Osteopenia, Osteoporosis
Conditions
Keywords
bone mineral content, bone mineral density, bone formation, bone resorption, pamidronate, children, DXA, bone marrow transplant
Brief summary
This is a Phase 2, open-label, randomized, controlled clinical study of pediatric subjects treated with pamidronate with calcium and vitamin D versus calcium and vitamin D alone following hematopoietic cell transplantation (HCT). The purpose of this study is to test the hypothesis that subjects receiving pamidronate with calcium and vitamin D will have higher lumbar spine bone mineral content (LBMC) measured by dual-energy X-ray tomography (DXA) at 1 year post-HCT than subjects receiving calcium and vitamin D alone (Control Group).
Interventions
DRUGPamidronate
Subjects randomized to pamidronate treatment will receive infusions, 1 mg/kg (to a max dose of 60mg) over 4 hours, every 3 months at approximately 100 days, 180 days, and 270 days after HCT.
All subjects will receive a standard recommended dose of 600 IU/day of vitamin D. Subjects who do not meet the RDA will receive additional calcium supplementation.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 20 Years
Healthy volunteers
No
Inclusion criteria
* Allogeneic hematopoietic cell transplant for hematologic malignancy (i.e. leukemia, lymphoma including ALL, AML, CML, NHL, HL) in complete remission; myelodysplastic syndrome (active dysplasia and/or blasts are permitted, but must not have active leukemia) or idiopathic severe aplastic anemia (SAA) * Non-malignant diseases including idiopathic severe aplastic anemia (SAA) and other bone marrow failure disorders, hemoglobinopathies, adrenoleukodystrophy, immune deficiencies/dysregulation disorders who will be receiving myeloablative or reduced toxicity preparative regimens that meet the following criteria: * Regimens include those that are TBI based if the TBI dose is \> 500cGy single dose or \> 800cGy fractionated, or doses \<500 cGy if combined with busulfan or treosulfan. These also include chemotherapy only based regimens that contain myeloablative doses of busulfan (\>8mg/kg) or treosulfan without TBI. * Patients with severe aplastic anemia are eligible regardless of conditioning regimen * Myeloablative preparative regimen (for SAA any conditioning therapy allowed) * Male or female ≥1 but ≤ 20 years of age at time of study enrollment * Patient or parent(s)/legal guardian(s) is able and willing to provide informed consent. Assent will be obtained per local institutional policy. Subjects who turn 18 during the course of the study will be consented at that time of their next visit by a member of the research staff.
Exclusion criteria
* History of a primary bone malignancy involving the lumbar spine * Prior and/or planned concomitant medical therapy during the study period (through Day 360 post-HCT) with other bisphosphonates, Denosumab, or Teriparatide * Pregnancy or breastfeeding - menstruating females must have a negative pregnancy test prior to study enrollment and agree to repeat pregnancy testing and contraception use per protocol as pamidronate is Pregnancy Category D - positive evidence of human fetal risk based on adverse reaction data * Renal insufficiency, defined as creatinine level greater than the upper limit of normal for age * Hereditary metabolic bone disease or skeletal dysplasia (e.g., osteopetrosis or OI) or primary hyperparathyroidism * Other indications for HCT, including Fanconi anemia, other form of inherited bone marrow failure diseases, metabolic disorder, hemoglobinopathy, or immune deficiency * Clinically significant fractures as defined by ISCD (a long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities) (88,89) indicated by a cast or a spine x-ray within the last 2 weeks * Known or suspected allergy to pamidronate or related products * Planned administration of an investigational study drug or agent that either can interact with pamidronate or have an independent effect on bone mineral density within the 4 weeks prior to randomization (Day 90) or planned use during study participation (Day 90 through Day 360) * Impending invasive dental procedure that would be expected to occur during study participation (through Day 360)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lumbar Spine Bone Mineral Content | 1 year after HCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Marker of Bone Resorption Deoxypyridinoline [DPD]) | 7, 14, 21, 90, 180, 360 days after HCT | DPD measured in mmol/L. |
| Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race) | 1 year after HCT | — |
| Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT | 1 year after HCT | Measured in g/cm2. |
| Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | 7 days, 14 days, 21 days, 90 days after HCT | Measured in pg/ml. |
| Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | 7 days, 14 days, 21 days, and 90 days after HCT | — |
| Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | 7, 14, 21, 90, 180, 360 days after HCT | CTX measured in ng/ml. |
| Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | 7, 14, 21, 90, 180, 360 days after HCT | P1NP measured in ng/ml. |
| Marker of Bone Formation Osteocalcin [OCN]) | 7, 14, 21, 90, 180, 360 days after HCT | OCN measured in pg/ml. |
| Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | 7 days, 14 days, 21 days, and 90 days after HCT | Measured in pg/ml. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Subjects will receive a standard recommended dose of calcium and vitamin D.
