Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial

The bone mineral content (B.M.C.) in both forearms (related to total body calcium) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic outpatients, comprising 226 patients treated with one or two major anticonvulsant drugs (phenytoin, phenobarbitone, primidone).Initially the mean B.M.C. value for all epileptic patients was 87% of normal. During treatment with 2,000 international units of vitamin D₂ daily for three months an average B.M.C. increase of 4% was found, whereas the B.M.C. values remained unchanged in the placebo group and in the control groups. The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12% and 43% respectively. The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia, and, possibly, receive prophylactic treatment with vitamin D.     

Latent Osteomalacia in Epileptic Patients on Anticonvulsants

The bone mineral content was measured in 10 epileptic patients on long-term treatment with phenytoin before and during treatment with vitamin D. None of the patients showed biochemical signs of osteomalacia. Initially subnormal values for bone mineral content were found, which increased significantly during treatment. The results suggest the occurrence of latent osteomalacia in a fairly high proportion of epileptic patients on anticonvulsants.     

Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia.

In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia.     

“Anticonvulsant Action” of Vitamin D in Epileptic Patients? A Controlled Pilot Study

The frequency of epileptic seizures was observed in a controlled therapeutic trial on 23 epileptic inpatients before and after treatment with vitamin D₂ or placebo in addition to anticonvulsant drugs. The number of seizures was reduced during treatment with vitamin D₂ but not with placebo. The effect was unrelated to changes in serum calcium or magnesium. The results may support the concept that epileptics should be treated prophylactically with vitamin D.     

Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes

Our purpose is to assess whether genotypes of the vitamin D receptor (VDR) and estrogen receptor (ER) and their interaction influence changes in bone mass in postmenopausal Caucasian women with and without hormone replacement therapy (HRT). A population of 108 US Mid-West women who participated in a study of low-dose continuous estrogen/progestin was genotyped at the VDR BsmI site and the ER XbaI and PvuII sites. Adequate vitamin D and calcium nutritional intakes were assured in all the study subjects. For the 3.5-year duration of the study, we analyzed changes in bone mineral density (BMD) at the spine, femoral neck, distal radius, and the total body (total body bone mineral content, tbBMC). We adjusted for confounding factors, such as age and weight, in the analysis. We found that VDR and/or ER genotypes and/or their interaction generally had significant effects on the changes in the bone mass measurements in both the placebo and HRT groups. When a significant gene-by-gene interaction exists between VDR and ER genotypes, failure to account for them in analyses may yield nonsignificant results, even if significant genotypic effects exist. The amount of variation in changes in bone mass measurements explained by the total genotypic effects of the VDR and ER loci varies from ∼1.0% (for the tbBMC changes in combined placebo and HRT groups) to ∼18.7% (for the spine BMD changes in the HRT group). These results suggest that individual genotypes are important factors in determining changes in bone mass in the elderly with and without HRT and thus may need to be considered with respect to the treatment to preserve bone mass in elderly Caucasian women. Received: 31 July 1998 / Accepted: 11 September 1998     

Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study.

OBJECTIVE--To study the dose related response of salmon calcitonin (salcatonin) given intranasally on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Outpatient clinic for research into osteoporosis. SUBJECTS--208 healthy women aged 68-72 years who had a bone mineral content of the distal forearm on average 30% below the mean value for healthy premenopausal women. INTERVENTIONS--The 208 women were allocated randomly in blocks of four to two years of treatment with either salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups received a calcium supplement of 500 mg. 32 of the women left the study before its end and 164 women complied with the study criteria throughout. MAIN OUTCOME MEASURES--Bone mineral content of the distal forearm and lumbar spine and rates of vertebral and peripheral fractures after two years of treatment. RESULTS--The average changes in bone mineral content of the spine showed positive outcomes of 1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU. There was a significant dose related response to salcatonin, manifested by an increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new fractures was reduced significantly in the women treated with salcatonin to about one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07 to 0.77)). CONCLUSION--The results suggest that, compared with calcium alone, salcatonin given intranasally reduces the rates of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.     

