Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children

• ClinicalTrials.gov Identifier: NCT00106028
• Recruitment Status: Completed
• First Posted: March 21, 2005
• Results First Posted: June 28, 2010
• Last Update Posted: April 22, 2013
• Sponsor: Warner Chilcott
• Information provided by (Responsible Party): Warner Chilcott

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Osteogenesis Imperfecta
• Interventions: Drug: risedronate sodium (Actonel); Drug: Placebo
• Enrollment: 143

Participant Flow

Recruitment Details	147 children > or = 4 and < 16 years of age with Osteogenesis Imperfecta (OI) enrolled at 20 North American and international study centers starting 16NOV2004. Patients weighing 10-30 kg received risedronate 2.5 mg or placebo daily and patients weighing more than 30 kg received risedronate 5 mg or placebo daily.
Pre-assignment Details

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Period Title: Overall Study
Started	49 [1]	94 [1]
Month 12 Completed/Started Open Label	49	87
Completed	43 [2]	82 [2]
Not Completed	6	12
Reason Not Completed
Adverse Event	3	2
Protocol Violation	1	1
Withdrawal by Subject	2	8
Lost to Follow-up	0	1
[1] ITT Population: Patients Randomized and Received at least 1 Dose of Study Drug; [2] Completed Month 36

Baseline Characteristics

Arm/Group Title		Placebo Daily	Risedronate Daily	Total
Arm/Group Description		placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day	Total of all reporting groups
Overall Number of Baseline Participants		49	94	143
Baseline Analysis Population Description		[Not Specified]
Age, Categorical [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants	94 participants	143 participants
	<=18 years	49 100.0%	94 100.0%	143.0
	Between 18 and 65 years	0 0.0%	0 0.0%	0.0
	>=65 years	0 0.0%	0 0.0%	0.0
		[1] Measure Description: There were 147 children enrolled in the study (stated in the protocol). However, 4 children were randomized but did not receive a dose of the study drug. Therefore, only 143 received at least 1 dose of study drug.
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	49 participants	94 participants	143 participants
		8.6 (3.1)	8.9 (3.4)	8.825 (3.313)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants	94 participants	143 participants
	Female	22 44.9%	49 52.1%	71.0
	Male	27 55.1%	45 47.9%	72.0
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	49 participants	94 participants	143 participants
Australia		8	16	24
Belgium		1	1	2
Chile		4	9	13
Czech Republic		1	4	5
Finland		5	7	12
Germany		5	8	13
Hungary		2	2	4
Italy		1	2	3
Poland		5	9	14
South Africa		0	1	1
Spain		1	1	2
United Kingdom		9	21	30
United States		7	13	20

