R = 0.29, p = 0.02), serum OC (R = 0.35, p = 0.01), serum bAP (R = 0.34, p = 0.01), serum PCIP (R = 0.36, p = 0.01). T score (? 0.7 ± 1.5, vs ? 1.7 ± 1.3 p < 0.05) was higher in DD group (n = 19) compared to II + ID group (n = 29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.     

High Prevalence of Osteoporosis and Morphometric Vertebral Fractures in Indian Males Aged 60 Years and Above: Should Age for Screening Be Lowered?

Current guidelines recommend bone mineral density (BMD) measurement in asymptomatic men above age 70 years and vertebral fracture (VF) assessment above 80 years with T-score <?1.0 with risk factors. We studied the prevalence of osteoporosis and morphometric VF in asymptomatic males aged 60 years and above in North India. Free-living community-dwelling men (n?=?241, age: mean?±?standard deviation 68.0?±?6.2 years) underwent a detailed history, physical examination, biochemical evaluation, and BMD measurements at 3 sites: lumbar spine, total hip (TH), and femoral neck (FN). Morphometric VF were assessed by instant vertebral assessment using Genant et al's semiquantitative method. We observed osteoporosis, osteopenia, and normal BMD in 19%, 56%, and 25% of subjects, respectively. The decade wise prevalence of osteoporosis in the age groups 60–70 years, 71–80 years, and >80 years was 16.9%, 17%, and 50%, respectively. Mean serum 25OHD levels were 17.2?±?10.3?ng/mL. Vitamin D deficiency (<20?ng/mL) and secondary hyperparathyroidism (plasma intact parathyroid hormone >65?ng/mL) were present in 68.8% and 45.4%, respectively. VF were present in 29.6% subjects (grade I: 58%, grade II: 32.4%, and grade III: 8.8%). Age and iPTH had significant negative correlation with BMD at FN and TH. Serum 25OHD had no correlation with BMD at any site. The prevalence of VF was positively associated with age (p?=?0.018) and negatively associated with BMD at FN (p?=?0.002) and TH (p?=?0.013). Osteoporosis and VF are common in asymptomatic Indian males aged 60 years and above. Screening for osteoporosis and instant vertebral assessment may be recommended earlier than currently existing guidelines.     

Vitamin D deficiency and seasonal variation over the years in São Paulo,Brazil

Summary

Brazil is a tropical/subtropical geographic area with elevated ultraviolet (UV) radiation. We report very high prevalence of vitamin D deficiency in a large database of Brazilian subjects and show seasonal and reciprocal relationship between vitamin D and parathyroid hormone (PTH) over the years in this tropical area.

Introduction

We aim to examine the prevalence of vitamin D deficiency, characterize the temporal relationship between 25-hydroxyvitamin D levels (25(OH)D) and intact PTH (iPTH) according to seasons, and investigate potential associations between 25(OH)D levels and extra-skeletal outcomes in a Brazilian population.

Methods

We retrospectively determined population weekly mean concentrations of unpaired 25(OH)D and iPTH using 39,004 laboratory results of Brazilian individuals of both genders aged 2 to 95 years. The 25(OH)D and iPTH distributions were normalized, and the means fit with a sinusoidal function. Potential associations between 25(OH)D serum levels and inflammatory markers, fasting glucose, HbA1c and Homeostasis Model Assessment index (HOMA) were examined.

Results

Of the samples, 33.9 % had 25(OH)D serum concentrations lower than 20 ng/mL, while the vast majority (70.7 %) were found to be vitamin D deficient or insufficient (<30 ng/mL). Vitamin D deficiency was significantly higher during the winter as compared to the summer (38.4 % <20 ng/mL and 75.5 % <30 ng/mL versus 23.3 % <20 ng/mL and 62.5 % <30 ng/mL, respectively; p?<?0.001). Seasonal variation was observed for both 25(OH)D and iPTH. 25(OH)D peaks occurred in March and troughs in September. iPTH levels showed an inverted pattern of peaks and troughs with a delay of 1?±?5 week. 25(OH)D was significantly associated with inflammatory markers but not with glucose homeostasis.

Conclusions

A sinusoidal interrelationship has been detected between vitamin D and PTH in this tropical population. A large percentage of the individuals showed vitamin D deficiency. Public health strategies are needed to better understand and manage this very high and apparently contradictory prevalence of vitamin D deficiency.

