Question 1 Say some thing about calcitonin

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Calcitonin Injections

By JilleWhite May 28, 2008 at 12:24 am 16 replies In Osteoporosis medications Recommend More options Problem

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Why do they not seem to use Calcitonin Injections as an option anymore? I did this in the beginning of my diagnosis (16 years ago) & saw significant increase. Am curious and have been revisiting the thought since I seem to be losing bone mass again. Jill Explore topics in this post

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By MotherGoose Reply 85488 May 28, 2008 at 7:06 am Report post

Calcitonin is now given by nasal spray. This is a more user friendly method of administration. (This medication cannot be given orally). Lucy Buckley PT aka Mother Goose

By JilleWhite Reply 85646 May 28, 2008 at 12:21 pm Report post

Lucy ~ I also did the nasal spray years ago, but did not have the same positive effects as I did with the injections. Do studies show that they should have the same effects, or do you know? Jill

By Donnalc Reply 356836 In reply to 85488 by MotherGoose April 17, 2009 at 5:10 pm Report post

Calcitriol can be taken orally. Donnalc

By Donnalc Reply 356838 April 17, 2009 at 5:11 pm Report post

Calcitriol can be taken orally. Donnalc

By MotherGoose Reply 357248 In reply to 356836 by Donnalc April 18, 2009 at 6:40 am Report post

Calcitonin and calcitriol are not the same thing. Lucy Buckley PT aka Mother Goose

By Donnalc Reply 358673 In reply to 357248 by MotherGoose April 19, 2009 at 7:51 pm Report post

In what way are they different? In the need to know. Donnalc

By MotherGoose Reply 358975 In reply to 358673 by Donnalc April 20, 2009 at 6:56 am Report post

Calcitriol is another name for Vitamin D. Calcitonin is a hormone that suppresses bone resorption and is a 32 amino acid peptide. Lucy Buckley PT aka Mother Goose

By rmchavin (Inactive) Reply 421711 June 13, 2009 at 12:27 pm Report post

Dear JilleWhite: You wanted to know why calcitonin is not used much more frequently than it actually is for treating severe osteoporosis. Believe it or not, that's a very good question. The only bad things I could find about calcitonin are from non-scientific websites such as these: http://www.drugs.com/sfx/calcitonin-sideeffects.htmlhttp://www.drugs.com/mtm/calcitonin-nasal.html http://www.rxlist.com/miacalcindrug.htm I remember my medical doctor telling me he almost never prescribes calcitonin because it was inconvenient and could cause a reaction. However, the PubMed research studies on calcitonin all say only very positive things about calcitonin and never anything negative about calcitonin. For example, these:http://www.ncbi.nlm.nih.gov/pubmed/8935399http://www.ncbi.nlm.nih.gov/pubmed/18 713548http://www.ncbi.nlm.nih.gov/pubmed/18071651 Perhaps you could do us a favor? You might want to try natural salmon calcitonin and you could report back to everybody at NOF Inspire regarding how well your experience went.

By slansing Reply 422423 June 14, 2009 at 12:48 am Report post

My sister just had a bone scan this week after a year on calcitonin nasal spray. She's gone all the way from osteo back to just shy of normal! My doctor had pooh poohed my question about calcitonin last year, but now I'm seriously interested! I was planning to start some research, so this discussion is really valuable.

By letshope Reply 422727 June 14, 2009 at 11:27 am

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i was wondering about injections since i've never done well with anything administered in a nasal spray since i'm prone to chronic sinus infections. is the natural salmon cacitonin an injection as well?

By carmk5 Reply 422799 June 14, 2009 at 12:46 pm Report post

Hi, When I was first diagnosed ten years ago with Osteo, my primary doctor prescribed Calcitonin. I was not able to tolerate it. It made me dizzy and it inflamed my nasal passages. I was on it for a month, then she switched me to Fosomax. I wish I could try the injections of Calcitonin to see if it makes a difference but from everything I have learned, they just don't do it anymore. Carmen

By willamette Reply 423055 June 14, 2009 at 6:03 pm Report post

Hi I used Calcitonin for about 9 months. It gave me such severe constipation, I had to stop using it. Also thinning hair. I am afraid to take anything else, because i have so many problems with my teeth. Will see my doctor in August, to see whats next. I tried all kinds of things for the constipation, but nothing worked. Any suggestions to help???? Thanks Marla

By rmchavin (Inactive) Reply 423070 In reply to 423055 by willamette June 14, 2009 at 6:24 pm Report post

Dear willamette: The best way to counteract constipation is with psyllium husk capsules. Psyllium husk, which is grown in and imported from India, is rapidly increasing in popularity in the U.S., Europe, Japan, and elsewhere. The capsules are more convenient and are better able to be taken every 2 hours than the psyllium husk powder, which is cheaper but less convenient. Metamucil is mostly just psyllium husk plus aspartame (Equal/Nutrasweet). I buy my psyllium husk capsules from Sam's Club at a very good price. The second best way to fight constipation is with prunes. Plums and prunes contain a specific constipation-fighting chemical, dihydrophenylisatin, which no other fruit or vegetable contains in any meaningful quantity. The third best way to fight constipation is with ground flaxseed meal. Pour boiling hot water over it and eat it five minutes later. Both prunes and flaxseed meal are high in calories, while psyllium husk is low in calories. All 3 of the above solutions for constipation have many additional health benefits. The medical doctors prescribe softgels containing docusate sodium to treat constipation. It works but takes a long time - too long. Also, docusate sodium has no other health benefit and can cause side effects.

By willamette Reply 423303 June 14, 2009 at 10:34 pm Report post

To rmchacin Thank you I will definately try the psylliun husk capsules. Do you take them every two hours.? I know as long as I take the calcitonin, I will need to take something. This could be a lifesaver for me. Thank you again.

By rmchavin (Inactive) Reply 423394 In reply to 423303 by willamette June 15, 2009 at 2:08 am Report post

Dear willamette: The instructions say to conveniently swallow about six psyllium husk capsules per day depending on the severity of your constipation. Six to eight capsules per day should be enough for successfully treating most cases of constipation. However, there is no harm in swallowing twelve or more capsules per day as long as you never swallow more than two capsules per 20 minutes. Never swallow more than one capsule at a time. Always drink at least a half cup of fluid together with one capsule. As a practical matter, it's too inconvenient to keep watching the clock. Therefore, just leave a whole bunch of capsules out in the open where it won't collect dust. (One good place would be inside your refrigerator where they won't collect dust). Just swallow one capsule every time you realize that you want to drink some fluid and enough time has transpired since your last swallowing of one capsule. You might want to try to estimate how many capsules you normally end up swallowing each day using this method. If your constipation is extremely severe, you might want to combine psyllium husk capsules with prunes, ground flaxseed meal, and/or docusate sodium (now available at Sam's Club without a prescription). In extremely rare cases, constipation can be caused by colorectal cancer so it's a good idea to obey the American Cancer Society and schedule a colonoscopy once every ten years starting at age 50. Swallowing probiotic (acidophilus) capsules might help slightly.

By willamette Reply 424533 June 15, 2009 at 8:13 pm Report post

Dear rmchavin Thank you so much for your help I did have a colonoscopy, so I am ok there.

I will try this. I hope it works. Will keep you posted. I really appreciate you response to me.

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Revilla 06-06-2008, 01:35 PM I was under the impression calcitonin increased Ca and PTH decreased it, but my review book is exactly the opposite. Can someone verify that calcitonin decreases Ca while PTH increases it? Andrew4010 06-06-2008, 01:37 PM Calcitonin decreases the blood calcium level whereas PTH increases it. cwfergus 06-06-2008, 01:38 PM Nope Calcitonin reduces Ca2+ concentrations, PTH will increase it iA-MD2013 06-06-2008, 01:41 PM Calcitonin decreases the blood calcium level whereas PTH increases it. Nope Calcitonin reduces Ca2+ concentrations, PTH will increase it They are both correct :thumbup: supertrooper66 06-06-2008, 01:48 PM I was under the impression calcitonin increased Ca and PTH decreased it, but my review book is exactly the opposite. Can someone verify that calcitonin decreases Ca while PTH increases it?

that's what my book says, too. calcitonin decreases blood Ca and PTH increases it. that's coming from kaplan. i hate the hormones. not sure how many of them we really need to know. seems like the more obscure ones, like the ones you listed, would be included in a passage instead. ones like the catecholamines, aldosterone, and vasopressin i would assume you should know, though. no way I can prove that, tho! Revilla 06-06-2008, 02:36 PM Thanks guys! I've had it backwards in my head this whole time. DrMattOglesby 06-06-2008, 02:49 PM I always had trouble with these two hormones. the things to remember are: Parathyroid gets rid of Ca2+ from the bones and sends it to the bloodstream. Calcitonin will tone up the bones by depositing Ca2+ from the bloodstream into the bones. Alliteration is a fun game everyone can play! Revilla 06-08-2008, 04:16 PM So that's where I was confused! Calcitonin increases Ca+2 in the bones by taking it from the bloodstream and Parathyroid increases Ca+2 in the blood stream by taking it from the bones. nityking 06-08-2008, 04:23 PM you GOT IT! Since production of Estrogen/Progestrone decreases siginificantly in post-menopausal women, they cause increase osteoclast activity to increase blood calcium and decrease osteoblast activity (to form bones). Thus they are at high risk of suffering from osteoperosis than men! Now you would ask then why do they have to take regular Calcium pills if their blood Ca2+ will be technically higher? They are not higher cuz higher blood Ca2+ causes increase in its excretion by kidneys so they are still deficient of Ca2+ regardless of decrease in bone resorption. facetguy 06-09-2008, 11:55 AM Calcitonin "puts the bone-in"! (i.e., puts the calcium INTO the bone). PTH does the opposite. DrMattOglesby 06-09-2008, 12:02 PM lol i love how everybody pretty much said the same thing in their reply to this thread <i'm guilty too>! As if more people saying the correct answer made it MORE accurate. Almost as if its correct by general consensus. :hardy: facetguy 06-09-2008, 01:08 PM lol i love how everybody pretty much said the same thing in their reply to this thread <i'm guilty too>! As if more people saying the correct answer made it MORE accurate. Almost as if its correct by general consensus. :hardy: I learned that little mnemonic over 15 years ago and it continues to stick, so I thought I'd share it here. BloodySurgeon 06-09-2008, 01:20 PM Also another idea to keep in mind would be to understand how other systems work with PTD and Calcitonin. Bone is made up of inorganic mineral hydroxyapatite that includes Calcium and Phosphates. So what happens to the phosphates after the calcium is removed? Where does the calcium and phosphates go? How

