Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study

Study Overview
=================
Brief Summary
-----------------
This study explores the effect of zoledronic acid on incident vertebral fractures and osteonecrotic lesions in children recently diagnosed with acute lymphoblastic leukemia.

Official Title
-----------------
Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study

Conditions
-----------------
Osteoporosis, Osteonecrosis, Acute Lymphoblastic Leukemia

Intervention / Treatment
-----------------
* Drug: Zoledronic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject or subject's legally acceptable representative has provided informed consent. Children aged 8 to 16 years at the time of enrolment with a confirmed diagnosis of acute lymphoblastic leukemia (ALL). Children with vertebral fractures or osteonecrotic lesions according to the following criteria: children with vertebral fractures on lateral spine x-ray and/or osteonecrotic lesions on MRI of the hips and/or knees identified through routine clinical screening at least 8 weeks following chemotherapy initiation OR children with vertebral fractures on lateral spine x-ray and/or osteonecrotic lesions of the hips and/or knees on MRI that are identified at any time in the first 12 months after chemotherapy initiation following presentation with back pain (in the case of vertebral fractures, identified by lateral spine x-rays) and/or hip pain (in the case of osteonecrotic lesions, identified by MRI) and/or knee pain (in the case of osteonecrotic lesions, identified by MRI). Exclusion Criteria: Any child for whom the treating physician feels participation is not advised. Prior treatment with an osteoporosis agent (e.g. bisphosphonate). Co-morbidities affecting musculoskeletal health (e.g. cerebral palsy). Children with renal failure (eGFR<60ml/min/1.73m2). Children with untreated vitamin D deficiency (vitamin D <50nmol/L). Children with hypocalcemia. Children planning dental procedures and/or dental surgery during the course of the study. Children with asthma who are acetylsalicylic acid (ASA) sensitive. Children with a documented history of atrial fibrillation. Currently pregnant or planning a pregnancy during the study. Currently breastfeeding or planning on breastfeeding during the study.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Zoledronic Acid<br>Intravenous Zoledronic Acid 0.025mg/kg at baseline and 6 months | Drug: Zoledronic acid<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of zoledronic acid on preventing incident vertebral fractures | To assess the effect of zoledronic acid on preventing incident vertebral fractures as measured by lateral spine radiographs at 15 months post-diagnosis compared to baseline (with baseline occurring 3 months post-diagnosis). An incident vertebral fracture on lateral spine radiographs will be defined as a new fracture (Genant Grade 1 or more) in a previously normal vertebral body, or worsening of an existing fracture (increase in Genant Grade by at least 1) on the follow-up x-ray that takes place 12 months after the first dose. | 15 months post-diagnosis (12 months after baseline visit) |