Bone Lesions and Damage
Bone lesions from multiple myeloma are the primary cause of bone pain, which is one of the most common symptoms of multiple myeloma. Bone lesions result in destruction of the bones in myeloma patients and primarily affecting the spine, pelvis or rib cage. In the majority of patients with myeloma, soft spots develop where the bone structure has been damaged. These can extend from the inner bone marrow to the outside surface of the bone. Soft spots appear as “holes” on a standard bone x-ray and are referred to as osteolytic lesions. These bone lesions weaken the bone, causing pain and increasing the risk of fractures. Bone loss frequently accompanies multiple myeloma, and 85% of patients diagnosed with multiple myeloma have some degree of bone loss.
Causes of bone destruction in myeloma
Normally, osteoclasts function with bone-forming cells called osteoblasts to rebuild areas of bone that are wearing out (fatigued). This process is called bone remodeling and healthy bone is continually being remodeled.
Bone destruction by osteolytic lesions is caused by two separate events. Rapid growth of myeloma cells inhibits normal bone-forming cells, damaging bone. In addition, production of substances that activate the cells that resorb bone, called osteoclasts, is increased. Osteoclasts normally break down old or worn out bone and work with bone-forming cells to repair bone. In the case of multiple myeloma, however, the increased activity of osteoclasts causes bone loss with concomitant loss of bone repair and growth from the suppression of bone formation.
Bone cell activity in myeloma
Normally, the activity of the osteoclasts and osteoblasts is well balanced – the osteoclasts clear out the fatigued bone and the osteoblasts begin the rebuilding of new bone. In patients with multiple myeloma, bone resorption by the osteoclasts is increased and exceeds bone reformation. Calcium lost from the bones appears in increasing amounts in the patient’s serum and urine. This increase in bone resorption may result in pain, bone fractures, spinal cord compression, and hypercalcemia.
In myeloma there is an increase in osteoclast activity that is caused by factors called osteoclastic activating factors or OAFs. These osteoclastic activating factors are known to be released by tumor cells.
The bone marrow microenvironment and its role in bone resorption
The bone marrow microenvironment is the area within the bone (the marrow) where stem cells develop into blood cells and the cells of the immune system. In multiple myeloma, the bone marrow microenvironment is the area where the malignant plasma cells develop and grow. An important and promising area of myeloma research is the investigation of ways to make the bone marrow microenvironment less hospitable to myeloma cells.
The bone marrow microenvironment plays an important role in the increased bone resorption that occurs in myeloma.