25-hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C-reactive protein (c-CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r(2) = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c-CRP plateaued at 25(OH)D concentrations of 100-120 ng mL(-1) . Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL(-1) . Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL(-1) (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.

BACKGROUND

Denosumab is widely used for bone diseases with increased bone resorption. Its effectiveness in patients with severe secondary hyperparathyroidism on dialysis is unclear.

OBJECTIVE

This study aimed to evaluate the efficacy and safety of denosumab in patients with severe secondary hyperparathyroidism who are on dialysis.

METHODS

This 6-month prospective, open-labeled study evaluated 12 patients (five women, seven men; mean age 53.5 ± 3.8 y). All had intact PTH (iPTH;>> 1000 pg/mL), low bone mass (T-score < -1.0 SD), and bone pain and were poor surgical candidates. Serum calcium, phosphorus, alkaline phosphatase (AP), and iPTH levels were assessed at baseline and every month thereafter. Vertebral spine x-rays and bone mineral densities (BMDs) (lumbar spine and femoral neck) were assessed at the start and end of the study. All patients received denosumab (60 mg), calcitriol, phosphate binders, and dialysate calcium that were adjusted according to the biochemistry data.

RESULTS

The BMD increased in both the femoral neck (mean increase 23.7% ± 4.0%) and lumbar spine (17.1% ± 2.6%) after 6 months. In the first month, most patients had increased iPTH levels, which dramatically decreased from 1702.1 ± 181.9 to 518.8 ± 126.8 pg/mL by the end of the study after increasing the calcitriol dose. All patients had significant decreases in AP, calcium × phosphorus, and bone pain. Changes in femoral neck BMD correlated only with AP and iPTH levels.

CONCLUSIONS

Denosumab is effective in restoring bone mass and reducing bone pain in patients on dialysis with secondary hyperparathyroidism. It also allows for a more aggressive use of calcitriol to control hyperparathyroidism.

OBJECTIVE

Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy.

METHODS

In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations.

RESULTS

Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison's disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients.

CONCLUSIONS

Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients. Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation.

BACKGROUND

The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant (RT) population.

METHODS

In this 12-month, randomized, double-blind, multicenter trial, 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate (n = 24) or placebo (n = 15), at surgery and 3 months post-RT. All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry (DXA) and X-rays were performed at RT, 6 and 12 months post-RT. Biochemical and hormonal determinations were performed before and after treatment.

RESULTS

Pamidronate significantly reduced spinal bone loss, but no significant benefit was found for the incidence of fractures. Elevated baseline intact parathyroid hormone (iPTH) and bone remodeling markers returned to normal levels 3 months post-RT. However, normal procollagen type I N propeptide (PINP) concentrations were only maintained in the pamidronate group. After RT, a comparable graft function was observed in both groups according to creatinine values, 25-hydroxyvitamin-D (25-OH-D) levels were improved, and serum calcium levels normalized after a transient fall during the first 3 months.

CONCLUSIONS

A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT.

BACKGROUND

An increase in aortic stiffness, as reflected by an increase in pulse wave velocity (PWV), is an important predictor of cardiovascular mortality in dialysis patients. Decreased serum concentration of calcification inhibitor, such as fetuin-A, is inversely related to mortality in haemodialysis patients. Our aim is to investigate the factors associated with aortic stiffness and its change over time in peritoneal dialysis (PD) patients.

METHODS

As a prospective observational study, we analysed 67 PD patients, aged 50 ± 14 years (mean ± SD) and with dialysis duration of 26 (5-58) months (median, interquartile range). At baseline, age, mean arterial pressure (MAP), left ventricular mass (LVM) index, diabetes, serum albumin, calcium (Ca), phosphorus (P) and intact parathyroid hormone (iPTH), uric acid, total bilirubin, high-sensitivity C-reactive protein (hsCRP), fetuin-A, and residual renal function were included in association analysis with aortic stiffness represented by heart-to-femoral PWV (hfPWV). We also evaluated simple vascular calcification score (SVCS) with plain radiograph of the pelvis and both hands. PWV was measured both at baseline and at 1 year. Change of aortic stiffness was determined by △PWV (difference between 1-year PWV and baseline PWV). Time-averaged concentrations were used to evaluate the relation between biologic markers and changes of aortic stiffness.

