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Osteoporosis

Osteoporosis has been defined as "systemic skeletal disease characterized by low bone mass and micro-architectural deterioration." In this particular scanning electron micrograph you can very easily see what the sequelae of this problem are. This is trabecular bone. If you recall, there are two types of bone in the skeleton; cortical bone, which makes up the arms and legs primarily, and cancellous bone with honeycombed arrangements that you see that is more prevalent in the spine to lesser extent than the hip. But if this is a normal trabecular pattern over here, one can see that an area is where these trabecular plates are fractured and then higher magnification completely discontinuous that the mechanical strength of that bone is not going to be very good. And then at a higher magnification can show you an osteoclast digging a pit in this particular bone which has caused discontinuity osteoporosis, thinning of the bones, thin bones, osteoperosis.

Basically our skeleton is constantly in a process of renewal and turnover. In packets that we call BMUís, or basic multicellular units - each of which is about 0.1 cubic millimeter - the skeleton is constantly being turned over. There is a process of activation by an agent or agents that are not yet completely defined and then the osteoclast moves into this area, digs out a pit of bone and then after a period of quiescence the osteoblast moves in and reforms bone and at the end of the period there is - in theory, in a healthy individual - the same amount of bone as prior to the resorptive process. Obviously, as you can imagine, anything that would enhance the activity of the osteoclast so that they would dig a deeper pit or conversely, decrease the activity of the osteoblast so that less bone would be laid down, would over time result in osteoporosis.

What influences your ultimate bone density when one is an older individual is a combination of two factors. The first one being your peak bone mass. How much you have to lose from. Then obviously the rate of loss once peak bone mass is achieved. The different components that go into determining the peak bone mass are many. Genetic influence is probably the most important one. So that if a woman walks into your office and gives you a story that every female relative in her family fractured at the age of 60, even if she is 45 you can assume that she has a very high likelihood.

Diseases which are associated with an increase in incidence of osteoporosis include hyperparathyroidism, hyperthyroidism, Cushingís disease, certainly rheumatoid arthritis. In some of them, such as osteomalacia and in renal failure, the balance is tipped in favor of bone loss by a decrease in bone formation.

So what do you do when somebody comes into your office with a question, or questions about their skeletal integrity. Obviously your history and physical exam are targeted to finding out anything about risk factors or perhaps factors that would suggest a secondary or underlying cause of low bone density. Laboratory evaluation once osteoporosis is confirmed should include a serum calcium level, thyroid function, and S-Pap for individuals of the right age, plasma cortisol, malabsorption studies, again if indicated, so that the workup is generally tailored to the individual patient. Vitamin D metabolites are important these days because we are becoming a vitamin D deficient society. Now that many of us are trying to avoid the sun, and no one drinks milk - which is the only dairy product which is actually fortified in the United States - there is a huge group of middle aged people, men and women - but we are particularly interested in women who are more at risk for osteoporosis - who are coming in with very low vitamin D levels.

Bone x-rays are not indicated and I am here to tell you they are not unless there is a particular site that a patient is complaining about. That is because you need to lose 30% of your bone density in order for osteoporosis to show up on a plain film. On the other hand, bone densitometry - which Iíll talk about in a second - is an excellent way to show low bone mass. Basically the reason that one looks for techniques such as bone densitometry was the need for a reliable and inexpensive scan that had much lower radiation exposure than plain x-rays would, but also was able to predict and diagnose small changes in bone mass. Using the techniques that are available in the dual photon x-ray photometer is the main means that we are using today. The Dexa-scan. The World Health Organization has decided that the definition of osteoporosis is anyone whose peak bone mass is more than 2.5 standard deviations below the peak for a young individual. Osteopenia describes anyone whose bone density is between -1 and -2.5 standard deviations below peak bone mass for a young individual.