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population
Description	Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. Duplicate scans obtained at screening and Month 12.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	7.592; (5.106 to 10.078)	16.159; (14.295 to 18.024)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.567
	Confidence Interval	95%; 5.590 to 11.545
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population
Description	Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	21.316; (17.357 to 25.275)	25.754; (22.860 to 28.648)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0625
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.438
	Confidence Interval	(2-Sided) 95%; -0.235 to 9.111
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population
Description	Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	33.216; (28.191 to 38.241)	34.753; (31.076 to 38.429)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6103
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.537
	Confidence Interval	(2-Sided) 95%; -4.424 to 7.497
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMD at Month 12, ITT Population
Description	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	4.252; (2.762 to 5.743)	5.806; (4.740 to 6.872)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0808
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.554
	Confidence Interval	95%; -0.193 to 3.301
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMD at Month 24, ITT Population
Description	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	9.716; (7.897 to 11.535)	10.214; (8.899 to 11.528)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6466
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.498
	Confidence Interval	(2-Sided) 95%; -1.648 to 2.644
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMD at Month 36, ITT Population
Description	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	13.540; (11.204 to 15.876)	13.076; (11.374 to 14.777)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7391
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.465
	Confidence Interval	(2-Sided) 95%; -3.224 to 2.294
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	17.885; (13.645 to 22.124)	28.218; (25.038 to 31.398)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS Means and p-value are from ANCOVA model adjusted by baseline and with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	10.333
	Confidence Interval	95%; 5.258 to 15.408
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	42.367; (34.871 to 49.863)	48.407; (42.921 to 53.894)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	01789
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.040
	Confidence Interval	(2-Sided) 95%; -2.807 to 14.887
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	68.054; (57.564 to 78.544)	68.333; (60.607 to 76.060)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9646
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.280
	Confidence Interval	(2-Sided) 95%; -12.196 to 12.755
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	16.483; (13.395 to 19.570)	21.977; (19.772 to 24.181)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0030
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.494
	Confidence Interval	95%; 1.912 to 9.077
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	36.465; (31.582 to 41.347)	37.938; (34.406 to 41.470)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6106
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.473
	Confidence Interval	(2-Sided) 95%; -4.245 to 7.192
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	56.211; (49.470 to 62.952)	56.526; (51.549 to 61.503)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9372
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.315
	Confidence Interval	(2-Sided) 95%; -7.598 to 8.229
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population
Description	Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	-6.028; (-14.899 to 2.844)	25.648; (18.993 to 32.302)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted for baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	31.675
	Confidence Interval	95%; 21.051 to 42.300
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population
Description	Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	15.608; (2.327 to 28.889)	29.637; (19.911 to 39.363)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0793
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	14.029
	Confidence Interval	(2-Sided) 95%; -1.667 to 29.726
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population
Description	Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	19.325; (5.162 to 33.488)	25.640; (15.313 to 35.967)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4575
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.315
	Confidence Interval	(2-Sided) 95%; -10.477 to 23.107
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population
Description	Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population, Population Description Number of Participants Analyzed = Number of participants at baseline and LOCF data

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	-20.661; (-47.090 to 5.769)	16.933; (-1.793 to 35.660)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0172
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	37.594
	Confidence Interval	95%; 6.801 to 68.386
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population
Description	Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	8.371; (-22.631 to 39.373)	7.879; (-14.273 to 30.032)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9786
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.492
	Confidence Interval	(2-Sided) 95%; -36.807 to 35.824
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population
Description	Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	7.146; (-20.474 to 34.766)	-1.494; (-21.400 to 18.411)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5971
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.640
	Confidence Interval	(2-Sided) 95%; -40.952 to 23.672
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population
Description	Measured by DXA.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	8.803; (6.751 to 10.856)	9.817; (8.278 to 11.356)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4154
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.014
	Confidence Interval	95%; -1.442 to 3.470
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population
Description	Measured by DXA.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	16.381; (13.214 to 19.549)	17.266; (14.945 to 19.586)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6404
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.884
	Confidence Interval	(2-Sided) 95%; -2.855 to 4.623
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population
Description	Measured by DXA.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	24.952; (20.877 to 29.027)	23.292; (20.296 to 26.289)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4978
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.660
	Confidence Interval	(2-Sided) 95%; -6.499 to 3.179
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	11.405; (8.708 to 14.101)	14.939; (13.028 to 16.850)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0270
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.534
	Confidence Interval	95%; 0.410 to 6.658
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	24.051; (20.684 to 27.417)	25.116; (22.699 to 27.533)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5925
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.065
	Confidence Interval	(2-Sided) 95%; -2.868 to 4.998
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
Description	[Not Specified]
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	37.109; (32.144 to 42.074)	38.303; (34.674 to 41.931)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6840
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.193
	Confidence Interval	(2-Sided) 95%; -4.604 to 6.991
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	New Morphometric Vertebral Fracture at Month 12, ITT Population
Description	Morphometric Vertebral Fracture measured by semi-quantitative (SQ) analysis of x-rays using the Genant scoring system at endpoint. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Participants
At Least One New Fracture Vertebra	8	28
No New Fractured Vertebra	40	60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0680
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

26. Secondary Outcome

Title	New Morphometric Vertebral Fracture at Month 36, ITT Population
Description	Morphometric Vertebral Fracture measured by SQ analysis of x-rays using the Genant scoring system. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Participants
At Least One New Fracture Vertebra	14	20
No New Fractured Vertebra	31	62

