Rebecca S. Mason

Osteoporosis influences the early period of fracture healing in a rat osteoporotic model

Osteoporotic fractures commonly occur in the elderly. Although current therapies are aimed at the prevention and treatment of osteoporotic fractures, studies examing the fracture healing process in osteoporotic bone are limited. We produced an osteoporotic rat model by ovariectomy (ovx) and maintained a low calcium diet (LCD) in order to evaluate the influence of osteoporosis on fracture healing. Callus formation and strength was monitored over a 3 week period by histological and biomechanical assessment. Data collected simultaneously on a group of rats undergoing sham surgery (sx) were used for comparison. A 40% reduction in fracture callus cross-sectional area and a 23% reduction in bone mineral density in the healing femur of the ovx rats was observed on day 21 following fracture as compared with the sx group (p < 0.01). Biomechanical data from the healing femur of the ovx rats revealed a fivefold decrease in the energy required to break the fracture callus, a threefold decrease in peak failure load, a twofold decrease in stiffness and a threefold decrease in stress as compared with the sx group (p < 0.01, respectively). Histomorphological analysis revealed a delay in fracture callus healing with poor development of mature bone in the ovx rats. This study provides physical evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new treatments for osteoporosis on fracture healing.

Vitamin D Conversion by Sarcoid Lymph Node Homogenate

Recent studies suggest that hypercalcemia of sarcoidosis is due to high blood concentrations of calcitriol and that this compound may be synthesized at an extra-renal site. We report that sarcoid lymph node homogenate metabolized calcifediol to a substance indistinguishable from calcitriol, whereas six nonsarcoid lymph nodes failed to produce this compound.

Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes.

The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D. In this study, topically applied 1,25(OH)2D3, enhanced the suppressive capacity of CD4+CD25+ cells from the draining lymph nodes. The effects of topical 1,25(OH)2D3 were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)2D3 production in skin. CD4+ cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)2D3-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4+CD25+ cells. Furthermore, purified CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated or UVB-irradiated mice compared with equal numbers of CD4+CD25+ cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4+Foxp3+ cells of donor origin significantly increased in recipients of CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)2D3 may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects.

Vitamin D and health in adults in Australia and New Zealand: a position statement

The prevalence of vitamin D deficiency varies, with the groups at greatest risk including housebound, community‐dwelling older and/or disabled people, those in residential care, dark‐skinned people (particularly those modestly dressed), and other people who regularly avoid sun exposure or work indoors. Most adults are unlikely to obtain more than 5%–10% of their vitamin D requirement from dietary sources. The main source of vitamin D for people residing in Australia and New Zealand is exposure to sunlight. A serum 25‐hydroxyvitamin D (25‐OHD) level of ≥ 50 nmol/L at the end of winter (10–20 nmol/L higher at the end of summer, to allow for seasonal decrease) is required for optimal musculoskeletal health. Although it is likely that higher serum 25‐OHD levels play a role in the prevention of some disease states, there is insufficient evidence from randomised controlled trials to recommend higher targets. For moderately fair‐skinned people, a walk with arms exposed for 6–7 minutes mid morning or mid afternoon in summer, and with as much bare skin exposed as feasible for 7–40 minutes (depending on latitude) at noon in winter, on most days, is likely to be helpful in maintaining adequate vitamin D levels in the body. When sun exposure is minimal, vitamin D intake from dietary sources and supplementation of at least 600 IU (15 μg) per day for people aged ≤ 70 years and 800 IU (20 μg) per day for those aged > 70 years is recommended. People in high‐risk groups may require higher doses. There is good evidence that vitamin D plus calcium supplementation effectively reduces fractures and falls in older men and women.

Osteoblasts play key roles in the mechanisms of action of strontium ranelate

Background and purpose:  Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non‐clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts.

Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women

The aim of this study was to investigate modifiable predictors of vitamin D status in healthy individuals, aged 55-74, and living across the USA. Vitamin D status [serum 25-hydroxyvitamin D (25(OH)D)] was measured along with age and season at blood collection, demographics, anthropometry, physical activity (PA), diet, and other lifestyle factors in 1357 male and 1264 female controls selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Multivariate linear and logistic regression analyses were used to identify associations with vitamin D status. Three%, 29% and 79% of the population had serum 25(OH)D levels<25, <50 and <80 nmol/L, respectively. The major modifiable predictors of low vitamin D status were low vitamin D dietary and supplement intake, body mass index (BMI) >30 kg/m2, physical inactivity (PA) and low milk and calcium supplement intake. In men, 25(OH)D was determined more by milk intake on cereal and in women, by vitamin D and calcium supplement and menopausal hormone therapy (MHT) use. Thus targeting an increase in vigorous activity and vitamin D and calcium intake and decreasing obesity could be public health interventions independent of sun exposure to improve vitamin D status in middle-aged Americans.

Curcumin and its Derivatives: Their Application in Neuropharmacology and Neuroscience in the 21st Century

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Since the second half of the last century, this traditional medicine has attracted the attention of scientists from multiple disciplines to elucidate its pharmacological properties. Of significant interest is curcumin’s role to treat neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) and malignancy. These diseases all share an inflammatory basis, involving increased cellular reactive oxygen species (ROS) accumulation and oxidative damage to lipids, nucleic acids and proteins. The therapeutic benefits of curcumin for these neurodegenerative diseases appear multifactorial via regulation of transcription factors, cytokines and enzymes associated with (Nuclear factor kappa beta) NFκB activity. This review describes the historical use of curcumin in medicine, its chemistry, stability and biological activities, including curcumins anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory properties. The review further discusses the pharmacology of curcumin and provides new perspectives on its therapeutic potential and limitations. Especially, the review focuses in detail on the effectiveness of curcumin and its mechanism of actions in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and brain malignancies.

Associations Between Drug Burden Index and Falls in Older People in Residential Aged Care

OBJECTIVES: To evaluate the association between the Drug Burden Index (DBI), a measure of a persons total exposure to anticholinergic and sedative medications that includes principles of dose‐response and maximal effect and is associated with impaired physical function in community‐dwelling older people, and falls in residents of residential aged care facilities (RACFs).

Skin cancer prevention: A possible role of 1,25dihydroxyvitamin D3 and its analogs

We previously reported that the natural hormone 1,25dihydroxyvitamin D3 (1,25(OH)(2)D(3)) protects human skin cells from ultraviolet radiation (UVR)-induced apoptosis. UVR-induced pre-mutagenic cyclobutane pyrimidine dimers are diminished in number from 0.5h after cessation of UVR in all skin cell types, by treatment with three different Vitamin D compounds: by 1,25(OH)(2)D(3), by the rapid acting, low calcemic analog, 1alpha,25(OH)(2)lumisterol(3) (JN) and by the low calcemic but transcriptionally active hybrid analog 1alpha-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3 QW-1624F2-2 (QW), which may explain the enhanced cell survival. The rapid response antagonist analog 1beta,25(OH)(2)D(3) (HL) abolished the photoprotective effects of 1,25(OH)(2)D(3) whilst a genomic antagonist, (23S)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647), had no effect. UVR increased p53 expression in human skin cells, whilst concurrent treatment with 1,25(OH)(2)D(3) further enhanced this effect several fold, at 3 and 6h after UVR. Combined with previously reported lower nitrite levels with 1,25(OH)(2)D(3), this increased p53 expression may favor DNA repair over apoptosis. We now report that topical application of 1,25(OH)(2)D(3) or QW also suppressed solar simulated UV (SSUVR-induced pyrimidine dimers in the epidermis of irradiated hairless Skh:HR1 mice, measured 24h after irradiation. Furthermore, UVR-induced immunosuppression in the mice was markedly reduced by topical application of either 1,25(OH)(2)D(3) or QW. These preliminary results show, for the first time, a protective effect of Vitamin D compounds against DNA photodamage in vivo.

Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement.

The recommended level for serum 25‐hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10–20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. Vitamin D deficiency can be treated with daily low‐dose vitamin D supplements, although barriers to adherence have been identified. High‐dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D3 daily for at least the first year of life. There is increasing evidence of an association between low vitamin D and a range of non‐bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.