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bone resorption inhibitors [keywords]
- Intravenous Zoledronate for a Patient with Paget's Disease. [Journal Article]
- J Bone Metab 2014 Aug; 21(3):223-6.
Paget's disease (PD) of bone is characterized by increase of bone resorption by atypical osteoclasts, followed by rapid new bone formation resulting in a disorganized mosaic bone. Although the pathophysiology is not fully understood, bisphosphonate, which is a potent anti-resorptive agent for treatment of osteoporosis, have been the most effective agents available for the treatment of PD. We report a case of PD of bone in a 49-year-old woman patient, who was treated with intravenous zoledronate.
- A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-β-catenin signaling. [Journal Article]
- Cell Death Differ 2014.:e1422.
Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/β-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/β-catenin signaling to reduce phosphorylation of GSK3-β and subsequent nuclear accumulation of β-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in β-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/β-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose ∼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.
- Osteoporosis drugs: which one is right for you? There's no one-size-fits-all answer. Understanding your options begins with knowing what's available. [Journal Article]
- Harv Womens Health Watch 2014 Jul; 21(11):4-5.
- Effect of intravenous hydration in patients receiving bisphosphonate therapy. [JOURNAL ARTICLE]
- Int J Clin Pharm 2014 Sep 10.
Background Patients with advanced cancers are at high risk for bone metastases, which accelerate bone resorption and skeletal complications. Therefore, bisphosphonates, which are strong inhibitors of bone resorption, are widely used to prevent pathological fractures, pain and tumour-induced hypercalcaemia. Intravenous infusion of bisphosphonate is associated with dose- and infusion rate-dependent adverse renal effects. Objective The present study investigated the effect of hydration on bisphosphonate efficacy and safety. Settings The 600-bed CHOV Hospital (Neufchâteau, France) and the Université de Lorraine (Nancy, France). Methods Patients who received pamidronate or zoledronic acid treatments were identified: 50 patients [16 of whom were hydrated and 34 of whom were non-hydrated]. Data on serum calcium levels, creatinine clearance and clinical tolerance were collected. Main outcome measure The impact of hydration on these parameters was analysed between day 1 and day 7. Results Bisphosphonate normalized calcaemia and hydration did not induce further reduction of calcium levels. Patient kidneys were significantly preserved by hydration in both groups (median clearance: +6.2 %), whereas dehydrated patients had lower creatinine clearance (median clearance: -1.1 %). Hydration did not influence other clinical or biological parameters tested. Conclusion Hydration plays an important role in the treatment of hypercalcaemia by pamidronate and zoledronic acid: it enhances kidney protection (i.e., creatinine clearance).
- Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. [Journal Article]
- Adv Exp Med Biol 2014.:500-25.
Recent evidence suggests that vitamin D deficiency has harmful effects on health and that recent vitamin D intake recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, fractures, cancer prevention, incident hypertension and mortality. For all endpoints, levels in the deficient range (< 50 nmol/l; < 20 ng/ml) are associated with no benefit or adverse effects, while the most advantageous serum levels for 25(OH)D appeared to be close to 75 nmol/l (30 ng/ml). An intake of 800 IU (20 microg) of vitamin D3 (cholecalciferol) per day for all adults may bring 97% of the population to level of at least 50 nmol/l and about 50% up to 75 nmol/l. Thus, higher doses of vitamin D than currently recommended are needed to bring most individuals to75 nmol/l. While estimates suggest that 1600 to 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of higher doses for the total adult population need to be addressed in future studies.
- Health initiatives for the prevention of skin cancer. [Journal Article]
- Adv Exp Med Biol 2014.:485-99.
Skin cancer is the most frequent type of cancer in white population worldwide. However, because the most prominent risk factor-solar UV-radiation and/or artificial UV from sunbeds-is known, skin cancer is highly preventable be primary prevention. This prevention needs, that the public is informed by simple and balanced messages about the possible harms and benefits of UV-exposure and how a person should behave under certain conditions of UV-exposure. For this purpose information and recommendations for the public must be age- and target-group specific to cover all periods of life and to reach all sub-groups of a population, continuously. There is a need that political institutions together with Health Institutions and Societies (e.g., European Commission, WHO, EUROSKIN, ICNIRP, etc.), which are responsible for primary prevention of skin cancer, find a common language to inform the public, in order not to confuse it. This is especially important in connection with the ongoing Vitamin D debate, where possible positive effects of UV have to be balanced with the well known skin cancer risk of UV. A continuously ongoing evaluation of interventions and programs in primary prevention is a pre-requisite to assess the effectiveness of strategies. There is surely no "no message fits all" approach, but balanced information in health initiatives for prevention of skin cancer, which use evidence-base strategies, will further be needed in the future to reduce the incidence, morbidity and mortality skin cancer.