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4121
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

27. Secondary Outcome

Title	Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT
Description	Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and >0 at post-baseline.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Participants
No New Fractured Vertebra	40	60
One Fractured Vertebra	3	17
Two Fractured Vertebra	2	8
Three or more Fractured Vertebra	3	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3658
	Comments	[Not Specified]
	Method	Savage Exact Test
	Comments	[Not Specified]

28. Secondary Outcome

Title	Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT
Description	Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and >0 at post-baseline.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Participants
No New Fractured Vertebra	31	62
One Fractured Vertebra	6	10
Two Fractured Vertebra	5	7
Three or more Fractured Vertebra	3	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3408
	Comments	[Not Specified]
	Method	Savage Exact Test
	Comments	[Not Specified]

29. Secondary Outcome

Title	Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population
Description	Patients aged 4-9 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

ITT Population, Number of Participants Analyzed = Number of participants with baseline and Month 12 data

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	28	53
Measure Type: Number; Unit of Measure: Participants
Number Patients with New Vertebral Fractures	7	19
Number of New Vertebral Fractures	19	32
Number Patients New Fractures & Mild SQ Score	7	17
Number Patients New Fractures & Mod/Sev SQ Score	3	3

30. Secondary Outcome

Title	Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population
Description	Patients aged 10-15 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

ITT Population, Number of Participants Analyzed = Number of participants at baseline and Month 12 data

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	21	41
Measure Type: Number; Unit of Measure: Participants
Number Patients with New Vertebral Fractures	1	10
Number of New Vertebral Fractures	1	13
Number Patients New Fractures & Mild SQ Score	1	10
Number Patients New Fractures & Mod/Sev SQ Score	0	1

31. Secondary Outcome

Title	Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population
Description	Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Time Frame	Time to First Event (days) up to 12 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Probability of Fractures
Number Patients All Fractures	24	29
All Fractures/Kaplan-Meier Cumulative Incidence	0.5043	0.314
Number Patients Vertebral Fractures	0	0
Vertebral Fractures/Kaplan-Meier Cumulative Incid.	0	0
Number Patients Non-Vertebral Fractures	24	29
Non-Vertebral Fractures/Kaplan-Meier Cum. Incid.	0.5043	0.314
Number Patients Long Bone Non-Vertebral Fractures	17	18
Long Bone Non-Vertebral Fractures/Kaplan-Meier Cum	0.3618	0.1954
Number Patients Other Non-Vertebral Fractures	10	12
Other Non-Vertebral Fractures/Kaplan-Meier Cum.	0.204	0.1311

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0253
	Comments	All Fractures
	Method	Cox proportional hazards
	Comments	Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.534
	Confidence Interval	95%; 0.310 to 0.922
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0253
	Comments	All Non-Vertebral Fractures
	Method	Cox Proportional Hazard
	Comments	Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.534
	Confidence Interval	(2-Sided) 95%; 0.310 to 0.922
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0501
	Comments	Long Bone Non-Vertebral Fracture
	Method	Cox Proportional Hazards
	Comments	Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.487
	Confidence Interval	(2-Sided) 95%; 0.250 to 0.950
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2141
	Comments	Other Non-Vertebral Fracture
	Method	Cox Proportional Hazard
	Comments	Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.608
	Confidence Interval	(2-Sided) 95%; 0.262 to 1.410
	Estimation Comments	[Not Specified]

