Functional hypoparathyroidism in postmenopausal women with fragility fracture

IntroductionSecondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture.MethodsWe conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit.ResultsTwo hundred and thirty seven women (72.9 ± 11.6-year-old) were included and 90.4% had VDI (25[OH]D ≤ 30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n = 214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range.ConclusionIn a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.     

Low utility of serum 25–hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 in predicting peripheral Treg and Th17 cell counts in ESRD and renal transplant patients

BackgroundVitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients.MethodsEighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study. The absolute counts of CD4 + and CD8 + T, CD16 + CD56 + NK, CD19 + B, CD4 + CD25 + CD127- Foxp3 + (Tregs), Helios + Tregs, CD38 + Tregs, and CD4 + CD17 + (Th17) cells were analyzed in peripheral blood in both patient groups. In addition, serum 25 (OH) D₃, 1, 25 (OH)₂ D₃, IL-6, IL-17, IL-23, and TGF-β₁ were measured. The association between lymphocyte subset counts and 1, 25 (OH)₂ D₃ or 25 (OH) D₃ was studied, as was the association between serum IL-6, IL-17, IL-23, or TGF-β₁ and 1,25 (OH)₂ D₃ or 25 (OH) D₃.ResultsSerum 25 (OH) D₃ and 1,25 (OH)₂ D₃ levels were not independently associated with peripheral CD4 + T, CD19 + B, CD16 + CD56 + NK, Treg, or Th17 cell counts. In contrast to serum 25 (OH) D₃, serum1, 25 (OH)₂ D₃ was positively associated with CD8 + T cells counts in renal transplant recipients.ConclusionOur findings indicate low utility of serum 25 (OH) D₃ and 1, 25 (OH)₂ D₃ levels in predicting a change in lymphocyte subset counts in ESRD and renal transplant patients.     

25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis

It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis.MethodsWe included 120 postmenopausal osteoporotic women (aged 68 ± 8 years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss > 2% and/or the presence of fragility fractures during the last year.ResultsThirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4 ± 1.3 vs. 26.6 ± 0.3 ng/ml, p = 0.01), a higher frequency of 25(OH)D levels < 30 ng/ml (91% vs. 69%, p = 0.019) and higher urinary NTx values (42.2 ± 3.9 vs. 30.9 ± 2.3 nM/mM, p = 0.01). Patients with 25(OH)D > 30 ng/ml had a greater significant increase in lumbar BMD than women with values < 30 ng/ml (3.6% vs. 0.8%, p < 0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D < 30 (OR, 4.42; 95% CI, 1.22–15.97, p = 0.02).ConclusionsInadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels > 30 ng/ml is especially indicated for adequate response to BP treatment.     

Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

IntroductionBreast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.MethodsThe effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.ResultsIn vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)₂D₃ inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm² versus 1.68 ± 0.15 mm², P < 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm² versus 0.52 ± 0.11 mm² in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.ConclusionVitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.     

High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency

ObjectivesRecent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300 000 IU vitamin D3.MethodsOver a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D < 25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD ± 6.1). All patients were treated with a single oral dose of 300 000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake.ResultsBaseline mean 25(OH)D serum concentrations were 15 nmol/l (SD ± 5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD ± 29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD ± 17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD ± 0.11) at baseline, 2.28 mmol/l (SD ± 0.18) at 3 months, and 2.28 mmol/l (SD ± 0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months.ConclusionBased on our observations, a single oral dose of 300 000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia.     

Hypovitaminosis D and Bone Mineral Metabolism and Bone Density in Hyperthyroidism

Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D–deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D–deficient (<25 nmol/L) and vitamin D–sufficient groups (≥25 nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25 nmol/L, with mean ± standard deviation (SD) level of 16.5 ± 3.2 (vitamin D–deficient group 1), and the remainder had a mean ± SD of 46.0 ± 13.5 nmol/L (vitamin D–sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2 ± 16.3 vs 18.0 ± 13.1 pg/mL; p = 0.041). In the vitamin D–deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (?2.65 ± 1.13 and ?3.04 ± 1.3) and in the osteopenia range at lumbar spine (?1.83 ± 1.71). However, in vitamin D–sufficient group, the mean BMD T-scores were in the osteopenia range (?1.64 ± 1.0, ?1.27 ± 1.6, and ?1.60 ± 0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D–deficient group compared with those in vitamin D–sufficient group. Finally, BMD values (gm/cm²) at the hip and forearm were significantly lower in the vitamin D–deficient group compared with those in the vitamin D–sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D–sufficient patients.     

Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice

IntroductionPreviously, little attention has been paid as to how disturbances in the parathyroid hormone (PTH)–calcium–vitamin D-axis, such as secondary hyperparathyroidism (SHPT), relate to mortality amongst hip fracture patients. This study aimed to (1) determine if SHPT is associated with mortality in this group of patients, (2) investigate the association between serum (s-) PTH, s-total calcium, s-25-hydroxyvitamin D (s-25(OH)D) and mortality and (3) determine the prevalence of SHPT amongst hip fracture patients and a control group.MethodThe study included 562 hip fracture patients (HF) (age ≥ 70 years) admitted to a Danish university hospital. The hip fracture patients were prospectively enrolled in a dedicated hip fracture database. Each hip fracture patient was exactly matched according to age and sex with two controls randomly chosen from a control population of 21,778 subjects who had s-PTH, s-total calcium and s-25(OH)D measured at the Copenhagen General Practitioners Laboratory after referral from their general practitioner. The control group (Con) thus consisted of 1124 subjects.ResultsGeneral 1-year mortality: Con-female 8.4%, Con-male 15.3%, HF-female 24.6%, HF-male 33.3%, p < 0.0001 (log rank).SHPT and related 1-year mortalityCon-no SHPT 8.9%, Con-SHPT 16.8%, HF-no SHPT 22.7%, HF-SHPT 34.9%, p < 0.0001 (log rank). The mortality rates were higher for controls with SHPT (OR 2.06, 95% CI: 1.32–3.23), hip fracture patients without SHPT (OR 3.00, 95% CI: 2.14–4.20) and hip fracture patients with SHPT (OR 5.46, 95% CI: 3.32–8.97) compared to the controls without SHPT.Prevalence of SHPTCon 16%, HF 20%, p = 0.09 (Chi-square).ConclusionsOur study clearly shows that SHPT is significantly associated with mortality in both hip fracture patients and the control group. In the multivariate Cox regression analysis, s-PTH and s-total calcium were both significantly associated with mortality, whereas s-25(OH)D was not associated with mortality in this analysis. Our study furthermore indicates that SHPT is almost equally prevalent amongst the hip fracture patients and the control group.     

Vitamin D metabolites and bone mineral density: The multi-ethnic study of atherosclerosis

Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH₂)D₃), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000–2002. Volumetric trabecular lumbar BMD was measured from computed tomography scans performed in 2002–2005 expressed as g/cm³. We used linear regression and graphical methods to compare associations of vitamin D metabolite and PTH concentrations with BMD as the outcomes measure among White (n = 714), Black (n = 353), Chinese (n = 249), and Hispanic (n = 457) participants. Serum 25(OH)D and 24,25(OH₂)D₃ concentrations were highest among Whites and lowest among Blacks. BMD was greatest among Black participants. Higher serum 25(OH)D was only associated with higher BMD among Whites and Chinese participants (P-for-interaction = 0.054). Comparing the lowest category of 25(OH)D (< 20 ng/ml) to the highest (≥ 30 ng/ml), the adjusted mean difference in BMD was –8.1 g/cm³ (95% CI − 14.8, − 1.4) for Whites; − 10.2 g/cm³ (− 20.4, 0.0) for Chinese vs. 8.8 g/cm³ (− 2.8, 20.5) for Black and − 1.1 g/cm³ (− 8.3, 6.2) for Hispanic. Similar results were observed for serum 24,25(OH₂)D_3. Serum PTH was not associated with BMD. In a multi-ethnic population, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Further studies are needed to determine optimal biomarkers for bone health for multiple ethnic groups.     

Pharmacokinetics of oral vitamin D3 and calcifediol

AimLong-term pharmacokinetics after supplementation with vitamin D₃ or calcifediol (the 25-hydroxyvitamin D₃ metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D₃ or calcifediol lead to 25(OH)D₃ plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D₃ during different vitamin D₃ and calcifediol supplementation regimens.MethodsIn this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitaminD₃ daily, 140 μg calcifediol or vitaminD₃ weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitaminD₃, or both. 25(OH)D₃ plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants.ResultsFor daily (weekly) dosing, the area under the concentration–time curve (AUC_0–24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D₃. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D₃ concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D₃ daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D₃ AUC_0–96h values than 140 μg vitamin D₃, while the simultaneous intake of both did not further increase exposure.ConclusionsCalcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D₃ concentrations than vitamin D₃. Plasma 25(OH)D₃ concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.     

