Bone mineral densiy (BMD) is known to be affected by serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD) in a cohort of Indian patients.
Materials and Methods:
Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate regression models were used to investigate the relationships between serum 25(OH) D, iPTH and BMD.
Total of 102 patients (male:female = 38:64) with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH) D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml (Normal = 30-74 ng/ml), confirming vitamin D deficiency. There was no association between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI) and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH) D was negatively associated with iPTH (P = 0.041).
Among our cohort of patients with low BMD, no direct relationship between serum 25(OH) D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of parathyroid hormone in bone metabolism and health.
Bone mineral density; osteoporosis; parathyroid hormone; vitamin D
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
Although several studies indicate a link between vitamin D status and blood pressure (BP), the results are inconsistent. The purpose of this study is to investigate whether in predominantly non-obese elderly people without vitamin D deficiency or very high intact parathyroid hormone (iPTH) levels serum 25-hydroxyvitamin D3 [25(OH)D3] and iPTH are independently associated with BP.
Cross-sectional data of 132 non-institutionalised subjects (90 women and 42 men, aged 66- 96 years) from Giessen, Germany, were analysed. Serum 25(OH)D3 and iPTH were measured by an electrochemiluminescence immunoassay and BP was determined with a sphygmomanometer. We performed univariate and multiple regression analyses to examine the influence of 25(OH)D3 and iPTH on BP with adjustments for age, body composition and lifestyle factors.
While iPTH had no impact on BP, 25(OH)D3 was negatively associated with systolic BP in men, but not in women. After splitting the cohort into antihypertensive medication users and non-users, 25(OH)D3 was a significant predictor for systolic and diastolic BP only in men not receiving antihypertensive medicine, even after multiple adjustment. Adjustment for 25(OH)D3 resulted in an inverse association of iPTH with diastolic BP also only in men without intake of antihypertensive medicine.
In elderly men without vitamin D deficiency and not taking antihypertensive medicine, 25(OH)D3 may be a negative determinant of BP, independent of iPTH, body composition and lifestyle factors. Furthermore, iPTH may be an independent negative determinant of diastolic BP in men not taking antihypertensive medicine.
25-Hydroxyvitamin D3; Parathyroid hormone; Blood pressure; Elderly
An inverse relationship between major depressive disorder (MDD) and bone mineral density (BMD) has been suggested, but prospective evaluation in premenopausal women is lacking.
Participants of this prospective study were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck, total hip, mid-distal radius, trochanter, and Ward's triangle, as well as serum intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6, 12, 24, and 36 months. 25-hydroxyvitamin D was measured at baseline.
At baseline, BMD tended to be lower in women with MDD compared to controls and BMD remained stable over time in both groups. At baseline, 6, 12, and 24 months intact PTH levels were significantly higher in women with MDD vs. controls. At baseline, ionized calcium and 25-hydroxyvitamin D levels were significantly lower in women with MDD compared to controls. At baseline and 12 months, bone-specific alkaline phosphatase, a marker of bone formation, was significantly higher in women with MDD vs. controls. Plasma ACTH was also higher in women with MDD at baseline and 6 months. Serum osteocalcin, urinary N-telopeptide, serum cortisol, and urinary free cortisol levels were not different between the two groups throughout the study.
Women with MDD tended to have lower BMD than controls over time. Larger and longer studies are necessary to extend these observations with the possibility of prophylactic therapy for osteoporosis.
ClinicalTrials.gov NCT 00006180
Emerging evidence indicates that there is an association between vitamin D and obesity. The aim of this study was to investigate whether the level of serum 25-hydroxyvitamin D3 [25(OH)D3] in the elderly is influenced by parameters of anthropometry and body composition independent of potential confounding lifestyle factors and the level of serum intact parathyroid hormone (iPTH).
Cross-sectional data of 131 independently living participants (90 women, 41 men; aged 66–96 years) of the longitudinal study on nutrition and health status in senior citizens of Giessen, Germany were analysed. Concentrations of 25(OH)D3 and iPTH were ascertained by an electrochemiluminescence immunoassay. Body composition was measured by a bioelectrical impedance analysis. We performed univariate and multiple regression analyses to examine the influence of body composition on 25(OH)D3 with adjustments for age, iPTH and lifestyle factors.
In univariate regression analyses, 25(OH)D3 was associated with body mass index (BMI), hip circumference and total body fat (TBF) in women, but not in men. Using multiple regression analyses, TBF was shown to be a negative predictor of 25(OH)D3 levels in women even after controlling for age, lifestyle and iPTH (ß = −0.247; P = 0.016), whereas the associations between BMI, hip circumference and 25(OH)D3 lost statistical significance after adjusting for iPTH. In men, 25(OH)D3 was not affected by anthropometric or body composition variables.