32. Secondary Outcome

Title	Number of Clinical Fractures, Month 12, ITT Population
Description	Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Measure Type: Number; Unit of Measure: Participants
Number of Fractures	38	42
Number of Patients with Fractures	24	29
Number of Vertebral Fractures	0	0
Number Patients with Vertebral Fractures	0	0
Number of Non-Vertebral Fractures	38	42
Number Patients with Non-Vertebral Fractures	24	29
Number Long-Bone Non-Vertebral Fractures	27	28
Number Patients Long-Bone Non-Vertebral Fractures	17	18
Number Other Non-Vertebral Fractures	11	14
Number Patients with Other Non-Vertebral Fractures	10	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0416
	Comments	All Fractures
	Method	Wald test
	Comments	Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.584
	Confidence Interval	95%; 0.348 to 0.980
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0416
	Comments	Non-Vertebral Fracture
	Method	Wald Test
	Comments	Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.584
	Confidence Interval	(2-Sided) 95%; 0.348 to 0.980
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0799
	Comments	Long Bone Non-Vertebral Fracture
	Method	Wald Test
	Comments	Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.543
	Confidence Interval	(2-Sided) 95%; 0.274 to 1.076
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.682
	Comments	Other Non-Vertebral Fracture
	Method	Wald Test
	Comments	Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.682
	Confidence Interval	(2-Sided) 95%; 0.304 to 1.532
	Estimation Comments	[Not Specified]

33. Secondary Outcome

Title	Serum BAP - Percent Change From Baseline to Month 12, ITT Population
Description	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	6.783; (-2.107 to 15.674)	-4.895; (-11.509 to 1.719)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0318
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-11.678
	Confidence Interval	95%; -22.325 to -1.031
	Estimation Comments	[Not Specified]

34. Secondary Outcome

Title	Serum BAP - Percent Change From Baseline to Month 24, ITT Population
Description	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	-11.196; (-20.748 to -1.643)	-11.128; (-18.286 to -3.971)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9907
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.067
	Confidence Interval	(2-Sided) 95%; -11.401 to 11.536
	Estimation Comments	[Not Specified]

35. Secondary Outcome

Title	Serum BAP - Percent Change From Baseline to Month 36, ITT Population
Description	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and 36 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	-19.884; (-28.658 to -11.109)	-24.570; (-31.304 to -17.836)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3826
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.686
	Confidence Interval	(2-Sided) 95%; -15.276 to 5.903
	Estimation Comments	[Not Specified]

36. Secondary Outcome

Title	Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population
Description	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and Endpoint / Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	-14.556; (-24.218 to -4.894)	-41.185; (-48.625 to -33.745)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-26.629
	Confidence Interval	95%; -38.089 to -15.169
	Estimation Comments	[Not Specified]

37. Secondary Outcome

Title	Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population
Description	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	-40.358; (-54.722 to -25.994)	-31.318; (-42.478 to -20.158)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3075
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	9.040
	Confidence Interval	(2-Sided) 95%; -8.433 to 26.512
	Estimation Comments	[Not Specified]

38. Secondary Outcome

Title	Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population
Description	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Change
	-47.570; (-57.317 to -37.823)	-52.609; (-60.203 to -45.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3998
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.039
	Confidence Interval	(2-Sided) 95%; -16.849 to 6.772
	Estimation Comments	[Not Specified]

39. Secondary Outcome

Title	Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population
Description	Wong-Baker FACES Pain Rating Scale (pain assessment scale using facial expressions, translated into a range from 0= no pain [smiling face] to 10= worst pain possible [distorted face with tears]; negative values indicate decrease in pain). Reference: Wong DL et al.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Units on a Scale
	-0.056; (-0.471 to 0.358)	-0.409; (-0.712 to -0.106)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1592
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.352
	Confidence Interval	95%; -0.845 to 0.140
	Estimation Comments	[Not Specified]

40. Secondary Outcome

Title	Bone Age (Years), Change From Baseline to Month 12, ITT Population
Description	Bone Age determined by visual assessment of hand / wrist radiographs.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Years
	0.956; (0.756 to 1.155)	1.083; (0.935 to 1.231)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2917
	Comments	[Not Specified]
	Method	ANOVA
	Comments	LS means and p-value are from ANOVA model with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.127
	Confidence Interval	95%; -0.111 to 0.365
	Estimation Comments	[Not Specified]

