A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00186901
• Collaborator: (none)
• Enrollment: 429
• Locations: 3
• Arms: 2
• Duration (Months): 134
• Patients Per Site: 143
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Research studies have shown that children who are long-term survivors of childhood leukemia may be at greater risk for early bone loss called osteoporosis. This bone loss may lead to a greater risk of broken bones and other spine and bone problems. However, researchers still do not know much about how frequently this long-term side effect may occur and how severe the problem is.

St. Jude Children's Research Hospital researchers want to determine the frequency and severity of this side effect. They are also studying whether taking calcium and Vitamin D supplements can help children at risk for osteoporosis and if certain factors can be identified -- such as age at diagnosis, cancer treatments, or family history -- that may increase the chances of having osteoporosis. Researchers will take an x-ray study called quantitative computed tomography (QCT) to measure bone mineral density (BMD). The BMD is a measure of bone strength. If a subject's BMD falls below the average, he/she will be assigned to one of two groups. Subjects will be randomly assigned (like tossing a coin) to receive calcium and vitamin D pills. The other half will receive placebo pills that look like the calcium and vitamin D pills.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphoblastic, Acute; Osteoporosis	Drug: Calcium carbonate (Tums), vitamin D; Other: Placebo	Phase 3

Detailed Description

The main objectives of the study are:

• To estimate, using quantitative computed tomography (QCT), the prevalence of diminished bone mineral density (BMD) in patients treated with contemporary, protocol-based multiagent chemotherapy (+cranial irradiation) for childhood acute lymphoblastic leukemia (ALL).

• To investigate possible risk factors for the development of diminished BMD in patients treated with contemporary protocol-based therapy for childhood ALL. Factors to be examined include patient characteristics (age at the time of treatment, gender, race, body mass index, physical activity and nutritional status, menarchal status, oral contraceptive use, growth hormone therapy, smoking and alcohol intake, birth weight, fracture history); treatment effects (intensity of treatment with antimetabolites and glucocorticoids; history of cranial irradiation); and genetic predisposition (i.e., vitamin D and CYP3A4 receptor polymorphism and family history of osteoporosis).

• To evaluate, in a prospective placebo-controlled double-blinded randomized trial, the effects of vitamin D and calcium supplementation in addition to nutritional counseling on BMD in patients with BMD scores below the mean for age- and gender-matched controls, compared to an educational program of nutritional counseling alone.

Secondary Aim

• To evaluate, in a prospective randomized trial, the correlation between BMD as determined by QCT and BMD as determined by dual energy x-ray absorptiometry (DEXA) in patients with BMD more than one standard deviation (SD) below the mean for age- and gender-matched controls.

Study Design

• Study Type: Interventional
• Actual Enrollment: 429 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Diminished Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Severity-Adapted Clinical Trial
• Study Start Date: Jul 1, 2000
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1A Nutritional counseling + placebo	Other: Placebo; Placebo
Experimental: 1B Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	Drug: Calcium carbonate (Tums), vitamin D; Calcium carbonate 100mg/day (Tums), vitamin D 800 units/day

Outcome Measures

Primary Outcome Measures

1. Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) [Baseline, 12 months, 24 months, and at 36 months or study end]

   The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits.

2. Bone Mineral Density in Male and Female ALL Survivors [Baseline]

   Using bone mineral density Z-score, assess relationship between predisposing factors (gender) and bone mineral density; a negative value indicates a deficit in bone mineral density.

3. Bone Mineral Density by Race of ALL Survivors [Baseline]

   Using bone mineral density Z-score, assess relationship between predisposing factors (race) and bone mineral density; a negative value indicates a deficit in bone mineral density.

4. Bone Mineral Density by Age Group of ALL Survivors [Baseline]

   Using bone mineral density Z-score, assess relationship between predisposing factors (age groups) and bone mineral density; a negative value indicates a deficit in bone mineral density.

Secondary Outcome Measures

1. Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. [Baseline]

   To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 121 patients at baseline were assessed by both method the QCT and DXA methods to assess Bone Mineral Density.

2. Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. [12 months]

   To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 218 patients were assessed at 12 months for QCT. 94 were evaluated using DXA. 94 patients received both scans.

3. Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. [24 months]

   To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 188 patients were assessed at 24 months by the QCT method and 90 were evaluated using the DXA methods to assess Bone Mineral Density. 90 patients received both scans.

4. Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. [36 months]

   To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 180 patients were assessed at 36 months by the QCT method and 89 were evaluated using the DXA methods to assess Bone Mineral Density. 89 patients received both scans.

5. Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype [At enrollment]

   The Apa1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood

6. Mean QCT Z-Score by Bsm 1 Vitamin D Receptor Genotype [At enrollment]

   The Bsm1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is a survivor of acute lymphoblastic leukemia.

• Patient was treated on St. Jude Children's Research Hospital's Total XI, XII, or XIII treatment protocol.

• Patient is at least five years out from completion of therapy and is in first remission

Exclusion Criteria:

• Active disease

• Pregnant or lactating females

• Inability to chew and swallow pills

• Currently taking more than 800 mg supplemental calcium or 800 IU vitamin D

• Anemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
2	Metabolic Bone Center at the University of Tennessee	Memphis	Tennessee	United States	38163
3	Preventive Medicine, University of Tennessee	Memphis	Tennessee	United States	38163

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Sue C. Kaste, D.O., St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital

Publications

• Crom DB, Tyc VL, Rai SN, Deng X, Hudson MM, Booth A, Rodrigues LN, Zhang L, McCammon E, Kaste SC. Retention of survivors of acute lymphoblastic leukemia in a longitudinal study of bone mineral density. J Child Health Care. 2006 Dec;10(4):337-50.
• Kaste SC, Rai SN, Fleming K, McCammon EA, Tylavsky FA, Danish RK, Rose SR, Sitter CD, Pui CH, Hudson MM. Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2006 Jan;46(1):77-87.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00186901
• Other Study ID Numbers: BONEII
• First Posted: Sep 16, 2005
• Last Update Posted: May 10, 2017
• Last Verified: Dec 1, 2011

• Keywords provided by St. Jude Children's Research Hospital: Bone Density
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Osteoporosis; Vitamin D; Calcium Carbonate; Calcium

Study Results

Participant Flow

Recruitment Details	429 patients were recruited at St. Jude Children's Research Hospital between August 7, 2000 and July 27, 2006. 4 patients were found to be ineligible and 1 patient was taken off study per the PI's request. 424 patients were available at baseline.
Pre-assignment Detail	424 total patients were enrolled on the study. 149 patients were ineligible for randomization. 275 patients were identified with Bone Mineral Density (BMD) Z-scores > 0 and thus were eligible for intervention and were randomized to receive either Calcium and Vitamin D supplementation or placebo.

Arm/Group Title	Placebo Group	Supplement Group	Patients Ineligible for Randomization
Arm/Group Description	Nutritional counseling + placebo	Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	424 patients were enrolled into the study, 149 were ineligible for randomization.
Period Title: Overall Study
STARTED	134	141	149
Baseline	134	141	0
12 Month Follow-up	117	122	0
24 Month Follow-up	106	107	0
COMPLETED	85	96	0
NOT COMPLETED	49	45	149

Baseline Characteristics

Arm/Group Title	Placebo Group	Supplement Group	Patients Ineligible for Randomization	Total
Arm/Group Description	Nutritional counseling + placebo	Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	424 patients were enrolled into the study, 149 were ineligible for randomization.	Total of all reporting groups
Overall Participants	134	141	149	424
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17.9 (5.6)	17.6 (6.3)	19.2 (6.6)	17.8 (5.9)
Sex: Female, Male (Count of Participants)
Female	56 41.8%	63 44.7%	87 58.4%	206 48.6%
Male	78 58.2%	78 55.3%	62 41.6%	218 51.4%

Outcome Measures

1. Primary Outcome

Title	Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD)
Description	The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits.
Time Frame	Baseline, 12 months, 24 months, and at 36 months or study end

Outcome Measure Data

Analysis Population Description

Of the 275 pts identified with BMD z-scores < 0, 134 were randomized to the placebo group and 141 to the supplement group. Bone Mineral Density QCT Z-scores were calculated at baseline, 12 months, 24 months, and at 36 months or study end.

Arm/Group Title	Placebo	Supplement
Arm/Group Description	Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.
Measure Participants	134	141
Baseline	-0.95	-0.97
12 Months	-0.87	-1.04
24 Months	-0.72	-0.76
36 Months (study end)	-0.56	-0.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments	Baseline where N=134
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Wilcoxon Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments	12 Month BMD Z-Score Calculation where N=109
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Wilcoxon Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments	24 Month BMD Z-Score calculation where N=91
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Wilcoxon Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments	36 Month (End of Study) BMD Z-Score calculation where N=84
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Wilcoxon Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Bone Mineral Density in Male and Female ALL Survivors
Description	Using bone mineral density Z-score, assess relationship between predisposing factors (gender) and bone mineral density; a negative value indicates a deficit in bone mineral density.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Baseline participants were assessed to determine whether gender was a pre-disposing factor for bone mineral density.