Calcium and vitamin D: All subjects will receive a standard recommended dose of 600 IU/day of vitamin D. Subjects who do not meet the RDA will receive additional calcium supplementation. | 32 |
| Pamidronate Group Subjects randomized to pamidronate treatment will receive infusions approximately 100, 180, and 270 days after HCT along with calcium and vitamin D.
Pamidronate: Subjects randomized to pamidronate treatment will receive infusions, 1 mg/kg (to a max dose of 60mg) over 4 hours, every 3 months at approximately 100 days, 180 days, and 270 days after HCT.
Calcium and vitamin D: All subjects will receive a standard recommended dose of 600 IU/day of vitamin D. Subjects who do not meet the RDA will receive additional calcium supplementation. | 31 |
| Total | 63 |
Baseline characteristics
| Characteristic | Control Group | Pamidronate Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 29 Participants | 30 Participants | 59 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 26 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 22 Participants | 24 Participants | 46 Participants |
| Region of Enrollment United States | 32 participants | 31 participants | 63 participants |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 27 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 9 / 32 | 19 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 |
Outcome results
Primary
Lumbar Spine Bone Mineral Content
Time frame: 1 year after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Lumbar Spine Bone Mineral Content | 41.4 Average grams | Standard Deviation 22.8 |
| Pamidronate Group | Lumbar Spine Bone Mineral Content | 38.7 Average grams | Standard Deviation 22.2 |
Secondary
Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α)
Measured in pg/ml.
Time frame: 7 days, 14 days, 21 days, 90 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 7 days after HCT | 37.4 pg/ml | Standard Deviation 46.6 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 14 days after HCT | 33.7 pg/ml | Standard Deviation 14.7 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 21 days after HCT | 22.0 pg/ml | Standard Deviation 63.9 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 21 days after HCT | 28.8 pg/ml | Standard Deviation 15.7 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 90 days after HCT | 14.3 pg/ml | Standard Deviation 6.5 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 90 days after HCT | 11.4 pg/ml | Standard Deviation 9.5 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 90 days after HCT | 10.7 pg/ml | Standard Deviation 33.9 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 7 days after HCT | 7.0 pg/ml | Standard Deviation 2.8 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 14 days after HCT | 23.6 pg/ml | Standard Deviation 19.9 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 14 days after HCT | 10.5 pg/ml | Standard Deviation 5.6 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 7 days after HCT | 35.8 pg/ml | Standard Deviation 15.6 |
| Control Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 21 days after HCT | 11.3 pg/ml | Standard Deviation 5.7 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 7 days after HCT | 33.4 pg/ml | Standard Deviation 19.3 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 90 days after HCT | 15.9 pg/ml | Standard Deviation 7.5 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 7 days after HCT | 41.4 pg/ml | Standard Deviation 49.4 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 14 days after HCT | 35.4 pg/ml | Standard Deviation 32.7 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 21 days after HCT | 18.1 pg/ml | Standard Deviation 17.5 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-6 90 days after HCT | 6.8 pg/ml | Standard Deviation 5 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 21 days after HCT | 12.7 pg/ml | Standard Deviation 7.2 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 14 days after HCT | 35.9 pg/ml | Standard Deviation 27.4 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 21 days after HCT | 31.5 pg/ml | Standard Deviation 25.9 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | IL-7 90 days after HCT | 13.1 pg/ml | Standard Deviation 11.6 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 7 days after HCT | 6.9 pg/ml | Standard Deviation 3.4 |
| Pamidronate Group | Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α) | TNFa 14 days after HCT | 11.4 pg/ml | Standard Deviation 9.4 |
Secondary
Marker of Bone Formation Osteocalcin [OCN])
OCN measured in pg/ml.
