Background: A non-invasive method for evaluation of high-turnover and low-turnover bone diseases is the measurement of certain important serum bone markers such as osteocalcin, procolagen-I-propeptide, dioxypiridinoline, hydroxyproline and alkaline phosphatase. Renal osteodystrophy (ROD) in pre-dialysis and dialysis patients, is manifested in 3 forms: high-turnover ROD, related to secondary hyperparathyroidism; low-turnover ROD and mixed ROD.
Material and methods: Serum levels of intact parathyroid hormone (iPTH), osteocalcin (OC), procolagen-I-propeptide (PIPC) and dioxypiridinoline (DYP) were measured in 20 patients on hemodialysis (HD) and 20 patients on continuous ambulatory peritoneal dialysis (CAPD) to assess the prevalence of ROD type in the HD and CAPD groups.
Results: We found lower mean levels of all bone markers in CAPD patients, (iPTH: 219±235 vs. 428±285 pg/ml; p<0.01; OC 10.2±7.5 vs. 21.3±7.2 ng/ml; p<0.01; PIPC 111±57.3 vs. 218±62.4 ng/ml; p<0.01; DYP 7.3±6.4 vs. 55.2±23.3nm/l; p<0.001; AP 164±66 vs. 325±188 U/l; p<0.01) and lower than normal in 11 of them and higher than normal PTH, AP and some of the other serum markers (PICP; DYP) in 14 HD patients.
Conclusions: The lower levels of the investigated serum bone markers in CAPD patients suggest that low-turnover ROD prevails in these patients than in HD pts.
serum bone markers; osteocalcin; procolagen-I-propeptide; dioxipyridinoline; hydroxyproline; alkaline phosphatase; intact parathyroid hormone; high-turnover ROD; low-turnover ROD
Aim: To determine the prevalence of vitamin D hypovitaminosis among obese and overweight schoolchildren.
Design: A cross−sectional population based sample.
Methods: In a cross−sectional study, 301 students (177 girls and 124 boys) aged 11−19 years were selected by multistage stratified sampling design. Subjects were classified according to their body mass index as obese, overweight and normal. Serum 25−hydroxyvitamin D (25−OHD), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) were measured in late winter months. Vitamin D deficiency was defined as a 25−OHD 20 ng/ml.
Results: The prevalence of hypovitaminosis D was found as 65% in all students. Vitamin D deficiency was found in 12% and insufficiency in 53% of all students. Vitamin D deficiency in female students was about two times more common than in males. In obese and overweight schoolchildren with hypovitaminosis D, serum 25−OHD levels decreased as BMI increased. There were no correlations between serum 25−OHD and ALP and iPTH levels.
Conclusion: Vitamin D deficiency and insufficiency are common in obese and overweight schoolchildren, especially in girls. Obesity could be a risk factor in terms of hypovitaminosis D in adolescents. Vitamin D supplementation should be administered particularly to adolescent girls.
Conflict of interest:None declared.
adolescents; obesity; Vitamin D; hypovitaminosis D; schoolchildren
Objective: Adiponectin and its receptors are known to be expressed in osteoblasts and may have important functions in normal bone cells. The aim of this study was to investigate the effect of vitamin D therapy on serum adiponectin levels in children with vitamin D deficiency rickets (VDDR).
Methods: 21 patients with VDDR were included in the study. Patients were treated with 300,000 U D3 (IM) and calcium lactate (50mg/kg/ day, PO, for 10 days). Anthropometric parameters and serum biochemical markers including calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), intact parathormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and adiponectin levels were measured before and after one month of therapy.
Results: Weight and length, but not BMI, increased significantly after treatment. Serum 25(OH)D level increased significantly after treatment, while serum adiponectin level decreased (4.21±1.84 vs 52.73±17.63 ng/ml, p<0.000; 150.1±66.14 vs 84.29±9.06 mg/ml, p<0.000, respectively). No significant correlations were found between serum adiponectin and 25(OH)D levels before and after treatment or between delta adiponectin concentrations and delta 25(OH)D levels.
Conclusion: Serum adiponectin levels are increased in patients with VDDR, a finding which is probably related to increased osteoblastic activity.
