Low Bone Mineral Density in Survivors of Childhood ALL

Children with acute lymphoblastic leukemia (ALL) who survive into young adulthood are at increased risk for low bone mineral density (BMD). A study by Inas H. Thomas, MD, pediatric endocrine fellow at the University of Michigan Medical Center in Ann Arbor, followed patients for an average of 24 years after diagnosis. Using dual energy x-ray absorptiometry (DEXA), Dr. Thomas found a much higher rate of low BMD than expected in 74 randomly selected patients.

“Before the 1970s, the survival rate for ALL was very low, but now we are fortunate that the majority of our patients are surviving into adulthood,” Dr. Thomas said. “Bone health has only recently started to become a concern, and we are just beginning to screen for osteopenia or osteoporosis.”

In addition to DEXA, Dr. Thomas conducted growth hormone (GH)-releasing hormone-arginine stimulation testing to evaluate peak GH level and evaluated insulin-like growth factor I (IGF-I) and other markers of endocrine function in relation to BMD. Of the 74 patients evaluated, 24% had low BMD; 1 patient had osteoporosis. Men were more likely to have low BMD, which strongly correlated to short stature. GH insufficiency, low IGF-I score, and current smoking were all found to be significant risk factors for reduced BMD in this cohort.

“Multiple studies have argued for and against low BMD being a problem for these survivors,” said Dr. Thomas. “We think that it is a significant issue, since 24% of our participants had osteopenia or osteoporosis. This was much higher, especially in men, than we expected, based on World Health Organization statistics.”

She said the study results stress the importance of monitoring bone health in ALL survivors. Simple treatments such as vitamin D or calcium supplementation may be warranted in those at risk. For those with more serious bone problems, a referral to an endocrinologist for more aggressive medications may be needed.

“If an adult survivor has growth hormone deficiency or has a history of childhood growth hormone deficiency, it should be a red flag that bone health could be a potential problem,” Dr. Thomas said. “IGF-I, which is easier to screen for than growth hormone, was also lower in those with a low BMD,” she added.

As patients age, they have an increased risk for osteopenia and osteoporosis. Dr. Thomas believes patients need to be screened more than once, but said further studies are needed to determine how often. “The major concern about osteopenia or osteoporosis is that it can potentially lead to fractures,” she explained. “However, we did not look at the risk of fracture in these patients. It will be interesting to see what happens as these young adults age.”

Willis Navarro, MD, medical director of transplant services at the National Donor Marrow Program in Minneapolis, Minnesota, said this study highlights something he feels is underappreciated for this patient population. “Although the incidence of frank osteoporosis was quite low, we don’t know if these folks will end up having earlier issues with bone fractures and other bone-related occurrences,” he said. “This study, however, only focuses on bone density and it doesn’t really provide any measure of long-term critical outcomes.”

Dr. Navarro said that based on the incidence of low BMD observed in patients of both genders, he does not feel it is unreasonable to conduct one-time BMD screening in this population, even clear indication of clinical risk is lacking. “Will someone who is in their mid-30s and with a low BMD measurement be at increased risk for fractures in their 60s?” Dr. Navarro asked. “We don’t know yet, because the lead cohort of ALL survivors hasn’t reached that age.” He noted, however, that the study clearly demonstrates something is going on with bone density in this group of patients that differs from young adults in the general population. “That alone,” he said, “would warrant taking at least one look [at evaluating BMD] even at younger ages.”

Cancer.

Thomas IH, et al. Bone mineral density in young adult survivors of acute lymphoblastic leukemia. 2008;113:3248-3256.