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Summer 1994 Volume 1, Issue 7:
Myeloma Is Also A Bone Disease: A Primer For Patients And Their Doctors
By Francesca M. Thompson MD
Patients suffer greatly from bone disease in myeloma; in general hematologists and oncologists concentrate on the treatment of the malignant cells and are unaware of the concept of protecting your bones, in other words, doing all that can be done to keep the bone you have.


Let's start with normal, healthy bone. This is a living tissue that is continually engaged in deconstruction and rebuilding activity in a balance that we call bone turnover. The deconstructors are cells called osteoclasts, which burrow into bone like little termites, dissolving the mineralized bone (the hard stuff). This is good in normal bone because you have to get rid of old bone to have someplace to put the new bone. The new bone is laid down by the rebuilders, cells called osteoblasts. Actually, they do not make the hard stuff, mineralized bone, rather they elaborate protein material called osteoid on the scaffolding of the bone already there which later petrifies because of the chemical environment in which it lives; in other words, it becomes mineralized.

In young adults the deconstruction and rebuilding are in perfect balance so that no bone is lost; after age 25 or 30 years, a little more is lost than is put back, and this trend continues through the decades. In post menopausal women this tendency is exaggerated and they wind up at the end of normal life with less bone than men. Older men generally lose bone at the same rate as elderly women, but they start this loss later and with more bone than women.

The synchrony of matching the amount of rebuilding with the amount of deconstruction is called coupling, or teaming up of osteoclasts with osteoblasts in what are essentially work crews, or bone remodeling units. The exact ways in which this occurs is the subject of much intense research activity.


There is a natural progression of untreated myeloma-associated bone disease. It starts with an uncoupling of the bone remodeling units, so that the osteoclasts show up for the work crew but their cohorts, the osteoblasts, are on strike. The malignant plasma cell of myeloma is probably the culprit here because it produces a protein called interleukin-6 (IL-6) which turns osteoclasts into a frenzy of bone destruction, i.e. they become activated; some think IL-6 shuts down osteoblasts. As if that isn't enough, activated osteoclasts themselves produce more IL-6. On top of that, the malignant plasma cell is stimulated by IL-6 to pump up and produce more IL-6, which in turn revs up the osteoclasts -- a vicious circle. Thus the malignant plasma cell is affected by IL-6 from two sources: an autocrine source (the IL-6 it makes itself) and a paracrine source (the IL-6 made next door by the osteoclasts).

The first result is osteopenia, which means loss of mineralized bone in general, but this particularly occurs in bone where there is more marrow, because that is where most of the plasma cells live. Osteopenia, a more generalized term than osteoporosis, is impossible to detect on regular x-rays in its early stages. The rule of thumb is that half of the mineral content of bone (the hard stuff) has to be lost before it is noticeable on x-ray. (More sensitive tests are now available which I will discuss later.) Because this occurs in bone with more marrow, the second result often is vertebral compression fractures and rib fractures as the first sign of something gone awry with the bone. Many myeloma patients are first diagnosed at this juncture.

The third result is called lytic bone disease, and is the stage from which multiple myeloma derives its name, in that it involves many little holes in the bone. How does this happen? The process is the same as described above, namely uncoupling of osteoclasts and osteoblasts, the slowing down of osteoblasts, and the extreme speed-up of osteoclasts, all puddled in the same area of bone, excavating a big hole in the bone which fills up with blood and millions of plasma cells. When this hole gets very big, say the size of an orange, it is called a plasmacytoma, or tumor of plasma cells. This can happen all over the skeleton, but some favorite places are the skull, the spine, and the pelvis. The skull can show many so-called "punched out" lesions, as if someone had dotted the skull with a hole puncher. The vertebral bodies can have major holes in the structural parts, and wind up collapsing in a lopsided or major way, much more than the little squish of the more routine vertebral stress fracture caused by osteopenia discussed above. Sometimes the collapse distorts the shape of the spinal canal enough to cause pressure or blockage on the spinal cord or nerves, leading to paralysis as well as pain. Another problem caused by the pain of vertebral fractures is that it hurts so much to move that patients are bedridden; this immobilization speeds the resorption of bone even more.

Although much of the marrow exists in the axial skeleton (i.e. the spine, the skull, the pelvis, and the ribs), and we see much myeloma bone disease in the axial skeleton, the long bones can be afflicted also. Because the limbs are appendages off the trunk, their bones are called the appendicular skeleton. The thigh bone, or femur, has a fair amount of marrow, and is subject to much stress in weight-bearing. Pathologic fractures can be expected when lytic lesions occur in the hard outer core of the long bone, the cortical diameter. When 50% or more of the cortical bone is lost, or when there is an "open-section" effect in which less than 50% of the diameter of the bone is eroded along a length that exceeds 75% of the diameter of the bone, a stress-riser, or weak point, is created. This decreases the torsional strength of the bone by more than 90%, leading to pathologic fracture from a seemingly minor postural adjustment.

When the osteoclasts chew up bone, calcium is released into the bloodstream. Eventually a point can be reached when the kidneys cannot excrete enough, and the blood level, or serum level, of calcium rises above normal. This is called hypercalcemia, or too much calcium in the blood. This is a lethal condition, and if it cannot be corrected, can cause death quite rapidly.


The occurrence of myeloma bone disease does not "just happen". By the time the patient is aware of a bone problem, much bone has been lost forever. It makes sense to do everything possible to avoid as many of these complications as possible. While there is no evidence at all that controlling bone disease will prolong overall survival, there are also no long term studies that show that it won't. Nevertheless, most patients suffer pain and decreased mobility caused by myeloma bone disease. There can be no doubt that spending one's remaining years without painful rib fractures, without the loss of several inches of spine from vertebral crush fractures, without a long bone fracture and the radiation and surgery that may be required is better than suffering these complications of an already harsh disease.

The above is an excerpt from the article which appeared in MYELOMA TODAY. Remaining sections dealing with treatment possibilities are outlined below{}

-Imaging Studies
-Estrogen Replacement Therapy
-Calcium and Vitamin D
-What Steroids Do to Bone
-Osteoclast Inhibitors
-Can We Make Bone Form Faster?

For the full text of this article, please contact the IMF.

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