Conflict of interest:None declared.
treatment; Vitamin D; Adiponectin; rickets
Vitamin D deficiency rickets (VDDR) is a disorder biochemically characterized by elevated serum alkaline phosphatase (ALP) activity, normal or decreased serum calcium (Ca) and inorganic phosphate concentrations, secondary hyperparathyroidism and decreased serum 25−hydroxyvitamin D (25(OH)D) levels. In stage 1 VDDR, urinary amino acid and phosphate excretion are normal with minimal or no findings of rickets on radiographs. Pseudohypoparathyroidism (PHP) is an inherited disorder characterized by end−organ resistance to parathormone (PTH). VDDR occasionally resembles PHP type 2 in clinical presentation and biochemical features, creating difficulties in the differential diagnosis of these two entities. Here we report an infant diagnosed with VDDR. In addition to inadequate vitamin D intake, usage of antiepileptic drugs (AED) may have led to the worsening of the vitamin D deficiency. The patient presented with a history of febrile convulsions, for which he received phenobarbital treatment. The initial findings of hypocalcemia, hyperphosphatemia and normal tubular reabsorption of phosphate, mimicking PHP 2, responded well to vitamin D and oral Ca treatment with normalization of serum Ca, phosphorus (P), ALP and PTH levels
Conflict of interest:None declared.
Vitamin D deficiency rickets; Pseudohypoparathyroidism; antiepileptic drugs
This study was carried out to evaluate the efficacy and safety of doxercalciferol as therapy for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 4 in a prospective clinical trial. A total of 35 CKD-4 patients who had a baseline parathyroid hormone (iPTH) >150 pg/mL and had not received any vitamin D analog in the preceding 8 weeks were followed up at intervals of 6 weeks for 18 weeks on oral therapy with doxercalciferol. The starting dose was 1.5 μg/day, and the dose was increased in steps of 1 μg/day if iPTH did not decrease by at least 30% on the subsequent visit. Doxercalciferol was stopped temporarily if low iPTH (<70 pg/mL), hypercalcemia (>10.7 mg/dL), or severe hyperphosphatemia (>8.0 mg/dL) occurred, and was restarted at a lower dose on reversal of these abnormalities. Calcium acetate was the only phosphate binder used. Mean iPTH decreased by 35.4 ± 4.4% from 381.7 ± 31.3 pg/mL to 237.9 ± 25.7 pg/mL (P < 0.001). The proportion of patients who achieved 30% and 50% suppression of iPTH levels was 83% and 72%, respectively. Mean serum calcium, phosphorus, and calcium-phosphorus product values did not differ significantly from the baseline values. Four, two, and nine patients developed hypercalcemia, severe hyperphosphatemia, and high CaxP (>55), respectively. Almost all patients recovered to an acceptable level within 2 weeks of stopping doxercalciferol and adjusting the phosphate binder dose. In all, 21 patients required temporary stoppage of therapy. Most of them were restarted on therapy at a reduced dose during the study. It can, therefore, be concluded that doxercalciferol is effective in controlling SHPT in CKD-4 patients with an acceptable risk of hyperphosphatemia and hypercalcemia.
Chronic kidney disease; doxercalciferol; parathyroid hormone; pre-dialysis; secondary hyperparathyroidism; vitamin D
Objective: To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects.
Methods: Twenty one active elderly subjects (11 men and 10 women; mean age 73.3 years) showing a mean theoretical Vo2max of 151.4% participated. Concentrations of plasma ionised calcium (iCa), serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and 1.25-dihydroxy-vitamin D3 (1.25(OH)2D3), as well as the bone biochemical markers type I collagen C-telopeptide for bone resorption and osteocalcin and bone alkaline phosphatase for bone formation, were analysed before and after a maximal incremental exercise test.
Results: At basal level, iPTH was positively correlated with age (r = 0.56, p<0.01) and negatively correlated with 25(OH)D (r = –0.50; p<0.01) and 1.25(OH)2D3 (r = –0.47; p<0.05). Moreover, 25(OH)D and 1.25(OH)2D3 levels were negatively correlated with age (r = –0.50, p<0.01 and r = –0.53, p<0.01, respectively). After exercise, iCa and 25(OH)D decreased (p<0.001 and p = 0.01, respectively) while iPTH increased (p<0.001). The levels of 1.25(OH)2D3, bone biochemical markers, haematocrit, and haemoglobin were unchanged. The variations in iCa and 25(OH)D were not related to age and/or sex. The iPTH variation was directly related to basal iPTH levels (p<0.01) and indirectly related to age.