RESULTS

hfPWV was 1022 ± 276 cm/s at baseline, and hfPWV determined at 1 year was 1069 ± 317 cm/s. Mean serum fetuin-A concentration was 0.34 ± 0.08 g/L. At baseline, aortic PWV positively correlated with age, smoking status, diabetes, MAP, total cholesterol and LDL cholesterol. On the other hand, aortic PWV inversely correlated with fetuin-A, log PTH, haemoglobin and albumin. In a multiple regression model, association of serum fetuin-A (β = -0.329, P = 0.003) with aortic PWV remained significant, along with age (β = 0.512, P < 0.001), MAP (β = 0.215, P = 0.047) and log PTH (β = -0.269, P = 0.025). At follow-up, △MAP (β = 0.500, P < 0.001) and time-averaged TG (aTG) (β = 0.259 P = 0.019) were determinants of △PWV.

CONCLUSIONS

For our PD patients, serum fetuin-A was an independent determinant of aortic stiffness, as well as age, MAP and log PTH. Although 1 year is not sufficient to observe the change of aortic stiffness, some patients exhibited >15% increase of PWV during this period. △MAP and aTG were factors affecting the change of PWV. Follow-up over a longer period is necessary to elucidate factors that determine changes of aortic stiffness over time from PD patients.

This study was undertaken to assess vitamin D status in nonmenopausal women with metabolic syndrome (MeS) and to evaluate its possible role in inflammation and other components of MeS. A case-control study was conducted during late fall and winter 2009-10. A total of 375 women with waist circumference (WC) ≥88 cm were examined to find 100 who met MeS criteria according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel (ATP) III criteria (NCEP/ATP III). Of those without MeS, 100 age- and residence area-matched women were selected as a control group. Anthropometric and laboratory evaluations were performed. Waist-to-hip ratio (WHR), body mass index (BMI), homeostatic model of insulin resistance (HOMA-IR) and body fat mass (FM) were also evaluated. Women with MeS had significantly higher BMI, waist circumference (WC) and FM but lower serum osteocalcin than controls. There was no significant difference in serum 25 hydroxyvitamin D (25[OH]D), intact parathyroid hormone (iPTH) or vitamin D status between the two groups. Serum highly sensitive C-reactive protein (hsCRP) concentration was significantly higher in the MeS group, compared to the controls (3.4 ± 3.3 vs 2.0 ± 1.9 mg/L, P < 0.001). The difference remained significant even after controlling for BMI (P = 0.011), WC (P = 0.014) and FM (P = 0.005). When comparison was made only in those subjects with insulin resistance (HOMA-IR>> 2.4), hsCRP was still higher in the MeS group (n = 79) than in the control group (n = 61) (P < 0.001). When data were categorized according to vitamin D status, in the MeS group significantly higher plasma glucose concentrations were observed in subjects with vitamin D deficiency compared to those with insufficiency or sufficiency (104.0 ± 11.7, 83.0 ± 11.3 and 83.2 ± 9.9 mg/dL, respectively, P < 0.001). Interestingly, their WC or WHR did not show any significant difference. In stepwise regression analysis, 25(OH)D was the main predictor of both hsCRP and plasma glucose. Vitamin D status may, at least in part, be a determining factor of systemic inflammation and the related metabolic derangements of MeS.

Long-term glucocorticoid treatment might interfere with the vitamin D metabolism. The serum concentrations of 25-OHD were significantly reduced whereas the circulating levels of 1,25-(OH)2D were normal in 50 patients with rheumatoid arthritis on long-term treatment with small doses of prednisone. The bone mineral content of the forearm was significantly reduced, but the degree of bone loss did not correlate with duration of treatment or dose of prednisone given. Quantitative bone histomorphometry was performed in 18 patients. Apart from a significant correlation between serum 25-OHD and the fractional trabecular bone volume, no relationships were observed between bone histomorphometry and vitamin D metabolites or serum iPTH. The results indicate that the bone loss was due to a decreased osteoblastic activity rather than to an impaired vitamin D metabolism.

Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40 patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had four glands removed, while only three glands were found in the remaining two. Perioperative complications consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%). No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37 (86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of 1084+/-505 pg/ml to 120+/-381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients. tPTX should be considered a safe and successful procedure for the treatment of severe secondary hyperparathyroidism associated with chronic kidney disease.

The purpose of this study was to determine the individual and combined effects on periprosthetic cancellous bone of intermittent parathyroid hormone administration (iPTH) and mechanical loading at the cellular, molecular, and tissue levels. Porous titanium implants were inserted bilaterally on the cancellous bone of adult rabbits beneath a loading device attached to the distal lateral femur. The left femur received a sham loading device. The right femur was loaded daily, and half of the rabbits received daily PTH. Periprosthetic bone was evaluated up to 28 days for gene expression, histology, and µCT analysis. Loading and iPTH increased bone mass by a combination of two mechanisms: (1) Altering cell populations in a pro-osteoblastic/anti-adipocytic direction, and (2) controlling bone turnover by modulating the RANKL-OPG ratio. At the tissue level, BV/TV increased with both loading (+53%, p < 0.05) and iPTH (+54%, p < 0.05). Combined treatment showed only small additional effects at the cellular and molecular levels that corresponded to a small additive effect on bone volume (+13% compared to iPTH alone, p>> 0.05). This study suggests that iPTH and loading are potential therapies for enhancing periprosthetic bone formation. The elucidation of the cellular and molecular response may help further enhance the combined therapy and related targeted treatment strategies.

The importance of the seasonal variation of calcitropic hormones to growing skeleton has not been established. We studied whether there exists a seasonal variation in calcitropic hormones, bone mineral density (BMD) and bone remodelling markers in early puberty girls. One hundred and ninety-six girls, mean age 11.4 (sd 0.4) years, in Tanner stage 2 (early puberty) and 3 (mid-puberty) were studied during September to March. The BMD was measured from the lumbar vertebrae and the left femur by dual-energy X-ray absoptiometry. Their serum 25-hydroxyvitamin D (S-25-OHD), serum intact parathyroid hormone (S-iPTH), serum osteocalcin, urinary pyridinoline and urinary deoxypyridinoline were analysed from fasting samples. The concentration of S-25-OHD and serum osteocalcin differed among months (P < 0.01), reflecting a seasonal variation. The parathyroid hormone correlated negatively with S-25-OHD (r -0.325, P < 0.001). Moreover, the BMD in the femur (P = 0.047) and to a lesser extent in vertebrae (P = 0.057) differed between months in early puberty girls but this was not seen in mid-puberty. Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

