Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men : a randomised controlled trial

Summary We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D3 did not enhance the response in this group of older well-nourished men.

Introduction This 12-month randomised controlled trial assessed whether calcium–vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men.

Methods Men (n  = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed.

Results There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site.

Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D3 did not enhance the osteogenic response.

Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers

Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)₂D₃ concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)₂D ₃ and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)₂D₃ concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)₂D₃ concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)₂D ₃ concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state.

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults

Objective: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover.

Design: Double-blinded randomised controlled intervention study.

Setting: University of Ulster, Coleraine, Northern Ireland.

Subjects: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18–27 years, were recruited from the university, with 27 completing the intervention.

Interventions: Subjects were randomly assigned, to receive either 15 mug (600 IU) vitamin D3 and 1500 mg calcium/day (vitamin D group), or 1500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention.

Results: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations.

Conclusions: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 mug vitamin D3 significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.

Use of calcium, folate and vitamin D3-fortified milk for 6 months improves nutritional status but not bone mass or turnover, in a group of Australia aged care

In residential care, inadequate calcium and folate intakes and low serum vitamin D (25(OH)D) concentrations are common. We assessed whether daily provision of calcium, folate, and vitamin D3-fortified milk for 6 months improved nutritional status (serum micronutrients), bone quality (heel ultrasound), bone turnover markers (parathyroid hormone, C-terminal collagen I telopeptide, terminal propeptide of type I procollagen), and/or muscle strength and mobility in a group of Australian aged care residents. One hundred and seven residents completed the study (mean (SD) age: 79.9 (10.1) years; body weight: 68.4 (15.4) kg). The median (inter-quartile range) volume of fortified milk consumed was 160 (149) ml/day. At the end of the study, the median daily vitamin D intake increased to 10.4 (8.7) μg (P < .001), which is 70% of the adequate intake (15 μg); and calcium density (mg/MJ) was higher over the study period compared with baseline (161 ± 5 mg/MJ vs. 142 ± 4 mg/MJ, P < .001). Serum 25(OH)D concentrations increased by 23 ± 2 nmol/L (83 (107)%, P < .001), yet remained in the insufficient range (mean 45 ± 2 nmol/L). Consumption of greater than the median intake of milk (160 ml/day) (n = 54, 50%) increased serum 25(OH)D levels into the adequate range (53 ± 2 nmol/L) and reduced serum parathyroid hormone by 24% (P = .045). There was no effect on bone quality, bone turnover markers, muscle strength, or mobility. Consumption of fortified milk increased dietary vitamin D intake and raised serum 25(OH)D concentrations, but not to the level thought to reduce fracture risk. If calcium-fortified milk also was used in cooking and milk drinks, this approach could allow residents to achieve a dietary calcium intake close to recommended levels. A vitamin D supplement would be recommended to ensure adequate vitamin D status for all residents.

Behavioural and physical characteristics associated with vitamin D status in women

For most people in Australia, the primary source of vitamin D is casual exposure to sunlight. Hypovitaminosis D has been reported for high-risk populations, but little has been documented for women of all ages living in the community. Using cross-sectional data, we aimed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D (25OHD) for such women and to determine the association of serum 25OHD with hypertension and bone health. Serum 25OHD, parathyroid hormone (PTH), blood pressure, bone mineral density (BMD) and anthropometry were measured in a random sample of 861 women aged 20–92 years enrolled in the Geelong Osteoporosis Study, set in a temperate region at latitude 38–39°S. Lifestyle factors (including diet, smoking, medication use, socio-economic status, residence, education, occupation, and physical activity) were documented by questionnaire. In season-adjusted models for women aged 20–54 years, physical activity and living with a partner were independently and positively associated with serum 25OHD; associations with weight and waist–hip ratio were negative. Among older women, physical activity, vitamin D intake and urban dwelling were positively associated with serum 25OHD; age, weight and smoking were negative. Compared with the lowest tertile, those in the highest serum 25OHD tertile were less likely to have elevated serum PTH (adjusted OR = 0.25, 95% CI 0.16–0.41) and high blood pressure (adjusted OR = 0.40, 95% CI 0.22–0.72), and more likely to have normal hip and spine BMD (adjusted OR = 1.65, 95% CI 1.08–2.52). In multivariable models adjusting for season, age, weight (and height), BMD was associated with serum 25OHD at the spine, hip and whole body; no associations were detected at the forearm and no other characteristics were identified as confounders. Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles. In contrast, excessive weight and smoking were associated with poorer vitamin D status. Women with high vitamin D were less likely to have elevated PTH, hypertension or bone deficits than women with poor levels.

Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10-9 M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit C AT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat . Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease ( p 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven C AT expression, while TNF- alpha -enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat /TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial

Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

Intervention 500 000 IU of cholecalciferol or placebo.

Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.

Patients presenting with fractures are likely to be vitamin D deficient: are we getting enough sun?