Conclusions: In active elderly subjects, strenuous exercise disturbed calcium homeostasis and bone related hormones without immediate measurable effect on bone turnover. Although an increase in iPTH could have an anabolic action on bone tissue, our findings from our short term study did not allow us to conclude that such action occurred.
Twenty-seven unselected patients were investigated three to eight years after jejunoileal bypass for morbid obesity. The serum levels of calcium, magnesium, and phosphorus, and the renal excretions of calcium and magnesium were reduced. The serum alkaline phosphatase levels were increased. The serum levels of the two vitamin D metabolites 25-hydroxyvitamin D (25-OHD) and 1.25-dihydroxyvitamin D (1.25-(OHD)2D) were reduced and inversely related to the increased serum levels of immunoreactive parathyroid hormones (iPTH). Serum 1.25-(OH)2D correlated positively and serum iPTH inversely with serum concentrations and renal excretion rates of calcium. Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a reduced bone turnover with an increased amount of osteoid due to an increase in both surface extent and mean width of osteoid seams. The increased volume of osteoid was caused by a decreased osteoblastic function with a longer life-span of bone-forming sites and a prolongation of the mineralisation lag time. The amount of trabecular bone was normal. The results indicate an impaired vitamin D metabolism with osteomalacia and secondary hyperparathyroidism.
Chronic kidney disease (CKD) is associated with elevations in serum phosphate, calcium–phosphorus product and bone-specific alkaline phosphatase (BAP), with attendant risks of cardiovascular and bone disorders. Active vitamin D can suppress parathyroid hormone (PTH), but may raise serum calcium and phosphate concentrations. Paricalcitol, a selective vitamin D activator, suppressed PTH in CKD patients (stages 3 and 4) with secondary hyperparathyroidism (SHPT) with minimal changes in calcium and phosphate metabolism.
The VITAL study enrolled patients with CKD stages 2–4. We examined the effect and relationship of paricalcitol to calcium and phosphate metabolism and bone markers in a post hoc analysis of VITAL. The study comprised patients with diabetic nephropathy enrolled in a double-blind, placebo-controlled, randomized trial of paricalcitol (1 or 2 μg/day). Urinary and serum calcium and phosphate, serum BAP, and intact PTH (iPTH) concentrations were measured throughout the study.
Baseline demographics and calcium, phosphate, PTH (49% with iPTH <70 pg/mL), and BAP concentrations were similar between groups. A transient, modest yet significant increase in phosphate was observed for paricalcitol 2 μg/day (+0.29 mg/dL; P < 0.001). Dose-dependent increases in serum and urinary calcium were observed; however, there were few cases of hypercalcemia: one in the 1-μg/day group (1.1%) and three in the 2-μg/day group (3.2%). Significant reductions in BAP were observed that persisted for 60 days after paricalcitol discontinuation (P < 0.001 for combined paricalcitol groups versus placebo). Paricalcitol dose-dependent reductions in iPTH were observed. Paricalcitol in CKD patients (±SHPT) was associated with modest increases in calcium and phosphate.
Paricalcitol reduces BAP levels, which may be beneficial for reducing vascular calcification.
Trial is registered with ClinicalTrials.gov, number NCT00421733.
bone-specific alkaline phosphatase; calcitriol; hypercalcemia; hyperphosphatemia; paricalcitol; vitamin D receptor activation
Optimal treatment for secondary hyperparathyroidism (SHPT) has not been defined. The IMPACT SHPT (ClinicalTrials.gov identifier: NCT00977080) study assessed whether dose-titrated paricalcitol plus supplemental cinacalcet only for hypercalcaemia is superior to cinacalcet plus low-dose vitamin D in controlling intact parathyroid hormone (iPTH) levels in patients with SHPT on haemodialysis.
In this 28-week, multicentre, open-label Phase 4 study, participants were randomly selected to receive paricalcitol or cinacalcet plus low-dose vitamin D. Randomization and analyses were stratified by mode of paricalcitol administration [intravenous (IV) or oral]. The primary efficacy end point was the proportion of subjects who achieved a mean iPTH value of 150–300 pg/mL during Weeks 21–28.