Time frame: 7, 14, 21, 90, 180, 360 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 7 days after HCT | 56832 pg/ml | Standard Deviation 31576 |
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 14 days after HCT | 57611 pg/ml | Standard Deviation 37994 |
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 21 days after HCT | 59890 pg/ml | Standard Deviation 37398 |
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 90 days after HCT | 48839 pg/ml | Standard Deviation 33380 |
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 180 days after HCT | 47077 pg/ml | Standard Deviation 45972 |
| Control Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 360 days after HCT | 85950 pg/ml | Standard Deviation 126169 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 180 days after HCT | 47459 pg/ml | Standard Deviation 18955 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 7 days after HCT | 59071 pg/ml | Standard Deviation 31740 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 90 days after HCT | 57638 pg/ml | Standard Deviation 34727 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 14 days after HCT | 68137 pg/ml | Standard Deviation 41600 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 360 days after HCT | 52972 pg/ml | Standard Deviation 25938 |
| Pamidronate Group | Marker of Bone Formation Osteocalcin [OCN]) | OCN 21 days after HCT | 58983 pg/ml | Standard Deviation 42097 |
Secondary
Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX]
CTX measured in ng/ml.
Time frame: 7, 14, 21, 90, 180, 360 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 7 days after HCT | 0.596 ng/ml | Standard Deviation 0.833 |
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 14 days after HCT | 0.341 ng/ml | Standard Deviation 0.165 |
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 21 days after HCT | 0.332 ng/ml | Standard Deviation 0.085 |
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 90 days after HCT | 0.327 ng/ml | Standard Deviation 0.117 |
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 180 days after HCT | 0.395 ng/ml | Standard Deviation 0.236 |
| Control Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 360 days after HCT | 0.291 ng/ml | Standard Deviation 0.119 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 180 days after HCT | 0.318 ng/ml | Standard Deviation 0.106 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 7 days after HCT | 0.455 ng/ml | Standard Deviation 0.44 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 90 days after HCT | 0.328 ng/ml | Standard Deviation 0.113 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 14 days after HCT | 0.347 ng/ml | Standard Deviation 0.185 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 360 days after HCT | 0.307 ng/ml | Standard Deviation 0.088 |
| Pamidronate Group | Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX] | CTX 21 days after HCT | 0.441 ng/ml | Standard Deviation 0.372 |
Secondary
Marker of Bone Resorption Deoxypyridinoline [DPD])
DPD measured in mmol/L.
Time frame: 7, 14, 21, 90, 180, 360 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 14 days after HCT | 71.4 mmol/L | Standard Deviation 65.7 |
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 90 days after HCT | 170 mmol/L | Standard Deviation 130 |
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 7 days after HCT | 133 mmol/L | Standard Deviation 113 |
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 180 days after HCT | 191 mmol/L | Standard Deviation 119 |
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 21 days after HCT | 91.6 mmol/L | Standard Deviation 78.8 |
| Control Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 360 days after HCT | 123 mmol/L | Standard Deviation 87 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 21 days after HCT | 112 mmol/L | Standard Deviation 103 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 7 days after HCT | 89.7 mmol/L | Standard Deviation 58.8 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 14 days after HCT | 70.7 mmol/L | Standard Deviation 58.7 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 360 days after HCT | 145 mmol/L | Standard Deviation 121 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 90 days after HCT | 146 mmol/L | Standard Deviation 108 |
| Pamidronate Group | Marker of Bone Resorption Deoxypyridinoline [DPD]) | DPD 180 days after HCT | 163 mmol/L | Standard Deviation 107 |
Secondary
Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP])
P1NP measured in ng/ml.