does Vitamin D promote strong bones? How does calcium get to the bones from the blood? What is osteoclast vs. osteoblast? Osteocytes? If you can answer all these, then you will have a better understanding of how calicium homeostasis works. Search these on wikipeda and you will find your answers. *hint* the small intestine and the kidneys play a role. nityking 06-20-2008, 03:33 PM tricky question on AAMC: Bone formation involves not only the use of Ca and PO43- but also hydroxyl molecules combined with them two. There was a discrete question on it and guessed the wrong one OH- :( instead of Potassium, which doesn't not belong to bone matrix. Was thinking of hematopoetic stem cells in the bones and K+ is a major intracellular ion. Too much knowledge + over thinking = bad for MCAT Farcus 06-20-2008, 03:58 PM remember this When I think of calcitonin I think of something strong... if something is strong it needs a lot of Calcium in the bones, and thus a DECREASE in Ca2+ in bloodstream. I think of bloodstream as soft plushy weak sauce :).

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Shinpe 07-30-2009, 01:41 AM So I have a couple of things in the survey of natural sciences I couldn't figure out from Achiever's test 1 solutions: 1. In question 6's solution it says that osteoblasts deposit Ca2+ in response to Calcitonin's presence. I know Calcitonin lowers blood calcium but I thought it does so by reducing osteoclast activity, confirmed by wikipedia. But does anyone have other resources confirming what Achiever is claiming? 2. In quesiton 38, it's asking "The maximum number of chromosome combinations among the gametes of a diploid organism (2n =10) is" and then in the answer it says since the haploid has 5 chromosomes, it's 2^5. Can some one explain this quesiton? I don't get the question, yet alone the answer lol. 3. In OC question 72, it is asking which compound is not aromatic. There are two possibilities I think. One is the cyclooctene (8-C ring with 4 pi bonds), which is anti-arommatic and I agree. But another option is a

three-C ring cation. Where there is a double bond between two of the carbons and the third has a positive charge. Then it says it passes Huckel's rule, so it's arommatic, but isn't the other requirements for aromaticity that it is planar and all carbons have a pair of pi-electrons on them? I don't feel like that is satisfied here. Any thoughts? 4. In 82, it's adding HBr to an alkene in presence of hv and says that it is anti-mark since a free radical would form. I get it that radicals add anti-mark, but don't u need Br2 instead of HBr? I mean wouldnt HBr dissociate completely in water anywayz (well it doesn't say what the solvent is, but anywayz) or wouldn't the bond be too polar for an equal split? Thanks in advance for answers. Shinpe Any comments??? Sepx 07-30-2009, 12:23 PM 1. In question 6's solution it says that osteoblasts deposit Ca2+ in response to Calcitonin's presence. I know Calcitonin lowers blood calcium but I thought it does so by reducing osteoclast activity, confirmed by wikipedia. But does anyone have other resources confirming what Achiever is claiming? I don't have achiever, i don't understand your other questions, except the bio one and a ochem one. The stimulus is the raising of Ca in the blood, then thyroid hormone secretes calcitonin. NOW, calicitonin lowers the Ca in two ways, one by increasing deposition of Ca on to bones. Ca deposition on to bones ("making bones") is done by osteoblast, therefore increase osteoblast activity. Another thing calcinotin does is REDUCING Ca uptake in kidney. If you have campbell, got to endocrine chapter, look for figure about controling blodd calcium: PTH vs Calcitonin. they are antogonistic. 07-30-2009, 11:41 AM

4. In 82, it's adding HBr to an alkene in presence of hv and says that it is anti-mark since a free radical would form. I get it that radicals add anti-mark, but don't u need Br2 instead of HBr? I mean wouldnt HBr dissociate completely in water anywayz (well it doesn't say what the solvent is, but anywayz) or wouldn't the bond be too polar for an equal split? You need to hit the text book on this one, you getting rxns confused. Study the mechanism for both, they are diffrent. They are both electrophilic addition rxns though and there is no carobocation rearengement in either one! (but if you additng HBr w/o peroxide, there could be rearengement, always check!) >addition of HBr w/ peroxide is anti mark addition of Br radical to alkene. >but addition of Br2 (or Cl2), adds two bromide (chloride) to the alkene. >also Addition of Br2 with presensence of water results in formation of Halohyrine (alcohol with a halogen). Sepx oops i meant thyroid gland* :D Sepx also meant halohydrine..sorry about the typos... Shinpe 07-30-2009, 12:30 PM 07-30-2009, 12:24 PM

07-30-2009, 12:54 PM Yeah I just had read somewhere (I think kaplan and forsure wiki) that Calcitonin lowers blood Calcium but LOWERING Osteoclast activity (bone resorption) as opposed to increasing bone deposition by osteoblasts. I guess Campbell does say in the figure "stimulates calcium deposition in bones" which I guess must be done by osteoblasts, but it never mentions it in the text of the chapter, weird.

For that second one, I looked, and I guess you need trace concentrations of HBr, usually delieverd by NBS, to be able to do the radical electrophilic addition, but I guess I should have just taken the hv hint and gone with radical. Here are the pictures for the other Orgo question. One is cyclooctatetraene, which is anti-aromatic, and the other is the carbocation of cyclopropene. Take the second figure and add a positive charge to the carbon on top. cyclooctatetraene http://upload.wikimedia.org/wikipedia/commons/2/2a/Cyclooctatetraene.png Cyclopropene (add a + charge to the top C) http://upload.wikimedia.org/wikipedia/commons/e/eb/Cyclopropene-2D-skeletal.png Shinpe 07-30-2009, 01:06 PM And question number 2 is word for word out of Achiever, I really don't have any idea WTF it's talking about. pauly11235 07-30-2009, 01:11 PM 3. the cyclopropene is aromatic because it does not have any sp3 carbons and it follows the 4n +2 rule where n is equal to zero. Aromatic must NOT have any sp3 carbons and by putting a + charge on the top carbon it signifies that it is rather sp2. Shinpe 07-30-2009, 01:24 PM So having a pair of pi electrons is not a definite requirement? although I guess I could see that drawing resonance structures will put that double bond on each bond so it is really shared with all of them. Thanks Shinpe 07-30-2009, 06:45 PM 1. In question 6's solution it says that osteoblasts deposit Ca2+ in response to Calcitonin's presence. I know Calcitonin lowers blood calcium but I thought it does so by reducing osteoclast activity, confirmed by wikipedia. But does anyone have other resources confirming what Achiever is claiming? I don't have achiever, i don't understand your other questions, except the bio one and a ochem one. The stimulus is the raising of Ca in the blood, then thyroid hormone secretes calcitonin. NOW, calicitonin lowers the Ca in two ways, one by increasing deposition of Ca on to bones. Ca deposition on to bones ("making bones") is done by osteoblast, therefore increase osteoblast activity. Another thing calcinotin does is REDUCING Ca uptake in kidney. If you have campbell, got to endocrine chapter, look for figure about controling blodd calcium: PTH vs Calcitonin. they are antogonistic.

Ok so this was on my nerve. I found 5-6 places online that said calcitonin decrease blood calcium by inhibiting bone resorption by lowering osteoclast activity. I also went through my old physiology book and it says the same thing. So I'm pretty sure it lowers blood calcium by lowering osteoclast activity. Since bone is constantly being deposited and resorbed, this has the same net effect as depositing calcium from blood onto bones. The Campbell book doesn't say anything about osteoblasts/osteoclasts, just says "calcium deposited onto bone" due to calcitonin, so maybe they just didn't wanna go through that much detail. Well afterall, the exact opposite effect of PTH would be to decrease osteoclast activity, not increase osteoblast activity, per se. Anywayz, I'm kinda convinced that it lowers osteoclast activity, unless you guys have any other resources that say otherwise??? Am I being too anal??? lol

And I guess no one has an answer for that second question yet? I really have zero clue ...... Orgolover question 2 solution. well the question first i guess, cause it was a worded a little funny. 07-30-2009, 09:54 PM

They want to know if 2n = 10, how many different combination of chromosomes can you have in a gamete cell. This is kind of QR related, but not too bad. So if 2n = 10 that means that there are 5 pairs of homologous chromosomes, and when they align, each member of the 5 pairs can go either way; right or left yielding 2 options. since 5 pairs have 2 options each, there are 5^2 possible gamete combinations. hope this helps. Shinpe question 2 solution. well the question first i guess, cause it was a worded a little funny. 07-30-2009, 09:57 PM

They want to know if 2n = 10, how many different combination of chromosomes can you have in a gamete cell. This is kind of QR related, but not too bad. So if 2n = 10 that means that there are 5 pairs of homologous chromosomes, and when they align, each member of the 5 pairs can go either way; right or left yielding 2 options. since 5 pairs have 2 options each, there are 5^2 possible gamete combinations. hope this helps. I trust you meant 2^5 in your last statement, but here comes another question then, wouldn't there be crossing over and all those good stuff happening at prophase I? The 4 chromatids resulting from each chromosome are all different, right? So at the end you have really 4 options for each chromosome, shouldn't that make it 4^5 possible ways??? Orgolover Agreed. it is 2^5 ( ... and also 1 am in the morn- forgive me). 07-30-2009, 10:07 PM

I believe there would be crossing over, but it seems that this question seems to ignore that. I thought of it as how many combinations of chromosomes coming from the dad and mom are there. Perhaps its better to think of them like that. So even though there is crossing over, they treat the ones from dad the same, and the ones from mom the same. ALSO. I recall thinking the same thing and realizing that 32 is the largest option choice they offer. ... so no brainer. Although I do agree with you, crossing over is fun stuff. First time i heard it, i thought of that old show on upn, "crossing over" guy tells over messages to relatives of dead people. yes. all this goes through my head during topscore exam ! ! ! ;) txchexmex For what its worth, Destroyer also says that calcitonin lowers osteoclast activity Shinpe Agreed. it is 2^5 ( ... and also 1 am in the morn- forgive me). 07-30-2009, 10:19 PM

07-30-2009, 10:21 PM

I believe there would be crossing over, but it seems that this question seems to ignore that. I thought of it as how many combinations of chromosomes coming from the dad and mom are there. Perhaps its better to think of them like that. So even though there is crossing over, they treat the ones from dad the same, and the ones from mom the same.