Of 272 subjects randomized, 268 received one or more dose of study drug; 101 in the IV and 110 in the oral stratum with two or more values during Weeks 21–28 were included in the primary analysis. In the IV stratum, 57.7% of subjects in the paricalcitol versus 32.7% in the cinacalcet group (P = 0.016) achieved the primary end point. In the oral stratum, the corresponding proportions of subjects were 54.4% for paricalcitol and 43.4% for cinacalcet (P = 0.260). Cochran–Mantel–Haenszel analysis, controlling for stratum, revealed overall superiority of paricalcitol (56.0%) over cinacalcet (38.2%; P = 0.010) in achieving iPTH 150–300 pg/mL during Weeks 21–28. Hypercalcaemia occurred in 4 (7.7%) and 0 (0%) of paricalcitol-treated subjects in the IV and oral strata, respectively. Hypocalcaemia occurred in 46.9% and 54.7% of cinacalcet-treated subjects in the IV and oral strata, respectively.
Paricalcitol versus cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low incidence of hypercalcaemia.
cinacalcet hydrochloride; paricalcitol; secondary hyperparathyroidism; kidney disease; haemodialysis
Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n = 23) or who did not develop refractory SHPT (control subjects; n = 25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.
To describe the prevalence and clinical characteristics of transient hyperphosphatasemia (TH) in a cohort of healthy infants and toddlers.
Patients and Methods
We performed a secondary data analysis of children enrolled in a study examining the epidemiology of vitamin D deficiency among healthy infants and toddlers. Children aged 8 to 24 months were enrolled at well-child visits conducted from 2005 - 2007 in an urban primary care pediatric clinic. Children with a chronic disease or using medications known to affect bone metabolism were excluded. At enrollment, we collected data regarding child age, gender, height, and weight; and maternal race/ethnicity. We measured serum levels of alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, magnesium and phosphorus. We divided participants into three categories, based on serum AP levels at enrollment: normal (AP 110 to 400 U/L), intermediate (AP >400 to 1000 U/L), and TH (AP >1000 U/L). We used the Fisher exact test and analysis of variance to evaluate differences in clinical characteristics among the three groups.
Nine of 316 children (2.8%) had an AP > 1000 U/L (mean 2165 U/L, range 1006 to 4293 U/L). Sixteen children (5.1%) had an intermediate serum AP (mean 544 U/L, range 423 to 835 U/L). Mean weight-for-age z-score, length-for-age z-score and weight-for-length z-scores were similar across all three AP groups. Compared to the 291 children without TH, children in the intermediate AP and TH groups had similar mean serum levels of 25-hydroxyvitamin D, PTH, calcium, magnesium, and phosphorus.
TH appears to be a relatively common condition among healthy infants and toddlers. TH was not associated with anthropometric measures, vitamin D status, PTH, or serum minerals. Recognition of this benign condition is important to avoid unnecessary investigations.
Vitamin D deficiency further increases circulating parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism (pHPT), with potential detrimental effects on bone mass.
This was an observational clinical study in consecutive conservatively treated postmenopausal women (n=40) with pHPT and coexistent 25-hydroxyvitamin D deficiency (25OHD ≤50 nmol/l (≤20 ng/ml)). Patients who showed an increase in serum 25OHD above the threshold of vitamin D deficiency (>50 nmol/l; n=28) using treatment with various commonly prescribed vitamin D preparations were, for the purposes of statistical analyses, allocated to the treatment group. Patients who were retrospectively identified as having received no treatment with vitamin D and/or remained vitamin D deficient were considered as non-responders/controls (n=12). Adjusted calcium (adjCa), PTH and 25OHD concentrations were monitored in all subjects up to 54 months (mean observation period of 18±2 months).
Prolonged increased vitamin D intake, regardless of the source (serum 25OHD, increase from 32.2±1.7 nmol/l at baseline to 136.4±11.6 nmol/l, P<0.0001), significantly reduced serum PTH (13.3±1.1 vs 10.5±1.0 pmol/l, P=0.0001), with no adverse effects on adjCa levels (2.60±0.03 vs 2.60±0.02 mmol/l, P=0.77) and renal function tests (P>0.73). In contrast, serum PTH remained unchanged (15.8±2.6 vs 16.3±1.9 pmol/l, P=0.64) in patients who remained vitamin D deficient, with a significant difference between groups in changes of PTH (P=0.0003). Intrapartial correlation analyses showed an independent negative correlation of changes in 25OHD with PTH levels (r
Prolonged treatment with vitamin D in various commonly prescribed preparations appeared to be safe and significantly reduced PTH levels by 21%.
parathyroids; hormone action; calcium; bone
Vitamin D deficiency has recently been implicated as a contributory factor in the development of peripheral arterial disease (PAD).