The results indicate that 25(OH)D3 levels are affected by TBF, especially in elderly women, independent of lifestyle factors and iPTH.
25-Hydroxyvitamin D3; Body composition; Fat mass; Elderly
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.
Objective. To evaluate vitamin D status and serum parathyroid hormone (IPTH) of healthy adults living in Guiyang. Design and Participants. We conducted a cross-sectional evaluation in the General Community in Guiyang by cluster sampling method. The data was a part of 1510 participants (634 men, 876 women) aged 20–79 years median 45.2 years from November 2009 to February 2010 in Guiyang Health Measures Survey. Measurements. Aradioimmunoassay was used to measure the level of 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone (iPTH). Results.The mean serum 25(OH)D level was (20.4 ± 9.0) ng/mL and the highest level among participants aged 40–59 years (22.8 ng/mL). The mean serum PTH level was (32.1 ± 13.7) pg/mL and the lowest level among participants aged 40–50 years (30.8 ng/mL). Serum 25(OH)D was below 50 nmol/liter in 52.3%, below 75 nmol/liter in 84.6%, and above 75 nmol/liter in 15.4% of the respondents. Secondary hyperparathyroidism was 5.4% (5.4% among men and 4.6% among women). The prevalence of secondary hyperparathyroidism increased (5.8%, 6.5%, and 7.1%, resp.) with decreasing serum 25(OH)D levels among subjects who were 30 to 20, 19.9 to 10, and <10 ng/mL, respectively. Serum 25(OH)D was inversely associated with serum PTH. Conclusions. Vitamin D insufficiency and its complication of secondary hyperparathyroidism are common.
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.
The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin.
Vitamin D levels ≥30 ng/ml are commonly considered “normal” based upon maximal suppression of intact parathyroid hormone (iPTH); however, this has recently been challenged and the optimal 25(OH)D level among non-Caucasians is unclear. We evaluated the cross-sectional relationship between serum 25(OH)D and iPTH in a sample of Caucasian and African American adults.
We used baseline serum samples of participants from the Multicenter Osteoarthritis Study (MOST) for this analysis, and used three methods to model the relationship between 25(OH)D and iPTH: ordinary least squares regression (OLS), segmented regression, and Helmert contrasts.
Among Caucasians (n=1,258), 25(OH)D and iPTH ranged from 4-51 ng/ml and 2-120 pg/ml and from 3-32 ng/ml and 3-119 pg/ml in African Americans (n=423). We observed different thresholds between African Americans and Caucasians using each analytic technique. Using 25(OH)D as a categorical variable in OLS, iPTH was statistically higher at lower 25(OH)D categories than the 24-32 ng/ml referent group among Caucasians. However, in African Americans, the mean iPTH was only significantly higher at 25(OH)D levels below 15 ng/ml. Using segmented regression, iPTH appeared to stabilize at a lower 25(OH)D level in African Americans (19-23 ng/ml) compared to in Caucasians (>32 ng/ml). Helmert contrasts also revealed a lower threshold in African Americans than Caucasians.
Among MOST participants, the 25(OH)D thresholds at which no further change in iPTH was observed was approximately 20 ng/ml in African Americans versus approximately 30 ng/ml in Caucasians, suggesting optimal vitamin D levels in Caucasians may not be applicable to African Americans.
vitamin D; parathyroid hormone; racial differences; African American; thresholds; osteoporosis
We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D3) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D3 levels ≥ 30 ng/mL (75 nmol/L) and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the <30 ng/mL group 25-OH-Vitamin D3 with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D3 in the entire patient sample (r = −0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D3 levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.
PTH; vitamin D; peripheral bone mineral density; QUS
Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7−19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH)D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.
Hypoparathyroidism, a disorder characterized by low parathyroid hormone (PTH), is generally treated with oral calcium and vitamin D supplementation. We investigated the effects of PTH(1–84) treatment in 30 hypoparathyroid subjects for 24 months. PTH(1–84) treatment in hypoparathyroidism significantly reduced supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.
Hypoparathyroidism, a disorder characterized by low PTH, is associated with hypocalcemia, hypercalciuria, and increased bone mineral density (BMD). Conventional therapy with calcium and 1,25-dihydroxyvitamin D can maintain the serum calcium concentration, but doses are high, and control is variable. We investigated the effects of human PTH(1–84) treatment in hypoparathyroidism.
Thirty subjects with hypoparathyroidism were treated in an open-label study of PTH(1–84) 100 μg every other day by subcutaneous injection for 24 months, with monitoring of calcium and vitamin D supplementation requirements, serum and 24 h urinary calcium excretion, and BMD by dual energy X-ray absorptiometry.