41. Secondary Outcome

Title	Bone Age (Years), Change From Baseline to Month 24, ITT Population
Description	Bone Age determined by visual assessment of hand / wrist radiographs.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Years
	2.147; (1.888 to 2.407)	2.155; (1.962 to 2.347)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9622
	Comments	[Not Specified]
	Method	ANOVA
	Comments	LS mean and p-value are from ANOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.007
	Confidence Interval	95%; -0.304 to 0.319
	Estimation Comments	[Not Specified]

42. Secondary Outcome

Title	Bone Age (Years), Change From Baseline to Month 36, ITT Population
Description	Bone Age determined by visual assessment of hand / wrist radiographs.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Years
	3.087; (2.800 to 3.374)	3.096; (2.879 to 3.312)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9596
	Comments	[Not Specified]
	Method	ANOVA
	Comments	LS means and p-value are from ANOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.009
	Confidence Interval	(2-Sided) 95%; -0.336 to 0.354
	Estimation Comments	[Not Specified]

43. Secondary Outcome

Title	Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population
Description	Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Population, Number of Participants Analyzed = Number of participants at baseline and Month 12 data

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Change in Annualized Growth Velocity
	0.895; (0.709 to 1.080)	1.002; (0.865 to 1.138)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3400
	Comments	[Not Specified]
	Method	ANOVA
	Comments	LS means and p-value are from ANOVA model with fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.107
	Confidence Interval	95%; -0.114 to 0.328
	Estimation Comments	[Not Specified]

44. Secondary Outcome

Title	Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population
Description	Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

ITT Population, Number of Participants Analyzed = Number of participants at baseline and Month 12 data