Arm/Group Title	Male	Female
Arm/Group Description	218 males were eligible for the study	206 females were eligible for the study
Measure Participants	218	206
Median (Standard Error) [Z-score]	-0.62 (1.18)	-0.3 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.32
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Bone Mineral Density by Race of ALL Survivors
Description	Using bone mineral density Z-score, assess relationship between predisposing factors (race) and bone mineral density; a negative value indicates a deficit in bone mineral density.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Assess baseline participants to determine whether race contributed to bone mineral density.

Arm/Group Title	White	Non-white
Arm/Group Description	365 white patients were eligible for the study	59 non-white were eligible for the study
Measure Participants	365	59
Median (Standard Error) [Z-score]	-0.54 (1.14)	0.15 (1.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.69
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Bone Mineral Density by Age Group of ALL Survivors
Description	Using bone mineral density Z-score, assess relationship between predisposing factors (age groups) and bone mineral density; a negative value indicates a deficit in bone mineral density.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Assess baseline participants to determine whether age was a contributing factor in bone mineral density.

Arm/Group Title	9 to 13 Years	13 to 18 Years	18 to 22 Years	Above 22 Years
Arm/Group Description	98 patients between the ages of 9 and 13 were eligible for the study	139 patients between the ages of 13 and 18 were eligible for the study	74 patients between the ages of 18 and 22 were eligible for the study	113 patients greater than 22 years of age were eligible for the study
Measure Participants	98	139	74	113
Median (Standard Error) [Z-score]	-0.6 (1.1)	-0.54 (1.21)	-0.59 (1.2)	-0.25 (1.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years, Above 22 Years
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0092
	Comments
	Method	Kruskal-Wallis
	Comments

5. Secondary Outcome

Title	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
Description	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 121 patients at baseline were assessed by both method the QCT and DXA methods to assess Bone Mineral Density.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

275 patients were assessed at baseline and received a QCT Scan. 121 patients were also assessed using the DEXA Scan. Comparison of the two methods used 121 paired studies to arrive at a correlation coefficient.

Arm/Group Title	Placebo - (QCT)	Placebo - (DXA)	Supplement - (QCT)	Supplement - (DXA)
Arm/Group Description	134 patients were assessed at baseline using the QCT scan.	60 of the 134 baseline patients also had a DXA scan.	141 patients were assessed at baseline using the QCT scan.	61 of the 141 baseline patients also had a DXA scan.
Measure Participants	134	60	141	61
Mean (Standard Deviation) [Z-score]	-1.06 (0.70)	-1.30 (1.21)	-1.09 (0.74)	-1.18 (1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years, Above 22 Years
	Comments	275 received a QCT and 121 received a DXA scan. 121 paired scans were evaluated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Z-test
	Comments
Method of Estimation	Estimation Parameter	Correlation coefficient
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
Description	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 218 patients were assessed at 12 months for QCT. 94 were evaluated using DXA. 94 patients received both scans.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

218 patients were assessed at the 12 months interval and received a QCT Scan. 94 patients were also assessed using the DXA Scan. Comparison of the two methods used 94 paired studies to arrive at a correlation.

Arm/Group Title	Placebo - (QCT)	Placebo - (DXA)	Supplement - (QCT)	Supplement - (DXA)
Arm/Group Description	109 patients were assessed at 12 months using the QCT scan.	47 of the 109 patients assessed at 12 months also had a DXA scan.	109 patients were assessed at 12 months using the QCT scan.	47 of the 109 patients assessed at 12 months also had a DXA scan.
Measure Participants	109	47	109	47
Mean (Standard Deviation) [Z-score]	-1.02 (0.87)	-1.20 (1.36)	-1.04 (0.89)	-0.79 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years, Above 22 Years
	Comments	218 patients were assessed at 12 months and received a QCT Scan. 94 patients were also assessed using the DEXA Scan. Comparison of the two methods used 94 paired studies to arrive at a correlation coefficient.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Z-test
	Comments
Method of Estimation	Estimation Parameter	Correlation coefficient
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
Description	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 188 patients were assessed at 24 months by the QCT method and 90 were evaluated using the DXA methods to assess Bone Mineral Density. 90 patients received both scans.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

188 patients were assessed at the 24 months interval and received a QCT Scan. 90 patients were also assessed using the DXA Scan. Comparison of the two methods used 90 paired studies to arrive at a correlation.

