How are our bones structured? How do ONJ problem occur?
June 5, 2006 21:20

Bone is a physical structure shaped like a honey-comb . That is, our bones are not "solid" all the way through. Like a honey-comb, the bone is comprised of "chambers" which are occupied by living cells. These living cells, just like all cells in our bodies, require blood flow (oxygen, nutrients) to stay healthy. The bone cells, that occupy the bone matrix chamber, when mature, form a hard calcium (and other mineral) structure around them. The mature bone cells are known as osteocytes.

What is the life span of an Osteocyte? How do bisphosphonates promote ONJ — jaw bone necrosis?
June 7, 2006 21:23

An osteocyte cell (the mature cell inside the bone) has a normal life of 150 days. Therefore, after 150 days, the cell must be replaced with a new cell. The osteoclast cells attach to the outside of the "chamber" and soften the wall of the chamber. This allows the old dying osteocyte cell to escape from the boney calcium matrix and for a new osteoblast (immature osteocyte) cell to penetrate the chamber. As the saying goes, "Out with the old and in with the new." The osteoblast then matures, hardens up the chamber with new calcium and minerals, and lives there for the next 150 days, when the process starts all over again.

When do we lose bone? Can Fosamax help? How can Fosamax cause harm?
June 9, 2006 21:24

An example of problems that occur naturally as we age is the condition of Osteoporosis. This can occur when the body's production of osteoblasts can not keep up with the demand for new bone. Conditions like osteoporosis can also be caused by taking other prescription drugs, such as the birth control Depo Provera, which is known to reduce bone mass density.

Bisphosphonates also treat hypercalcemia (which is accompanied by tumors 20% of the time). Calcium enters through the small intestine and is excreted by the kidney as described above, within a feedback loop. In the case of hypercalcemia, normal calcium regulation system becomes overwhelmed by an excess of PTH, calcitriol, some other serum factor that can mimic a huge calcium load. The result is that the body has too much calcium in the blood flow. To reduce this, the bisphosphonate retards the osteoclast production - and the calcium simply stays in the bone matrix.

What can go wrong? The problems occur when the any of these three types of cells begin to operate out of balance with the others. For example, in the case of certain cancerous tumors, the body is stimulated into producing more osteoclast cells. This causes the softening of the "body armor" that surrounds the osteocytes - the stuff that makes up the hard calcium part of our bone. When the bone is softened by the osteoclasts, openings in the bone matrix are created. The cancer cells use these openings to penetrate and metastasize into the bones.