Low Bone Mass and Osteoporosis in Hispanic Acute Lymphoblastic Leukemia Survivors. Is It a Real Problem ?
Authors: Orozco Alfonso , Rangel-Patiño Juan , Valdez-Carrizales Mayra , Demichelis Roberta 
Published: November 2021

Abstract
Introduction: The survival rates in children and adolescent or young adults with acute lymphoblastic leukemia (ALL) have improved in the last decades. Cancer survivors can have reduced bone mineral density (BMD) related both to the underlying disease and the treatment. This can persist for up to 20 years, increasing the risk of osteopenia / osteoporosis and the development of fractures that can generate disability and loss of function. The risk factors for the development of disorders of BMD in the adult ALL survivors has been little studied and there are no formal guideline recommendations on the long-term follow-up and treatment of these patients. We evaluated ALL-survivor patients in Mexico; both ALL and osteoporosis are more prevalent in Hispanic patients, therefore we implemented conducting a dual-energy x-ray absorptiometry (DXA) during follow-up.
Primary objective: Our main objective was to know the prevalence of alterations in bone mineral density (BMD) in a cohort of Hispanic ALL-survivors. Secondary objectives: To identify risk factors and the incidence of complications associated with BMD alterations.
Methods: An observational, case-control study in a cohort of adult ALL survivors with follow-up at a referral center´s acute leukemia clinic in Mexico City. We include patients with more than one year of elective cessation of treatment in whom a DXA was performed as the routine follow-up for survivors. We compared the characteristics of the cases (patients with alterations in BMD) with the controls (patients without alterations in BMD). We define alterations in BMD by the WHO and the International Society of clinical DXA: the term of low BMD was used for younger patients and osteoporosis/osteopenia for older.
Results: 61 ALL survivors were identified, 86.9% had B-Cell ALL and 13.1% T-Cell ALL. The median age at diagnosis was 12 years (1-55 years) and at the time of the study, 27 years (20-69 years). The majority (78.8%) had less than 18 years-old at diagnosis. The median follow-up from treatment cessation to densitometry was 142 months (10-499 months).
An alteration in BMD was found in 63.9% of the patients: 84.6% were classified as low BMD for age and 15.4% as osteopenia/osteoporosis. The most frequently affected site was the spine (40%) followed by the hip and spine (32.5%) and the hip (10%). The median T-score and Z-score by area are shown in Table 1.
Table 2 shows the characteristics of ALL-survivors with or without alterations in BMD. The median follow-up time was not different between the 2 groups. Gender, age at diagnosis, the use of induction dexamethasone and other chemotherapeutic agents, vitamin D deficiency, and hypogonadism were not associated with an increased risk of alterations in BMD. Receiving induction chemotherapy between 8 and 18 years of age (age where the highest bone mass is acquired) does not affect in the BMD at follow-up.
During follow-up, three patients developed fractures: one pathological and 2 associated with trauma. The patient with a pathological fracture is a man with ALL diagnosed at 8 years of age and had an ankle fracture at 12 years associated with osteoporosis.
Discussion and Conclusions:
Alterations in BMD are very frequent in our cohort of ALL-survivors despite being a very young population (90% are under 50 years of age). We could not replicate the classically associated risk factors for altered BDM. We only found a non-significant trend for hematopoietic-stem cell transplantation (HSCT) and radiotherapy. This was previously been associated with alterations in different hormonal axes. Despite the high-prevalence of alterations in BMD, the incidence of fractures is very low. This may be related to the fact that it is unknown how to interpret DXA in a group of patients who received chemotherapy/radiotherapy in growth stages. Despite the limitations (small number of patients, the time between treatment and densitometry is heterogeneous and hormonal axes are not measured in all patients), given the high prevalence of BMA alterations, a better understanding of DXA findings in this group of patients is needed.
Figure 1 Figure 1.

Disclosures
Rangel-Patiño: Bristol: Consultancy; Abbvie: Speakers Bureau. Demichelis: AMGEN: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy; Bristol/Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; ASH: Research Funding; Gilead: Consultancy; Abbvie: Consultancy, Speakers Bureau.