     

No change in calcium absorption in adult Pakistani population before and after vitamin D administration using strontium as surrogate

Summary

Vitamin D, parathyroid hormone levels and calcium absorption was assessed before and after cholecalciferol using Strontium as a surrogate. Increase in 25OHD, lowering of iPTH with no effect on Sr absorption was seen, suggesting the possibility that maximal Ca absorption had already been achieved in these volunteers.

Introduction

This paper discusses the determination of calcium (Ca) absorption, using strontium (Sr) as a surrogate, before and after a single IM injection of vitamin D₃ (600,000 IU).

Methods

Baseline serum 25-hydroxyvitamin D (25OHD), Sr, Ca, P, and intact parathyroid hormone (iPTH) were determined in 53 fasting volunteers, followed by administrating (PO) 0.03 mM (4.8 mg/kg) SrCl₂ and collecting blood at 0.5, 1 and 4 h to determine the absorption (AUC_0→t ) of Sr. Following the initial absorption test, volunteers received a single IM injection of 600,000 IU vitamin D₃. Two months later, the fasting serum and the Sr absorption test were repeated, as described above.

Results

The IM injection of vitamin D₃ caused a significant increase in fasting 25OHD (from 43.5?±?19 to 66.1?±?19.1 nmol/L (p?<?0.001)) and a trend toward lower serum iPTH (from 59.8?±?27.8 to 53?±?31 ng/L). Fasting serum Ca and P remained unchanged. A higher 25OHD level failed (p?=?0.32) to translate into a higher rate of Sr absorption. AUC_0→4 h were almost identical before and after the IM injection of vitamin D₃.

Conclusion

A single vitamin D₃ injection of 600,000 IU significantly increase mean 25OHD concentration and tended to lower iPTH concentrations in volunteers with initially low 25OHD status, suggesting to utilize this simple form of treatment to improve vitamin D status and to have a possible biological effect on Ca homeostasis. However, we found no obvious effect on Sr absorption, suggesting the possibility that maximal vitamin D-dependent Ca absorption had already been achieved in these volunteers at a lower vitamin D status.     

Effects of Growth Hormone Administration on Bone Mineral Metabolism,PTH Sensitivity and PTH Secretory Rhythm in Postmenopausal Women With Established Osteoporosis

Introduction : Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH‐deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor‐1 (IGF‐1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Materials and Methods : Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half‐hourly blood and 3‐h urine samples were collected. PTH, calcium (Ca), phosphate (PO₄), nephrogenous cyclic AMP (NcAMP), β C‐telopeptide of type 1 collagen (βCTX), procollagen type I amino‐terminal propeptide (PINP), and 1,25‐dihydroxyvitamin D [1,25(OH)₂D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t‐test and general linear model ANOVAs for repeated measures were used where appropriate. Results : IGF‐1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 ± 8.9 versus 140.9 ± 10.8 μg/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty‐four‐hour mean PTH concentration was higher in the osteoporotic women (5.4 ± 0.1 pM) than in healthy controls (4.4 ± 0.1 pM, p < 0.001) and decreased after 1 (5.2 ± 0.1 pM, p < 0.001), 3 (5.0 ± 0.1 pM, p < 0.001), 6 (4.7 ± 0.1 pM, p < 0.001), and 12 mo (4.9 ± 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 ± 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 ± 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 ± 2.5 nM GFR, p < 0.05), 3 (27.3 ± 1.5 nM GFR, p < 0.001), and 6 mo (32.4 ± 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24‐h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO₄ at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)₂D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). βCTX concentration increased progressively from 0.74 ± 0.07 μg/liter at baseline to 0.83 ± 0.07 μg/liter (p < 0.05) at 1 mo and 1.07 ± 0.09 μg/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 ± 5 μg/liter) to 6 mo (126 ± 11 μg/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than βCTX (p < 0.05). Conclusions : Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long‐term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age‐related postmenopausal osteoporosis.     

Increased Serum 1,25-Dihydroxyvitamin D after Growth Hormone Administration is not Parathyroid Hormone-Mediated

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)₂D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2? days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)₂D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TRP), and maximum tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 μg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean ± SEM. Whereas serum 1,25(OH)₂D (58.9 ± 7.7 versus 51.6 ± 7.4 pg/ml, P < 0.01), serum phosphorus (4.5 ± 0.1 versus 3.7 ± 0.1 mg/dl, P < 0.01), TRP (92.0 ± 0.5 versus 87.8 ± 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 ± 0.1 versus 3.5 ± 0.2, P < 0.005), and urinary calcium (602 ± 49 versus 346 ± 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 ± 1.9 versus 26.8 ± 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(OH)₂D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)₂D. Received: 2 May 1996 / Accepted: 18 October 1996