ALSO. I recall thinking the same thing and realizing that 32 is the largest option choice they offer. ... so no brainer. Although I do agree with you, crossing over is fun stuff. First time i heard it, i thought of that old show on upn, "crossing over" guy tells over messages to relatives of dead people. yes. all this goes through my head during topscore exam ! ! ! ;) How I guessed was that it has to have something to do with the haploid number (5) and the only thing out of 2,4,8,16,32 that has anything to do with 5 is 32. I hope actual DAT questions are this easy to guess lol. But yea I think if a question like this came up on the test, it should really be 4^5, crossing over doesn't like to be taken lightly ;p Shinpe For what its worth, Destroyer also says that calcitonin lowers osteoclast activity 07-30-2009, 10:23 PM

So that's where else I had seen it lol. I also asked my friend and she looked it up in her endocrinology book and confirmed this, that's why it's used as a drug against osteoporosis. Orgolover girls are icky... don't trust them. 09-03-2009, 09:56 PM

The Official "Lessons Learned from MCAT Studying" Thread [Archive ...
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ADeadLois 04-21-2006, 08:48 AM

I'm feeling very contemplative about by MCAT studying experience, so I've decided to summarize some of what I learned from the experience. I hope I'll be able to post this in 30+ MCAT tips above, but for know, it'll stay down here. 1. Believe in EK, but don't rely too much on Audio Osmosis After sampling a bit of Kaplan, TPR, and EK, I have come to the conclusion that EK makes the best MCAT prep material, bar none. The books cover what you need to know, and are written in such a way that you will remember the material. However, don't go too nuts about Audio Osmosis. It's a great product, but it's not "complete MCAT preparation" as they boast on the CDs. It's good for going over material when you're walking to class or in the car, but it's not substitute for book studying and practice problem. It's worth buying however, because even though it's pricey, you can very likely get most of the money back if you re-sell it on Amazon or eBay. However, one thing to keep in mind is that EK also thinks they are the best. I don't know the exact stats, but I'm rather confident that they are still 3rd to Kaplan and TPR in total profitability and popularity. They thus overcompensate by putting down other test prep companies. However, I still think Kaplan and TPR have tremendous value, if only for their wealth of practice material. EK likes to boast that they are the best, but don't limit yourself to what they have to say. 1A. If you only buy one MCAT prep book, make it EK's 101 Passages in Verbal Reasoning. And do all of them. My scores on practice tests went up significantly because of this book. Use whatever strategy you are most comfortable with, just make sure you practice with this book. There really isn't much more to say about verbal than that. 2. Get AAMC practice tests however you can. This has been beaten to death on this forum, so I won't go into too much detail. However, one thing I should mention: Kaplan gives AAMC material to college libraries. I discovered this before nearly spending $40 on AAMC 9. Kaplan claims it's only for Kaplan students, but I was able to get the AAMC material on reserve with only my school ID. This isn't true for all colleges, but it's worth looking into. I have a feeling they do this with schools that are far away from Kaplan centers. 3. Take as many Kaplan Full-Lengths as you can, even those dreaded PS sections. For the most part, Kaplan Full-Lengths are not representative of the actual MCAT, but that doesn't mean they are not worth doing. They make the PS sections super hard for a reason. I took AAMC 8 PS and thought it was a breeze. It really boosts your confidence when you take an AAMC test after a Kaplan Full-Length. Trust me on this. 4. Ignore other people's scoring trends posted in this forum. Everyone is different. Getting hyped about other people's performance just make you more anxious and less confident. 5. If you don't like studying in groups, don't feel obligated to. I hate studying in groups. It just makes me nervous that other people know more than me. If you are in the same boat, don't feel that you're at a disadvantage if you're not in a study group. This is just a matter of personal preference. And the most important lesson I learned... 6. Studying for the MCAT is not about learning the material. It's about building confidence. A little vague, but very true. No matter how long you study, you will not know everything. Instead, you should be trying to study so that you have the right attitude going into the test. This means taking practice tests, and not

stressing out. It's tough to grasp at first, but I think this is the most crucial element to MCAT studying. mangos3 04-21-2006, 09:43 AM What did you do to improve on verbal?? You said you took a lot of practice tests, but what did you learn to do/not do after doing all that practice? To me, it just seems like half luck most of the time. Mr. Tee 04-21-2006, 09:52 AM What did you do to improve on verbal?? You said you took a lot of practice tests, but what did you learn to do/not do after doing all that practice? To me, it just seems like half luck most of the time. Since VR is multiple choice, that means that only ONE choice will be correct, and the others will be categorically incorrect. It's your objective to find out why those answer choices are incorrect. Over time, your gut feel will be developed and you'd already be subconsciously analyzing why those answer choices are incorrect. Taking practice tests is good for honing speed and rhythm. You have to read at a decent pace and think through the questions rather quickly if you want to finish the VR section. The main thing is to dissect the questions so that you know what they're really asking for. Nutmeg 6. Studying for the MCAT is not about learning the material. It's about building confidence. 04-21-2006, 12:04 PM

A little vague, but very true. No matter how long you study, you will not know everything. Instead, you should be trying to study so that you have the right attitude going into the test. This means taking practice tests, and not stressing out. It's tough to grasp at first, but I think this is the most crucial element to MCAT studying. I heartily concur. :thumbup: QuantumMechanic :thumbup: :thumbup: :thumbup: :thumbup: :thumbup: :thumbup: Excellent post, OP! This is my exact advice to friends studying for the MCAT. Its funny how they write off EK (especially verbal 101 :laugh: :laugh: :laugh: ) as not being as good, in the end they aren't going to score as highly as I did (which was solely due to EK and AAMC practice tests). EMH 04-21-2006, 12:24 PM Great post, only thing I would add is go over your practice tests soon after taking them, so you can determine why you got problems right and wrong. This is how you develop that feel for the MCAT. Kind of being able to pick out a good wrong answer. 41@31 6. Studying for the MCAT is not about learning the material. It's about building confidence. Wow, great post. Since I've been back at school as a post-bac, I've always said the same thing to myself before every exam: "You know enough to ace this test. You knew enough a month ago. Relax." Most of us on this forum have studied for this, and most of us know our calcitonin from our Delta G. At this point, its just mind over matter. I'm gonna kill this test. Good luck everyone. 04-21-2006, 05:23 PM 04-21-2006, 12:18 PM

-S txguy Nice post...........especially #6........... good luck :luck: -tx I'm feeling very contemplative about by MCAT studying experience, so I've decided to summarize some of what I learned from the experience. I hope I'll be able to post this in 30+ MCAT tips above, but for know, it'll stay down here. 1. Believe in EK, but don't rely too much on Audio Osmosis After sampling a bit of Kaplan, TPR, and EK, I have come to the conclusion that EK makes the best MCAT prep material, bar none. The books cover what you need to know, and are written in such a way that you will remember the material. However, don't go too nuts about Audio Osmosis. It's a great product, but it's not "complete MCAT preparation" as they boast on the CDs. It's good for going over material when you're walking to class or in the car, but it's not substitute for book studying and practice problem. It's worth buying however, because even though it's pricey, you can very likely get most of the money back if you re-sell it on Amazon or eBay. However, one thing to keep in mind is that EK also thinks they are the best. I don't know the exact stats, but I'm rather confident that they are still 3rd to Kaplan and TPR in total profitability and popularity. They thus overcompensate by putting down other test prep companies. However, I still think Kaplan and TPR have tremendous value, if only for their wealth of practice material. EK likes to boast that they are the best, but don't limit yourself to what they have to say. 1A. If you only buy one MCAT prep book, make it EK's 101 Passages in Verbal Reasoning. And do all of them. My scores on practice tests went up significantly because of this book. Use whatever strategy you are most comfortable with, just make sure you practice with this book. There really isn't much more to say about verbal than that. 2. Get AAMC practice tests however you can. This has been beaten to death on this forum, so I won't go into too much detail. However, one thing I should mention: Kaplan gives AAMC material to college libraries. I discovered this before nearly spending $40 on AAMC 9. Kaplan claims it's only for Kaplan students, but I was able to get the AAMC material on reserve with only my school ID. This isn't true for all colleges, but it's worth looking into. I have a feeling they do this with schools that are far away from Kaplan centers. 3. Take as many Kaplan Full-Lengths as you can, even those dreaded PS sections. For the most part, Kaplan Full-Lengths are not representative of the actual MCAT, but that doesn't mean they are not worth doing. They make the PS sections super hard for a reason. I took AAMC 8 PS and thought it was a breeze. It really boosts your confidence when you take an AAMC test after a Kaplan Full-Length. Trust me on this. 4. Ignore other people's scoring trends posted in this forum. Everyone is different. Getting hyped about other people's performance just make you more anxious and less confident. 5. If you don't like studying in groups, don't feel obligated to. I hate studying in groups. It just makes me nervous that other people know more than me. If you are in the same boat, don't feel that you're at a disadvantage if you're not in a study group. This is just a matter of personal 04-21-2006, 05:34 PM

preference. And the most important lesson I learned... 6. Studying for the MCAT is not about learning the material. It's about building confidence. A little vague, but very true. No matter how long you study, you will not know everything. Instead, you should be trying to study so that you have the right attitude going into the test. This means taking practice tests, and not stressing out. It's tough to grasp at first, but I think this is the most crucial element to MCAT studying. WAOZA Here are my lessons: 1. Most of the answers are in the passages. 2. The verbal section is an open book test. Also, because you cannot study for that part of the test, it is a crapshoot. 3. As other people have stated, this test is mostly about confidence. 4. Kaplan's Full Length Physical Science Sections are insanity, but if you can master those, the AAMC Phy Sci Sections are cake. sweetstuff25 just thinking about EK gives a level of confidence. i just feel good with their books. :) 04-21-2006, 07:36 PM 04-21-2006, 06:14 PM

