so prolia is a new drug and it's innovativein that it's the first directed human immunoglobulin monoclonal antibody. so it's actually workingon the immune system and what it does is it interferes with this protein called rank-ligandprotein, which actually affects osteoclasts and it actually prevents their formation andmaturation and their survival rates and so what happens really is that prolia is workingby affecting the whole remodelling of bone. it's actually similar in mechanism of actionto the bisphosphonates that everyone is most familiar with, but this is working on theimmune system and that sort of mechanism whereas bisphosphonates are more of a chemical interaction,so it's very, very different, but similar in mechanism of action to bisphosphonatesbut it's working on the immune system.
again, there have been several large studiesshowing significant benefits, both to fracture rates and improvements in bone density. it'sbeen compared in one study to the bisphosphonate alendronate and again it's shown superiorresults in fracture and bone density to the bisphosphonates. of course, of concern isthe more serious potential where there's potential lowering of blood calcium, higher rates ofinfections, even higher rates of skin problems. and also in several of these studies higherrates of cancer, but not being significant at this point. this is of course the concern, is that it'sworking in a new way, it's interfering with the immune system, which of course has a role,particularly those very important cells called
t-lymphocytes, which are very important inthe immune system. so is it increasing rates of infections or cancers or some other conditionsthat we weren't aware of and that we have only a 3-year study, so the longest it's beenstudied is 3 years and there's some extensions of the existing study, which are going aslong as 5 years. absolutely, that's the big concern isn't it?what is happening in the long term with this drug. i think this is what happened with thebisphosphonates is you have this migration to preventative to people who are at verylow risk of an actual fracture being prescribed drugs preventatively. we really want to becautious with prolia, which is a new mechanism of action which affects immune system, whichhas potentially some serious, long-term effects
which we aren't aware of over time. that itis absolutely used in people who are at the most risk of actually having a fracture. peoplethat have high risk of an actual osteoporotic fracture and that it is not used until moredata is available in people who are at low to moderate risk or no risk or being usedpreventatively. so when i use that word of concern i thinkthat's very, very strong, but i think it's really important that people use it appropriatelyand they're using other very well established and safe treatments for mild to moderate orprevention, which is exercise and nutrition. in the drug-only options i think certainlyit's more effective in the current studies than bisphosphonates. it's certainly not aspowerful as forteo, but it has some advantages
in that it doesn't interact with some otherdrugs, it doesn't have some of the esophageal effects, it's very convenient in dosing andit seems to have very little effects in terms of problems with respect to kidney clearanceand liver function, so it has kind of unique profile. the big concern of course, is whatis it doing in the long term and is it being reserved for currently at-risk patients. soyou don't want to cause all these problems long term that are more dangerous than theactual drug, the risk of a fracture, so that's the main concern. when people are arriving here, we're lookingat all their drugs, insuring that there's not other agents that are interfering withtheir bone density. we want to make sure that
they're using a superior exercise program.we do assessments and measure their actual vitamin d levels, so that it's not left tochance. because they are variations in absorption of vitamin d, so we insure that all our clientsare above 100 nanamoles per liter of 25-hydroxy vitamin d. we establish adequate calcium intakeat a minimum of 500 milligrams per day. we assess other nutrients, and other functionsin the body that have been proven to increase bone density. so we're trying to create avery holistic approach in our recommendations.