This study examined the effects of daily oral magnesium (Mg) supplementation on bone turnover in 12 young (27-36 yr old) healthy men. Twelve healthy men of matching age, height, and weight were recruited as the control group. The study group received orally 15 mmol Mg (Magnosolv powder, Asta Medica) daily in the early afternoon with 2-h fasting before and after Mg intake. Fasting blood and second void urine samples were collected in the early morning on days 0, 1, 5, 10, 20, and 30, respectively. Total and ionized Mg2+ and calcium (Ca2+), and intact PTH (iPTH) levels were determined in blood samples. Serum biochemical markers of bone formation (i.e. C-terminus of type I procollagen peptide and osteocalcin) and resorption (i.e. type I collagen telopeptide) and urinary Mg level adjusted for creatinine were measured. In these young males, 30 consecutive days of oral Mg supplementation had no significant effect on total circulating Mg level, but caused a significant reduction in the serum ionized Mg+ level after 5 days of intake. The Mg supplementation also significantly reduced the serum iPTH level, which did not appear to be related to changes in serum Ca2+ because the Mg intake had no significant effect on serum levels of either total or ionized Ca2+. There was a strong positive correlation between serum iPTH and ionized Mg2+ (r = 0.699; P < 0.001), supporting the contention that decreased serum iPTH may be associated with the reduction in serum ionized Mg2+. Mg supplementation also reduced levels of both serum bone formation and resorption biochemical markers after 1-5 days, consistent with the premise that Mg supplementation may have a suppressive effect on bone turnover rate. Covariance analyses revealed that serum bone formation markers correlated negatively with ionized Mg2+ (r = -0.274 for type I procollagen peptide and -0.315 for osteocalcin), but not with iPTH or ionized Ca2+. Thus, the suppressive effect on bone formation may be mediated by the reduction in serum ionized Mg2+ level (and not iPTH or ionized Ca2+). In summary, this study has demonstrated for the first time that oral Mg supplementation in normal young adults caused reductions in serum levels of iPTH, ionized Mg2+, and biochemical markers of bone turnover. In conclusion, oral Mg supplementation may suppress bone turnover in young adults. Because increased bone turnover has been implicated as a significant etiological factor for bone loss, these findings raise the interesting possibility that oral Mg supplementation may have beneficial effects in reducing bone loss associated with high bone turnover, such as age-related osteoporosis.

OBJECTIVE

Vascular calcifications are frequently found among dialysis patients, and the calcification process may influence the patient's outcome. The aim of the present study was to determine the role that vascular calcifications may have on autologous arteriovenous fistula (AVF) survival.

METHODS

This study included 90 patients (49 males, mean age 62 ± 11) with a native AVF treated by chronic hemodialysis (HD) for more than one year. The overall vascular calcification scores ranged from 0-11 (Adragao score + vascular access calcification score); patients were categorized into mild (score 0-3; n = 36), moderate (score 4-7; n = 24) and severe (score 8-11; n = 30) calcification groups. AVF survival was then followed for 5 years after calcification measurement or until the patient's death/transplantation.

RESULTS

Patients with more pronounced vascular calcifications were more frequently diabetic and male. Multiple linear regression analysis showed a significant relationship between calcification score and male gender, diabetes mellitus, previous duration of AVF, low dialysis flow rate and intact parathormone (iPTH) values. After multivariate adjustment for basal differences, Cox proportional analysis revealed a graded impact of calcification scores on AVF failure: moderate scores (were associated with a hazard rate (HR) of 3.82 (95% confidence interval (CI) 1.10-13.23) and severe scores with an HR of 4.65 (CI 0.97-22.38).

CONCLUSIONS

Vascular calcifications are associated with worse survival of native arteriovenous hemodialysis fistulas.

Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes net loss of bone mass, despite accelerating bone formation by osteoblasts. Intermittent treatment with PTH analogs represents the only Food and Drug Administration (FDA)-approved bone anabolic osteoporosis treatment strategy. Functional PTH receptors are present on cells of the osteoblast lineage, ranging from early skeletal stem cells to matrix-embedded osteocytes. In addition, bone remodeling by osteoclasts liberates latent growth factors present within bone matrix. Here, we will provide an overview of the multiple cellular and molecular mechanisms through which PTH influences bone homeostasis. Notably, net skeletal effects of continuous versus intermittent can differ significantly. Where possible, we will highlight mechanisms through which continuous hyperparathyroidism leads to bone loss, and through which intermittent hyperparathyroidism boosts bone mass. Given the therapeutic usage of intermittent PTH (iPTH) treatment for osteoporosis, particular attention will be paid toward mechanisms underlying the bone anabolic effects of once daily PTH administration.

OBJECTIVE

Vitamin D insufficiency drives secondary hyperparathyroidism (SHPT) and is associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). SHPT is poorly addressed by current vitamin D repletion options. The present study evaluated a novel investigational vitamin D repletion therapy: a modified-release (MR) formulation of calcifediol designed to raise serum 25-hydroxyvitamin D in a gradual manner to minimize the induction of CYP24 and, thereby, improve the SHPT control.