Question 13
www.guideline.gov/content.aspx?id=3876 - 227k

Guideline Title Management of osteoporosis. A national clinical guideline. Bibliographic Source(s) Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Jun. 45 p. (SIGN publication; no. 71). [149 references] Guideline Status

This is the current release of the guideline. The guideline was reaffirmed by the developer in 2007. Any amendments to the guideline will be noted on Scottish Intercollegiate Guidelines Network (SIGN) Web site .

Scope Methodology Recommendations Evidence Supporting the Recommendations -

Qualifying Statements Implementation of the Guideline Institute of Medicine (IOM) National Healthcare Quality Report Categories Identifying Information and Availability

Benefits/Harms of Implementing the Guideline Recommendations Contraindications Back to top

Disclaimer

Scope
Disease/Condition(s)

Osteoporosis Note: The guideline does not address corticosteroid induced osteoporosis.
Guideline Category Diagnosis Management Risk Assessment Treatment Clinical Specialty Family Practice Geriatrics Internal Medicine Obstetrics and Gynecology Orthopedic Surgery Preventive Medicine Intended Users Advanced Practice Nurses Allied Health Personnel Dietitians Nurses Patients Physical Therapists Physician Assistants Physicians Guideline Objective(s)

To ensure the timely identification of those individuals at highest risk of osteoporosis, as well as those who already have the disease To explore the treatment options that can be used in these patients to reduce their increased risk of further fractures with the aim of achieving "secondary prevention of fracture"

Target Population

Individuals at high risk for, or who currently have, osteoporosis, including women and men over 50 who present with fractures (that occur in the absence of major trauma, such as road traffic accidents)
Interventions and Practices Considered

Risk Assessment
1. Assessment of risk factors including history of falls/fracture, age, sex, ethnicity, reproductive factors, family history, weight, smoking history, alcohol use, exercise, diet, and risk scores

Diagnosis
1. Techniques for measuring bone mineral density, including: Dual-energy X-ray absorptiometry (DEXA or DXA) Peripheral dual-energy X-ray absorptiometry (pDXA) (not recommended) Peripheral quantitative computed tomography (pQCT) (not recommended) Single photon absorptiometry (SPA)(not recommended) Single-energy X-ray absorptiometry (SEXA or SXA) (not recommended) Radiograph absorptiometry 2. Techniques discussed but not specifically recommended: Quantitative ultrasound (QUS) to assess bone quality and structure Biochemical markers such as resorption markers to assess bone turnover Quantitative computed tomography (QCT)

Treatment Non-pharmacological
1. Exercise 2. Calcium + vitamin D 3. Interventions discussed but not specifically recommended: Fluoridation of water Use of ipriflavone Elimination of caffeine

Pharmacological
1. Bisphosphonates (alendronate, etidronate, risedronate) 2. Hormone replacement therapy (considered but not recommended)

3. Raloxifene 4. Calcitonin Major Outcomes Considered

Fracture rates and risk Fracture related morbidity

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Methodology
Methods Used to Collect/Select the Evidence Searches of Electronic Databases Description of Methods Used to Collect/Select the Evidence

The evidence base for this guideline was synthesised in accordance with Scottish Intercollegiate Guidelines Network (SIGN) methodology. A systematic review of the literature was carried out using an explicit search strategy devised in collaboration with members of the guideline development group. Searches were restricted to systematic reviews, meta-analyses, randomised controlled trials, and longitudinal studies. Internet searches were carried out on the websites of the Canadian Practice Guidelines Infobase, the UK Health Technology Assessment Programme, the US National Guidelines Clearinghouse, and the US Agency for Healthcare Research and Quality. Searches were also carried out on the search engines Google and OMNI, and all suitable links followed up. Database searches were carried out on Cochrane Library, Embase 1993 to 2000, and Medline 1990 to 2000. Searches were later updated to June 2001. The main searches were supplemented by material identified by individual members of the development group. All selected papers were evaluated using standard methodological checklists before conclusions were considered as evidence. 2007 Currency Review Process A scoping search for new evidence was carried out in 2007. The search was designed to identify guidelines, health technology appraisals, Cochrane reviews and other systematic reviews relevant to the contents of the guideline. Search terms included MeSH headings for the condition specified and any common variations as free text, plus terms for the interventions and care processes discussed in the guideline. Sources Searched

Guidelines: National Institute for Health and Clinical Excellence (NICE), National Library for Health guidelines finder, National Guideline Clearinghouse (NGC), Guidelines International Network (GIN) Web site.

Technology appraisals: NICE, UK HTA database (Southampton), INAHTA database Cochrane review: Cochrane library Other good quality systematic reviews: UK HTA database (Southampton), DARE

SIGN provided a summary of new evidence and how it might influence a potential update to the guideline. A Committee of 15 individuals provided feedback on the summary of new evidence (GPs 3, Academics 2, Physicians 1, Rheumatologists 1, Biochemists 1, Other 7). A standard template was used for responses. The Committee was asked to:

Comment on assessment of the impact of the new evidence and its likely effect on recommendations List any additions to the remit of the guideline that might be beneficial Indicate preferred option for review (no update, full update, selective update, withdrawal)

Number of Source Documents

Not stated
Methods Used to Assess the Quality and Strength of the Evidence Weighting According to a Rating Scheme (Scheme Given) Rating Scheme for the Strength of the Evidence

Levels of Evidence 1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias 1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias 1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias 2++: High quality systematic reviews of case control or cohort or studies; high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal 2+: Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal 2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3: Non-analytic studies, e.g. case reports, case series 4: Expert opinion

Methods Used to Analyze the Evidence Review of Published Meta-Analyses Systematic Review with Evidence Tables Description of the Methods Used to Analyze the Evidence

The Scottish Intercollegiate Guidelines Network (SIGN) carries out comprehensive systematic reviews of the literature using customized search strategies applied to a number of electronic databases and the Internet. This is often an iterative process whereby the guideline development group will carry out a search for existing guidelines and systematic reviews in the first instance and, after the results of this search have been evaluated, the questions driving the search may be redefined and focused before proceeding to identify lower levels of evidence. Once papers have been selected as potential sources of evidence, the methodology used in each study is assessed to ensure its validity. SIGN has developed checklists to aid guideline developers to critically evaluate the methodology of different types of study design. The result of this assessment will affect the level of evidence allocated to the paper, which in turn will influence the grade of recommendation it supports. Additional details can be found in the companion document titled "An Introduction to the SIGN Methodology for the Development of Evidence-based Clinical Guidelines" (Edinburgh [UK]: Scottish Intercollegiate Guidelines Network. [SIGN publication; no. 50]). Available from the SIGN Web site .
Methods Used to Formulate the Recommendations Expert Consensus Description of Methods Used to Formulate the Recommendations

The process for synthesising the evidence base to form graded guideline recommendations is illustrated in the companion document titled "An Introduction to the SIGN Methodology for the Development of Evidence-based Clinical Guidelines." (Edinburgh [UK]: Scottish Intercollegiate Guidelines Network. [SIGN publication; no. 50], available from the SIGN Web site . Evidence tables should be compiled, summarizing all the validated studies identified from the systematic literature review relating to each key question. These evidence tables form an important part of the guideline development record and ensure that the basis of the guideline development group's recommendations is transparent. In order to address how the guideline developer was able to arrive at their recommendations given the evidence they had to base them on, SIGN has introduced the concept of considered judgement. Under the heading of considered judgement, guideline development groups are expected to summarise their view of the total body of evidence covered by each evidence table. This summary

view is expected to cover the following aspects:

Quantity, quality, and consistency of evidence Generalisability of study findings Applicability to the target population of the guideline Clinical impact (i.e., the extent of the impact on the target patient population, and the resources need to treat them.)