Vitamin D inadequacy in French osteoporotic and osteopenic women

ObjectiveStudies have shown that low serum vitamin D levels are associated with secondary hyperparathyroidism, which decreases bone strength and increases fracture risk, most notably after 50 years of age. The objective of this study was to evaluate the vitamin D status of postmenopausal women in France.MethodsWe conducted a cross-sectional observational study of 1292 menopausal women with osteoporosis or osteopenia. The age range was 52–94 years. Serum 25-OH-vitamin D was assayed in each patient. Based on data in the literature, we used four 25-OH-D cutoffs to define vitamin D deficiency: 30, 50, 75, and 80 nmol/L (<12, <20, <30, and <32 ng/ml).ResultsMean serum 25-OH-D was 51.5 ± 26.1 nmol/L (about 20.6 ± 10.4 ng/ml). In the 343 (26.5%) patients taking supplemental vitamin D with or without supplemental calcium, the mean serum 25-OH-D level was significantly higher than in the other patients (65.0 ± 26.0 ng/ml vs. 46.6 ± 18.6 ng/ml; P < 0.001). In the subgroup not taking vitamin D supplements, the prevalence of vitamin D deficiency was 27.3%, 54.1%, 89.9%, and 93.2% with the 30, 50, 75, and 80 nmol/L cutoffs, respectively. The mean 25-OH-D level varied across seasons (P < 0.001), with the highest value being obtained in summer (53.4 ± 18.7 nmol/L; about 21.3 ± 7.5 ng/ml).ConclusionVitamin D deficiency is common among postmenopausal women with osteoporosis or osteopenia in France.     

Vitamin D deficiency in northern Vietnam: Prevalence,risk factors and associations with bone mineral density

PurposeVitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population.MethodsThis cross-sectional study involved 269 women and 222 men aged 13–83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry.ResultsThe prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p < 0.01) and age less than 30 years (p < 0.01), whereas use of contraceptive pills was protective (p < 0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p < 0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p < 0.001) and men (p < 0.001).ConclusionsThese data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.     

Vitamin D deficiency in northern Vietnam: Prevalence,risk factors and associations with bone mineral density

PurposeVitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population.MethodsThis cross-sectional study involved 269 women and 222 men aged 13–83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry.ResultsThe prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p < 0.01) and age less than 30 years (p < 0.01), whereas use of contraceptive pills was protective (p < 0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p < 0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p < 0.001) and men (p < 0.001).ConclusionsThese data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.     

25-Hydroxyvitamin D Measurement, 2009: A Review for Clinicians

As clinicians are more widely appreciating the endemic nature of low vitamin D status, measurement of serum 25-hydroxyvitamin D (25(OH)D), the accepted measure of vitamin D status, has increased. Challenges to 25(OH)D measurement include the presence of 2 forms of vitamin D—ergocalciferol and cholecalciferol (vitamin D₂ and vitamin D₃, respectively)— and the hydrophobic nature of vitamin D. The current state of 25(OH)D measurement is reviewed; modest differences between methodologies persist and confound the application of a single cut point (e.g., 30 ng/mL/75 nmol/L) for the diagnosis of low vitamin D status. The absence of standard calibrators contributes to between-laboratory differences in 25(OH)D measurement. Until there is improved assay standardization and subsequent evidence-based consensus, it seems premature to recommend widespread screening 25(OH)D measurement. Selectively obtaining 25(OH)D measurement in individuals at clinical risk for vitamin D deficiency and/or those most likely to promptly experience benefits from supplementation seems appropriate.     

