Many adolescents with acute lymphoblastic leukemia (ALL) have been found to have low bone density by the end of treatment. This can lead to long-term suffering in survivors due to poor bone health. Vitamin D is known to be associated with bone health and previous research has established that Vitamin D insufficiency is very common at diagnosis of ALL and worsens over the course of treatment. Researchers have also learned that a relationship exists between both Vitamin D and fat tissue and ALL and fat tissue.

In adolescents being treated for ALL as well as in early survivors, this randomized study will therefore examine the effect of Vitamin D and calcium supplementation on correcting Vitamin D insufficiency and on improving bone density in the context of changes in body composition and body fat. Bone density will be measured by a radiology exam called qCT (quantitative computed tomography) while body composition and body fat will be measured by a different radiology exam called a DXA (dual energy x-ray absorptiometry scan) . The study will also examine in depth the relationship between these three elements - Vitamin D insufficiency, obesity, and ALL - and their impact on bone density.

Inclusion Criteria:

GROUP A: Patients with newly diagnosed ALL

• Are greater than or equal to 10 years of age and less than or equal to 21 years of age at diagnosis of ALL
• Have a new diagnosis of untreated ALL classified as "high risk" per NCI criteria (due to being greater than 10 years of age)
• Are beginning treatment with a Children's Cancer Group/Children's Oncology Group "high risk" protocol with a 4-drug induction including steroids
• Are not pregnant

GROUP B: Early survivors of ALL

• Were treated for ALL and remain in first CR1 (complete remission)
• Were equal to or greater than 10 years of age and less than or equal to 21 years of age at diagnosis of ALL
• Have completed treatment on or as per a Children's Cancer Group/Children's Oncology Group "high risk" protocol between 12 and 48 months prior to enrollment in this study (consisting of a plan for a 4-drug induction including steroids in Induction, Delayed Intensification, and steroid pulses in Maintenance. Steroids are allowed to have been discontinued due to toxicity).
• Are not pregnant

GROUP C: Siblings of Group A

• Are either a full-sibling or a half-sibling of a patient in Group A
• Are living at the same residence as the sibling/half-sibling from Group A
• Are greater than or equal to 10 years of age and less than or equal to 21 years of age at the time of study entry, and within 3 years of the age diagnosis of ALL in the sibling/half-sibling from Group A
• Are on the same Vitamin D supplementation regimen (if any) as the sibling from Group A at the time of his or her diagnosis

Exclusion Criteria (All Groups):

• Have a diagnosis of Down syndrome (Trisomy 21) or any genetic disease associated with abnormal bone development
• Are undergoing treatment with other medicines that affect bones including chronic use of of steroids, bisphosphonate therapy, or Vitamin D at average dose greater than 400 international units (IU)/day
• Have an underlying diseases altering body structure (i.e. missing a limb, severe dysmorphism) or severely affecting mobility (i.e. total or hemiparesis)
• Have a history of chemotherapy or radiation for other cancers
• Cannot complete the radiology exams/radiology exams uninterpretable (i.e. people with a hip replacement or prosthesis)

6 months (Randomization to end of study)

Note that subjects in the On-Therapy "natural history" arm (i.e. Group A, not randomized) were not formally followed for adverse event reporting.

Subjects in Sibling group (Arm C) had a single visit for a laboratory draw with no adverse event reporting indicated.