The influence of bariatric surgery on calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity

INTRODUCTION: Obese patients may have abnormal calcium homeostasis because of unbalanced diet and decreased sun exposure. Bariatric surgery itself may lead to disturbances in calcium homeostasis (and in consequence changes in bone mass) or increase preexisting metabolic derangements. The aim of the study was: 1. To assess calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity. 2. To determine the impact of bariatric surgery on parameters mentioned above. 3. To establish recommendations for supplementation with calcium and vitamin D in morbidly obese patients after bariatric surgery. MATERIAL AND METHODS: Serum calcium, parathormone (PTH), vitamin D (25(OH)D), biochemical markers of bone turnover (beta-CrossLaps as a marker of bone resorption and osteocalcin as a marker of bone formation) and urine calcium as well as fat mass, lean mass and bone mineral content (by DXA) were measured before bariatric surgery of the stomach (VBG or GBP) in 57 morbidly obese patients (48 women, 9 men; mean age 35.9 y). The same procedures were repeated six months after operation in 28 of them (24 women, 4 men). Daily calcium intake was also determined based on food questionnaire. RESULTS: Biochemical findings in the group of patients before bariatric surgery were as follows: serum calcium, beta-CrossLaps and urine calcium were within normal range, PTH concentration was increased to 81.0 pg/ml and 25(OH)D as well as osteocalcin concentration decreased (4.9 ng/ml and 13.6 ng/ml, respectively). Six months after bariatric surgery there was no change in serum and urine calcium, PTH concentration decreased to normal level (46.8 pg/ml), 25(OH)D concentration increased to 6.5 ng/ml (not significant) and still remained below normal range. Markers of bone turnover--both resorption and formation--increased (beta-CrossLaps over normal range to 0.594 ng/ml, osteocalcin to normal range 26.8 ng/ml). Daily calcium intake was below RDA before and after bariatric procedure. CONCLUSIONS: 1. Patients with morbid obesity have secondary hyperparathyroidism and deficiency of vitamin D. 2. Abrupt weight loss after bariatric surgery is accompanied by the regression of secondary hyperparathyroidism, decrease of the deficiency of vitamin D and increase in bone turnover. 3. Supplementation with vitamin D and calcium is recommended for patients with morbid obesity after bariatric surgery.     

Vitamin D compounds exert anti-apoptotic effects in human osteosarcoma cells in vitro

Several studies have demonstrated that vitamin D regulates growth and differentiation in bone cells in vitro. In addition, in vivo studies have shown that vitamin D stimulates bone formation, increases the number of osteoblast precursor cells and prevents bone mineral loss. These observations indicate that vitamin D may have anabolic effects on bone, and thus therapeutic potential in the treatment of osteoporosis. However, little is known about the effects of vitamin D on apoptosis in bone cells and about the contribution of this process to the effect of vitamin D on bone mineral loss. To investigate this aspect in more detail, we studied the effect of 1alpha,25(OH)(2)D(3) and a series of analogues on apoptosis in human osteosarcoma cells. No significant induction of apoptosis was observed with any of the compounds after a 5 day treatment period. In contrast, some of the analogues showed a tendency to protect the cells from undergoing apoptosis. This anti-apoptotic effect of vitamin D was further confirmed by the ability of 1alpha,25(OH)(2)D(3) to suppress camptothecin- and staurosporin-induced DNA fragmentation in the cells. In cultures treated simultaneously with 1alpha,25(OH)(2)D(3) in combination with camptothecin or staurosporin, the level of DNA fragmentation was markedly reduced compared with cultures treated with camptothecin or staurosporin alone. On the basis of the present results, it is therefore concluded that vitamin D displays anti-apoptotic effects in human osteoblast-like osteosarcoma cells in vitro. This observation suggests that besides regulating growth and differentiation, vitamin D exerts its anabolic effects on bone by protecting osteoblastic cells from undergoing apoptosis.     

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.     

