People with multiple myeloma and its precursor conditions may be at risk for bone fractures and osteoporosis, found a review published in the journal Joint Bone Spine in March.

For those with multiple myeloma, this increased risk of osteoporosis means higher risk of fractures even in places in the bone that do not have cancerous cells. For those with monoclonal gammopathy of undetermined significance (MGUS), a blood disorder characterized by a high level of monoclonal protein, or those with smoldering multiple myeloma, their disease-caused osteoporosis may be an early sign of progression to cancer. Bisphosphonate therapy may help, but it has its limitations. (Smoldering myeloma is also known as asymptomatic myeloma.)

Osteolytic lesions, or small areas of bone damage, are already a well-known symptom of multiple myeloma. This review found that several studies show that people with multiple myeloma also have general loss of bone density. Women and people with IgA-type multiple myeloma are more often affected.

This loss of bone density can lead to fractures in healthy bone that does not have cancerous cells. One study of 165 people with multiple myeloma found that myeloma patients are nine times more likely to experience bone fractures than the general population. One-third of those fractures occurred in places in the bone that did not have myeloma cells.

People with MGUS also show bone density loss and bone fractures. MGUS is a precursor condition to multiple myeloma in which patients do not have osteolytic lesions or other myeloma symptoms. However, the review covered research that shows people with MGUS may still be at an increased risk for osteoporosis.

In one study of 65 women with MGUS, 35 of the study participants had osteopenia, or bone density loss that is not as severe as osteoporosis, and 17 had osteoporosis. More than half of the study participants had at least one fracture in the spine, compared to less than a quarter of post-menopausal women who do not have MGUS.

Another study of 488 men and women with MGUS found that compared to the general population, the study participants were 2.7 times more likely to experience a fracture in the spine. Older participants, participants who had MGUS longer, and participants who had taken corticosteroid drugs such as prednisone were at the greater risk for fractures.

Bone loss in MGUS may be an early sign of progression to multiple myeloma, the review found. It cited a study of 87 people with MGUS where bone breakdown was “significantly associated” with progression to multiple myeloma. However, it may be difficult to use this information to develop prognoses for patients, because it is not easy to see the breakdown in small bone biopsy samples.

To treat bone problems in multiple myeloma, doctors use bisphosphonate drugs, which decrease bone breakdown, osteolytic fractures, and bone pain. The review found that bisphosphonate therapy may also help increase bone mass and prevent fractures in people with MGUS. In smoldering multiple myeloma, another multiple myeloma precondition that is more advanced than MGUS, bisphosphonate therapy reduced the number of bone fractures in study participants.

However, the treatment did not reduce the amount of abnormal protein or plasma cells in people with smoldering multiple myeloma. Bisphosphonate treatment also did not help prolong or prevent the progression to multiple myeloma in people with either MGUS or smoldering multiple myeloma.

New research is increasingly linking multiple myeloma and its precursor conditions to general bone loss and fractures. This new information may impact how prognoses are developed and how precursor conditions are treated. The scientists who published this new review suggested that researchers further study what factors contribute to bone loss and how bone loss might be used to predict who will develop multiple myeloma from a precursor condition.

For more information, please see the related article in Joint Bone Spine (abstract).