Requirements for supplemental calcium decreased significantly (3,030±2,325 to 1,661±1,267 mg/day (mean± SD); p<0.05), as did requirements for supplemental 1,25-dihydroxyvitamin D (0.68±0.5 to 0.40±0.5 μg/day; p< 0.05). Serum calcium levels and 24 h urinary calcium excretion were mostly unchanged at 24 months. BMD increased at the lumbar spine by 2.9±4% from baseline (p<0.05), while femoral neck BMD remained unchanged and distal one third radial BMD decreased by 2.4±4% (p<0.05).
PTH(1–84) treatment in hypoparathyroidism significantly reduces supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.
Calcium; Hypoparathyroidism; PTH(1–84)
A new radioimmunoassay for human parathyroid hormone (PTH) in serum, which can measure the hormone present in 94% of the normal sera tested, is described. It is based on the ability of human PTH to compete with 131I-labeled bovine PTH for binding to an antiserum directed against porcine PTH. This antiserum distinguishes between human PTH extracted from parathyroid adenomata and that present in hyperparathyroid sera. Evidence is given to suggest that this is due to immunochemical changes in the hormone extracted from adenomata and not to immunochemical heterogeneity of the hormone present in serum.
Physiologic data supporting the validity and specificity of the assay are presented. Induced episodes of hypercalcemia and hypocalcemia resulted in appropriate responses in serum immunoreactive PTH (IPTH) in normal subjects and in patients with Paget's disease of bone. In normals, there was a progressive increase in serum IPTH in the late afternoon and evening, suggesting a diurnal secretory rhythm. A negative correlation was found between the serum calcium and serum IPTH over the normal range of serum calcium values; a positive correlation was found between these variables in patients with primary hyperparathyroidism. There was apparent overlap between serum IPTH values in normal subjects and patients with primary hyperparathyroidism, but formal discriminate analysis of values for serum calcium and IPTH demonstrated separation of these two groups, without overlap.
Corticosteroid-induced osteoporosis is the most common secondary cause of osteoporosis. We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy x-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SE) changes in BMD of the lumbar spine by QCT and DXA in the PTH group were 35+/-5.5% and 11+/-1.4%, respectively, compared with a relatively small change of 1.7+/-1.8% and 0+/-0.9% in the estrogen-only group. The differences in mean percentage between the groups at 1 yr were 33.5% for the lumbar spine by QCT (P < 0.001) and 9.8% for the lumbar spine by DXA (P < 0.001). The changes in the hip and forearm were not significantly different between or within the groups. During the first 3 mo of PTH treatment, markers of bone formation increased to nearly 150%, whereas markers of bone resorption increased only 100%, suggesting an early uncoupling of bone turnover in favor of formation. These results suggest that parathyroid hormone dramatically increases bone mass in the central skeleton of postmenopausal women with corticosteroid- induced osteoporosis who are taking hormone replacement.
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30–44 ml/min/1.73 m2).
Seven women and 14 men were included, mean age 65.6 ± 12.2 years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25 μg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l.
There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml, p = 0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9 pg/ml, p = 0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period.
In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies.
Trial Registration Number: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438
Active vitamin D; Chronic kidney disease; Fibroblast growth factor 23; FGF23; Phosphate-binder; Parathyroid hormone; PTH; Sevelamer carbonate
Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH).
The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold.
The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake.
A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L.
Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.
African Americans; vitamin D; parathyroid hormone; PTH; osteoporosis; calcium intake; secondary hyperparathyroidism
Two major species of serum immunoreactive parathyroid hormone (iPTH) were measured in 47 untreated patients with primary osteoporosis by using two highly specific radioimmunoassays. Mean iPTH was normal with one antiserum but was lower than normal (P < 0.001) with the other, iPTH values did not correlate with biochemical parameters or with the proportion of bone-resorbing surfaces in iliac crest bone biopsy specimens. These data suggest that the increased bone resorption is not due to increased parathyroid function in most osteoporotic patients. However, seven of our patients (15%) appear to represent a separate population because they had increased values with one or the other of the antisera.
Recent systematic reviews have cast doubt on the association between vitamin D and cardiovascular disease. No prior studies have investigated the association between 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D) and intact parathyroid hormone (iPTH) and cardiovascular disease mortality in a temperate climate.
1073 community-dwelling older adults were evaluated in 1997-99; serum levels of 25(OH)D (mean 42ng/mL), 1,25(OH)2D (median 29pg/mL) and iPTH (median 46pg/mL) were measured; mean estimated glomerular filtration rate (eGFR) was 74mL/min/1.73m2. Participants were followed up to 10.4 (mean 6.4) years with 111 cardiovascular disease deaths.
