Prospective bone ultrasound patterns during childhood acute lymphoblastic leukemia treatment.
OBJECTIVE
Bone impairment is a well-known complication in childhood acute lymphoblastic leukemia (ALL) survivors but less is known about bone dynamics during ALL therapy. We longitudinally assessed by Quantitative Ultrasound (QUS) skeletal modifications during this treatment.


METHODS
Forty-four newly diagnosed ALL children underwent bone measurement by QUS parameters BTT (Bone Transmission Time) and AD-SoS (Amplitude-Dependent Speed of Sound), mainly reliant on bone density and cortical thickness, respectively. Measurements were performed at diagnosis, and 6, 12, and 24 months thereafter. The occurrence of skeletal complications such as fractures, vertebral collapse, osteonecrosis, and osteopenia was related to measurement outcome.


RESULTS
A rapid deterioration of bone properties measured by BTT and AD-SoS was evident in the first semester of therapy (p<0.001). Subsequently, the next measurements were characterized by progressive uncoupling of the two QUS parameters (p<0.001). These were both significantly reduced at the end of therapy (p<0.001). Twelve subjects with in-treatment skeletal complications displayed an almost two-fold decrease of both parameters (p<0.001). BTT decreasing more than 1 Standard Deviation (SD) over 6 months of therapy was able to predict skeletal complication occurrence (p<0.001).


CONCLUSIONS
This report represents the largest longitudinal cohort systematically submitted to bone condition assessment from the beginning to the end of therapy for childhood ALL. Bone deterioration occurs early and persists throughout therapy, consistent with bone properties uncoupling. This pattern possibly reflects an initial impairment of both mineral density and cortical thickness with a subsequent recovery of this latter. QUS permits an early detection of bone deterioration and related skeletal complications in childhood ALL.
Mussa
Alessandro
A
Division of Pediatric Endocrinology, Department of Pediatric Endocrinology and Diabetology, University of Torino, Regina Margherita Children Hospital, Piazza Polonia 94, 10126, Torino, Italy. mussa_alessandro@yahoo.it
Bertorello
Nicoletta
N
Porta
Francesco
F
Galletto
Chiara
C
Nicolosi
Mario Guido
MG
Manicone
Rosaria
R
Corrias
Andrea
A
Fagioli
Franca
F
D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D003596:Cytosine / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000209:etiology; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D010020:Osteonecrosis / Q000000981:diagnostic imaging / Q000209:etiology; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011446:Prospective Studies; D013997:Time Factors; D014463:Ultrasonography; D014750:Vincristine / Q000627:therapeutic use
D014750:Vincristine; D003596:Cytosine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D008727:Methotrexate