What do we recommend for dealing with osteoporosis? Well, the first thing is obviously that it is a disorder that is better prevented than treated. I order to prevent it adequate calcium and vitamin D are essential, and Iíll talk about that in a moment. Exercise is helpful although we know that exercise alone, just as calcium and vitamin D alone, cannot counteract the effect of menopause to decrease bone mass. Lifestyle modifications; really responding to people with excess alcohol intake. Hormone replacement, unless it is contraindicated - and I will say this again and again today - and medications. These are three medications that we will talk about in a little that have been approved for the prevention of osteoporosis: estrogen, alendronate and the new one, reloxophine. Postmenopausal women need 1500 milligrams of calcium per day if they are not on estrogen.

With regard to calcium supplementation it is important to realize that the vitamin industry in general is a "buyer-beware" situation as Iím sure you have all encountered in your own lines and well as in your practices. Calcium carbonate and calcium citrate are well absorbed. Calcium carbonate requires stomach acid so that your patients who are popping Pepcid, Axid, Zantac, all of these things that are over-the-counter that they donít consider to be medications, can take calcium carbonate until the cows come home and it will all come out in their calcium-rich bowel movements.

The other agent to reiterate again is how important estrogen is for the prevention of osteoporosis. Despite the plethora of treatment and prevention modalities that are available, nobody counts their own product as anything but a second choice to estrogen. The therapeutic options in the management of osteoporosis are many and are increasing. Obviously, analgesics for pain associated with fracture, prevention of falls, is extremely important. These are basic. Physical therapy if itís necessary. Nutritional supplementation, which weíve discussed.

Iíd like to turn to pharmacologic therapy at this point. Estrogen actually is associated with a slight increase in bone mass and a prevention of bone loss. But more important, despite the fact that estrogen doesnít have the dramatic increase in bone density that some other agents do, the reduction for fracture risk associated with estrogen is as good as with any agent that is available. There is about a 50% reduction in fractures. In addition, obviously estrogen has a many other positive effects; reducing cardiovascular risks, vasomotor symptoms, etc. etc. Obviously there are some down sides in terms of the increased risk of breast cancer and thromboembolic disease and so in the individual patient these positives and negatives need to be balanced. The second class of drugs that Iím going to talk about are the bisphosphonates, which have extremely low intestinal absorption. Usually anywhere from 1 to 0.001 % of the oral dose is absorbed. Thatís the reason why they often have to be taken on an empty stomach. They bind to hydroxyapatite in bone and stay there forever and what they do is they have direct inhibitory effect on the osteoclasts which is chewing up the bone. Thatís good because the osteoblasts can still come in and lay down bone and over time will increase bone mass.

I mention calcitonin because after estrogen it was the first drug approved for the therapy of osteoporosis and because it doesnít really work. That is somewhat unfair. It actually does increase bone density of the spine. It has never been shown to do anything at the hip, and it does not clearly prevent fractures. I donít really care what my patientís bone density is if they are not going to break bones. So any agent that increases bone density without demonstrably decreasing fracture incidence is something to make people feel good but it is not going to really have a tremendous benefit. On the other hand, there is a new class of drugs that has significant potential and that is the SERMís, which are known as designer estrogens among the medical community and the New York Times. And those SERMís stand for selective estrogen receptor modulator. The drug industry, understanding and realizing that many postmenopausal women were reluctant to take estrogen both because they did not want to get menstrual periods again after menopause and because they were concerned about breast cancer, decided to try to modify the estrogen molecule.

The problems with raloxifene are the same problems as with estrogen; venous thromboembolic phenomenon, the incidence is similar to hormone replacement therapy and so only in individuals who are at high risk is that a concern. The drug is easy to take. It can be taken standing, sitting, in any position at all at any time of the day, with or without water. There are obviously many directions for new research in this area and other SERMís are just one of them. Fluoride which had been used in the past and had been associated with many adverse consequences, both in the skeleton and the GI tract, is being actively investigated by some studies and there are some preliminary data that suggests that it may function in causative ways.

So conclude on the osteoporosis front, it is clearly a not-so-silent epidemic anymore. What we want to do is prevent it but it is never too late to treat. So the recognition of osteoporosis, even at an advanced state and an advanced age, is amenable to intervention and treatment.