Bisphosphonate Drug Holiday: Who, When and How Long.

Bisphosphonate drug holiday: who, when and how long.

Ther Adv Musculoskelet Dis. 2013 Jun; 5(3): 107-11
Diab DL, Watts NB

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from numerous placebo-controlled trials demonstrating efficacy in fracture risk reduction over 3-5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about adverse effects related to long-term use. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a ‘drug holiday.’ There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit. HubMed – drug

Clinical and surgical approach of severe bone fragility fracture: clinical case of 4 fragility fracture in patient with heavy osteoporosis.

Clin Cases Miner Bone Metab. 2013 Jan; 10(1): 52-5
Giannotti S, Bottai V, Pini E, Dell’osso G, De Paola G, Guido G

An accurate diagnosis of osteoporosis and a proper treatment are today recognized to be the most important facts for prevention and for a correct arrangement and treatment of fragility fractures. In the text the Authors describe a case of severe osteoporosis aggravated by 2 femur fractures and 2 periprosthetic fractures occurred in 2 months. In such cases the orthopaedic surgeon needs to formulate first a clinical osteoporotic pattern, than its treatment together with a surgery suitable choice, that has to take into consideration of the bone structural characteristics. In the case described one can note that fractures healing occurred thanks to both an improvement in surgical techniques and antiosteoporotic pharmacological support; in the specific case the Authors used strontium ranelate for its osteoinductive capacity. In our opinion is crucial that the treatment used by orthopaedic surgeons is not related only to the “by-hand” treatment but take into consideration both the underlying disease and the possibility of positively affect bone healing with specific drug therapy. HubMed – drug

Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression.

J Carcinog. 2013; 12: 8
Yang QF, Dalgard CL, Eidelman O, Jozwik C, Pollard BS, Srivastava M, Pollard HB

Cardiac glycosides such as digitoxin have been shown to directly cause apoptotic death of cancer cells both in vitro, and in vivo. However, the mechanism connecting cardiac glycoside action to apoptosis is not known. It has been reported that compounds resembling digitoxin are able to reduce c-MYC expression. Furthermore, it has been previously shown that the transcription of c-MYC depends on nuclear factor of activated T-cells (NFAT) binding sites in the c-MYC promoter. We have therefore hypothesized that NFAT might mediate digitoxin effects on c-MYC mRNA message.We have chosen to study this process in HeLa cells where structurally intact c-MYC genes in 8q24 co-localize with human papilloma virus 18 at all integration sites.Here we show that within the 1(st) h following treatment with digitoxin, a significant reduction in c-MYC mRNA occurs. This is followed by a precipitous loss of c-MYC protein, activation of caspase 3, and subsequent apoptotic cell death. To test the NFAT-dependence mechanism, we analyzed the effects of digitoxin on NFAT isoform-dependent auto-activation of a NFAT-luciferase expression system. Drug dependent effects on expression varied according to each of the four canonical NFAT isoforms (1, 2, 3 or 4). The most digitoxin-sensitive NFAT isoform was NFAT1. Using c-MYC chromatin immune precipitation, we find that digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter.These results suggest that the carcinotoxic activity of digitoxin includes suppression of NFAT-driven c-MYC expression. HubMed – drug

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