METHODS

This randomized, double-blind, placebo-controlled trial evaluated MR calcifediol in CKD subjects (n = 78) with plasma intact parathyroid hormone (iPTH) >70 pg/ml and serum total 25-hydroxyvitamin D <30 ng/ml. Subjects received daily treatment for six weeks with oral MR calcifediol (30, 60 or 90 µg) or a placebo.

RESULTS

More than 90% of subjects treated with MR calcifediol achieved serum 25-hydroxyvitamin D levels ≥30 ng/ml versus 3% of subjects treated with placebo (p < 0.0001). Mean plasma iPTH decreased from baseline (140.3 pg/ml) by 20.9 ± 6.2% (SE), 32.8 ± 5.7 and 39.3 ± 4.3% in the 30, 60 and 90 µg dose groups, respectively, and increased 17.2 ± 7.8% in the pooled placebo group (p < 0.005). No clinically significant safety concerns arose during MR calcifediol treatment.

CONCLUSIONS

Oral MR calcifediol appears safe and highly effective in treating SHPT associated with vitamin D insufficiency in CKD.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) bone metabolism guidelines assume that clinicians use the Nichols intact parathyroid hormone immunoradiometric assay (iPTH IRMA) upon which K/DOQI was based. But for more than a decade, virtually all PTH assay results used for routine end-stage renal disease (ESRD) clinical management have not been generated with this test. Results from the most widely used PTH assays for ESRD patient testing in the United States have varied from 1999 to 2005. The Nichols chemiluminescent Advantage iPTH assay results shifted upwards significantly in 1999 and remained elevated until 2005. From 2003 to 2005, results from the Nichols Advantage Bio-Intact PTH assay shifted upward on average by 29% to 52%. These changes in the most widely used PTH assays have made use of the K/DOQI guidelines with these assays both inappropriate and potentially harmful to patients.

BACKGROUND

Vascular calcification significantly increases the rates of cardiovascular mortality in hemodialysis (HD) patients. Abnormalities in mineral metabolism may play a role in the pathogenesis of arterial calcification. Whether patients treated with non-calcium-based phosphate binders had reduced aortic vascular calcification compared to those treated with calcium-based phosphate binders is still unclear.

METHODS

We searched multiple databases for studies published through August 2013 that evaluated the effects of non-calcium-based phosphate binders (NCBP) versus calcium-based phosphate binders (CBP) on cardiovascular calcification and bone remodeling among dialysis patients. We summarized test performance characteristics with the use of forest plots, fixed and random effects models, and Egger regression test.

RESULTS

Eighteen eligible randomized controlled trials totaling 3676 patients were included. Meta-analysis results showed NCBP could significantly attenuate the progression of coronary artery calcification than CBP (WMD: -144.62, 95% CI: -285.62 to -3.63). The serum calcium levels significant lower in NCPB group than in CPB groups (WMD: -0.26, 95% CI: -0.37 to -0.14), but the serum iPTH levels were significantly higher in NCPB groups (WMD: 57.1, 95% CI: 13.42 to 100.78). The osteoid volume and osteoblast numbers were significant higher in NCPB group than in CPB group (WMD: 1.75, 95% CI: 0.78 to 2.73 for osteoid volume; WMD: 4.49, 95% CI: 1.83 to 7.15 for osteoblast numbers). The Egger regression test also showed no potential publication bias (p = 0.725).

CONCLUSIONS

Based on available data, NCBPs have equally effective with CBPs for serum phosphate control. But there was significantly lower incidence of coronary artery calcification and a significant higher bone formatting rate in NCBP groups than in CBP groups. So we recommend NCBPs as phosphate binders for HD patients.

BACKGROUND

In calcific aortic valve disease, the early lesion is similar to atherosclerotic plaque, but later calcification prevails. Parathyroid hormone (PTH) and vitamin D are the principal calcium pool regulators, so the present study was designed to assess their association with aortic stenosis (AS) in patients with significant coronary artery disease (CAD), and preserved renal function.