- Sunscreens in the United States: current status and future outlook. [Journal Article, Review]
- Adv Exp Med Biol 2014.:464-84.
Incidence rates of nonmelanoma skin cancer and melanoma has been on the rise in the United States for the past 20 years. UV radiation (UVR) exposure remains the most preventable environmental risk factor for these cancers. Aside from sun avoidance, sunscreens remain our best protection. UVR directly damages DNA and cause indirect cellular damage through the creation of reactive oxygen species, the sum of which leads to cutaneous immunosuppression and a tumorigenic milieu. The current generation of sunscreens protect from UVR through two main mechanisms: absorption and deflection. In the US, new Food and Drug Association rules require sunscreen manufacturers to evaluate their products not only on sun protection factor but also on broad spectrum UVA protection by the end of 2013. New labeling requirements will also be instituted. The American Academy of Dermatology and the American Academy of Pediatrics have provided specific recommendations for proper sun protection and sunscreen usage. Plant polyphenols such as those isolated from green tea, pomegranate, and grape seed remain an interesting avenue of research as additives to sunscreens or stand-alone products that appear to modulate the immunosuppressive effects of UVR on the skin. Additionally, although UVR induces endogenous cutaneous production of vitamin D, its damaging effects overshadow this positive benefit, especially in light of the ease of achieving recommended amounts of vitamin D through diet and supplementation.
- Sunscreens. [Journal Article]
- Adv Exp Med Biol 2014.:429-63.
Sunscreens have become since more than 40 years the most popular means of protection against UV radiation (UVR) in Western countries. Organic and inorganic filters with different absorption spectrum exist. They filter or scatter UVR. Protection from UVB is quantified as a minimal erythema dose-based sun protection factor. UVA protection testing is less standardized: Persistent pigment darkening and critical wavelength are currently used methods. Marketing and labeling of sunscreens underlay national regulation which explains major differences between the European and the US sunscreen market. Sunscreens are most performing in sunburn prevention. Broad spectrum UVB and UVA protection and regular application in sufficient amounts are essential for prevention of skin cancers, UV-induced immunosuppression, and skin aging. A significant benefit from regular sunscreen use has not yet been demonstrated for primary prevention of basal cell carcinoma and melanoma. Concerning the prevention of actinic keratoses, squamous cell carcinomas, and skin aging, the effect of sunscreens is significant, but it remains incomplete. Some organic UV filters (PABA derivatives, cinnamates, benzophenones, and octocrylene) have been described to cause photoallergy. Percutaneous absorption and endocrine disrupting activity of small-sized organic and nano-sized inorganic UV filters have been reported. On lesional skin and in pediatric settings, these products should be used with caution. Cutaneous vitamin D synthesis depending on skin-carcinogenic UVB radiation, the potential risk of vitamin D deficiency by sunscreen use has become a major subject of public health debate. Sunscreens indeed impair vitamin D synthesis if they are used in the recommended amount of 2 mg/cm2, but not in lesser thickness below 1.5 mg/cm2 that corresponds better to what users apply in real life conditions. Large molecular last generation UVB-UVA broad spectrum sunscreens have a better benefit-risk ratio than former organic filters: They offer better protection in the UVA band, they are non toxic and non allergenic. A better outcome of sunscreen efficacy especially in primary skin cancer prevention may be achieved with these molecules.
- Ultraviolet-radiation and health: optimal time for sun exposure. [Journal Article, Research Support, Non-U.S. Gov't]
- Adv Exp Med Biol 2014.:423-8.
Positive as well as negative health effects of exposure of human skin to UV radiation depend on spectra and fluence rates, both of which being dependent on latitude, time of the day and several other factors. The major positive effects are related to vitamin D photosynthesis and the major negative effect is skin cancer development. The action spectra for these effects are different. This lead us to conclude that for optimal vitamin D synthesis at minimal risk of cutaneous malignant melanoma (CMM), the best time for sun exposure is between 10 a.m. and 1 p.m. Thus, the common health recommendation (that sun exposure should be avoided between the hours of 10 a.m. and 4 p.m. and postponed to the afternoon) may be wrong.
- Ultraviolet exposure scenarios: risks of erythema from recommendations on cutaneous vitamin D synthesis. [Journal Article]
- Adv Exp Med Biol 2014.:406-22.
Exposure to sunlight is a major source of vitamin D for most people yet public health advice focuses overwhelmingly on avoiding exposure of unprotected skin because of the risks oferythema and skin cancer. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that the current recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year and for all the year at some (low) latitudes. At the higher proposed vitamin D dose of 1000 IU lunchtime sun exposure is still a viable route to the vitamin, but requires the commitment to expose greater areas of skin, or is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.