A review of the published literature on PAD and vitamin D was undertaken using Medline, PubMed, and Embase, and cross-referenced. All relevant published papers on the subject were reviewed.
Published studies have shown that there is a significant association between vitamin D and PAD. Populations with lower vitamin D levels are more likely to develop PAD in a graded manner. Higher amputation rates are also observed among patients with PAD and lower vitamin D levels. In addition, vitamin D deficiency is significantly associated with increased risk of cardiovascular adverse events. This was also observed in the mouse model where low vitamin D led to the development of atherosclerosis.
This study shows that vitamin D deficiency could be an independent risk factor for the development of PAD and that this risk factor is easily correctable. Further studies should look into the effects of vitamin D supplementation in patients with PAD.
peripheral arterial disease; claudication; gangrene; vitamin D deficiency; amputation; cardiovascular risk factors
Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P.
The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤4.5 and ≤5.5 mg/dL) in relation to achievement of iPTH ≤300 pg/mL during the efficacy assessment phase (EAP; weeks 17–23).
Patients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤4.5 mg/dL and 70% achieved P ≤5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤4.5 mg/dL during EAP in patients above this threshold at baseline.
This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received.
Clinicaltrials.gov identifier NCT00110890
We investigated the vitamin D status and the effect of vitamin D supplementation in Korean breast-fed infants. The healthy term newborns were divided into 3 groups; A, formula-fed; B, breast-fed only; S, breast-fed with vitamin D supplementation. We measured serum concentrations of vitamin D (25OHD3), calcium (Ca), phosphorus (P), alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and bone mineral density (BMD) at 6 and 12 months of age. Using questionnaires, average duration of sun-light exposure and dietary intake of vitamin D, Ca and P were obtained. At 6 and 12 months of age, 25OHD3 was significantly higher in group S than in group B (P<0.001). iPTH was significantly lower in group S than in group B at 6 months (P=0.001), but did not differ at 12 months. Regardless of vitamin D supplementation, BMD was lower in group B and S than in group A (P<0.05). Total intake of vitamin D differed among 3 groups (P<0.001, A>S>B), but total intake of Ca and P were higher in group A than in group B and S (P<0.001). In conclusion, breast-fed infants show lower vitamin D status and bone mineralization than formula-fed infants. Vitamin D supplementation (200 IU/day) in breast-fed infants increases serum 25-OH vitamin D3, but not bone mineral density.
Vitamin D; Nutritional Status; Bone Density; Vitamin D Deficiency; Dietary Supplements; Breast feeding; Infant
Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production.
To assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively.
Serum 25(OH)D was significantly lower in patients than in controls (26.33±12.05 vs. 42.66±9.20 respectively, p<0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p=0.03) and frequency of photosensitivity(p=0.02) and photoprotection (p=0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42–5.18, P=0.002), photosensitivity (OR: 3.6, 95% CI: 1.9–6.8, P<0.01) and photoprotection (OR: 6.7, 95% CI: 2.9–8.8, P<0.001) were significant predictors of 25(OH)D level among SLE cases.
Low vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted.
Egyptian; 25 hydroxy vitamin D; photosensitivity; systemic lupus erythematosus
Background and aims: Vitamin D deficiency is common in patients with small intestinal resection and may lead to secondary hypersecretion of parathyroid hormone (PTH), which in turn may result in increased bone turnover rate and loss of bone mineral. The aims of this study were to investigate the prevalence of vitamin D deficiency, as assessed by low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in patients with small intestinal resection and to explore the relation of 25(OH)D to PTH, markers of bone turnover rate, and bone mineral density (BMD) in these patients.
Patients: Forty two patients with small intestinal resection, a faecal energy excretion of more than 2.0 MJ/day, and a mean length of the remaining small intestine of 199 cm were included. Diagnoses were Crohn’s disease (n=35) and other (n=7).
Methods: 25(OH)D was analysed by radioimmunoassay and bone turnover rate was assessed by measurement of serum osteocalcin, serum alkaline phosphatase, urine pyridinoline, and urine deoxypyridinoline. BMD was measured by dual energy x ray absorptiometry.
Results: Mean 25(OH)D concentration was 13.4 (SD 9.7) ng/ml, which was significantly below the reference mean of 26.4 (SD 13.2) ng/ml (p<0.001). Vitamin D deficiency (25(OH)D concentration ≤8 ng/ml) was found in 38.1% of patients and was accompanied by raised concentrations of PTH and significantly increased markers of bone resorption (p<0.05). Low 25(OH)D concentrations correlated significantly with lower BMD z scores of the spine (r=0.38; p=0.02) and hip (r=0.33; p=0.04).
