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Osteoporosis is a widespread condition that causes fractures. Osteoporosis is defined as a systemic disease characterized by low bone mass, microarchitectural deterioration of bone tissue with the consequent increase in bone fragility and susceptibility of fracture. Osteoporosis is a disease of thin bones that break easily. We have nice strong vertebral structures on the left and thin porous bones that snaps easy. So the role really of your situation in this disease is trying to recognize these people before thereís a fracture, when you know theyíve got thin bones, and treat them and see if you can actually prevent the osteoporosis.

Criteria for osteoporosis is based on bone densitometry readings and a standard deviation or two below your peak bone mass would be considered osteopenia, or thin bones but not osteoporotic. A value of two standard deviations below would be osteoporosis and worthy of investigation. If you look at some of the typical rheumatic conditions, rheumatoid arthritis in this country and osteoarthritis, 2.1 million cases, 16 million cases of osteoarthritis, the number of cases of osteoporosis is overwhelming. There is a devastating toll with these hip fractures. A lifetime risk of death, similar to that of breast cancer. If youíve had a hip fracture, 20% excess mortality in the first year and about 50% of these survivors are permanently incapacitated. They need a walker, they need some help and 20% of them actually end up in some kind of skilled care facility.

A more common type of osteoporotic fracture, though - if hip fractures are devastating, the more common one that maybe not so devastating in terms of mortality, but easy to recognize in the office - the collapsed fractures of the spine. The vertebra compression fracture. Why do we consider this a female disease? Well if you look at the number of fractures, male versus female and parts of the body in which they occur, you begin to see some striking information. On the left hand graph here is males. As they age from 35 to 85 they begin to get this off the blue line going up. Those are hip fractures. And they get a few Collesí fractures of the wrist as well. If you look at females, they start getting hip fractures a little bit earlier.

Thereís a different type of osteoporosis, thereís other special cases that we need to consider. Steroid-induced osteoporosis - I put up here. Thatís a particular interest of mine because as a rheumatologist I fool around with a lot of steroids, as an allergist in asthma we treat with a lot of steroids. Remember that all our medications that we currently have available to us are anti-resorptive agents. Whether you are talking about the bisphosphates, estrogenís or calcitonin. These agents all work by inhibiting the osteoclasts in your bone from destroying bone. They do not stimulate the making of new bone. Pro-formation drugs such as fluoride and parathyroid hormone are not FDA approved, and in fact the fluoride that was looked at in one study by Dr. Pak in Texas is actually not commercially available. Neopsin is being evaluated. Itís a 25 mg b.i.d. slow release form. It has a generally very narrow therapeutic window. Itís available in Europe and Australia, but itís not something weíve latched onto. So what we really are doing is stopping your own resorption of bone and allowing your osteoblasts to make new bone. As it turns out it takes about three days to _ without osteoclasts, and itís a job for the osteoblasts to repair that and it takes about three weeks. So itís clear that inhibiting osteoclasts can really have a distinct role in simply permitting your own osteoblasts to repair it undisturbed, may be a reasonable way to pursue this. The question then comes up, "Is there any advantage in having somebody on two of these agents? Or three of them?" Well, there is data that looks at estrogenís plus bisphosphates and estrogenís plus calcitonin, and there seems to be at least a safety factor thatís been achieved. It doesnít seem to make any difference in terms of safety. And there may be some synergy. There may actually be some effect thatís better than either two alone. Itís not FDA approved that way. I think we may see alendronate, Fosamax, with estrogen as an approved co-therapy sometime this year or next. Iíve not seen any data that says thereís any advantage in putting someone on all three agents, a bisphosphate, and estrogen or estrogen-like drug and calcitonin. I am aware that some people have done it. Iím not sure thatís always appropriate, but itís an interesting concept.

Within the next five years probably five or six more bisphosphates with a different side chain on it with different properties, some of which might even be more potent than alendronate and some may be available in IV doses that you might give once a quarter or three days in a row once a year. So thereís lots of novel therapies coming down the pipeline with bisphosphate. The most remarkable thing about the only one thatís approved right now is its ability to reduce hip fractures, and if thatís the golden event that we are trying to prevent, this is the only one in which weíve got double-blind placebo controlled, randomized data in a large scale study population. These are patients who were treated for three years with alendronate versus placebo with osteoporosis and it reduced the hip fracture rate by 50%. That kind of perfected data has not been seen with any of the other agents. Pieced together you can

So alendronate then has two different doses. One, for preventing osteoporosis, of 5 mg where the patient is not yet osteoporotic but is on no other

Hormone replacement, as Iíve said, has been sort of the granddaddy - grandmother perhaps - of osteoporosis treatment. And in a lot of the studies that have been pieced together you see a significant increase in bone mineral density and reduction in fractures as well. The problem is once you stop taking the drug it has a remarkable wash-out effect, so I think you try to negotiate a long-term therapy with these patients so they donít basically go through combination with Fosamax for the patient with significant osteoporosis, may end up being the combination thatís reasonable in

Raloxifene is one of the newer drugs that we have available. The brand name is Evista. Itís part of a category of drug we call selective estrogen receptor modulators. It grew out of Tamoxifen and there was an idea at one point that if you gave somebody an antiestrogen, like Tamoxifen in breast cancer, not only was it going to inhibit what estrogen did in the breast but also inhibit what estrogen does in the bone and it was assumed therefor that these patients were going to get osteoporotic. But low and behold, it turned out they didnít. Some of them actually

Thereís one thing of concern clinically, as the antiestrogen effect of raloxifene does trigger hot flashes and so some women are not willing to undergo more hot flashes and other menopausal symptoms to get this reduction in bone loss prevention concept. That needs to be kept in mind, I think, when