A randomised trial investigating an exercise programme to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukaemia

Abstract

Because the survival rate of acute lymphoblastic leukemia (ALL) has improved, preventing side effects of chemotherapy has become increasingly important. Several studies have shown that motor performance, peripheral muscle strength and passive ankle dorsiflexion in children treated for ALL was impaired during treatment and also after cessation of chemotherapy [1–4]. These problems were mainly attributed to vincristine-induced neuropathy. Moreover, treatment protocols for ALL contain a considerable amount of prednisone and/or dexamethasone. This may cause steroid-associated myopathy with weakness of proximal musculature and muscle atrophy leading to a decreased lean body mass (LBM) [5]. In addition, corticosteroids and methotrexate (MTX) are known to cause reduction of bone mineral density (BMD). Several studies have shown that BMD is already lower at diagnosis of ALL and decreases further during the 2-year treatment period [6,7]. Although a decreased BMD is unlikely to affect motor performance directly, it is associated with an increased fracture risk [8]. Studies investigating BMD in long-term survivors of childhood ALL show conflicting results [9–13]. In general, BMD of patients treated without cranial irradiation shows a tendency to improve after cessation of therapy [8,14]. Several animal studies in which mechanical loads were applied showed that the crucial factor in stimulation of bone acquisition is the magnitude rather than the number of repetitions of the load applied [15,16]. Therefore, shortburst high-intensity activities might be effective to enhance BMD during childhood [17–21]. However, no studies have been performed to investigate this effect of exercise on BMD during treatment of childhood ALL. Because vincristine-related neuropathy causes weakness in the dorsiflexors of the foot, children are at risk for developing a plantigrade contracture of the ankle. Wright et al. [22] found positive effects of preventative education and physiotherapy consisting of stretching and strengthening exercises on passive ankle dorsiflexion during treatment for ALL. Another study reported positive effects of physical exercises on ankle dorsiflexion mobility and strength of knee extensors, but no improved functional outcome was found [23]. In the current prospective randomized study in childhood ALL we investigated whether an exercise program starting at onset and continued during 2-year treatment for ALL has a beneficial effect on BMD, body composition, motor performance and passive ankle dorsiflexion.