Guideline development groups are provided with a pro forma in which to record the main points from their considered judgement. Once they have considered these issues, the groups are asked to summarise their view of the evidence and assign a level of evidence to it, before going on to derive a graded recommendation. The assignment of a level of evidence should involve all those on a particular guideline development group or subgroup involved with reviewing the evidence in relation to each specific question. The allocation of the associated grade of recommendation should involve participation of all members of the guideline development group. Where the guideline development group is unable to agree on a unanimous recommendation, the difference of opinion should be formally recorded and the reason for dissent noted. The recommendation grading system is intended to place greater weight on the quality of the evidence supporting each recommendation, and to emphasise that the body of evidence should be considered as a whole, and not rely on a single study to support each recommendation. It is also intended to allow more weight to be given to recommendations supported by good quality observational studies where randomised controlled trials (RCTs) are not available for practical or ethical reasons. Through the considered judgement process guideline developers are also able to downgrade a recommendation where they think the evidence is not generalisable, not directly applicable to the target population, or for other reasons is perceived as being weaker than a simple evaluation of the methodology would suggest. On occasion, there is an important practical point that the guideline developer may wish to emphasise but for which there is not, nor is their likely to be, any research evidence. This will typically be where some aspect of treatment is regarded as such sound clinical practice that nobody is likely to question it. These are marked in the guideline as "good practice points." It must be emphasized that these are not an alternative to evidence-based recommendations, and should only be used where there is no alternative means of highlighting the issue.
Rating Scheme for the Strength of the Recommendations

The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation. A: At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target

population, and demonstrating overall consistency of results B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++ D: Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+
Cost Analysis

Cost Effectiveness of Diagnostic Approaches Only three relevant economic papers on the use of dual-energy X-ray absorptiometry (DXA) scanning were identified. These all involved modelling, rather than incorporation of economic evaluation into clinical trials. There is some evidence that for relatively expensive medication, such as bisphosphonates, treatment programmes with prior bone density screening are likely to be more cost-effective than those without and, in some circumstances, become cost saving. One recent paper concluded that diagnosis and treatment of women at risk of osteoporosis would be made more cost effective by targeting treatment to those with the lowest bone measurement results. Inclusion of another assessment, such as a risk profile, may improve the cost effectiveness of diagnosis. Cost Effectiveness of Treatment A recent Health Technology Assessment (HTA) examined the cost utility and cost effectiveness of different treatments for established osteoporosis. This study compared treatments using the cost per quality-adjusted life-year (QALY). It used a threshold of 30,000 or less per quality-adjusted life-year to represent cost effectiveness. Using an economic model developed by the authors, at age 50 years only hormone replacement therapy (HRT) and calcium plus vitamin D were likely to be considered cost-effective (assuming that the agent would decrease the risk of non-vertebral fractures at this age). In older age groups a wider range of treatments, including hormone replacement therapy, calcium with or without vitamin D and bisphosphonates were considered cost effective. This Health Technology Assessment demonstrates that age is an important determinant of cost effectiveness since the risk of fractures increases with age. High costs of intervention are associated

with poorer cost effectiveness since, in general, the variation in cost is greater than any proven variation in efficacy.
Method of Guideline Validation External Peer Review Internal Peer Review Description of Method of Guideline Validation

A national open meeting is the main consultative phase of Scottish Intercollegiate Guidelines Network (SIGN) guideline development, at which the guideline development group presents its draft recommendations for the first time. The national open meeting for this guideline was held in February 2002 and was attended by 328 representatives of all the key specialties relevant to the guideline. The draft guideline was also available on the SIGN website for a limited period at this stage to allow those unable to attend the meeting to contribute to the development of the guideline. The comments received from the national open meeting were considered when the guideline was redrafted for peer review. The guideline was also reviewed in draft form by independent expert referees, who were asked to comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting the recommendations in the guideline. As a final quality control check, the guideline is reviewed by an Editorial Group comprising the relevant specialty representatives on SIGN Council to ensure that the peer reviewers' comments have been addressed adequately and that any risk of bias in the guideline development process as a whole has been minimised. Each member of the guideline development group then approved the final guideline for publication.
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Recommendations
Major Recommendations

Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document. The strength of recommendation grading (A-D) and level of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field. Risk Factors for Osteoporosis B - Patients who have suffered one or more fragility fractures should be priority targets for investigation and treatment of osteoporosis.

C - Use of family history in assessing risk of osteoporosis should include maternal, paternal, and sister history. C - Family history should include not only a given diagnosis of osteoporosis but also kyphosis and low trauma fracture after age 50. B - Smokers should be considered at greater risk of osteoporosis than non-smokers, and advised to stop, for this and other reasons. Measurement, Diagnosis and Monitoring B - Conventional radiographs should not be used for the diagnosis or exclusion of osteoporosis. B - When plain films are interpreted as "severe osteopaenia" it is appropriate to suggest referral for dual-energy X-ray absorptiometry (DXA). A Bone mineral density (BMD) should normally be measured by DXA scanning performed on two sites, preferably anteroposterior spine and hip. B - Repeat measurements should only be performed if they influence treatment. C - If DXA investigations are repeated, anteroposterior (AP) spine and total hip measurements should be used to follow response to treatment. C - Following a DXA scan of the hip, the annual hip fracture risk (or 10 year fracture risk) should be included in the DXA report. C - Where lateral spine scans acquired with fan-beam DXA are available, visual assessment should be used to assess prevalent vertebral fractures. B - Evidence of existing vertebral deformity should be used to modify the hip fracture risk estimated from age, sex, and BMD. A - Biochemical markers of bone turnover should have no role in the diagnosis of osteoporosis or in the selection of patients for BMD measurement. Non-pharmacological Interventions B - High intensity strength training is recommended as part of a management strategy for osteoporosis. B - Low impact weight bearing exercise is recommended as part of a management strategy for osteoporosis. A - Postmenopausal women should aim for a dietary intake of 1,000 mg calcium per day.

B - Ipriflavone should not be used as a sole therapy for fracture reduction in patients with osteoporosis. Pharmacological Management For postmenopausal women with multiple vertebral fractures A - To reduce fracture risk at all sites: treatment with oral risedronate (5 mg daily or 35 mg once weekly + calcium + vitamin D). A - To reduce vertebral fracture risk: treatment with intermittent cyclical etidronate (400 mg daily for 14 days + 500 mg calcium daily for 76 days, repeating 3 monthly cyclical therapy). For postmenopausal women with osteoporosis determined by axial DXA and with a history of at least one vertebral fracture A - To reduce fracture risk at all sites: treatment with oral alendronate (10 mg daily or 70 mg once weekly + calcium + vitamin D). A - To reduce vertebral fracture risk: treatment with oral raloxifene (60 mg daily + calcium + vitamin D). B - To reduce vertebral fracture risk: treatment with intranasal calcitonin (200 IU daily + calcium + vitamin D). For postmenopausal women with osteoporosis determined by axial DXA, with or without previous non-vertebral fracture A - To reduce fracture risk at all sites: treatment with either oral alendronate (10 mg daily or 70 mg once weekly + calcium + vitamin D) or oral risedronate (5 mg daily or 35 mg once weekly + calcium + vitamin D). A - To reduce vertebral fracture risk: treatment with oral raloxifene (60 mg per day + calcium + vitamin D). For frail, elderly (aged 80+ years) women with a diagnosis of osteoporosis, with or without previous non-vertebral fractures A - To reduce fracture risk at all sites, elderly women who have suffered multiple vertebral fractures or who have had osteoporosis confirmed by DXA scanning should be considered for treatment with either oral risedronate (5 mg daily or 35 mg once weekly+ calcium + vitamin D) or oral alendronate (10 mg daily or 70 mg once weekly + calcium + vitamin D). A - To reduce hip fracture risk, frail elderly women who are housebound should receive oral calcium 1,000 to 1,200 mg daily + 800 IU vitamin D.

For men with a diagnosis of osteoporosis determined by axial DXA with or without previous osteoporotic fracture A - To reduce fracture risk at all sites, men with low BMD and/or a history of one or more vertebral fractures or one non-vertebral osteoporotic fracture should be treated with oral alendronate (10 mg + 500mg calcium + 400 IU vitamin D daily). Definitions: Grades of Recommendation A: At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++ D: Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+ Levels of Evidence 1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias 1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias 1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias 2++: High quality systematic reviews of case control or cohort studies; high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal 2+: Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3: Non-analytic studies, e.g. case reports, case series 4: Expert opinion
Clinical Algorithm(s)

An algorithm is provided in the original guideline document for the management of glucocorticoidinduced osteoporosis in men and women.
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Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").
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Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Reduction in the incidence of fractures Alleviation of fracture related morbidity Prevention of subsequent fractures Identification of risk factors to provide targeted treatment

Potential Harms

All bisphosphonates can potentially be associated with gastrointestinal side effects. For aminobisphosphonates such as alendronate, this can on rare occasions present as oesophageal ulceration. The risk of these symptoms can be lessened by the avoidance of lying flat within 30 minutes of ingestion or by using the once weekly preparations.
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Contraindications
Contraindications

Previous history of venous thromboembolism (VTE) contraindicates oral hormone replacement therapy (HRT) or raloxifene.

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Qualifying Statements
Qualifying Statements

This guideline is not intended to be construed or to serve as a standard of medical care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. These parameters of practice should be considered guidelines only. Adherence to them will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor in light of the clinical data presented by the patient and the diagnostic and treatment choices available. However, it is advised that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patients case notes at the time the relevant decision is taken.

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Implementation of the Guideline

Description of Implementation Strategy

Implementation of national clinical guidelines is the responsibility of each National Health System (NHS) Trust and is an essential part of clinical governance. It is acknowledged that every Trust cannot implement every guideline immediately on publication, but mechanisms should be in place to ensure that the care provided is reviewed against the guideline recommendations and the reasons for any differences assessed and, where appropriate, addressed. These discussions should involve both clinical staff and management. Local arrangements may then be made to implement the national guideline in individual hospitals, units and practices, and to monitor compliance. This may be done by a variety of means including patient-specific reminders, continuing education and training, and clinical audit. The National Osteoporosis Society (NOS) has produced an Osteoporosis Framework setting out standards for osteoporosis services in Scotland. This framework has been endorsed by the Chief Medical Officer. The key recommendations from the National Osteoporosis Society framework document are:

Include prevention of osteoporotic fractures in the local Health Improvement Plan (HIP) Identify lead clinicians in primary and secondary care to develop a local osteoporosis programme based on this framework. Each Local Health Cooperative, Primary Care, and Acute Trust should have a lead clinician for osteoporosis. Each Health Board should have a consultant in Public Health to assist in coordinating this osteoporosis strategy between primary and secondary care. Establish a local osteoporosis advisory group to facilitate multidisciplinary implementation of this framework.

