The purpose of this pilot study is to investigate the safety and preliminarily assess efficacy of early intervention with zoledronate in high risk pediatric hematopoietic stem cell transplantation (HSCT) patients to prevent the development of bone disease and fractures and reduce potential pain and suffering.

Bone disease, including low bone density and fragility fractures (osteoporosis), is common among survivors of pediatric hematopoietic stem cell transplantation (HSCT). Further, patients who develop graft-versus-host disease (GVHD) following HSCT or who have high cumulative doses of glucocorticoids are at even higher risk to develop bone complications. Recent data also suggest that a large number of HSCT candidates arrive to transplantation already with low bone mineral density, adding to the potential risk of developing bone disease following HSCT. Typically, treatment for osteoporosis in children using bisphosphonates, such as zoledronate, is recommended only after the development of fragility fractures.

The investigators propose to study the safety and efficacy of a novel method of early intervention with zoledronate in high risk pediatric HSCT patients to prevent the development of bone disease and fractures in order to reduce potential pain and suffering.

Inclusion Criteria:

• Patients ≥5 and ≤18 years old who are preparing for HSCT with a height-for-age corrected DXA Z-score of <-2.0 and admitted to a CCHMC inpatient unit.
• Patients ≥5 and ≤18 years old recovering from HSCT and who have developed de novo acute or chronic GVHD and are admitted to a CCHMC inpatient unit.

Exclusion Criteria:

• Age <5 years and >18 years
• Patients with Fanconi anemia or other radiation-sensitive syndromes with increased malignancy risk
• history of prior bisphosphonate use
• low 25-OH vitamin D levels (<20 ng/mL)
• active febrile illness
• uncontrolled infection
• Elevated creatinine at the time of enrollment, history or renal failure, or documented low glomerular filtration rate (GFR≤90)
• Active bone disease including history of abnormal PTH level for any reason, active bone fracture/healing, or primary disorder of bone development or metabolism.
• Women who are pregnant or breast feeding.