Time frame: 7, 14, 21, 90, 180, 360 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 7 days after HCT | 36.2 ng/ml | Standard Deviation 14.9 |
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 14 days after HCT | 36.9 ng/ml | Standard Deviation 16.8 |
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 21 days after HCT | 38.5 ng/ml | Standard Deviation 16.4 |
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 90 days after HCT | 41.2 ng/ml | Standard Deviation 17.9 |
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 180 days after HCT | 29.2 ng/ml | Standard Deviation 13.7 |
| Control Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 360 days after HCT | 28.6 ng/ml | Standard Deviation 14.5 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 180 days after HCT | 27.6 ng/ml | Standard Deviation 11.8 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 7 days after HCT | 38 ng/ml | Standard Deviation 18.6 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 90 days after HCT | 39.5 ng/ml | Standard Deviation 17.8 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 14 days after HCT | 35.7 ng/ml | Standard Deviation 14.2 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 360 days after HCT | 29.3 ng/ml | Standard Deviation 12.8 |
| Pamidronate Group | Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP]) | P1NP 21 days after HCT | 37.1 ng/ml | Standard Deviation 15.4 |
Secondary
Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG]
Time frame: 7 days, 14 days, 21 days, and 90 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 7 days after HCT | 0.154 ratio | Standard Deviation 0.186 |
| Control Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 14 days after HCT | 0.10 ratio | Standard Deviation 0.137 |
| Control Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 21 days after HCT | 0.121 ratio | Standard Deviation 0.139 |
| Control Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 90 days after HCT | 0.205 ratio | Standard Deviation 0.278 |
| Pamidronate Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 90 days after HCT | 0.127 ratio | Standard Deviation 0.109 |
| Pamidronate Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 7 days after HCT | 0.096 ratio | Standard Deviation 0.103 |
| Pamidronate Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 21 days after HCT | 0.095 ratio | Standard Deviation 0.086 |
| Pamidronate Group | Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG] | RANKL/OPG 14 days after HCT | 0.078 ratio | Standard Deviation 0.085 |
Secondary
Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG]
Measured in pg/ml.
Time frame: 7 days, 14 days, 21 days, and 90 days after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 7 days after HCT | 58.9 pg/ml | Standard Deviation 72.4 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 14 days after HCT | 45.5 pg/ml | Standard Deviation 64.6 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 21 days after HCT | 49.3 pg/ml | Standard Deviation 55.8 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 90 days after HCT | 56.6 pg/ml | Standard Deviation 65.8 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 7 days after HCT | 489 pg/ml | Standard Deviation 454 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 14 days after HCT | 617 pg/ml | Standard Deviation 651 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 21 days after HCT | 582 pg/ml | Standard Deviation 646 |
| Control Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 90 days after HCT | 499 pg/ml | Standard Deviation 589 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 90 days after HCT | 422 pg/ml | Standard Deviation 231 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 7 days after HCT | 40.5 pg/ml | Standard Deviation 36.3 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 7 days after HCT | 564 pg/ml | Standard Deviation 315 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 14 days after HCT | 42.1 pg/ml | Standard Deviation 44.7 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 21 days after HCT | 575 pg/ml | Standard Deviation 290 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 21 days after HCT | 51.0 pg/ml | Standard Deviation 48.6 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | OPG 14 days after HCT | 650 pg/ml | Standard Deviation 378 |
| Pamidronate Group | Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG] | RANKL 90 days after HCT | 41.4 pg/ml | Standard Deviation 27.5 |
Secondary
Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race)
Time frame: 1 year after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race) | 1231 Average grams | Standard Error 95 |
| Pamidronate Group | Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race) | 1204 Average grams | Standard Error 113 |
Secondary
Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT
Measured in g/cm2.
Time frame: 1 year after HCT
Population: Participants unable to be evaluated due to declining health or failure of follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT | 0.829 g/cm2 | Standard Deviation 0.202 |
| Pamidronate Group | Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT | 0.760 g/cm2 | Standard Deviation 0.189 |