IOF Offers Bone Health 'Blueprint' for Child Cancer Survivors

Pam Harrison

July 11, 2019

Childhood cancer survivors are at high risk for worsening bone health as they enter adulthood and should be carefully monitored for signs of skeletal deterioration once they enter long-term follow-up care, according to a new cornerstone recommendation from the International Osteoporosis Foundation (IOF) cancer and bone working group.

"In children and adolescents treated for cancer, the attainment of peak bone mass — which is a fundamental factor affecting bone mass in adulthood — can be negatively affected," Maria-Luisa Brandi, MD, PhD, head, bone metabolic disease unit, University of Florence in Italy and lead author of the new guideline, said in an IOF statement.

"That is why the bone health of children and adolescents with a cancer history should be carefully monitored and patients should be informed of possible late complications of their previous medical treatment," she added.

The guideline was published in the June issue of the Annals of Oncology.

Of Children With Cancer, 80% Now Survive

Over the past few decades, increasing numbers of children are triumphing over cancer, with a 5-year survival rate now approaching 80%.

However, as the guideline authors point out, "all cancer therapies can decrease bone mineral density (BMD) through long-term endocrine alterations such as gonadal dysfunction, growth hormone deficiency, and altered body composition."

Moreover, children undergoing cancer treatment are at risk for nutritional deficiency and low levels of physical activity, both of which can compromise bone mass and quality, the authors add.

Recommendations regarding bone health in childhood cancer survivors were thus thought to be important in order to better preserve and maintain bone mass and quality into adulthood.

Series of Recommendations: BMD Scans at Pediatric Centers, Vit D

Having reviewed the literature, available guidelines, and their own experience with children who have survived cancer, the working group proposed a series of recommendations for clinicians concerned about the optimal management of bone health in childhood cancer survivors.

Their first recommendation is to evaluate BMD on baseline entry into long-term follow-up care, usually about 2 years after cancer treatment is finished.

"We recommend the use of DEXA at the spine and femur, based on age, to diagnose and monitor BMD changes in these patients," the authors say.

They also recommend that BMD evaluations in young patients be carried out at specialized centers capable of interpreting pediatric scans.

It is also important to assess laboratory measures of bone metabolism, renal function, and factors associated with secondary osteoporosis.

And as vitamin D [25-hydroxyvitamin D] deficiency and inadequate calcium intake are common in children affected by cancer, "they may benefit from adequate dietary intake/supplementation of calcium and vitamin D," the authors explain.

In addition, weight-bearing physical activity promotes BMD growth in children and its maintenance in adults, and regular physical activity is highly recommended for childhood cancer survivors provided they are able to manage it.

Don't Use Growth Hormone in Childhood Cancer Survivors

The authors remain unconvinced that growth hormone replacement should be considered in children whose growth hormonal axis has been disrupted by cancer treatment, however.

Given the burden of multiple injections necessitated by this treatment and possible long-term harm, "the benefits to prevent or treat osteoporosis outside of hormone replacement for growth hormone deficiency do not justify its risks and costs," they caution.

They also warn that clinicians should be aware that gonadotoxic treatments increase the risk of both premature ovarian insufficiency and testosterone deficiency and that these effects may negatively affect future fertility.

Bisphosphonates Can Be Used but Not Denosumab

"Overall, evidence is limited for recommending bone-specific drugs such as bisphosphonates in young adults with secondary osteoporosis," the authors state.

There are no data supporting either the optimal dosing or duration of bisphosphonate treatment in young adults, for example.

Given intravenously, the bisphosphonates can also cause an acute-phase reaction as well as gastrointestinal side effects if taken orally.

Nevertheless, if childhood cancer survivors have either low BMD or fragility fractures, "the use of bisphosphonates can be envisioned," the working group suggests, and used according to long-term guidelines.

Data on the use of denosumab (Prolia, Amgen) in children are also limited, although there is some evidence that the drug does increase BMD in children.

But because the evidence is so scant, the working group suggests that further studies are needed before denosumab can be considered for a childhood cancer survivor population.

Similarly, teripartatide (Forteo, Eli Lilly) has a black box warning against its use in children because of an increased risk of osteosarcoma in the pediatric population.

Lastly, childhood cancer survivors are at increased risk of developing avascular osteonecrosis of bone — a devastating complication in children undergoing antileukemia treatment in particular.

Again, however, because there is no consensus on how to manage osteonecrosis in pediatric patients, further research is needed.

"Cancer treatments in youth have a multifactorial impact on bone fragility and a core objective, both during treatment and once the patient is in remission or cured, is to reduce the impact on future adult bone health," notes Rene Rizzoli, MD, PhD, chair of the working group.

"As clinicians, we must work together to help to maintain and protect our young patients' skeletal health," he concludes.

Brandi has reported serving as a consultant for Alexion, Bruno Farmaceutici, Shire, Servier, and Kyowa Kirin. She has received academic grants and/or speaker fees from Abiogen, Alexion, Amgen, Bruno Farmaceutici, Eli Lilly, Kyowa Kirin, MSD, NPS, Servier, Shire, and SPA, and honoraria from Amgen, Bruno Farmaceutici, and Kyowa Kirin.

Ann Oncol. 2019;30:908-920. Full text

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