Arm/Group Title	Placebo Daily	Risedronate Daily
Arm/Group Description:	placebo tablet, once a day for one year then for two years open label risedronate	risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Number of Participants Analyzed	49	94
Least Squares Mean (95% Confidence Interval); Unit of Measure: Change in Annualized Growth Velocity
	0.982; (0.886 to 1.077)	1.011; (0.941 to 1.081)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Daily, Risedronate Daily
	Comments	A total of 123 patients were to be randomized in 2:1 ratio. The sample size allowed detection of a difference of at least 5% in lumbar spine BMD percent change from baseline to 12 months with 90% power. Calculation based on assumption that common within-group SD would be approximately 7% and dropout rate within Year 1 would be 20%. A difference of 5% in lumbar spin BMD percent change from baseline was considered clinically meaningful.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6218
	Comments	[Not Specified]
	Method	ANOVA
	Comments	LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.029
	Confidence Interval	(2-Sided) 95%; -0.084 to 0.142
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo Daily		Risedronate Daily		Years 2 & 3 Placebo-Risedronate		Years 2 & 3 Risedronate
Arm/Group Description	placebo tablet, once a day for one year then for two years open label risedronate		risedronate tablet, once a day for one year then for two years open label risedronate once a day		Year 1 Placebo Double-Blind, Years 2 & 3 Open-Label Risedronate		Years 1-3 Risedronate, Double-Blind Year 1, Open-Label Years 2 & 3
All-Cause Mortality
	Placebo Daily		Risedronate Daily		Years 2 & 3 Placebo-Risedronate		Years 2 & 3 Risedronate
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Placebo Daily		Risedronate Daily		Years 2 & 3 Placebo-Risedronate		Years 2 & 3 Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/49 (16.33%)		11/94 (11.70%)		13/49 (26.53%)		16/87 (18.39%)
Cardiac disorders
Palpitations † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
Ear and labyrinth disorders
Tympanic Membrane Perforation † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Gastrointestinal disorders
Crohn's disease † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	0/49 (0.00%)	0	0/87 (0.00%)	0
Gastritis † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	0/49 (0.00%)	0	0/87 (0.00%)	0
General disorders
Device Failure † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Infections and infestations
Cellulitis † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	1/49 (2.04%)	1	0/87 (0.00%)	0
Mastoiditis † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	0/49 (0.00%)	0	0/87 (0.00%)	0
Gastroenteritis † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Pneumonia † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Tonsillitis † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Injury, poisoning and procedural complications
Femur fracture † 1	7/49 (14.29%)	8	4/94 (4.26%)	7	6/49 (12.24%)	7	3/87 (3.45%)	5
Forearm fracture † 1	0/49 (0.00%)	0	2/94 (2.13%)	2	1/49 (2.04%)	1	1/87 (1.15%)	1
Tibia fracture † 1	2/49 (4.08%)	2	2/94 (2.13%)	2	1/49 (2.04%)	1	2/87 (2.30%)	2
Fibula fracture † 1	1/49 (2.04%)	1	1/94 (1.06%)	1	1/49 (2.04%)	1	1/87 (1.15%)	1
Ulna fracture † 1	2/49 (4.08%)	2	1/94 (1.06%)	1	2/49 (4.08%)	2	2/87 (2.30%)	3
Upper limb fracture † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	0/49 (0.00%)	0	1/87 (1.15%)	1
Lower limb fracture † 1	1/49 (2.04%)	2	0/94 (0.00%)	0	0/49 (0.00%)	0	0/87 (0.00%)	0
Radius fracture † 1	2/49 (4.08%)	2	0/94 (0.00%)	0	2/49 (4.08%)	2	0/87 (0.00%)	0
Wrist fracture † 1	1/49 (2.04%)	1	0/94 (0.00%)	0	0/49 (0.00%)	0	0/87 (0.00%)	0
Concussion † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Humerus Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Ilium Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Pelvic Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Rib Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Cervical Vertebral Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