Use a selective case-finding approach to target treatment at individuals at high risk. Provide access to adequate levels of diagnostic and specialist services - e.g. a Local Health Care Cooperative serving a population of 50,000 would require approximately 500 dual-energy X-ray absorptiometry (DXA) scans per year. Promote the use of care pathways and audit to improve standards of care. Monitor performance to assess health impact.

Key points for audit are identified in the original guideline document.
Implementation Tools Clinical Algorithm Patient Resources Quick Reference Guides/Physician Guides For information about availability, see the Availability of Companion Documents and Patient Resources fields below. Back to top

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need Living with Illness IOM Domain Effectiveness Patient-centeredness Back to top

Identifying Information and Availability

Bibliographic Source(s) Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Jun. 45 p. (SIGN publication; no. 71). [149 references] Adaptation

Not applicable: The guideline was not adapted from another source.
Date Released 2003 Jun (reaffirmed 2007)

Guideline Developer(s) Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.] Source(s) of Funding

Scottish Executive Health Department

Guideline Committee

Not stated
Composition of Group That Authored the Guideline

Guideline Development Group: Dr Tricia Donald (Chair), General Practitioner, Edinburgh; Dr John Ennis (Secretary), General Practitioner, Edinburgh; Dr Lisa Mackenzie (Methodologist), SpR Rheumatology, Glasgow Royal Infirmary; Dr Graham Beastall, Clinical Biochemist, Glasgow Royal Infirmary; Dr Lucy Caird, Consultant Gynaecologist, Raigmore Hospital, Inverness; Dr Clare Campbell, General Practitioner, Broxburn; Dr Donald Farquhar, Consultant Geriatrician, St. Johns Hospital, Livingston; Dr Ailsa Gebbie, Community Gynaecologist, Edinburgh; Mr Alberto Gregori, Consultant Orthopaedic Surgeon, Hairmyres Hospital, East Kilbride; Dr Jim Hannan, Physicist, Western General Hospital, Edinburgh; Mr Robin Harbour, Quality & Information Director, Scottish Intercollegiate Guidelines Network; Ms Janice Harris, Senior Pharmacist, Royal Victoria Hospital, Edinburgh; Dr Andrew Jamieson, Consultant Physician, Queen Margaret Hospital, Dunfermline; Dr Justus Krabshuis, Highland Data Ltd; Ms Ann Lees, Health Planning Manager (Health Economist), Argyll and Clyde Acute Hospitals National Health System Trust; Dr Alastair McLellan, Consultant Endocrinologist, Western Infirmary, Glasgow; Ms Alice Mitchell, Health Visitor, Glasgow; Dr Sarah Mitchell, Physiotherapist, Glasgow Royal Infirmary; Dr Caroline Morrison, Public Health Consultant, Greater Glasgow Health Board, Dr Anne Payne, Lecturer in Clinical Nutrition and Dietetics, Glasgow Caledonian University; Dr Colin Perry (Methodologist), Specialist Registrar (Endocrinology), Glasgow Royal Infirmary; Dr Nigel Raby, Consultant Radiologist, Western Infirmary, Glasgow; Professor David Reid, Consultant Rheumatologist, Foresterhill, Aberdeen; Dr Mary Scott, General Practitioner, Dunfermline; Mrs Anne Simpson, National Osteoporosis Society Coordinator for Scotland
Financial Disclosures/Conflicts of Interest

All members of the Scottish Intercollegiate Guidelines Network (SIGN) guideline development groups are required to complete a declaration of interests, both personal and non-personal. A personal interest involves payment to the individual concerned (e.g., consultancies or other fee-paid work commissioned by or shareholdings in the pharmaceutical industry); a non-personal interest involves payment which benefits any group, unit, or department for which the individual is responsible (e.g., endowed fellowships or other pharmaceutical industry support). Details of the declarations of interest of any guideline development group member(s) are available from the SIGN executive.
Guideline Status

This is the current release of the guideline. The guideline was reaffirmed by the developer in 2007. Any amendments to the guideline will be noted on Scottish Intercollegiate Guidelines Network (SIGN) Web site .
Guideline Availability

Electronic copies: Available from the Scottish Intercollegiate Guidelines Network (SIGN) Web site:

HTML format Portable Document Format (PDF)

Availability of Companion Documents

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Abstract Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients

with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the nonskeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk patients for bone density testing it is possible to diagnose this disease before the first fracture occurs, and initiate appropriate treatment to reduce the risk of future fractures. Keywords: osteoporosis, management, treatment, bone density testing, DXA, glucocorticoid, fracture, risk

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Background Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. It is a major public health concern, with about 44 million American men and women, or 55% of the population age 50 and over, having osteoporosis or low bone density that can lead to fractures [1]. About 80% of osteoporosis occurs in women and 20% in men. The prevalence is increasing, with over 61 million expected to have osteoporosis or low bone density by 2020. About 30% of Caucasian women age 50 and over have osteoporosis, when defined as a T-score of less than -2.5 at the spine, hip, or mid-forearm [2]. In men age 50 and older, the prevalence of osteoporosis is about 19% [3]. There are about 1.5 million fragility fractures in the USA each year, with 700,000 vertebral fractures, 300,000 hip fractures, 250,000 wrist fractures, and 250,000 at other skeletal sites. The lifetime risk of fracture is substantial. Population data from Rochester, Minnesota, estimate that at the age of 50, a Caucasian woman has about a 40% lifetime risk and a Caucasian man a 13% lifetime risk of fracture of fracture at hip, spine, or distal forearm [4]. In Malm, Sweden, the lifetime risk of fracture of the hip, spine, forearm or proximal humerus at age 50 was reported to be 46% in women and 22% in men [5]. The Dubbo study found that at the age 60 there was a residual lifetime fracture risk of 56% for women and 29% for men, assuming average life expectancy [6]. A woman's risk of hip fracture is equal to her combined risk of breast, uterine, and ovarian cancer [7]. Fractures of the spine and hip are associated with an increased risk of chronic pain, deformity, depression, disability, and death. About 50% of those with a hip fracture will be permanently unable to walk without assistance and 25% will require long-term care [8]. The mortality rate five years after a fracture of the hip or a clinical vertebral fracture is about 20% greater than expected [9], with men having higher mortality rates than women, even when standardized for age [10]. The direct cost of osteoporotic fractures in the USA was about $17 billion per year in 2001 [11], extrapolated from 1995 figures using the Medical Index of the Consumer Price Index, with this value expected to rise greatly in future years.

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Bone density and bone strength Osteoporosis is defined as "a skeletal disease characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and quality." [12] Bone mineral density (BMD) correlates very well with fracture risk, with the relative risk of fracture approximately doubling (range 1.62.6) for every standard deviation decrease in BMD, depending on the skeletal site measured and the type of fracture [13]. Many devices and technologies are available for measuring BMD. Dual-energy X-ray absorptiometry (DXA) is the method used to diagnose osteoporosis according to criteria established by the World Health Organization [14] [Table [Table11]. Table 1 Classification of Bone Mineral Density (World Health Organization) [14].

Non-BMD factors that may alter bone strength include bone turnover, architecture (size and shape, or bone geometry), microarchitecture, damage accumulation, matrix properties, mineralization, and mineral properties. These factors and probably many others that have not yet been well-defined are collectively called "bone quality" or "bone qualities." Accumulating knowledge regarding bone qualities offers insight into the pathophysiology of osteoporosis and metabolic bone disease, and helps in understanding the mechanisms of action of bone-active drugs. However, with the exception of bone turnover markers and bone geometry, none of these are these presently have clinical applications. The adult skeleton is in a constant state of remodeling, a process whereby bone and bone matrix (mostly composed of type 1 collagen) is continually being removed by osteoclasts in discrete packets, or bone remodeling units, followed by osteoblast-mediated bone formation and mineralization. With high bone turnover states, such as occurs with estrogen deficiency in the early postmenopausal years, there are more bone remodeling units resulting in a greater number of "stress-risers," or weakened areas of bone. A stress-riser in bone is analogous to a scored line on a sheet of glass, where the glass is more likely to break than in an area that is not scored. Ultimately, thinning and perforation of trabecular structures may occur, as well as impaired mineralization. High bone turnover, which is detected clinically by the finding of elevated markers of bone resorption, has been shown to be an independent risk factor for fracture [15]. Small bones, as in individuals with a small frame or in women compared to men, are weaker than large bones. This is consistent with the engineering concept that a tubular structure, such as a long bone, has a greater ability to resist bending forces as the diameter increases. Longer hip axis length (the distance from the lateral surface of the greater trochanter to the inner surface of the pelvis, along the axis of the femoral neck), larger femoral neck-shaft angle (the angle between the axis of the femoral neck and the femoral shaft), and wider femoral neck diameter (the width of the femoral neck at its narrowest portion) are associated with increased risk of hip fracture [16]. This may explain, in part, the lower risk of hip fracture in Chinese and Japanese women compared to Caucasians, despite similar BMD. A larger vertebral body is less likely to fracture than a smaller one, even with the same BMD, since a larger cross-sectional area has greater resistance to compressive forces [17].

