May 04, 2015
During the past two decades, there has been an increase in the number of long-term survivors of autologous and allogeneic hematopoietic stem-cell transplantations (HSCT). For patients, surviving long-term after HSCT means experiencing a greater number of down the road, late effects of treatment. One of these late effects of HSCT is bone loss, which can lead to osteoporosis, fractures, and loss of quality of life. But while bone loss is well-established as a known late effect among patients who receive HSCT, little is known about how often these patients experience fractures, a condition that stems from bone loss and can lead to pain, loss of function, and death.
Now, a study in the Journal of Clinical Oncology (JCO), “Increased Incidence of Fractures in Recipients of Hematopoietic Stem-Cell Transplantation,” published online, ahead of print, March 16, 2015, is among the first to quantify the incidence of fractures among survivors of HSCT and to compare the rate of fractures to that of the general U.S. population. The study, which used data from the charts of 7,620 patients who had undergone HSCT from 1997 to 2011 at the University of Texas MD Anderson Cancer Center, found that 8% of patients who received HSCT experienced fractures, and that this risk was significantly higher than in the general population. Specifically, among 45 to 64 year olds, the risk of fracture was eight times greater among women and seven to nine times greater among men, compared to the general population. In addition, the study found that both men and women who received HSCT fractured at similar rates; in contrast, in the general population, women experience a higher rate of fractures.
The study’s data on the incidence of fractures in the general U.S. population was gathered from the 1994 National Health Interview Survey and the 2004 National Hospital Discharge Survey.The study's first author is Xerxes N. Pundole, MD, MPH, a doctoral student in Epidemiology at the school of Public health of the University of Texas.
‘We . . . see those patients fracture and how they suffer’
Study coauthor Huifang Lu, MD, explained that part of the motivation for the study came from doctors firsthand witnessing of patients’ pain. “Bone loss, as a late effect, has been gaining momentum—we’re seeing more publications about patients losing bone. And in clinic, we actually see those patients’ fractures and how they suffer from pain and other comorbidities that accompany fractures.”
Survivors of HSCT can experience rapid bone mineral density loss within six months after treatment, and while some parts of the body, such as the spine, can recover some bone density over time, other parts of the body may never reach baseline levels.
According to Dr. Lu, several factors might explain why patients who receive HSCT are at greater risk for fractures. “To make sure patients do not reject the transplanted stem cells, many receive immunosuppressive medication such as glucocorticoid, which is well known to be associated with fractures.” Additional risk factors may include chemotherapy, low vitamin D and calcium intake, and other factors associated with cancer and its treatment.
Comprehensive risk assessment tool for fractures
Dr. Lu said that knowing the rate of fractures among patients who receive HSCT is the first step to understanding the risk factors underlying those fractures—and thus helping doctors identify which patients could benefit from early preventive measures.
“The best medicine is probably preventive medicine, and for now, for patients who received HSCT, we don’t have a clear idea of when to screen patients and when to treat them for fractures,” said Dr. Lu. To find out more, Dr. Lu and her colleagues are carrying out a study looking into a comprehensive risk assessment tool for fractures in this population. “This will help us identify patients who are at risk, based on factors such as lifestyle, underlying malignancies, and medications received after stem cell transplant,” said Dr. Lu.
Until that risk assessment tool is available, Dr. Lu recommends that all patients who receive stem cell transplants should be considered as high risk for fractures and should receive a bone mineral density study at baseline and six months after transplant.
“Right now we’re using bone mineral density study as a surrogate marker for potential future fractures, which is what we do in post-menopausal situations. However, some studies have shown that patients with normal bone mineral density also fracture and this needs to be studied further,” said Dr. Lu. “Currently we would like to see all patients receiving counselling on general preventive measures for bone health, for example, education on physical exercise as simple as walking, diets with calcium, and vitamin D supplements. In addition, pharmacological interventions should be considered when appropriate.”
Huifang Lu, MD, is a Rheumatologist at the University of Texas, MD Anderson Center.
Xerxes Pundole, MD, MPH, is a doctoral student in Epidemiology at the school of Public health of the University of Texas. He has been an ASCO memeber since 2014.
Abstract of the original JCO article.
PDF of the original JCO article.
Pundole XN, Barbo AG, Lin H, et al. Increased incidence of fractures in recipients of hematopoietic stem-cell transplantation. J Clin Oncol. Epub 2015 March 16.
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@ 2014 American Society of Clinical Oncology