• Changes in bone mineral density (BMD) [ Time Frame: At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT]), and 465 days post-HSCT ]
  Day 100 dual x-ray absorptiometry (DXA) scan and day 465 DXA scan will be compared based on the percent change in BMD in the dual femur and/or lumbar spine in allogeneic HSCT patients who have experienced either at least 5% BMD loss between baseline (pre- HSCT) and day + 100 post-HSCT, or who have osteopenia or osteoporosis at either the pre-bone marrow transplant or day + 100 DXA scan.
• Slope in bone mineral density (g/cm^2) regressed on time in dual femur and lumbar spine (average of L1-L4) [ Time Frame: From the time of enrollment up to 465 days post-HSCT ]
  The analysis for both the femur and lumbar spine will consist of a regression model of the percent change from enrollment to 465 days post HSCT regressed on the enrollment BMD levels. The analysis model will be fit using Ordinary Least Square methods. A secondary model will include and expand upon a list of covariates to explore the effects of demographic, disease and treatment characteristics on BMD loss and effectiveness of denosumab using an analysis-of-covariance model. Both models will be tested at alpha = 0.05 (two-sided). Residual plots and other diagnostic methods will be used to evaluate compliance with model assumptions and goodness of fit.

• Changes in bone mineral density (BMD) [ Time Frame: At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT]), and year post-HSCT ]
  Day 100 dual x-ray absorptiometry (DXA) scan and one year DXA scan will be compared based on the percent change in BMD in the dual femur and/or lumbar spine in allogeneic HSCT patients who have experienced either at least 5% BMD loss between baseline (pre- HSCT) and day + 100 post-HSCT, or who have osteopenia or osteoporosis at either the pre-bone marrow transplant or day + 100 DXA scan.
• Slope in bone mineral density (g/cm^2) regressed on time in dual femur and lumbar spine (average of L1-L4) [ Time Frame: From the time of enrollment up to 1 year post-HSCT ]
  The analysis for both the femur and lumbar spine will consist of a regression model of the percent change from enrollment to 1 year post HSCT regressed on the enrollment BMD levels. The analysis model will be fit using Ordinary Least Square methods. A secondary model will include and expand upon a list of covariates to explore the effects of demographic, disease and treatment characteristics on BMD loss and effectiveness of denosumab using an analysis-of-covariance model. Both models will be tested at alpha = 0.05 (two-sided). Residual plots and other diagnostic methods will be used to evaluate compliance with model assumptions and goodness of fit.

• Percent change in BMD [ Time Frame: Baseline up to 465 days post-HSCT ]
  Will be compared between the pre-HSCT and the day 465 post-HSCT DXA scans for dual femur and/or lumbar spine (L1-L4). Will be tabulated overall.
• Frequency of bone fractures [ Time Frame: Up to 1 year post-HSCT ]
  Will be tabulated overall.
• Incidence of adverse events [ Time Frame: Up to 30 days ]
  Including but not limited to the following: Injection/hypersensitivity related reactions; osteonecrosis of the jaw; graft versus host disease. Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and tabulated by grade.

• Percent change in BMD [ Time Frame: Baseline up to 1 year post-HSCT ]
  Will be compared between the pre-HSCT and the one-year post-HSCT DXA scans for dual femur and/or lumbar spine (L1-L4). Will be tabulated overall.
• Frequency of bone fractures [ Time Frame: Up to 1 year post-HSCT ]
  Will be tabulated overall.
• Incidence of adverse events [ Time Frame: Up to 30 days ]
  Including but not limited to the following: Injection/hypersensitivity related reactions; osteonecrosis of the jaw; graft versus host disease. Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and tabulated by grade.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy and safety of denosumab therapy for the treatment of bone loss in patients who have received an allogeneic hematopoietic stem cell transplant.

OUTLINE:

Patients receive 2 doses of denosumab subcutaneously (SC) between days 70-130 and days 250-310 after allogeneic hematopoietic stem cell transplant in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up at 6 months.

• Allogeneic Hematopoietic Stem Cell Transplantation Recipient
• Osteopenia
• Osteoporosis

Inclusion Criteria:

• The patient has undergone an allogeneic hematopoietic stem cell transplant
• The patient has completed a base line dual x-ray absorptiometry (DXA) scan =< 3 months prior to transplantation
• The patient has completed a post-transplant DXA scan at day 100 (+/- 30 days) post transplantation

• The patients post-transplantation DXA scan denotes one or more of the following:

  • >= 5% decrease in bone mineral density (g/cm^2) in either the dual femur or lumbar spine (average of L1-L4), or both, between the pre-hematopoietic stem cell transplant (HSCT) and ~ day + 100 post-HSCT DXA scans
  • Osteopenia in either the dual femur or lumbar spine (L1-L4) at either the pre-HSCT or day + 100 post-HSCT timepoint
  • Osteoporosis in either the dual femur or lumbar spine (L1-L4) at either the pre-HSCT or day + 100 post-HSCT timepoint
• The patient has completed and passed a dental clearance exam after transplantation and before the administration of denosumab.
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• The patient has a history of a hypersensitivity reaction to denosumab
• The patient has a history of osteonecrosis of the jaw

• The patient has predisposing risk factors for hypocalcemia including the following:

  • Hypoparathyroidism
  • Creatinine clearance (CrCl) < 30 mL/min
  • Dialysis
  • Malabsorption syndrome
• The patient has history of any bone fracture =< 30 days prior to denosumab therapy
• Pregnant or nursing female patients.
• The patient has clinically significant GVHD leading to hospitalization at the time of denosumab dose per prescriber discretion.
• The patient has clinically significant infection leading to hospitalization at the time of denosumab dose (excluding hospitalization due to complexity of treatment leading to inability to treat outpatient, ie. Foscarnet) per prescriber discretion
• The patient is unwilling or unable to follow protocol requirements
• The patient has any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug including relapsed malignancy