Bone microarchitecture, best evaluated by bone biopsy, concerns bone properties at the microscopic level, such as the spatial distribution of trabecular rods and plates, trabecular thickness and connectivity, cortical thickness and cortical porosity. The horizontal trabeculae, which stabilize the load-bearing vertical trabeculae, are subject to thinning and perforation in patients with osteoporosis, resulting in loss of bone strength and increased fracture risk [18]. The number, size, and distribution of cortical porosities may play a role in determining bone strength [19]. Damage accumulation, such as the increasing number of microfractures with advancing age, occurs at multiple skeletal sites in some, but perhaps not all individuals [20]. While this has adverse effects on the biomechanical properties of bone, the relationship between microfractures and clinical fractures is not clear, and the significance of increased microdamage accumulation with antiresorptive therapy is not known. Bone matrix is the noncalcified portion of bone, 90% of which is composed of type 1 collagen. It provides elasticity and flexibility to bone. Inherited and acquired disorders of the collagen fibrils, crosslinking, or non-collagenous proteins may have serious consequences on bone strength and fracture risk. Mild forms of metabolic bone disease with abnormal collagen, such as osteogenesis imperfecta and Ehlers-Danlos syndrome, may sometimes masquerade as postmenopausal osteoporosis. Mineralization is responsible for stiffness, or mechanical rigidity, of bone. Too much (osteopetrosis) or too little (osteomalacia) bone mineral can have adverse effects on bone strength. Mineralization takes place in two phases: the primary, or active bone formation phase, occurring over a period of months, and the secondary, or slow phase, which takes years. The second phase, which may be responsible for as much as 50% of bone mineralization, is incomplete in high bone turnover states. The rapid increase in BMD over the first 612 months of bisphosphonate therapy is due to "filling of the remodeling space" associated with the first phase of mineralization, while the slower increase in BMD over the following years is due to increased secondary mineralization allowed by the reduced rate of bone turnover [21]. Even the size and distribution of hydroxyapatite crystals may affect the mechanical properties of bone, with animal studies suggesting that a mix of small and large crystals are stronger than only large crystals or only small crystals [22].

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Clinical risk factors Consideration of risk factors can provide helpful information for patient management. It is enlightening to distinguish risk factors for osteoporosis from risk factors for fracture, risk factors for hip fracture from risk factors for vertebral fracture, and skeletal risk factors for fracture from non-skeletal ones, since the clinical implications will vary accordingly. For example, risk factors for osteoporosis, such as advanced age, small stature, or family history, are commonly used in selecting patients for bone density testing, and may determine whether the test is covered by insurance. Clinical risk factors for osteoporosis are not a substitute for bone density testing, and in fact cannot accurately predict which individual patients have low bone density [23]. Risk factors for fracture, which overlap risk factors for osteoporosis but are not totally the same, can help determine which patients require medical intervention. Skeletal risk factors for fracture, such as low bone density or high bone turnover, may be treated with pharmacologic agents. Nonskeletal risk factors for fracture, such as poor balance and high risk for falling, require other

types of intervention, such as balance training and hip protectors. Advancing age is a risk factor for osteoporosis and fractures for which there is no antidote. Good nutrition, regular weightbearing exercise, and avoidance of cigarette smoking, alcohol excess and bone-toxic drugs can maximize the genetic potential for skeletal integrity. Validated risk factors for fracture also vary according to the type of fracture, with many more risk factors identified for hip fracture than for vertebral fracture. A list of common skeletal and nonskeletal risk factors for hip fracture is in Table Table2.2. The best validated risk factors for vertebral fracture are low BMD, advancing age, and previous fracture. Table 2 Selected Skeletal and Nonskeletal Risk Factors for Hip Fracture [15,48]. Long-term glucocorticoid therapy A meta-analysis of 66 BMD studies and 23 fracture studies showed that oral glucocorticoid treatment with more than prednisolone 5 mg per day or equivalent leads to a decrease in BMD and increased risk of fracture [24]. The increase in fracture risk begins within 36 months of starting glucocorticoids, decreases soon after stopping, and is independent of age, sex, or underlying disease. Analysis of the United Kingdom General Practice Research Database (UK GPRD) of 244,235 patients on oral glucocorticoid therapy showed that a low dose (less than 2.5 mg per day) was associated with an increased risk of vertebral and nonvertebral fractures, and doses greater than 2.5 mg per day were associated with increased risk of vertebral, nonvertebral, and hip fractures [25]. Fracture risk was dose-dependent, increasing dramatically as the dose increased. The fracture risk associated with glucocorticoid therapy appears to be related to average daily dose rather than cumulative dose, suggesting that the adverse skeletal effects are acute rather than chronic [26]. Some [27], but not all [28], studies have shown that patients on glucocorticoid therapy fracture at a higher BMD than patients not on glucocorticoid therapy, suggesting problems with bone quality that are independent of BMD, and that perhaps treatment thresholds should be more aggressive for glucocorticoid patients. A UK GPRD study of 170,818 patients on inhaled glucocorticoids showed increased risk of vertebral, nonvertebral, and hip fractures compared to controls, but suggested that the risk increase may have been due to the underlying respiratory disease rather than the inhaled glucocorticoids [29]. A meta-analysis of 27 studies showed that inhaled glucocorticoids (triamcinolone, budesonide, beclomethasone) in doses over 1.5 mg per day (0.75 mg per day for fluticasone propionate) may be associated with a significant reduction in bone density [30]. In a 2-year randomized placebo-controlled trial of inhaled fluticasone in asthma patients, there was no significant change in BMD with doses of 0.176 mg per day [31]. There is no convincing evidence that intranasal glucocorticoids in normally prescribed doses have any clinically significant adverse effect on skeletal integrity [32], although some studies have demonstrated suppression of the hypothalamic-pituitary-adrenal axis [33]. Further study is needed to define the impact of intranasal glucocorticoid formulation, dose, and combination with oral or inhaled glucocorticoids on the development of bone disease. The prevalence of glucocorticoid-induced osteoporosis is often difficult to determine due to the confounding effects of comorbidities and polypharmacy. A study of general practice patients in Iceland showed that 26% of those treated with oral glucocorticoids for more than 3 months were diagnosed with osteoporosis, and 20% had a history of fragility fractures [34]. The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, and includes 1.) impairment of osteoblast, osteocyte, and osteoclast function, leading to decreased bone turnover

and reduced microfracture repair; 2.) disordered calcium metabolism, with reduced intestinal absorption, increased renal excretion, and possible secondary hyperparathyroidism; and 3.) decreased synthesis of sex hormones [35].

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Diagnosis Bone density testing A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, provided other causes of fracture have been ruled-out. A fragility fracture is any fracture occurring after trivial trauma, such as falling from the standing position, coughing, bending, or reaching. Most fractures in adults, except those from major trauma, such as auto accident or falling off a ladder, are fragility fractures. The preferable method of diagnosing osteoporosis is by bone density testing, before the first fracture has occurred. The WHO criteria may be used to classify BMD, expressed as T-score, as normal, osteopenia, or osteoporosis. A T-score is the standard deviation (SD) variance of the patient's BMD compared to a healthy young-adult reference population. It is calculated according to the following formula, with BMD and SD expressed as g/cm2:

This formula shows that the T-score is dependent on factors other than the patient's BMD, and that a change in the mean or SD of the reference population can result in a different T-score. For example, if the mean young-adult BMD in the reference population is higher, the T-score will decrease, and if the SD is lower, the T-score will increase. This is a clinically import concept, since the reference population may vary according to the manufacturer of the instrument, the software version installed, or the region of interest being measured. For this reason, comparison of serial DXA studies should always be done with absolute BMD values in g/cm2, and not with T-scores. A Z-score is the standard deviation (SD) variance of the patient's BMD compared to an age- and sex-matched reference population, and should not be used to diagnose osteoporosis. It is calculated according to the same formula as the T-score, except that the reference population is age- and ethnicity-matched instead of young-adult matched. The WHO classification system was originally devised as a public health tool for evaluating the prevalence of osteoporosis in populations of postmenopausal women. It was not intended for use in the diagnosis of osteoporosis in individual patients. However, in the absence of a better yardstick, it quickly came to be used in that fashion. The T-score cut-off of -2.5 for diagnosing osteoporosis was selected because it identified approximately 30% of postmenopausal Caucasian women as having osteoporosis, which is roughly the same as the lifetime risk of clinical fragility fractures in this population. The WHO criteria apply to BMD measurement by DXA of the spine, hip and forearm in postmenopausal women and in men age 65 and older [36]. At the present time, the WHO criteria should not be used with BMD measurement devices other than DXA, nor for measurement at skeletal sites other than spine, hip, and forearm. Perhaps in the future, with standardization of reference databases, and acquisition of device-specific data on prevalence of osteoporosis and fracture risk, the diagnosis of osteoporosis will be made with devices other than DXA. Who should be tested?

Bone density testing should be considered in anyone at risk for osteoporosis, or being monitored for treatment of osteoporosis, provided that the results of the test are likely to play a role in patient management decisions. Of all the published guidelines of indications for bone density testing, the most comprehensive are those of the International Society for Clinical Densitometry (ISCD) [36], listed in Table Table33. Table 3 Indications for Bone Density Testing [36] (Official Position of the International Society for Clinical Densitometry).

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Evaluation of low bone density It is prudent to have a high index of suspicion for contributing factors in every patient with low density. A T-score of -2.5 or below is not always osteoporosis. It could be metabolic bone disease, such as osteomalacia, or a localized bone disorder, such as a bone cyst in the measured skeletal site. A postmenopausal woman with osteoporosis does not always have postmenopausal osteoporosis. She could have malabsorption due to undiagnosed celiac disease, or possibly multiple myeloma. Table Table44 lists diseases, conditions, and medications commonly associated with low bone density. In every patient with low BMD, it is reasonable to consider measuring a complete blood count, serum calcium, phosphorous, creatinine, alkaline phosphatase, liver enzymes, and thyroid stimulating hormone. Tests that are often helpful include a 24-hour urine for calcium, celiac antibodies, and in older patients, a serum and urine protein electrophoresis. In selected patients, a serum intact parathyroid hormone level, urinary free cortisol (or other tests to rule out Cushing's syndrome), or additional studies may be helpful. Table 4 Causes of Low Bone Mineral Density.