Arm/Group Title	Placebo - (QCT)	Placebo - (DXA)	Supplement - (QCT)	Supplement - (DXA)
Arm/Group Description	91 patients were assessed at 24 months using the QCT scan.	39 of the 91 patients assessed at 24 months also had a DXA scan.	97 patients were assessed at 24 months using the QCT scan.	51 of the 97 patients assessed at 24 months also had a DXA scan.
Measure Participants	91	39	97	51
Mean (Standard Deviation) [Z-score]	-0.75 (0.82)	-0.77 (1.31)	-0.84 (0.86)	-0.60 (1.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years, Above 22 Years
	Comments	188 patients were assessed at baseline and received a QCT Scan. 90 patients were also assessed using the DEXA Scan. Comparison of the two methods used 90 paired studies to arrive at a correlation coefficient.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Z-test
	Comments
Method of Estimation	Estimation Parameter	Correlation coefficient
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.36 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
Description	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 180 patients were assessed at 36 months by the QCT method and 89 were evaluated using the DXA methods to assess Bone Mineral Density. 89 patients received both scans.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

180 patients were assessed at the 36 months interval and received a QCT Scan. 89 patients were also assessed using the DEXA Scan. Comparison of the two methods produced 89 paired studies to arrive at a correlation.

Arm/Group Title	Placebo - (QCT)	Placebo - (DXA)	Supplement - (QCT)	Supplement - (DXA)
Arm/Group Description	84 patients were assessed at 36 months using the QCT scan.	36 of the 84 patients assessed at 36 months also had a DXA scan.	96 patients were assessed at 36 months using the QCT scan.	53 of the 96 patients assessed at 36 months also had a DXA scan.
Measure Participants	84	36	96	53
Median (Standard Deviation) [Z-score]	-0.54 (0.86)	-0.63 (1.14)	-0.71 (0.98)	-0.63 (1.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years, Above 22 Years
	Comments	180 patients were assessed at 36 months and received a QCT Scan. 89 patients were also assessed using the DXA Scan. Comparison of the two methods used 89 paired studies to arrive at a correlation coefficient.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Z-test
	Comments
Method of Estimation	Estimation Parameter	Correlation coefficient
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.30 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype
Description	The Apa1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood
Time Frame	At enrollment

Outcome Measure Data

Analysis Population Description

Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Apa 1 vitamin D receptor, only 68 had the AA genotype, 104 had the Aa genotype, and 49 had the aa genotype.

Arm/Group Title	Apa 1 - AA Genotype	Apa 1 - Aa Genotype	Apa 1 - aa Genotype
Arm/Group Description	The AA genotype was observed in 68 (16.31%) out of 417 participants, with a median BMD Z score (a unit-less measure comparing to the age and gender matched national average) of -0.56.	The Aa genotype was observed in 104 (24.94%) out of 417 participants, with a median BMD Z score of -0.44.	The aa genotype was present in 49 (11.75%) out of 417 participants, with a median BMD Z score of -0.57.
Measure Participants	68	104	49
Mean (Standard Deviation) [QCT Z-Score]	-0.56 (1.27)	-0.44 (1.28)	-0.57 (1.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Kruskal Wallis
	Comments

10. Secondary Outcome

Title	Mean QCT Z-Score by Bsm 1 Vitamin D Receptor Genotype
Description	The Bsm1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood
Time Frame	At enrollment

Outcome Measure Data

Analysis Population Description

Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Bsm 1 vitamin D receptor, only 41 had the BB genotype, 65 had the Bb genotype, and 77 had the bb genotype.

Arm/Group Title	Bsm - BB Genotype	Bsm - Bb Genotype	Bsm - bb Genotype
Arm/Group Description	The BB genotype was observed in 41 (09.83%) out of 417 participants, with a median BMD Z score (a unit-less measure comparing to the age and gender matched national average) of -0.5.	The Bb genotype was observed in 65 (15.59%) out of 417 participants, with a median BMD Z score of -0.17.	The bb genotype was observed in 77 (18.47%) out of 417 participants, with a median BMD Z score of -0.17.
Measure Participants	41	65	77
Mean (Standard Deviation) [QCT Z-Score]	-0.5 (1.2)	-0.17 (1.25)	-0.17 (1.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Supplement, 18 to 22 Years
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Kruskal Wallis
	Comments

Adverse Events

Time Frame	Patients were assessed for adverse events from August, 2000 through July, 2006.
Arm/Group Title	Placebo Group		Supplement Group		Patients Ineligible for Randomization
Arm/Group Description	Nutritional counseling + placebo		Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period		424 patients were enrolled into the study, 149 were ineligible for randomization.
All Cause Mortality
	Placebo Group		Supplement Group		Patients Ineligible for Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Group		Supplement Group		Patients Ineligible for Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/134 (0%)		0/141 (0%)		0/149 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Group		Supplement Group		Patients Ineligible for Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/134 (0%)		0/141 (0%)		0/149 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.