In unadjusted Cox proportional hazards models, higher levels of 1,25(OH)2D were protective against cardiovascular mortality, while higher levels of iPTH predicted increased risk of cardiovascular death. After adjusting for age alone or multiple covariates, there was no significant association between 25(OH)D, 1,25(OH)2D or iPTH and cardiovascular mortality; results did not differ by eGFR≥60mL/min/1.73m2 or <60mL/min/1.73m2.
In this prospective study of Caucasian, middle-income, community-dwelling older adults living in sunny southern California, serum levels of 25(OH)D, 1,25(OH)2D, or iPTH were not independently associated with cardiovascular mortality.
aging; cardiovascular mortality; chronic kidney disease; parathyroid hormone; vitamin D
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
Serum immunoreactive parathyroid hormone (IPTH) was measured by radioimmunoassay in 54 patients with primary hyperparathyroidism and in 18 consecutive patients with ectopic hyperparathyroidism due to nonparathyroid cancer without apparent skeletal metastasis. Although serum calcium concentration was higher in the group with ectopic hyperparathyroidism, serum IPTH was lower (rank sum test, P < 0.001) and was undetectable in eight. A second anti-PTH antiserum also differentiated between IPTH in the two groups, although IPTH was undetectable in only 1 of 14 sera. When IPTH values in serial dilutions were plotted, slopes for the two patients with ectopic hyperparathyroidism who had relatively high IPTH were less (P < 0.001) than slopes for standard hyperparathyroid sera. By using differences in either IPTH rank or slope of the dilutional curve of sera, primary hyperparathyroidism could be excluded as a cause of the hypercalcemia in 16 of the 18 patients with ectopic hyperparathyroidism. The data are interpreted as indicating that PTH-like material in the serum of these patients with ectopic hyperparathyroidism is immunologically different from the PTH in the serum of patients with primary hyperparathyroidism.
Elevated parathyroid hormone (PTH) is a risk factor for increased morbidity and mortality. PTH levels increase with adiposity in older adults but the basis for this association is unclear. The objective of this study was to examine the association of percent body fat (%Fat) with serum PTH in 307 older men and women and to determine the extent to which it may be explained by vitamin D status, bone turnover, calcium metabolism, and glucose homeostasis. The data are from the baseline visit of a clinical trial of calcium and vitamin D to prevent bone loss. %Fat was measured by dual-energy X-ray absorptiometry and fasting blood and urine samples were collected. Serum PTH levels increased by about 0.4 pmol/l per 10 unit increase in percent body fat (P = 0.003). The variables that we examined, including plasma 25-hydroxyvitamin D and serum osteocalcin, calcium, phosphorus, and insulin explained only a small proportion of this association (18%). Further work is needed to identify the mediators of the higher PTH levels in subjects with greater adiposity. This is important in view of worldwide increases in overweight and obesity and the potential contribution of elevated PTH to morbidity and mortality.
Body fat; Parathyroid hormone; Bone turnover; Calcium binding; Insulin; Glucose
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
Symptomatic hypocalcemia after thyroidectomy is a barrier to same day surgery, and the cause of ER visits. A standard protocol of calcium and vitamin D supplementation, dependent on intact parathyroid hormone (iPTH) levels, can address this issue. How effective is it? When does it fail?
We performed a retrospective review of the prospective Thyroid Database from January 2006 to December 2010. 620 patients underwent completion (CT) or total thyroidectomy (TT), and followed our post-operative protocol of calcium carbonate administration for iPTH levels ≥10pg/ml and calcium carbonate and 0.25μg calcitriol BID for iPTH <10pg/ml. Calcium and iPTH values, pathology and medication, were compared to evaluate protocol efficacy. A p value <0.05 was considered statistically significant.
Using the protocol, sixty-one (10.2%) patients were chemically hypocalcemic but never developed symptoms and twenty-four (3.9%) patients developed breakthrough symptomatic hypocalcemia. The symptomatic (SX) and asymptomatic (ASX) groups were similar with regard to gender, cancer diagnosis, and pre-operative calcium and iPTH. The symptomatic group was significantly younger (39.6 ± 2.8 vs. 49 ± 0.6 years, p=0.01), with lower post-operative iPTH levels. 33% (n=8) of SX patients had an iPTH ≤5 pg/ml vs. only 6% (n=37) of ASX patients. While the majority of patients with a PTH <5 pg/ml were asymptomatic, 62.5% (n=5) of SX patients with iPTH levels ≤5 pg/ml, required an increased in calcitriol dose to achieve both biochemical correction and symptom relief.
Prophylactic calcium and vitamin D supplementation based on post-operative iPTH levels can minimize symptomatic hypocalcemia after thyroidectomy. An iPTH ≤ 5pg/ml may warrant higher initial doses of calcitriol in order to prevent symptoms.
intact parathyroid hormone; symptomatic; hypocalcemia; protocol
The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications.
Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires.
Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected.
High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.