Randomized comparison of the effects of the vitamin D(3 )adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients

BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 ± 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D(3 )in patients who needed additional vitamin D

Generation and characterization of two immortalized human osteoblastic cell lines useful for epigenetic studies

Different model systems using osteoblastic cell lines have been developed to help understand the process of bone formation. Here, we report the establishment of two human osteoblastic cell lines obtained from primary cultures upon transduction of immortalizing genes. The resulting cell lines had no major differences to their parental lines in their gene expression profiles. Similar to primary osteoblastic cells, osteocalcin transcription increased following 1,25-dihydroxyvitamin D3 treatment and the immortalized cells formed a mineralized matrix, as detected by Alizarin Red staining. Moreover, these human cell lines responded by upregulating ALPL gene expression after treatment with the demethylating agent 5-aza-2 Œ-deoxycytidine (AzadC), as shown before for primary osteoblasts. We further demonstrate that these cell lines can differentiate in vivo, using a hydroxyapatite/tricalcium phosphate composite as a scaffold, to produce bone matrix. More importantly, we show that these cells respond to demethylating treatment, as shown by the increase in SOST mRNA levels, the gene encoding sclerostin, upon treatment of the recipient mice with AzadC. This also confirms, in vivo, the role of DNA methylation in the regulation of SOST expression previously shown in vitro. Altogether our results show that these immortalized cell lines constitute a particularly useful model system to obtain further insight into bone homeostasis, and particularly into the epigenetic mechanisms regulating sclerostin production

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

Abstract Supra-physiological levels of vitamin D induce skeletal muscle atrophy, which may be particularly detrimental in already sarcopaenic elderly. Neither the cause nor whether the atrophy is fibre type specific are known. To obtain supraphysiological levels of circulating vitamin D (1,25(OH)2D3) 27.5-month-old female Fischer344 9 Brown Norway F1 rats were orally treated for 6 weeks with vehicle or the vitamin D analogue alfacalcidol. Alfacalcidol treatment induced a 22% decrease in body mass and 17% muscle atrophy. Fibre atrophy was restricted to type IIb fibres in the low-oxidative part of the gastrocnemius medialis only (-22%; P\0.05). There was a concomitant 1.6-fold increase in mRNA expression of the ubiquitin ligase MuRF-1 (P\0.001), whereas those of insulin-like growth factor 1 and myostatin were not affected. Circulating IL-6 was unaltered, but leptin and adiponectin were decreased (-39%) and increased (64%), respectively. The treated rats also exhibited a reduced food intake. In conclusion, supraphysiological levels of circulating 1,25(OH)2D3 cause preferential atrophy of type IIb fibres, which is associated with an increased expression of MuRF- 1 without evidence of systemic inflammation. The atrophy and loss of body mass in the presence of supra-physiological levels of vitamin D are primarily due to a reduced food intake

The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age-related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients

Vitamin D deficiency and causative factors in the population of Tehran

<p>Abstract</p> <p>Background</p> <p>There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran.</p> <p>Methods</p> <p>1210 subjects 20–64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire.</p> <p>Results</p> <p>A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 ± 330.8 mg/day vs 503.39 ± 303.1, 577.93 ± 304.9,595.84 ± 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group.</p> <p>Conclusions</p> <p>Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential.</p