Vitamin D supplementation after parathyroidectomy: effect on bone mineral density-a randomized double-blind study.

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25-OH-vitamin D <50 nmol/L) that could worsen the negative effect on the bone. In this double-blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D+) or calcium carbonate alone (D-). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual-energy X-ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30-80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25-OH-D <50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D+ : 3.6%, 3.2%, and 2.7%, p<0.001, respectively; and D-: 3.0%, 2.3%, and 2.1%, respectively, p<0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, -1.7% to 5.4%; p=0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p<0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p<0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD.

Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

BACKGROUND: Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT). OBJECTIVE: To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX). DESIGN AND METHODS: Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000 mg daily and 75 to calcium carbonate 1000 mg and cholecalciferol 1600 IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition. RESULTS: The 25-hydroxyvitamin D (25-OH-D)-level was <50 nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups. CONCLUSION: Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.

Evaluation of cancer tests of 1,3-butadiene using internal dose, genotoxic potency, and a multiplicative risk model.

In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted quantitatively on the basis of the concentration over time in blood (AUC) of the epoxide metabolites, their mutagenic potency, and a multiplicative cancer risk model, which has earlier been used for ionizing radiation. Published data on hemoglobin adduct levels from inhalation experiments with BD were used for the estimation of the AUC of the epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were then weighed together to a total genotoxic dose, by using the relative genotoxic potency of the respective epoxide inferred from in vitro hprt mutation assays using EB as standard. The tumor incidences predicted with the risk model on the basis of the total genotoxic dose correlated well with the earlier observed tumor incidences in the cancer tests. The total genotoxic dose that leads to a doubling of the tumor incidences was estimated to be the same in both species, 9 to 10 mmol/Lxh EB-equivalents. The study validates the applicability of the multiplicative cancer risk model to genotoxic chemicals. Furthermore, according to this evaluation, different epoxide metabolites are predominating cancer-initiating agents in the cancer tests with BD, the diepoxide in the mouse, and the monoepoxides in the rat.

Risks of repeated miscarriage.

There is a lack of well-designed epidemiological studies of possible risk factors for repeated miscarriage. In this Swedish population-based case-control study, we investigated the association between sociodemographic and anthropometric factors, obstetric history and life-style factors, with respect to the risks of first-trimester repeated miscarriage. Information on maternal characteristics was collected through in-person interviews. Plasma blood samples were analysed for cotinine and folate concentrations. Adjusted odds ratios (OR) with 95% confidence interval [CI] were used to estimate the relative risk of repeated miscarriage. The risks of repeated miscarriage were increased for women aged > or = 35 years (adjusted OR 2.9 [95% CI 1.4, 5.8]), as well as for women aged < or = 24 years (OR 2.8 [95% CI 1.1, 6.8]). Women with a history of at least one preceding miscarriage prior to the two index pregnancies, women reporting prolonged time to conceive, and women with a history of myoma, faced a more than fourfold increased risk of repeated miscarriage. Smokers were at an increased risk of repeated miscarriage (OR 2.1 [95% CI 1.1, 4.1]). Among non-smoking women with high caffeine intake, there was an increased risk of repeated miscarriage, whereas there was no such association among smokers. Low plasma folate levels were not associated with increased risks.

Plasma folate levels and risk of spontaneous abortion.

CONTEXT: Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. OBJECTIVE: To study the association between plasma folate levels and the risk of spontaneous abortion. DESIGN, SETTING, AND POPULATION: Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. MAIN OUTCOME MEASURE: Risk of spontaneous abortion vs maternal plasma folate level. RESULTS: Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33). CONCLUSION: Low plasma folate levels were associated with an increased risk of early spontaneous abortion.