Conclusions: We found reduced 25(OH)D concentrations in patients with small intestinal resection, and showed that a deficient 25(OH)D concentration is associated with significantly increased markers of bone resorption and decreased BMD values.
vitamin D; bone metabolism; small intestinal resection
Patients with chronic kidney disease often develop secondary hyperparathyroidism because of decreases in 1,25(OH)2-vitamin D (calcitriol) levels. These changes may be ameliorated with appropriate administration of oral calcitriol during the predialysis period. A calcitriol administration protocol was used with patients beginning on June 1, 2001. Mean serum intact parathyroid hormone (iPTH), calcium, and phosphorous levels from the three months preceding and three months following initiation of dialysis were measured. A significant difference in iPTH levels between patients treated under the calcitriol protocol and patients in the control group was observed. In addition, patients treated under the protocol were more likely to receive calcitriol than those who were not. No significant difference in serum calcium or phosphorous levels was observed. Administration of calcitriol via a protocol in predialysis patients reduced iPTH levels among patients after the initiation of dialysis.
Vitamin D deficiency, which continues to be widespread amongst persons of Asian descent in the UK, is often detected from abnormal results on routine biochemistry. The aim of this study was to assess the frequency of abnormal results from routine baseline tests of serum calcium, phosphate, and alkaline phosphatase in patients who subsequently proved to have vitamin D deficiency and secondary hyperparathyroidism. A retrospective examination was undertaken to assess these baseline indices in a cohort of 84 such patients seen in Bradford—5 male; 80 of Asian descent; median age 46 years (range 16-82); serum 25-hydroxyvitamin D<10 μg/L; parathyroid hormone >54 ng/L.
Calcium was normal in 55 patients (66%), phosphate in 68 (81%) and alkaline phosphatase in 24 (29%). In only 5 patients were all three indices outside the normal range. The median parathyroid hormone concentration was significantly greater in patients with abnormal routine biochemistry (145 [range 55-1662] ng/L) than in patients with normal routine biochemistry (88 [59-322] ng/L) but the median 25-hydroxyvitamin D levels did not differ (3.1 [1.3-9.9] and 3.0 [1.5-7.3] μg/L). Routine biochemistry was normal in 20% of cases.
If routine biochemistry is relied upon to detect vitamin D deficiency and osteomalacia, a substantial minority of cases will be missed.
The calcium, vitamin D, and osteocalcin concentrations were investigated in 17 patients with anorexia nervosa. Serum 25-hydroxyvitamin D (25 OHD) concentrations below normal were observed in 15 (88%); only two patients has serum 1,25 dihydroxycholecalciferol (1,25(OH)2D) concentrations below normal. Serum parathyroid hormone (PTH) concentration was also normal in all except these two patients. Serum osteocalcin concentration was below normal in seven of 14 patients. Although a low concentration of serum 25 OHD is common in patients with anorexia nervosa in the United Kingdom, 1,25(OH)2D concentrations are usually normal. Hypovitaminosis D with secondary hyperparathyroidism is relatively uncommon. The subnormal osteocalcin concentrations observed in these patients probably reflect diminished osteoblastic activity, which may contribute to their osteopenia.