RESULTS

The 122 consecutive patients with AS (mean gradient>> or =30 mmHg) plus CAD, and 101 patients with nonobstructive aortic sclerosis (mean gradient < or =10 mmHg) plus CAD, as controls, were prospectively enrolled. The AS patients were older (71+/-7 vs 66+/-7 years; p<0.001), had higher serum intact (i)PTH (51.4 [39-70] vs 37.4 [27-50] pg/ml; p<0.001), and lower plasma vitamin D (32.0 [25-40] vs 35.8 [27-55] nmol/L; p=0.003) levels than those with aortic sclerosis. The groups did not differ significantly in creatinine level (93 [82-105] vs 96 [85-107] micromol/L, p=0.19), calcium - phosphate product, occurrence of hypertension, smoking, diabetes, dyslipidemia, or body mass index. The iPTH (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.05; p<0.001) and vitamin D levels (OR 0.97, 95% CI 0.95-0.99; p=0.003) were independently associated with AS.

CONCLUSIONS

Higher serum iPTH with lower vitamin D levels were independently associated with calcific AS in CAD patients.

Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n = 88, 32 and 74, respectively). The mean sun-index (12.0 ± 6.25, 4.3 ± 2.20 and 0.7 ± 0.62, respectively; P < 0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0 ± 8.61, 19.1 ± 5.73 and 10.9 ± 4.19 ng/ml, respectively; P < 0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2 ± 88.77, 239.3 ± 83.40 and 216.6 ± 63.93 µg/ml, respectively; P = 0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r = -0.401, -0.269 and -0.236, respectively; P < 0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03 ng/ml per hour of sun-exposure (95 % confidence interval 1.77-2.28; P < 0.001). Outdoor workers with prolonged sun-exposure were vitamin D-sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status.

OBJECTIVE

To document lifestyle-associated variations in biochemical markers of bone metabolism in advanced age.

METHODS

Cross-sectional study.

METHODS

Department of Geriatrics, University Hospital, Basel, Switzerland.

METHODS

Three hundred twelve ambulatory and 193 institutionalized men and women, aged 54 to 99 yrs.

METHODS

Biochemical markers of bone resorption (urinary deoxypyridinolin and N-telopeptides), serum vitamin D metabolites, and serum intact parathyroid hormone (iPTH) concentrations were assessed. Mean values of all parameters were correlated with a six-grade activity score. Physical activity score reflected the degree of weight bearing, ranging from walking independently to primarily bed-bound. Ambulatory subjects were measured in summertime and institutionalized subjects in wintertime to accentuate seasonality of vitamin D hormone levels.

RESULTS

Excretion of bone resorption markers was significantly higher in the institutionalized and physically inactive patients compared with those who were ambulatory and physically active (p = .0001). Vitamin D deficiency (25-hydroxyvitamin D of <12 ng/mL) was present in 86% of institutionalized and 15% of ambulatory subjects, and 1,25-dihydroxyvitamin D serum concentrations were lower in institutionalized than in ambulatory subjects (p = .0001). Mean serum concentrations for iPTH were similar for both the institutionalized and ambulatory groups. When subjects were arranged according to activity score, mean excretion of urinary bone resorption markers increased with degree of inactivity.

CONCLUSIONS

Despite the difference in vitamin D metabolites, iPTH serum concentrations did not differ significantly between the institutionalized and ambulatory groups. However, institutionalized and physically inactive participants had markedly elevated excretion of urinary bone resorption markers compared with ambulatory and physically active subjects. These results suggest that high bone turnover in the elderly may be caused by physical inactivity related to low mechanical loading rather than secondary hyperparathyroidism.

