Click here to view next page of this article OsteoporosisOsteoporosis is obviously a systemic skeletal disease characterized by low bone mass and changes in the micro-architecture, etc. etc., and they get risk of fracture. A lot of people are at risk for osteoporosis, thinning bones, bone thinning. Two out of five people are women who have osteoporotic problems, or osteoporotic fractures and women at age 50 have a 40% lifetime risk of fracture due to osteoporosis. That’s a huge risk. The incidence of fracture per 100,000 person years, you can see that as age goes up the risk becomes significant, particularly when we get to vertebral and hip fractures. And if you notice, somewhere here around 50-ish, or 50-60 particularly. When you get up to around 70, 75, that’s when the risk of hip fracture greatly increases. Osteoporotic fractures cause a lot of problems, including quality of life deterioration, morbidity and mortality and a significant percentage of people with hip fracture, never fully recover. Actually that percentage is huge and there is a significantly increased mortality rate in people right after hip fractures. There’s over 500,000 vertebral fractures a year, causing loss of height, pain - I think this is the main thing that bothers people - long term deformities and the difficulties that these deformities cause with lack of mobility, with the postural changes and the disfigurement, become very challenging to many patients. Hip fractures; there’s over a quarter of a million annually with about 20% excess mortality due to those hip fractures and 50% never fully recover. That’s a dramatic number of patients that have significant quality of life deterioration due to hip fractures. Huge cost, over 10 billion dollars a year due to rehab, hospitalization and long term care. What choices do we have in dealing with osteoporosis? We have inhibitors of bone resorption, we have stimulators of bone formation and we have these other things that we are not really sure how they work. The inhibitors of bone resorption primarily are the hormones, the estrogens, maybe the progesterones. Anti-resorptive agents may be most effective when the bone turnover is high. It does have the greatest effect on cancellous bone. Most of these anti-resorptive agents may increase the bone mass, but not a huge percentage. And the reason is, what do they do? They prevent resorption and the way they increase bone mass is actually by a little phenomenon that typically early on they slow down the resorption before they slow down the production. So you get a net increase initially. This is one of the classic estrogen studies, where they did an estrogen controlled study, estrogen versus placebo and they measured bone mass. At about two years they did a crossover with a percentage of the patients. You’ll see patients on estrogens had an increase in their bone mass over two years. They were up a whopping 2% over their baseline, and off of estrogens they were down about 4%. So that’s certainly a significant change between estrogen replacement and non-estrogens. They then took half of this population and started them on estrogens and half on placebo, and you can see that this curve begins to go up very The other medications that we think about as anti-resorptive agents is the bisphosphonates. Etidronate has been around for ages and ages. Anybody use etidronate for osteoporosis? Etidronate, or Didronel, is typically used at 400 mg daily for two weeks. And the then the remainder of that 13 week period you just use calcium. They have shown benefit in bone mineral density over a three-year period. It went up about 3% in the hip over a three-year period. Unfortunately they didn’t have enough patients in their study to show statistical significance for fracture data. They claim trends, I don’t know if they are even bothering to do further studies at this point. But certainly it does have its utility. Intermittent dosing is used because of the potency of the bisphosphonate and there is a potential for osteomalacia and that’s the thing the Fosamax people like to make a big deal about. "Oh, gosh you can’t use etidronate because it causes osteomalacia." The expense of this is fractional compared to other bisphosphonates. Alendronate, or Fosamax, is the one that sort of really has been part of the push for osteoporosis management in our county. Alendronate though, I think shows a reasonable efficacy. It is approved for osteoporosis and Paget’s disease. The bone density at the hip after three years shows about a 4-5% increase, at the spine about 6-8% and they’ve shown less loss of stature which makes sense if they’ve had less fractures. They’ve shown about a 50% decrease in vertebral fractures. The toxicity, at least they claim, is not that significant. How many people use Fosamax in their patients? I use it a significant amount in my practice. Calcitonin: who uses calcitonin? Do you like it? Yeah, it’s been much nicer since they came out with intranasal calcitonin. When I was a resident they had a intranasal calcitonin in Europe and it took them like 37,000 extra years to get it approved in this country. But it is a lot nicer. People did not like intramuscular injections or sub-cu injections and there was a lot of nausea associated with the sub-cu injections. There is good bone mineral density data with calcitonin. The intranasal calcitonin is a 200 IU dosing and it does show significant improvement. The numbers aren’t quite the same as with Fosamax. It’s a little bit lower in percentage. The fracture data with calcitonin is not definitive. I assume at some point it will be. I think their trend is certainly good, but their studies haven’t been going on quite as long and as focused on osteoporosis as some of the other agents that we just addressed. The one thing I do want to mention, does anybody use calcitonin because of its pain-relieving quality? I think that’s something that everybody should be aware of. Calcitonin, whether by injection and probably intranasally as well - at least the drug company claims that it also has it when used intranasally - people with osteoporotic fractures. Calcium: calcium is obviously an important element for preventing osteoporosis. Certainly there’s a benefit to children and adults. There’s less dramatic benefit demonstrated in the perimenopausal period where the estrogen deficiency becomes of major importance. When you get to the older population, 70’s and 80’s, calcium once again becomes a very important avenue for the prevention of osteoporosis. The typical supplemental goal is 1 to 1.5 grams. There are other inhibitors of bone resorption. Disaprivalone, aprifola, flavone is something that is used in Europe and Japan. I don’t think it’s available in this country but we may see it in the near future. It does show some bone mass improvement in postmenopausal women. Again, they are still working on anti-fracture efficacy data. Fluoride: anybody been around touting low-dose sodium fluoride lately? No? I had a couple of people come into my office a couple of years ago when this doctor in Texas was touting a study on low dose sodium fluoride for osteoporosis. Everybody is familiar with the data from a number of years ago that showed yes, the bone mineral density got better. Vitamin D: vitamin D is certainly an important supplement in patients with osteoporosis, or at risk for osteoporosis. The main thing I want to mention is that people who are elderly or institutionalized, because these people don’t get out much, they are often vitamin D deficient and there has been a significant amount of research at this point at coming up with an optimal dose. And particularly these patients at real high risk may be more benefited from 800 IU of vitamin D instead of the standard 400 IU. Management of osteoporosis: in general, analgesics, physical therapy, long term - certainly not in an acute fracture - but particularly weight-bearing exercises. Fall prevention is very important particularly in our elderly citizens. Back braces. I have the same feeling about braces in osteoporosis as I do in other diseases. That sometimes supporting things is not necessarily good. There’s only a couple of braces that have been shown to be of significant benefit for osteoporosis. Bone mineral testing: how many people own a bone densitometer? You know, DEXA’s are sort of the standard of care or the gold standard these days for bone density. There’s a whole lot of reasons you want to use low radiation, high precision, high accuracy, etc. but there’s a whole bunch of different kinds of studies that are useful in doing bone densitometry, the dual x-ray, or the DEXA, which is the gold standard. |