Mineral bone disorder (MBD) is an important complication of chronic kidney disease (CKD). However, there are limited data on the pattern of MBD in Indian CKD population. The aim of this study was to describe spectrum of MBD in patients with CKD in our center. This was a hospital-based cross-sectional observational study. Patients with stage 4 and 5 CKD were included in this study. Those receiving calcium supplement, vitamin D or its analogues, and calcimimetic were excluded. Serum/plasma levels of creatinine, albumin, calcium, phosphate, total alkaline phosphatase (TAP), intact parathormone (iPTH), and 25-OH vitaminD (25-vitD) were measured. Radiological survey of bones was carried out in all cases, and echocardiography done in selected patients. Statistical analysis was done using Sigmaplot 10.0 software. A total of 150 patients (114 males, 36 females) were included in this study. Mean age was 45.67±16.96 years. CKD stage 4 and 5D were found in 26% (n=39) and 74% (n=111) of study population, respectively. The most common underlying native kidney diseases in patients of CKD 4 and 5D were diabetic nephropathy (41.03%) and CGN (41.44%), respectively. Median (first quartile, third quartile) values for serum levels of corrected calcium (cCa), phosphate, cCaXPO4 product, TAP, plasma iPTH, and 25-vitD in stage 4 CKD were 8.36 (7.79, 8.91) mg/dL, 4.9 (3.92, 6.4) mg/dL, 41.11 (34.01, 53.81) mg2/dL2, 97 (76.5, 184.25) IU/L, 231 (124.5, 430.75) pg/mL, and 12 (6.98, 23.55) ng/mL, respectively; and in stage 5D CKD were 8.36 (7.66, 8.95) mg/dL, 5.7 (4.23, 6.95) mg/dL, 46.5 (37.16, 54.47) mg2/dL2, 180 (114.5, 276.25) IU/L, 288 (169.75, 625.0) pg/mL, and 18.4 (10.0, 26.4) ng/mL, respectively. Prevalence of hypocalcemia (56.41% vs. 54.95%), hyperphosphatemia (64.10% vs. 70.27%), and hyperparathyroidism (84.62% vs. 88.29%) was not different between patients with CKD 4 and 5D. However, iPTH level outside the target range and increased TAP level were significantly (P<0.001) more common in CKD stage 5D. Multiple logistic regression analysis for hyperparathyroidism revealed significant inverse correlation with cCa in CKD 5D. There were no significant differences in vitamin D status and prevalence of valvular calcification between CKD stage 4 and 5D. X-ray revealed renal osteodystrophy in 8 (5.33%) patients, while it was normal in 118 (78.67%) patients. Secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, increased TAP, and 25-OH vitamin D deficiency and insufficiency were quite common in CKD 4 and 5 patients. The commonest type of MBD in CKD 4 and 5D was secondary hyperparathyroidism.
Chronic kidney disease; hyperparathyroidism; hyperphosphatemia; hypocalcemia; mineral bone disorder
AIM: To investigate the correlation between hepatic osteodystrophy and osteoporosis in patients with liver cirrhosis.
METHODS: Bone mineral density of the patients (n = 55) and that of the control group (n = 30) were measured by dual-energy X-ray absorptiometry. All the women in the study were premenopausal. Deoxypyridinoline, pyridinoline and urinary Ca2+ were measured as bone destruction markers, while alkaline phosphatase (ALP), osteocalcin and insulin-like growth factor-1 (IGF-1) were measured as bone formation markers. Furthermore, interleukin-1 (IL-1), IL-6, tumor necrosis factor α (TNF-α), vitamin D3, direct bilirubin, albumin, cortisol and parathyroid hormone (PTH) levels were measured. The independent Student t test and χ2 test were employed in comparing both groups, and the Pearson correlation test was used to determine associations.
RESULTS: Comparing cirrhosis and control groups, lumbar total T-score (-1.6 ± 1.2 g/cm2 vs -0.25 ± 1.3 g/cm2, P < 0.001), lumbar total Z-score (-1.2 ± 1.23 g/cm2 vs -0.6 ± 1.3 g/cm2, P < 0.001), total femur T-score (-0.05 ± 1 g/cm2 vs -0.6 ± 0.9 g/cm2, P = 0.003) and total femur Z-score (-0.08 ± 1.5 g/cm2 vs 0.7 ± 0.9 g/cm2, P = 0.003) showed significantly lower values in the cirrhosis group. Blood ALP level (109.2 ± 57 U/L vs 62.6 ± 32.5 U/L, P < 0.001), IL-6 level (27.9 ± 51.6 pg/mL vs 3.3 ± 3.1 pg/mL, P = 0.01), TNF-α level (42.6 ± 33.2 pg/mL vs 25.3 ± 12.3 pg/mL, P = 0.007) and direct bilirubin level (0.9 ± 0.7 mg/dL vs 0.3 ± 0.2 mg/dL, P < 0.001) were significantly higher in the cirrhosis group. IGF-1 level (47.7 ± 26.2 ng/mL vs 143.4 ± 53.2 ng/mL, P < 0.001), osteocalcin level (1.05 ± 2.5 ng/mL vs 7.0 ± 13 ng/mL, P = 0.002) and 24 h urinary Ca2+ (169.6 ± 227.2 mg/dL vs 287 ± 168.6 mg/dL, P = 0.003) were significantly lower in the cirrhosis group. Urinary deoxypyridinoline/creatinine (9.4 ± 9.9 pmol/μmol vs 8.1 ± 5.3 pmol/μmol, P = 0.51), urinary pyridinoline/creatinine (51.3 ± 66.6 pmol/μmol vs 29 ± 25.8 pmol/μmol, P = 0.08), blood IL-1 level (3.4 ± 8.8 pg/mL vs 1.6 ± 3.5 pg/mL, P = 0.29), vitamin D3 level (18.6 ± 13.3 μg/L vs 18.4 ± 8.9 μg/L, P = 0.95), cortisol level (11.1 ± 4.8 μg/dL vs 12.6 ± 4.3 μg/dL, P = 0.15) and PTH level (42.7 ± 38 μg/dL vs 34.8 ± 10.9 μg/dL, P = 0.27) were not significantly different.