老年女性类风湿关节炎合并骨质疏松症的代谢特点分析

目的:探讨老年女性类风湿关节炎(RA)合并骨质疏松症的代谢特点。方法:选择老年绝经后女性RA患者共59例,检测患者血生化代谢指标如血糖、血脂、CRP等和骨代谢指标如骨钙素(OC)、β-胶原特殊序列(β-Crosslaps)甲状旁腺素(iPTH)等,并进行统计分析。结果:骨质疏松患者的绝经时间、病程长度、OC、β-Crosslaps、iPTH显著高于骨量正常和骨量减少的患者,25羟基维生素D显著低于骨量正常和骨量减少的患者(P均0.05)。RA患者的骨密度水平与是否使用激素和X线分期情况无关。结论:老年女性RA患者易发生骨质疏松,出现骨质疏松的RA女性患者绝经时间更长,可出现脂代谢紊乱及明显的维生素D缺乏,并具有高转换型骨代谢特点。     

ED-71, a new active vitamin D3, increases bone mineral density regardless of serum 25(OH)D levels in osteoporotic subjects

A previous randomized placebo-controlled double-blinded clinical trial revealed that treatment of osteoporotic subjects supplemented with 200 or 400 IU/day vitamin D3 with 0.75 μg/day ED-71 for 12 months increased lumbar and hip bone mineral density (BMD) by 3.4 and 1.5%, respectively, compared to placebo group (JCE&M 90:5031,2005). These effects on BMD were stronger than any previous results using 1(OH)D3 or 1,25(OH)2D3. However, there still was a concern that the effect of ED-71 could be observed because serum 25(OH)D in many of these subjects were below its optimal level. In order to address this issue, we performed post hoc analysis to compare the effect of ED-71 on lumbar and hip BMD between subjects with upper (>29 ng/mL) and lower tertiles (<25 ng/mL) of serum 25(OH)D. Lumbar BMD after 12-month treatment with 0.5, 0.75 and 1.0 μg/day ED-71 increased similarly in both lower and upper tertile groups of serum 25(OH)D. In addition, hip BMD also showed a tendency to increase when 0.75 and 1.0 μg/day ED-71 groups were combined together in both upper and lower serum 25(OH)D tertile groups, although the increase was not statistically significant. These results demonstrate that the effect of ED-71 on bone is independent of supplementary effect for nutritional vitamin D insufficiency, and suggest that ED-71 may exert its effect as a unique VDR ligand with stronger effect on bone compared to the natural ligand, 1,25(OH)2D3.     

Alfacalcidol restores cancellous bone in ovariectomized rats

Active vitamin D metabolites have been demonstrated to reduce vertebral and hip fractures in elderly patients. A number of in vitro and in vivo pre-clinical studies have suggested that vitamin D may effectively stimulate osteoblastic activity and exert an anabolic effect on bone. The current study was designed to further explore the ability of an active vitamin D analog to restore bone in a skeletal site with established osteopenia in ovariectomized (OVX) rats. Female Sprague Dawley rats at five months of age and 8 weeks after sham ovariectomy or ovariectomy were randomly divided into 7 groups with 10 per group. At the beginning of the treatments, one group of sham-operated rats and one group of OVX rats were sacrificed to serve as baseline controls. Another group of sham-operated rats and one group of OVX rats were treated with vehicle for 4 weeks. The OVX rats in the remaining groups were treated with alfacalcidol at 0.05, 0.1 or 0.2 microg/kg/d by daily oral gavage, 5 days/week for 4 weeks. As expected, estrogen depletion caused high bone turnover and cancellous bone loss in lumbar vertebra of OVX rats. Alfacalcidol treatment at 0.1 or 0.2 but not 0.05 microg/kg/d increased serum calcium and phosphorus in OVX rats as compared with vehicle treatment. In addition, serum parathyroid hormone was suppressed, whereas serum osteocalcin was increased by alfacalcidol at all dose levels. Furthermore, histomorphometric data of 2nd lumbar vertebral body revealed that cancellous bone volume in OVX rats treated with alfacalcidol at 0.1 or 0.2 microg/kg/d was increased to the level of sham-operated rats treated with vehicle. This increment in cancellous bone mass was accompanied by increases in trabecular number and thickness and a decrease in trabecular separation. Moreover, osteoclast surface and number were significantly decreased, whereas bone formation variables such as mineralizing surface and bone formation rate were significantly increased in alfacalcidol- treated OVX rats compared with those of vehicle-treated OVX rats. Finally, a linear regression analysis showed that alfacalcidol treatment dose-dependently altered most of the variables measured in the current study. In conclusion, alfacalcidol completely restores cancellous bone by stimulating bone formation and suppressing bone resorption in lumbar vertebra of OVX rats when the treatment is started at an early phase of osteopenia. The evidence of increased bone formation by alfacalcidol treatments further supports the notion that active vitamin D metabolites or their analogs may exert anabolic effects on bone.     