This study was designed to determine whether the serum calcium or immunoparathormone (iPTH) level would be of value in predicting the size or weight of the parathyroid gland in patients with single-gland enlargement caused by primary hyperparathyroidism. Ninety-two patients who underwent parathyroidectomy with removal of a single enlarged gland at the North Carolina Memorial Hospital (1974 to 1984) were reviewed. The preoperative calcium and immunoparathormone levels were correlated to the weight and calculated volume of the removed gland. The calcium level was found to be significantly associated with parathyroid gland weight and volume (p less than 0.001), as determined by linear regression analysis. Despite the statistical association, the correlation coefficient (calculated with the Pearson correlation matrix) was low, 0.16 for the relation of calcium to gland weight and 0.25 for the relation of calcium to calculated gland volume. The calculated coefficients of correlation of iPTH (three different assays) to gland weight and volume were similarly low. These findings demonstrate a variable relationship between the preoperative serum calcium level or the iPTH level to the weight or volume of the enlarged hyperfunctioning parathyroid gland. Identification of the pathologic parathyroid gland(s) in primary hyperparathyroidism cannot be based on a perceived relation of preoperative calcium or iPTH levels to the size of the enlarged glands.

BACKGROUND

The level of parathyroid hormone (iPTH) serum has been controversial in the prediction of postthyroidectomy hypocalcemia. Analysis of the decrease between preoperative and postoperative iPTH levels should be more accurate. Therefore, the aim of our study was to prospectively establish the reliability of the iPTH decrease for early diagnosis of postoperative hypocalcemia and to identify the patients who are not at risk for hypocalcemia.

METHODS

A prospective study of 137 consecutive patients who underwent total thyroidectomy was performed. Serum iPTH level was measured preoperatively and 4 hours postoperatively (iPTH(H4)). The sensitivity, specificity, and positive and negative predictive values for the iPTH(H4) and for the iPTH decline were estimated by confidence interval from thresholds determined by ROC curve analysis.

RESULTS

Thirty-nine patients developed hypocalcemia (28.5%). Patients who developed hypocalcemia had a significantly lower iPTH(H4) and a significantly greater iPTH decrease (P < .001). The thresholds enabling prediction of hypocalcemia were 19.4 ng/L for iPTH(H4) and 68.5% for iPTH decline. Sensitivity, specificity, and positive and negative predictive values for iPTH(H4) were 84.6%, 92.9%, 82.5%, and 93.8% (overall accuracy, 90.5%). iPTH decline was more accurate to predict hypocalcemia (sensitivity, 97.4%; specificity, 95.9%; positive predictive values 90.5%; negative predictive values, 98.6%; and overall accuracy, 96.4%).

CONCLUSIONS

The decrease in iPTH is more precise than the iPTH(H4) alone and can accurately predict hypocalcemia after total thyroidectomy. Patients with a decrease in iPTH less than 68.5% can be discharged at postoperative day one without any supplementation. Patients with iPTH decline more than 68.5% should be administered calcium and vitamin D supplementation before symptoms appear.

BACKGROUND

Hyperphosphatemia is one of the main factors in the pathogenesis of secondary hyperparathyroidism. In addition, in dialysis patients elevated levels of phosphate and calcium times phosphate (Ca x P) ion product are associated with extraskeletal calcifications, as well as an increased risk of death. Cardiovascular calcifications may possibly be related to the high cardiovascular mortality seen in dialysis patients. In the USA the prevalence of hyperphosphatemia among dialysis patients is very high, over 60% of patients having serum P levels>> 5.5 mg/dl, but no data are available for the Italian population, which follows different diet and dialysis schedules.

METHODS

We looked at a random sample of 638 patients enrolled in 29 outpatient dialysis units in Southern Italy (Campania and Sicily). Data were centrally analyzed after extraction from a computerized database. In each patient the average of two or more values obtained in the six-month observation period (from Jan. 99 to June 99) was calculated. Mean age was 61.2 years (95% CI 59.9-62.5) years, dialytic age 72.2 months (95% CI 67.4-77.0).