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Prevention and treatment Nonpharmacologic therapy Nonpharmacologic therapy can be divided into the categories of nutrition, lifestyle, and fall prevention. These represent the foundation for the management of osteoporosis, without which patients are unlikely to achieve the full benefit of pharmacologic therapy. Calcium and vitamin D supplementation have been shown to increase BMD [37] and reduce the risk of fractures [38] in prospective trials. The average American diet is deficient in calcium, and many Americans have an insufficient daily intake of vitamin D. The National Osteoporosis Foundation recommends

that all adults have a daily intake of at least 1200 mg elemental calcium with diet plus supplements, and 400800 IU vitamin D per day for patients at risk of deficiency [39]. Lifestyle intervention for osteoporosis includes regular weight-bearing exercise and avoidance of unhealthy behavior, such as cigarette smoking and excess alcohol intake. Patients with low BMD and high risk for falling may benefit from additional measures, such as muscle strengthening, fall prevention, balance training, Tai Chi, extra care with the dosing of certain drugs (e.g., sedatives, hypnotics, antihypertensives, anticonvulsants), nightlights, handrails, grab-bars, removal of slippery carpets and dangerous obstacles at home, correction of impaired eyesight and hearing, and the wearing of hip protectors. The decision to treat Since the goal of treatment is to prevent fractures, selection of patients for drug treatment should be based on level of fracture risk. Current guidelines for initiation of pharmacologic therapy [Table [Table5]5] are based on T-score or T-score plus clinical risk factors. While these guidelines are a helpful for appropriate patient populations, over-reliance on T-scores alone may underestimate or overestimate absolute fracture risk and lead to inappropriate therapy. For example, a healthy 30 year-old premenopausal woman with a T-score (or Z-score) of -2.1 probably has a low 510 year absolute fracture risk and would probably not benefit from pharmacologic therapy, while an elderly man or woman with a T-score of -1.4 and a history of fragility fracture is at high risk for future fracture and could expect a significant reduction in fracture risk with therapy. Efforts are currently underway to develop a standardized methodology for calculating and expressing absolute fracture risk, which is arguably the best way of establishing therapeutic thresholds. Personal issues and non-skeletal effects of medications are also important to consider in the decision to treat and drug selection [Table [Table66] Table 5 Indications for Pharmacologic Therapy.

Table 6 Nonskeletal Effects of Pharmacologic Therapy.

Pharmacologic therapy The medications that are FDA-approved for the management of osteoporosis may be divided into antiresorptive agents (estrogen, alendronate, risedronate, and calcitonin) and anabolic agents, of which there is now only one-teriparatide. These agents can be expected to stabilize or increase BMD [Table [Table7]7] and reduce fracture risk by approximately 50% in most patients. All of the FDA-approved medications have been shown to reduce the risk of vertebral fractures, while only estrogen, alendronate, and risedronate have reduced the risk of hip fractures in prospective clinical trials. [Table [Table88]

Table 7 Bone Density Response to Therapy.

Table 8 Fracture Risk Reduction in Response to Therapy.

The Women's Health Initiative was the first large prospective randomized placebo-controlled trial to show reduction of hip fracture, vertebral fracture, and other nonvertebral fractures with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) [40] and CEE alone [41]. However, the study was stopped before its planned completion date due to increased risk of adverse events. Considering the small but significant increase in the risk of breast cancer, stroke, coronary heart disease, and venous thromboembolic disease with CEE plus MPA, and the increase risk of stroke with CEE alone, it is likely that estrogen will not be used as a drug of first choice for the treatment of osteoporosis, and that its main use will be for the control of menopausal symptoms. The bisphosphonates, alendronate and risedronate, are both proven to reduce the risk of hip fractures, and may be good choices in elderly patients and any patients with high risk of hip fracture. Raloxifene and calcitonin are useful agents where reduction of hip fracture risk is not a primary concern, with the added benefit that raloxifene may reduce the risk of breast cancer and calcitonin may have an analgesic effect in patients with acute painful vertebral fractures. Teriparatide, human recombinant 134 parathyroid hormone, is approved for use in women and men at high risk for fracture. Despite its greater expense and the inconvenience of daily subcutaneous injections for a 2-year course of therapy, this agent is a welcome addition to the pharmacologic armamentarium for selected patients. Current evidence suggests that there is no added benefit to combining teriparatide with alendronate, but giving a bisphosphonate following a course of treatment with teriparatide may serve to preserve the bone mass previously gained. Combination therapy in general is discouraged, since there are no studies showing that it offers additional benefit in terms of fracture risk reduction. Glucocorticoid-induced osteoporosis (GIO) Long-term term glucocorticoid therapy may have devastating consequences in terms of loss of bone density and increased fracture risk. Any patient being started on oral glucocorticoid therapy with the intent to treat for more than 3 months should be considered for bone density testing and bone-protective medication. Table Table99 shows the guidelines of the American College of Rheumatology for the prevention and treatment of GIO [42].

Table 9 Management of Glucocorticoid-Induced Osteoporosis [42].

Monitoring treatment The ultimate indicator of efficacy for osteoporosis therapy is reduction of fracture risk. In clinical trials, this is done by comparing fractures rates in a group receiving active medication compared to placebo. For individual patients in clinical practice, BMD is normally used as a surrogate measurement of changes in bone strength and fracture risk in response to therapy. An increase or stabilization of BMD is associated with reduction in fracture risk [43], although other measures of bone qualities, particularly changes in bone turnover markers [44], are correlated to changes in fracture risk as well. Patients started on pharmacologic therapy are typically retested in 12 years in order to be sure there has been no loss of BMD, and retested at longer intervals once response to therapy has been shown. Patients at very high risk for bone loss, such as those on glucocorticoid therapy, may need to be tested as often as every 6 months, until stability of bone mass has been demonstrated. Discontinuation of treatment It is intuitive that pharmacologic therapy should be continued as long as fracture risk is high, and stopped when that is no longer the case. Prolonged therapy adds to patient cost and inconvenience, and possibly increases the risk of drug toxicity due to longer exposure. Clinical trials and knowledge of drug mechanisms of action are helpful in predicting the likely outcome of discontinuation, and suggestive of appropriate measures for follow-up. Discontinuing estrogen, raloxifene, or calcitonin therapy is likely to be associated with rapid loss of therapeutic effect and subsequent bone loss due to sex hormone deficiency and/or aging. Therefore, patients at high risk for fracture who stop these drugs should probably soon be started on another antifracture drug. Bisphosphonates, having a strong affinity for bone and a long bone half-life, have been shown to have persistence of suppression of bone turnover for months to years after cessation of therapy. This suggests that patients who have been taking an oral bisphosphonates for years may continue to benefit from drug effects for a long time after discontinuation, with the duration of persistent effect varying according to the pharmacological properties of the bisphosphonate used. With teriparatide, there is evidence that discontinuation may be quickly followed by bone loss, which can be prevented by initiating bisphosphonate therapy. Nonresponders In clinical trials, the overwhelming majority of patients treated for osteoporosis with antiresorptive or anabolic medication stabilize or increase BMD and benefit from a reduction in fracture risk. In clinical practice, approximately 10% of elderly patients treated with a bisphosphonate have been shown to lose BMD [45], defined as a BMD decrease more than the Least Significant Change (LSC) at a 95% level of confidence, a value that can be calculated for each bone densitometry center. Medical evaluation of these BMD losers revealed a previously unrecognized contributing factor, or secondary cause of osteoporosis in about 50%. Although there is no universal consensus on the definition of non-response to therapy, defining nonresponse in terms of BMD loss more than the LSC is a useful tool in clinical practice, and is cause for further medical investigation. Common causes for nonresponse include poor adherence

(not taking medication or not taking it correctly), calcium or vitamin D deficiency, and comorbidities (diseases, conditions or medication that impair drug effect or are associated with osteoporosis) [46]. When to refer to an osteoporosis specialist The care of osteoporosis patients crosses all medical specialty lines. Primary care specialists and most medical subspecialists may justifiably claim the right to manage osteoporosis in their patients, and do it well. In a small percentage of patients with unusual clinical presentations, intolerance to standard medications, or poor response to therapy, additional expertise may be required. Table Table1010 shows established guidelines for referral to an osteoporosis specialist [47]. Table 10 When to Refer to an Osteoporosis Specialist [47].

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Summary Osteoporosis is a common disorder of low bone strength due to a combination of factors that include low BMD, high bone turnover, altered microarchitecture, geometry, damage accumulation, and mineralization, leading to increased risk of fractures. The consequences of fragility fractures are serious-disability, loss of independence, chronic pain, and increased mortality. Patients on long-term oral glucocorticoid therapy, even at low doses, are at increased risk for fracture. Inhaled glucocorticoids in sufficiently high doses may increase fracture risk. Intranasal glucocorticoids, in doses normally prescribed, do not appear to have clinically significant adverse skeletal effects. BMD testing is the most important clinical tool for diagnosing high risk patients before the first fracture occurs, allowing for timely and appropriate medical intervention to strengthen bones and reduce the risk of fracture. Competing interests Grant / Research Support: Merck, Eli Lilly, Novartis, Aventis, Amgen, Pfizer, Kyphon, WyethAyerst, Roche, GE Lunar, Procter & Gamble. Consultant, Advisory Board, or Speakers' Bureau: Merck, Eli Lilly, Novartis, Procter & Gamble, Aventis, Kyphon, Roche, Wyeth-Ayerst, GE Lunar. Authors' contributions The author is solely responsible for all content of this review. Acknowledgements Special thanks to Lance A. Rudolph, MD, for manuscript review and editing.

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Management of osteoporosis E Michael Lewiecki 1 1 New Mexico Clinical Research & Osteoporosis Center, 300 Oak St. NE, Albuquerque, New Mexico 87106, USA Corresponding author. E Michael Lewiecki: LEWIECKI@aol.com Received May 12, 2004; Accepted July 14, 2004. This article has been cited by other articles in PMC.