骨密度检测对婴幼儿佝偻病早期诊断的临床意义

目的:探讨骨密度检测在佝偻病早期诊断中的应用价值。方法:收集衡水市哈励逊国际和平医院门诊诊治的600例婴幼儿,以血清维生素D327.5 nmol/L为判定标准分为非佝偻病组和佝偻病组,比较两组婴幼儿维生素D3、骨碱性磷酸酶和骨密度,绘制维生素D3、骨碱性磷酸酶、骨密度诊断结果的ROC曲线图,对骨密度检测结果进行评价。结果:佝偻病组婴幼儿维生素D3和骨密度Z值明显低于非佝偻病组,骨碱性磷酸酶显著高于非佝偻病组(P0.05)。维生素D3诊断佝偻病的ROC曲线下面积为0.951,灵敏度为0.973,特异度为0.840;骨碱性磷酸酶诊断佝偻病的ROC曲线下面积为0.866,灵敏度为0.824,特异度为0.747;骨密度Z值诊断佝偻病的ROC曲线下面积为0.923,灵敏度为0.826,特异度为0.875,骨密度指标诊断佝偻病的曲线下面积和维生素D3比较无统计学意义(P0.05),但骨密度指标诊断佝偻病的曲线下面积大于骨碱性磷酸酶(P0.05)。结论:超声骨密度检测在婴幼儿佝偻病早期诊断中具有一定价值,其诊断敏感性、特异性、准确率与维生素D3诊断基本相当,且骨密度检测存在无创、可重复性高等优点。     

Effects of vitamin K2 administration on calcium balance and bone mass in young rats fed normal or low calcium diet

OBJECTIVE: The purpose of this study was to examine the effects of vitamin K2 administration on calcium balance and bone mass in young rats fed a normal or low calcium diet. METHODS: Forty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into four groups with 10 rats in each group: 0.5% (normal) calcium diet, 0.1% (low) calcium diet, 0.5% calcium diet + vitamin K2 (menatetrenone, 30 mg/100 g chow diet), and 0.1% calcium diet + vitamin K2. After 10 weeks of feeding, serum calcium and calciotropic hormone levels were measured, and intestinal calcium absorption and renal calcium reabsorption were evaluated. Bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. RESULTS: Feeding a low calcium diet induced hypocalcemia, increased serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels with decreased serum 25-hydrovyvitamin D [25(OH)D] level, stimulated intestinal calcium absorption and renal calcium reabsorption, and reduced cortical bone mass as a result of decreased periosteal bone gain and enlarged marrow cavity, but did not significantly influence cancellous bone mass. Vitamin K2 administration in rats fed a low calcium diet stimulated renal calcium reabsorption, retarded the abnormal elevation of serum PTH level, increased cancellous bone mass, and retarded cortical bone loss, while vitamin K2 administration in rats fed a normal calcium diet stimulated intestinal calcium absorption by increasing serum 1,25(OH)2D level, and increased cortical bone mass. CONCLUSION: This study clearly shows the differential response of calcium balance and bone mass to vitamin K2 administration in rats fed a normal or low calcium diet.     

Predictors of Osteodystrophy in Patients with Chronic Nonalcoholic Pancreatitis with or without Diabetes

ObjectiveTo study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables.MethodsThirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated.ResultsIn patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D.ConclusionPancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC. (Endocr Pract. 2011;17:897-905)     