RESULTS

Mean +/- SD (95% CI) levels of phosphate were 5.74 +/- 1.57 (5.62-5.86) mg/dl; total calcium 9.06 +/- 0.98 (8.98-9.14) mg/dl; Ca x P 51.4 +/- 14.4 (50.3-52.5) mg2/dl2; alkaline phosphatase was 167 +/- 119 (157-177) IU/L; intact parathyroid hormone (PTH) levels, available in a subset of 239 patients, were 318 +/- 413 (265-370) pg/ml. Among these patients 51.6% had serum P>> 5.5 mg/dl, 36%>> 6 mg/dl; Ca x P levels were>> 55 mg2/dl2 in 35.5% of the population, 24%>> 60 mg2/dl2; iPTH levels were < 100 pg/ml in 43%; 25.4% had hyperparathyroidism (defined as iPTH>> 400 pg/ml), and only 19.5% of patients had PTH in the desired interval of 100 to 250 pg/ml.

CONCLUSIONS

Compared to data reported from the USA, mean levels of phosphate, Ca x P, and PTH seem better controlled in this Italian hemodialysis population. However, in a significant number of patients these parameters were still outside the normal range. Both over-suppression of PTH levels and hyperparathyroidism are present, although surprisingly the former was more frequent. Treatment of hyperphosphatemia should be more aggressive in hemodialysis patients; PTH levels are difficult to maintain in the desired range of 100-250 pg/ml.

The standard measurement of parathyroid hormone (PTH) is the intact PTH (iPTH) assay, which is used for approximately 90% of Japanese dialysis patients. The iPTH assay reacts not only with 1-84 PTH, but also with large truncated fragments of non-1-84 PTH, including 7-84 PTH. On the other hand, the whole PTH assay is specific for 1-84 PTH. The aim of the current study was to define the validity of both whole and intact PTH assays. A total of 738 hemodialysis patients were enrolled from twelve dialysis services. The serum PTH level was evaluated by both intact and whole PTH assays simultaneously. Non-1-84 PTH was determined by subtracting the whole PTH value from that of the intact PTH assay. The median level of whole PTH was 121 pg/mL, and that of iPTH was 210 pg/mL. The whole PTH assay had a very high correlation with the iPTH assay (r = 0.870, P < 0.001). For 43 out of 738 patients (5.8%) the value for intact PTH-whole PTH was <0. Both assays significantly correlated with non-1-84 PTH (P < 0.001), while the iPTH assay, particularly, had a very high correlation with non-1-84 PTH (r = 0.791). As a whole, 18% of the total population was misclassified into a different Japanese guideline category. Stratified by Japanese guideline classifications, 28% of patients within an iPTH target range were misclassified. Using Bland-Altman plot analysis, as the serum PTH level increased, there was a large difference between two assays. Both PTH assays correlate strongly, although the whole PTH assay may be more useful for precise evaluation of PTH function than the iPTH assay.

OBJECTIVE

Assessment of bone turnover for management of renal osteodystrophy is part of routine care in chronic kidney disease Stage 5 (CKD-5) patients. Measurement of intact parathyroid hormone (iPTH) is the most commonly used surrogate marker for bone turnover in these patients. The current study was conducted to evaluate the predictive value of the five most commonly used iPTH assays for bone turnover.

METHODS

In a cross-sectional study, 84 CKD-5 patients underwent bone biopsy and blood drawings for determination of iPTH and total serum alkaline phosphatase (AP).

RESULTS

Histologically, patients presented with a broad range of bone turnover abnormalities as determined by activation frequency and bone formation rate/bone surface. Results of the five iPTH assays in each patient correlated but were significantly different. There were also significant differences between iPTH measurements at the same bone turnover level. Using Kidney Disease Outcome Quality Initiative recommended iPTH ranges, all assays showed comparably poor diagnostic performance. At 80% specificity, cut-off values of the 5 iPTH assays for low bone turnover varied from 165 to 550 pg/ml and for high bone turnover from 404 to 1,003 pg/ml. Sensitivities at these cutoffs remained below acceptable standards. Addition of AP measurements to iPTH did not improve diagnostic accuracy.

CONCLUSIONS

Precise assessment of bone turnover will require utilization of established and novel bone markers reflecting effects of bone turnover rather than measuring only iPTH or other effectors.