BACKGROUND: 25-Hydroxyvitamin D serves a crucial role in bone metabolism through its role on osteoclast and osteoblastic function. To assess the implication of vitamin D and its relationship to bone fracture and fracture force, we have examined vitamin D levels in patients requiring inpatient fracture management. METHODS: We performed serological testing of vitamin D levels, calcium, parathyroid hormone and liver function tests on patients admitted to our rural institution in southeastern Australia for inpatient fracture management. All participants completed a questionnaire designed to screen for potential contributing factors to bony fragility. Demographic data were also obtained including age, gender and body mass index. Fracture location and the type of inpatient management as well as the force of injury were included in our analysis. RESULTS: We recruited 100 patients to the study, with a median age of 72 (range 22-98) of whom 66 were women. Most had low-energy fractures (79%), treated by internal fixation (73%) or arthroplasty (9%) with 18 treated non-operatively. The majority of the patients were at best vitamin D insufficient, <75 nmol/L (77%), and 38% were vitamin D deficient (<50 nmol/L). Only 14 patients had a formal diagnosis of osteoporosis at presentation, with 63 patients claiming daily sun exposure in line with recommendations for vitamin D sufficiency. CONCLUSIONS: Our data suggest that the prevalence of vitamin D insufficiency and deficiency is common in patients presenting with fractures in southeastern Australia and is not confined to elderly patients. All patients with fractures should be assessed for vitamin D levels and treated in accordance with vitamin D deficiency guidelines.

Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hiperparatireoidismo em gatos com hipertireoidismo experimental

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Possible association between Carney complex and multiple endocrine neoplasia type 1 phenotypes

Complexo de Carney (CNC) e neoplasia endócrina múltipla tipo 1 (MEN1) são formas de neoplasias endócrinas múltiplas de herança autossômica dominante. O diagnóstico do CNC ocorre quando dois critérios maiores (lentiginose, doença nodular pigmentosa primária das adrenais, mixomas cardíacos e cutâneos, acromegalia, neoplasia testicular, carcinoma de tireóide) são observados e/ou um critério maior associado a um critério suplementar (familiar afetado, mutação do gene PRKAR1A) ocorre. Por outro lado, o diagnóstico de MEN1 dá-se pela detecção de dois ou mais tumores localizados na glândula hipofisária, paratireóide e/ou células pancreáticas. O presente caso descreve um homem de 55 anos, com diagnóstico de acromegalia, hiperparatireoidismo primário e carcinoma papilífero de tireóide, exibindo critérios diagnósticos para as duas condições descritas. Embora possa ter ocorrido apenas uma associação esporádica, ou a acromegalia per se tenha predisposto ao carcinoma papilífero, novos mecanismos moleculares podem estar envolvidos.

Prolactin and zinc in dialysis patients

The objectives of the present study were to investigate the frequencies of hyperprolactinemia and hypozincemia in patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), the associations between blood levels of zinc (Zn2+) and hormones, and dietary zinc intake amount and its relation to zincemia. We studied 28 patients (14 HD and 14 CAPD) who had their blood levels of Zn2+, prolactin (PRL), parathyroid hormone (PTH), and gonadotropins (LH, FSH) evaluated. Thirteen patients had dietary nutrient amounts evaluated from a 3-d nutritional record. Hyperprolactinemia occurred in 29% patients (HD = CAPD), hypozincemia in 62% (20% HD and 42% CAPD), and low dietary Zn2+ intake in 90% of patients. No correlation among blood concentration of Zn2+ and PRL, PTH, LH, and FSH were observed in the two modalities of dialysis or between zincemia and Zn2+ ingestion. We concluded that the occurrence of hyperprolactinemia and hypozincemia were not related to dialysis modality and that zincemia did not reflect the observed low dietary intake of Zn2+.

Subcutaneous and testicular metastasis from prostatic adenocarcinoma with neuroendocrine differentiation

The pathological finding of testicular metastasis in cases of disseminated prostatic adenocarcinoma is rare, but was more frequently reported in the past, when bilateral castration was performed more often. The existence of skin and subcutaneous metastasis adds a worse prognosis, because generally it is sign of advanced disease with an average survival time of less than one year. The synchronous occurrence of such metastasis has not been described previously, neither their association to neuroendocrine differentiation. The presence of such differentiation of prostatic adenocarcinoma represents a very unfavorable prognostic factor, as suggested in recent literature. Herein, we discuss the case of a 53 year old man, who presented with macroscopic hematuria and frequency associated to several painless subcutaneous nodules in left axilla and shoulder, as well as in the lower abdominal wall. The right testis was painful, endured and on rectal examination, the prostate was diffusely enlarged. Serum PSA was elevated, reaching 1760 ng/ml and prostatic biopsy disclosed a Gleason 10 prostatic adenocarcinoma with neuroendocrine differentiation. The same pathological pattern was detected in the right testis and in all subcutaneous nodules, documented by positive staining of chromogranin, a marker of neuroendocrine cells. He was submitted to a prostate tunnelization and maximal androgen blockade plus adjuvant chemotherapy, nevertheless, he died 5 months latter.