Bisphosphonates in multiple myeloma: a network meta-analysis

Multiple myeloma (MM) is a cancer of the plasma cells, a type of white blood cell generally responsible for the production of antibodies. In MM, collections of abnormal plasma cells accumulate in the bone marrow, interfering with the production of healthy cells. The most common symptoms of MM include renal dysfunction, infections and bone lesions. Severe back pain is also a common symptom. In the majority of patients, progressive bone damage caused by MM may lead to fractures of the long bones or compression fractures in the spine.

Bisphosphonates are a group of drugs that prevent loss of bone mass. They are used in the management of MM as supportive therapy, and treatments currently in use include etidronate, pamidronate, and zelodronate. There is uncertainty regarding their effectiveness in this role, particularly in comparing one type of bisphosphonate with another using clinical trial data.

In conducting this newly updated Cochrane Review, the authors incorporated findings from additional studies, and revised the conclusions accordingly. Four trials made direct comparisons between different drugs. In the remaining trials, the effects of the drugs were compared to those of placebos or no treatment and the researchers made indirect comparisons by combing the data from these trials. Head-to-head trials suggested that zoledronate was more effective at reducing fractures compared to etidronate, but taken together with the indirect comparisons, the researchers conclude that no one drug can be regarded as superior.

“Whether zoledronate is superior to any other bisphosphonate drug remains an open question,” said lead researcher Ambuj Kumar of the Center for Evidence Based Medicine and Health Outcomes Research at the University of South Florida, in Tampa, Florida. “In light of the inconsistencies we see in the data, it is difficult to recommend any drug as a preferential treatment for clinical practice.”

The researchers analysed data from a total of 20 trials involving 6,692 participants who took bisphosphonate drugs in addition to their myeloma treatments. Bisphosphonates reduced the occurrence of fractures and pain. For all types of fractures, the researchers estimated that between six and 15 patients would need to be treated to prevent fractures in one patient. For pain, between five and 13 patients would need to be treated to reduce pain in one patient.