CONCLUSION: Hepatic osteodystrophy is an important complication encountered in patients with liver cirrhosis and all patients should be monitored for hepatic osteodystrophy.
Liver cirrhosis; Osteoporosis; Hepatic osteodystrophy
The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium–vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)2D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)2D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)2D levels and increased bone turnover markers.
Hereditary hypophosphatemic rickets represented
by X-linked hypophosphatemic rickets (XLH) is a rare disorder characterized by
hypophosphatemia, elevated alkaline phosphatase (ALP) and undermineralization of bone.
Active vitamin D and phosphate are administered to correct hypophosphatemia and elevation
of ALP. Overtreatment with phosphate leads to secondary hyperparathyroidism, and a large
dose of active vitamin D has a risk of hypercalciuria. To understand the situation
concerning treatment of patients with hereditary hypophosphatemic rickets in Japan, we
conducted a questionnaire survey of pediatric endocrinologists. Answers were obtained from
53 out of 68 hospitals where the pediatric endocrinologists worked. One hundred and
thirty-five patients were treated in 28 hospitals during November 2009 and May 2010; 126
patients suffered from hereditary hypophosphatemic rickets, and 9 had hypophosphatemia
caused by other miscellaneous reasons. The distribution of patient age was as follows: 27
(21%) were between 6 mo and 6 yr of age, 39 (31%) were between 6 and 12 yr of age, and 60
(48%) were more than 12 yr of age. Active vitamin D was given to 123 patients, and
phosphate was given to 106 patients. As for the dose of phosphorus, 37.2–58.1 mg/kg/d was
given divided into 2 to 6 aliquots. There were various control targets of treatment,
including serum phosphate, serum ALP, rachitic change, urinary Ca/Cr, parathyroid hormone
and growth. It is very important to avoid side effects of these treatments. No evidence is
available about the optimal dose of phosphate or number of administrations in the
treatment of patients with hypophosphatemic rickets. Although there is a recommendation
for clinical management of patients with hypophosphatemic rickets, we should set a
clinical guideline for it in Japan.
hypophosphatemia; phosphaturia; rickets; active vitamin D; phosphate
Vascular calcification (VC), long thought to result from passive degeneration, involves a complex process of biomineralization resembling osteogenesis, frequently observed in diabetes and is an indicator of diabetic peripheral vascular disease with variable implications.
Aim and Objective:
To study the association between vascular calcification and calcium homeostasis in diabetic patients with foot ulcers without stage 4, 5 chronic kidney disease.
Materials and Methods:
A total of 74 patients with diabetic foot ulcer were enrolled, and VC was detected by X-ray and Doppler methods. Serum calcium, phosphate, alkaline phosphatase (ALKP), fasting and post-prandial glucose levels, and glycosylated hemoglobin (HbA1C) were recorded. Serum iPTH and 25 (OH) vitamin D were estimated by immune radiometric assay and radioimmunoassay, respectively. Data was analyzed by SPSS 16.0.
Vascular calcification was present in 42% of patients. Significant difference in the mean (±SD) of vitamin D, HbA1C, and eGFR was observed in VC +ve compared to VC –ve. There was no significant association of age, duration, BMI, PTH, Ca, PO4, ALKP with that of VC incidence. Severe vitamin D deficiency was more common in VC +ve (51.6%) compared to in VC –ve (18.6%). Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05, 95% C.I. = 0.058-2.88) in patients with vitamin D < 10 ng/ml compared to others.
Vitamin D deficiency could be a risk for vascular calcification, which possibly act through receptors on vascular smooth muscle cells or modulates osteoprotegerin/RANKL system like other factors responsible for VC in diabetic foot patients.
Diabetic foot; vascular calcification; calcium homeostasis