Bone and Gastric Bypass Surgery: Effects of Dietary Calcium and Vitamin D

Objective:To examine bone mass and metabolism in women who had previously undergone Roux‐en‐Y gastric bypass (RYGB) and determine the effect of supplementation with calcium (Ca) and vitamin D. Research Methods and Procedures: Bone mineral density and bone mineral content (BMC) were examined in 44 RYGB women (≥3 years post‐surgery; 31% weight loss; BMI, 34 kg/m²) and compared with age‐ and weight‐matched control (CNT) women (n = 65). In a separate analysis, RYGB women who presented with low bone mass (n = 13) were supplemented to a total 1.2 g Ca/d and 8 μg vitamin D/d over 6 months and compared with an unsupplemented CNT group (n = 13). Bone mass and turnover and serum parathyroid hormone (PTH) and 25‐hydroxyvitamin D were measured. Results:Bone mass did not differ between premenopausal RYGB and CNT women (42 ± 5 years), whereas postmenopausal RYGB women (55 ± 7 years) had higher bone mineral density and BMC at the lumbar spine and lower BMC at the femoral neck. Before and after dietary supplementation, bone mass was similar, and serum PTH and markers of bone resorption were higher (p < 0.001) in RYGB compared with CNT women and did not change significantly after supplementation. Discussion: Postmenopausal RYGB women show evidence of secondary hyperparathyroidism, elevated bone resorption, and patterns of bone loss (reduced femoral neck and higher lumbar spine) similar to other subjects with hyperparathyroidism. Although a modest increase in Ca or vitamin D does not suppress PTH or bone resorption, it is possible that greater dietary supplementation may be beneficial.     

Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded,Placebo-Controlled Trial

Background

Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods

In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results

Both 25(OH)vitamin D and 1,25(OH)₂vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion

High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)₂vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00952562","term_id":"NCT00952562"}}NCT00952562.     

Correlation of Symptoms with Vitamin D Deficiency and Symptom Response to Cholecalciferol Treatment: a Randomized Controlled Trial

ObjectiveTo examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a randomized, double-blind, placebo-controlled trial.MethodsAdult primary care patients in Duluth, Minnesota, were screened for vitamin D deficiency in February 2007. Participants completed questionnaires pertaining to a variety of symptoms, vitamin D intake, and selected medical conditions. Patients with mild to moderate vitamin D deficiency (25-hydroxyvitamin D [25(OH)D], 10-25 ng/mL) participated in a randomized controlled trial (RCT) of vitamin D replacement and its effect on symptoms. Participants were randomly assigned to receive 50000 units of cholecalciferol (vitamin D₃) weekly or placebo for 8 weeks. Patients with severe vitamin D deficiency (25[OH]D < 10 ng/mL) were treated in an unblinded fashion, and symptoms were reevaluated post treatment.ResultsA total of 610 patients underwent initial screening, and 100 patients with mild to moderate vitamin D deficiency participated in the RCT. Thirty-eight severely deficient patients were treated in an unblinded fashion. On initial screening, 46.2% of participants were deficient in vitamin D. Self-reported vitamin D supplementation, milk intake, celiac disease, gastric bypass, and chronic pancreatitis were predictive of vitamin D status. Severely deficient participants reported increased musculoskeletal symptoms, depression (including seasonal), and higher (worse) scores on a fibromyalgia assessment questionnaire. In the RCT, the treated group showed significant improvement in fibromyalgia assessment scores (P = 0.03), whereas the placebo-treated participants did not. Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later.ConclusionsCompared with participants in the placebo group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living. (Endocr Pract. 2009;15:203-212)     

雌激素改善维生素D受体基因敲除雌性小鼠的骨、钙代谢

以维生素 D 受体基因敲除雌性小鼠为模型,研究雌激素对骨、钙代谢的调节作用。外源性给予雌二醇一个月后,观察小鼠血钙水平的变化,同时测定小鼠骨密度,并利用胫骨非脱钙 von Kossa 染色观察钙化的骨小梁和未钙化的类骨质面积的变化。结果显示,外源性给予雌二醇一个月后,维生素 D 受体基因敲除小鼠的血钙水平,从(2.10±0.37) mmol/L 上升到(2.80±0.41) mmol/L (P<0.05); 骨密度从(0.037±0.006) g/cm2增高到(0.048±0.007) g/cm2,显著改善(P<0.05) ;钙化骨小梁面积显著增加,未钙化的类骨质面积显著缩小。结果提示,外源性雌二醇对骨、钙代谢具有非依赖于维生素 D 的正向调节作用。