The attention to treatment-related toxicity has increased since the survival of children with
acute lymphoblastic leukemia (ALL) has improved significantly over the past few decades. Intensive ALL treatment schedules including
corticosteroids and
asparaginase have been shown to give rise to skeletal abnormalities such as
osteonecrosis and
low bone mineral density (BMD), which may lead to debilitating sequelae in survivors. Although
osteonecrosis and low BMD are different entities with suggested separate pathophysiological mechanisms, recent studies indicate that
osteonecrosis is associated with accelerated BMD decline. Common underlying mechanisms for
osteonecrosis and BMD decline are considered, such as an enhanced sensitivity to
corticosteroids in children who suffer from both
osteonecrosis and low BMD. In addition, restriction of weight-bearing activities, which is generally advised in patients with
osteonecrosis, could aggravate BMD decline. This induces a clinical dilemma, since bone stimulation is important to maintain BMD but alternative interventions for
osteonecrosis are limited. Furthermore, this recent finding of accelerated BMD decline in children with
osteonecrosis emphasizes the need to develop effective preventive measures for
osteonecrosis, which may include targeting BMD decline.