What’s the Story with FOSAMAX (Alendronate)?
Posted by
Armand RossettiSeptember 15, 2008 2:37 PMTags:
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That is a complex question for which there is no easy answer. However, it might help for us to gain a basic understanding of Fosamax’s composition; the specialized way that it works; and how the body eliminates Fosamax. It would also be interesting to address any specialized concerns about how Fosamax reacts with the specialized bone that makes up the jaw.
Fosamax the Drug:
Fosamax (alendronate sodium) is a bisphosphonate drug used to combat osteoporosis and several other bone diseases in men and women. Merck’s patent on Fosamax will expire this year. As of February 2006, the FDA has approved the first generic versions of Fosamax. As a result, generic manufacturers, Teva and Barr, are now shipping their versions of alendronate to stores. Learn more about the drug’s composition here.
How the Body Eliminates Fosamax:
Most prescribed drugs do not remain in the body for more than a few hours to a few weeks. For example, analgesics do not remain for any more than 12 hours. Such is not the case with Fosamax, which can combine with bone and remain in its native state for at least 10 years and maybe for decades. Unlike the vast majority of other drugs, the body does not metabolize Fosamax; it either exits, unchanged, via the kidneys, or deposits, unchanged, in the bone.
The amount of Fosamax in the bone will accumulate with use, and there is no known method of removing Fosamax from the bones. Perhaps the most important thought to hold is that the duration of whatever effect the body might derive from Fosamax’s long residence in boney tissue is unknown. Even after a patient has discontinued taking Fosamax for five years, bone resorption formation markers remain suppressed.
Reportedly, Fosamax’s long half life and effects on bone physiology are not well advertized and are not well recognized as a result. It would be interesting to know how many doctors and patients are aware of Fosamax’s staying power.
How Fosamax Works:
Fosamax's interaction with bones and blood vessels in the body is fascinating. Bone is a living tissue, and contrary to popular belief, bone is not static, but it goes through a continuous remodeling process. During the remodeling process, cells called osteoclasts take old bone away and cells called osteoblasts create and deposit new bone. This constant interplay of resorption and deposit is called coupling. When some force interferes with coupling, diseases like osteoporosis may occur.
Fosamax is a member of the amino-bisphosphonate family of substances well known for being able to stop osteoclasts from resorbing, or taking away, bone. While bone naturally remodels using the coupling effect referred to above, if a patient takes Fosamax, that prescription interferes with the osteoclastic part of the coupling process. Osteoblastic bone formation actually follows osteoclastic bone resorption (the two processes need each other to form new bone properly). Therefore, Fosamax’s inhibition of bone resorption also results in the inhibition of bone formation. Studies have shown that the Fosamax can suppress the bone forming surface by 60% to 90% with usual dosages.
That means that Fosamax is not anabolic, and bone volume does not increase. However, bone mass measurements have shown that bone density increases because the bone is no longer remodeling, and is no longer creating any new bone. Instead, the older bone remains behind and that older bone is denser than newer bone would have been. The increase occurs because there is less water and more mineral in older bone. Since osteoporosis takes minerals away from bone, Fosamax causes the accumulation of more fortified bone and it slows down the creation of less mineralized new bone, improving overall bone strength. Fortunately Parathyroid hormone can reverse part of this growth suppressive response, but once Fosamax intertwines itself with bone, there is no known way to separate it and remove it.
The jaws are made up of trabecular plates that are analogous to “scaffolding." When Fosamax deposits in bone its presence there reduces the chance that trabecular plates will perforate. If the trebeculae should perforate, a loss of mechanical signaling and a cascade of bone resorption would result. As the bone loses some of its trabecular structure, the remaining trebeculae become overly stressed, that stress increases the possibility of bone damage and it further stimulates bone turnover. However that turnover is not enough to replace all of the former trabecular structure, and the body's attempt to regenerate bone results in an overall bone decrease. Therefore, Fosamax should be able to improve bone strength. But how much Fosamax bone deposition is beneficial and how much is dangerous?
Potent inhibition of bone turnover can be harmful and scientists have not determined the optimal mineralization density for the human skeleton. Therefore, once Fosamax has worked to inhibit bone resorption a beneficial amount, there is no need for any further and possibly harmful inhibition. This is true because increased bone mineralization creates brittle bone that encourages fracture. In addition, scientists are concerned about micro cracks that often occur in bone as a result of daily activities. The body has a repair mechanism for these stress cracks.
Osteocytes detect micro cracks and initiate bone remodeling using coupling. If Fosamax is chemically combined with bone for decades, and continuously interfering with remodeling, osteoclasts cannot dissolve old bone and osteoblasts will not make new bone. As a result, micro damage will accumulate and eventually weaken the bone.
Recently, an article appeared in the Wall Street Journal entitled, Femur Fractures in Fosamax Patients. That article referred to a study from the Journal of Orthopaedic Trauma, which addressed Fosamax’s connection with micro damage, its interference with bone repair, and resulting bone fractures.
Fosamax and its Interaction with the Jaw:
Another recent study that appeared in the Lancet indicated that treatment in excess of 3.5 years with a bisphosphonate is a risk factor for osteonecrosis, which is an unexpected appearance of necrotic (dead) bone in the oral cavity. However, other side effects that are attributable to Fosamax may act synergistically to result in bone necrosis rather than bone fracture, and that side effect is the inhibition of angiogenesis.
Doctors are using bisphosphonates to treat patients with bone cancer, because these compounds inhibit bone resorption. And bisphosphonate's interference with angiogenesis works to "starve" and ultimately reduce tumors. However, a lack of blood source can cause other harmful effects. Interference with angiogenesis may be a factor in causing bone necrosis.
The jaws remodel bone more often than any other bones in the body. A good example is what occurs use braces to straighten teeth. Dentists literally move teeth in the jaw by using the action of osteoclasts and osteoblasts to remodel bone around tooth sockets, as dentists slowly move a patient’s teeth over time into alternate positions. As with any tissue generation and repair, bone regeneration requires an ample blood supply. And due to the abundance of bone trabeculation in the jaws, this regeneration requires an abundant supply of blood. However, bisphosphonates diminish the body’s ability to form new appended blood vessels.
When patients use of Fosamax to combat osteoporosis, that drug is also slowing down the formation of new blood vessels. In fact, one study showed that Fosamax interfered with angiogenesis, and this interference caused ulcers not to heal.
A paper entitled, Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue; A pilot study appeared in Dental Traumatology, and suggested the following:
“Presence of micro-abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo.”
Of course, there is yet no suggestion that an oral prescription of Fosamax prescribed for osteoporosis has the same immediate cause and effect as the preparation used in the study referred to above. However, the following is true: Fosamax has at least a 10 year half life; Fosamax interferes with bone regeneration; Fosamax interrupts blood vessel proliferation; and Fosamax interferes with the body’s ability to repair bone micro damage. Therefore, it seems highly likely that one or all of these Fosamax induced interferences could be responsible for bone necrosis of the jaw.