International panel of experts releases first consistent guidelines for protecting bone health of childhood cancer survivors
August 20, 2021
By Kristi Birch
Children and teenagers who survive cancer can have problems with their bone health later in life because cancer treatments such as radiation and chemotherapy can reduce bone mineral density (BMD). A panel of clinical experts from around the world, including a member from the University of Kansas Medical Center, has created the first set of consistent recommendations for evaluating and protecting the bone health of these survivors.
The guidelines were published July 30 in The Lancet by the panel, which included 36 experts from 10 countries. This subgroup from the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) was formed specifically to advise the long-term follow-up of young cancer survivors.
"We need to look at the long-term ramifications to the overall health of pediatric and adolescent cancer survivors, because it's more than just quantity or length of life, it's also quality of life," said Kimberly J. Templeton, MD, professor of orthopedic surgery at the University of Kansas Medical Center and one of two orthopedic surgeons—and the only one from the U.S.—on the IGHG panel.
Longer lives, more need for guidelines
Survivors of cancer are prone to low bone mineral density because of the toll that their cancer treatments take on their bodies, but BMD also can be brought about by the cancer itself as well as a sedentary lifestyle or secondary problems in the endocrine system.
Low BMD makes the 206 bones in the human body more brittle and likely to break. This can be especially consequential for children with cancer, who are developing bone at the same time they are undergoing cancer treatment. As a result, these fragile bones can be fractured with low impact when the cancer survivor is still relatively young. The fractures cause pain, reduce mobility and can interfere with school, work or other activities.
New and better cancer treatments devised over the past 50 years have meant that more young people are surviving their cancers. And while that's great progress, it means that even more young people are susceptible to the quality-of-life issues that arise from being a survivor, such as low BMD and related fractures.
"This is such important work. For physicians, guidelines such as these help us make informed decisions with our patients on understanding their individual risks and outlining a plan for their care," said Becky Lowry, M.D., associate professor of internal medicine at KU Medical Center and medical director of the University of Kansas Cancer Center Survivorship Transition Clinic, one of less than a dozen clinics in the country that specializes in the long-term effects of childhood cancer treatment. "These are the types of conversations we have every day in our survivorship clinic but also conversations patients can have with their primary care provider."
Building a consensus
The IGHG, which formed in 2010 to guide the long-term follow-up of childhood, adolescent and young adult cancer survivors, created the bone health subgroup three years ago. This panel, which represents a range of clinical specialties, was tasked with creating recommendations explicitly for the surveillance of BMD.
"Low bone mineral density in this age group means they are at higher risk for low-impact fractures at an earlier age," said Templeton. "Moreover, they are undergoing treatment for their cancers at the time when they should be achieving peak bone mass, which people reach by the time they are 30. The greatest accumulation of bone mass is during the teens, when a lot of these kids are being treated."
Templeton was asked to be on the panel in part as a result of a presentation she gave at a meeting of SWOG (formerly the Southwest Oncology Group) Cancer Research Network, an NCI-supported organization, about the current evidence regarding bone health in survivors of childhood sarcoma, a disease of bone and soft tissue. The data are scarce, which is not uncommon, she said: "Given the relative rarity of sarcomas, the data we have is usually from a single institution. There is more data regarding patients with hematologic malignancies, like leukemia, which are much more common than sarcomas, but even with that, there was previously no consensus on a bone health protocol."
As part of the panel for BMD, Templeton and the other experts spent three years systematically analyzing available data and the literature to establish evidence-based risk factors for low BMD and fractures for childhood cancer survivors. They evaluated the quality of the evidence they summarized using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and used the GRADE Evidence-to-Decision framework to formulate recommendations for the best ways to test for and monitor BMD in these patients and then treat them.
Risk factors for low BMD
The panel identified these as the main treatment-related risk factors for low or very low BMD:
- craniospinal radiation therapy
- total body irradiation
- abdominal/pelvic irradiation
Other risk factors included:
- hypogonadism, a well-established cause of bone loss and a condition that can be caused by cancer treatments
- growth hormone and sex hormone deficiencies that can be caused by cancer treatment
- low body mass or being underweight
- a diet lacking in calcium and vitamin D
- lifestyle factors such as smoking and not getting enough exercise.
- White race
Being male was also found to be a risk factor. "This is likely because they are achieving peak bone mass later because boys mature later," said Templeton. "So if you're treating a 10-year-old boy versus a 10-year-old girl, the girl has achieved more bone mass already than the boy, and you may be interrupting more of the boy's bone mass development." Definitive sex-based differences in this area were not identified, however, and the study authors cited the need for more research.
Surveillance guidelines for BMD in survivors
The panel made following recommendations for testing and monitoring BMD:
- Using dual-energy X-ray absorptiometry scans, commonly known as DEXA scans. Quantitative CT (computed tomography) scans are not recommended.
- This surveillance should begin between two to five years after cancer therapy is completed.
- If the test is normal (Z-score greater than -1), then surveillance should be repeated at 25 years of age, around the time when peak bone mass should be reached, and then done as clinically indicated based on the results and risk assessment.
If the testing indicates abnormalities, these panel establish:
- For survivors with very low bone mineral density (Z-scores of -2 or lower), the panel recommends consulting a bone health specialist for more evaluation, treatment and follow-up.
- For those with Z-scores between -1 and -2, they also recommended a referral to a bone health specialist for further evaluation and interpretation of findings, and then monitoring BMD by repeating the scans every two years.
Because of insufficient evidence, the panel was unable to make recommendations about surveillance for survivors treated with corticosteroids, and, ironically, for patients who had sarcomas, Templeton's initial interest. The panel expects the guidelines will provide a framework for future research to address these gaps in recommendations.
"Where this paper could hopefully have an impact is not necessarily among the oncology community, and not necessarily among the pediatric community, but among those who take care of cancer survivors who are young adults or adults," said Templeton. "We're looking at the challenging issue of transitioning care from a pediatric focus to an adult focus and making sure that those that are treating these patients as adults understand what they went through earlier on in their lives, and that their cancer or its treatment could have lifelong consequences."