Vitamin D insufficiency: evaluation of an oral standardized supplementation using 100,000 IU vials of cholecalciferol, depending on initial serum level of 25OH vitamin D

ObjectivesThere is no protocol of vitamin D supplementation used worldwide due to a great disparity of vitamin D supplements available in different countries. The aim of this study was to evaluate the efficiency of the protocol most often used in France to correct vitamin D deficiency defined by a serum 25-hydroxy vitamin D (25OHD) level of less than 30 ng/mL.MethodsThis was a pragmatic multicentric study of vitamin D supplementation in 257 osteopenic/osteoporotic, vitamin D deficient patients who received 100,000 UI vitamin D3 vials every two weeks according to their initial serum 25OHD level (four vials when 25OHD less than 10 ng/mL, three when 25OHD was 10–19 ng/mL, two when 25OHD was 20–29 ng/mL). Blood samples were obtained at baseline, one (M1), two (M2), and three months (M3), after the end of the supplementation protocol.ResultsAt M1, 198/257 (77%) patients had a serum 25OHD level more than 30 ng/mL. Eighty-five percent of those with a BMI less than 25 kg/m² had a 25OHD concentration more than 30 ng/mL, whereas only 66% of those with a BMI more than 25 had a level more than 30 ng/mL. At M2 and M3, 25OHD levels decreased significantly with 55% and 46% having still a level more than 30 ng/mL respectively, without any significant difference according to the initial 25OHD level.ConclusionThis protocol was effective in rising serum 25OHD of most vitamin D insufficient patients with a BMI less than 25 kg/m², but not in overweight patients. As almost one half of our patients had a serum 25OHD level less than 30 ng/mL at M2, we suggest that regular doses should be started quite soon after this initial supplementation.     

Regulation of PTH secretion by 25-hydroxyvitamin D and ionized calcium depends on vitamin D status: A study in a large cohort of healthy subjects

IntroductionPrevious papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered.DesignCross-sectional.Materials and methodsIn 1050 healthy men (547) and women (503), serum ionized calcium (iCa), creatinine (Cr), albumin, 25OHD, and PTH were measured. After conventional analysis, a regression tree was fitted on the data set.Results25OHD and PTH values showed significant opposite seasonal changes. 25OHD levels negatively correlated with PTH, which in turn negatively correlated with iCa. A regression tree was fitted to the whole data set using PTH as the response variable and 25OHD and iCa as covariates. PTH concentration depended on that of iCa only in subjects with 25OHD levels > 16.35 ng/mL, while for 25OHD <16.35 ng/mL it depended on 25OHD values.ConclusionsOur results indicated that PTH levels were highly conditioned by those of 25OHD in subjects with 25OHD values lower than 16.35 ng/mL and by those of iCa only for higher 25OHD concentration.     

Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patients

BackgroundThe effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D₂ 50,000 IU once daily for 28 days for vitamin D insufficiency.MethodsRetrospective chart review of pediatric CF patients from 2006–2008. Vitamin D₂ 50,000 IU daily for 28 days was given to patients with 25-OHD < 30 ng/mL and repeat 25-OHD levels were obtained after completion of therapy.ResultsOne hundred forty-seven levels from 97 individuals were assessed. Success of treatment was 54% (n = 80/147). Seventeen of 39 patients (43%) followed for an additional 6–18 months were able to maintain levels of ≥ 30 ng/mL.ConclusionsVitamin D₂ 50,000 IU daily for 28 days was effective in correcting vitamin D insufficiency in approximately 50% of subjects. However, almost half of successfully treated patients were unable to maintain normal 25-OHD levels > 6 months after completion of therapy, implying that this effect is transient.     

Vitamin D insufficiency defined by serum 25-hydroxyvitamin D and parathyroid hormone before and after oral vitamin D3 load in Japanese subjects

Vitamin D insufficiency is a risk for both skeletal and nonskeletal health. However, some ambiguity remains about threshold serum 25(OH)D for vitamin D insufficiency. To determine the threshold serum 25(OH)D to maintain normal calcium availability without elevation in serum parathyroid hormone (PTH) among Japanese subjects with various calcium intakes, we conducted a multicenter prospective open-labeled study. We recruited 107 ambulatory subjects without disorders affecting vitamin D metabolism to whom oral vitamin D₃ 800?IU/day for 4?weeks or 1,200?IU/day for 8?weeks was given. Serum 25(OH)D, PTH, calcium, phosphate, and magnesium were measured before and after vitamin D₃ supplementation. Calcium intake was assessed by questionnaires. When all the data were combined, serum 25(OH)D was negatively correlated with PTH. The cubic spline curve between serum 25(OH)D and PTH indicated PTH reached its plateau between 35 and 40?pg/ml at 25(OH)D between 25 and 30?ng/ml. Vitamin D₃ supplementation increased serum 25(OH)D and decreased PTH. Change in PTH correlated positively with baseline serum 25(OH)D. From the regression analyses, baseline serum 25(OH)D above 28?ng/ml corresponded to the threshold level without reduction in PTH after vitamin D₃ supplementation. In multivariate regression analyses, age but not calcium intake was a significant determinant of PTH. We concluded that a serum 25(OH)D level of 28?ng/ml was identified as a threshold for vitamin D insufficiency necessary to stabilize PTH to optimal levels.     

Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: A retrospective clinical study

ObjectivesWe have previously demonstrated reduced bone density and an increased incidence of 25-hydroxy vitamin D₃ (25-OH D₃) deficiency in adults with neurofibromatosis 1 (NF1) compared to healthy controls. Vitamin D₃ is a cheap, safe, and effective supplement in the general population, but its value in NF1 patients has not been demonstrated. This study investigates the therapeutic potential of oral vitamin D₃ on bone mineral density (BMD) in NF1 patients with vitamin D₃ deficiency.MethodsWe measured serum 25-OH D₃, parathyroid hormone, calcium, and bone alkaline phosphatase concentrations, urinary deoxypyridinoline concentrations, and BMD in 35 adults with NF1. Nineteen patients received vitamin D₃ supplementation for 2 years, six patients received supplementation for 1 year and 10 patients received no supplementation. Supplementation was administered in a dose that maintained the serum 25-OH D₃ level above 30 μg/l. BMD was measured again at 1 and 2 years, and biochemical assessments of bone metabolism were measured at least every half year during therapy.ResultsTreated subjects had significantly reduced loss of BMD, as measured by T score at the hip (p = 0.011) and lumbar spine (p = 0.022). The effect on hip BMD was apparent at 1 year in comparison to baseline (p = 0.02) and was greater at 2 years in comparison to measurements at 1 year (p = 0.02).ConclusionsVitamin D₃ supplementation improves BMD in adult NF1 patients. Further studies are needed to elucidate the mechanisms responsible for reduced BMD in NF1 patients.     

High prevalence of vitamin D deficiency among middle-aged and elderly individuals in northwestern China: Its relationship to osteoporosis and lifestyle factors

PurposeVitamin D deficiency has reached epidemic proportions; this deficiency has been associated with osteoporosis and certain lifestyle factors in adults. This relationship is not well documented among the Lanzhou population in northwest China. This study sought to determine the prevalence of vitamin D deficiency and its risk factors in addition to its relationship with osteoporosis in a Chinese population living in Lanzhou.MethodsThis cross-sectional study involved 2942 men and 7158 women aged 40–75 years who were randomly selected from 3 communities in the Lanzhou urban district and examined medically. Levels of 25-hydroxy-vitamin D [25(OH)D] and other parameters were measured according to detailed inclusion criteria. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. Calcaneus bone mineral density (BMD) was measured by quantitative ultrasound (QUS).ResultsThe prevalence of vitamin D deficiency (25(OH)D levels < 20 ng/mL) was present in 75.2% of the entire study population. Vitamin D deficiency was more prevalent in women (79.7%) than in men (64%; P < 0.001). Multiple logistic regression analysis revealed that the significant predictors of vitamin D deficiency included coronary heart disease (CHD), obesity, dyslipidemia, older age, female sex, and smoking (all P < 0.05), whereas tea intake, moderate physical activity, milk intake, vitamin D supplementation and sun exposure were protective (all P < 0.05). No significant difference in calcaneus BMD measured by QUS was noted between subjects with < 20 ng/mL and ≥ 20 ng/mL vitamin D levels (0.53 ± 0.13 vs. 0.54 ± 0.13; P = 0.089). The risk of having osteoporosis did not increase when vitamin D levels decreased from ≥ 20 ng/mL to < 20 ng/mL after multiple adjustments (OR = 1.00; 95% CI 0.85–1.16; P = 0.357).ConclusionsVitamin D deficiency is prevalent in the middle-aged and elderly northwestern Chinese population and is largely attributed to CHD, obesity, dyslipidemia, older age, female sex, and smoking. Reduced 25(OH)D levels are not associated with an increased osteoporosis risk.