Hand Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
Patella Fracture † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back Pain † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	0/49 (0.00%)	0	1/87 (1.15%)	1
Scoliosis † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Bone Neoplasm † 1	0/49 (0.00%)	0	0/94 (0.00%)	0	1/49 (2.04%)	1	0/87 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (12.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Daily		Risedronate Daily		Years 2 & 3 Placebo-Risedronate		Years 2 & 3 Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/49 (95.92%)		86/94 (91.49%)		46/49 (93.88%)		79/87 (90.80%)
Ear and labyrinth disorders
Ear Pain † 1	1/49 (2.04%)	1	0/94 (0.00%)	0	3/49 (6.12%)	3	1/87 (1.15%)	4
Eye disorders
Eye disorders † 1	3/49 (6.12%)	3	4/94 (4.26%)	6	3/49 (6.12%)	3	1/87 (1.15%)	1
Gastrointestinal disorders
Vomiting † 1	3/49 (6.12%)	5	14/94 (14.89%)	28	5/49 (10.20%)	13	5/87 (5.75%)	7
Abdominal pain upper † 1	4/49 (8.16%)	6	10/94 (10.64%)	10	6/49 (12.24%)	7	3/87 (3.45%)	6
Abdominal pain † 1	7/49 (14.29%)	14	8/94 (8.51%)	8	6/49 (12.24%)	6	5/87 (5.75%)	6
Diarrhoea † 1	3/49 (6.12%)	3	6/94 (6.38%)	6	3/49 (6.12%)	4	7/87 (8.05%)	7
Nausea † 1	6/49 (12.24%)	7	4/94 (4.26%)	4	4/49 (8.16%)	5	4/87 (4.60%)	4
General disorders
Pain † 1	5/49 (10.20%)	6	14/94 (14.89%)	16	1/49 (2.04%)	1	3/87 (3.45%)	5
Pyrexia † 1	2/49 (4.08%)	2	8/94 (8.51%)	8	7/49 (14.29%)	8	5/87 (5.75%)	12
Immune system disorders
Seasonal allergies † 1	0/49 (0.00%)	0	5/94 (5.32%)	5	1/49 (2.04%)	2	3/87 (3.45%)	6
Infections and infestations
Upper respiratory tract infection † 1	3/49 (6.12%)	4	8/94 (8.51%)	13	4/49 (8.16%)	7	7/87 (8.05%)	9
Bronchitis † 1	3/49 (6.12%)	7	7/94 (7.45%)	13	2/49 (4.08%)	5	8/87 (9.20%)	13
Nasopharyngitis † 1	3/49 (6.12%)	3	7/94 (7.45%)	8	3/49 (6.12%)	3	9/87 (10.34%)	10
Respiratory tract infection † 1	1/49 (2.04%)	2	6/94 (6.38%)	11	3/49 (6.12%)	10	7/87 (8.05%)	16
Influenza † 1	2/49 (4.08%)	3	5/94 (5.32%)	6	2/49 (4.08%)	2	8/87 (9.20%)	8
Varicella † 1	0/49 (0.00%)	0	5/94 (5.32%)	5	1/49 (2.04%)	1	0/87 (0.00%)	0
Otitis media † 1	3/49 (6.12%)	3	3/94 (3.19%)	7	2/49 (4.08%)	2	1/87 (1.15%)	1
Tonsillitis † 1	3/49 (6.12%)	3	3/94 (3.19%)	3	1/49 (2.04%)	1	3/87 (3.45%)	3
Gastroenteritis † 1	5/49 (10.20%)	5	1/94 (1.06%)	1	4/49 (8.16%)	8	8/87 (9.20%)	9
Injury, poisoning and procedural complications
Fall † 1	14/49 (28.57%)	21	19/94 (20.21%)	24	22/49 (44.90%)	31	36/87 (41.38%)	55
Femur fracture † 1	8/49 (16.33%)	9	9/94 (9.57%)	12	9/49 (18.37%)	11	4/87 (4.60%)	7
Joint sprain † 1	4/49 (8.16%)	4	9/94 (9.57%)	12	3/49 (6.12%)	6	6/87 (6.90%)	6
Contusion † 1	3/49 (6.12%)	3	6/94 (6.38%)	6	2/49 (4.08%)	2	7/87 (8.05%)	10
Foot fracture † 1	1/49 (2.04%)	1	6/94 (6.38%)	7	5/49 (10.20%)	5	7/87 (8.05%)	7
Hand fracture † 1	3/49 (6.12%)	3	5/94 (5.32%)	6	11/49 (22.45%)	11	12/87 (13.79%)	17
Tibia fracture † 1	2/49 (4.08%)	3	5/94 (5.32%)	5	7/49 (14.29%)	11	7/87 (8.05%)	7
Joint injury † 1	3/49 (6.12%)	4	4/94 (4.26%)	4	4/49 (8.16%)	6	5/87 (5.75%)	5
Limb injury † 1	3/49 (6.12%)	5	3/94 (3.19%)	4	3/49 (6.12%)	3	4/87 (4.60%)	8
Ulna fracture † 1	4/49 (8.16%)	5	2/94 (2.13%)	3	5/49 (10.20%)	6	9/87 (10.34%)	12
Muscle strain † 1	3/49 (6.12%)	4	2/94 (2.13%)	3	1/49 (2.04%)	1	1/87 (1.15%)	1
Radius fracture † 1	4/49 (8.16%)	5	1/94 (1.06%)	1	3/49 (6.12%)	3	11/87 (12.64%)	11
Wrist fracture † 1	3/49 (6.12%)	3	0/94 (0.00%)	0	0/49 (0.00%)	0	2/87 (2.30%)	2
Humerus Fracture † 1	0/49 (0.00%)	0	1/94 (1.06%)	1	3/49 (6.12%)	3	5/87 (5.75%)	6
Forearm Fracture † 1	2/49 (4.08%)	2	3/94 (3.19%)	3	5/49 (10.20%)	6	3/87 (3.45%)	3
Clavicle Fracture † 1	2/49 (4.08%)	2	0/94 (0.00%)	0	3/49 (6.12%)	3	2/87 (2.30%)	2
Fibula Fracture † 1	2/49 (4.08%)	2	2/94 (2.13%)	2	4/49 (8.16%)	4	2/87 (2.30%)	2
Dyspepsia † 1	1/49 (2.04%)	1	1/94 (1.06%)	1	3/49 (6.12%)	3	2/87 (2.30%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	8/49 (16.33%)	8	20/94 (21.28%)	27	7/49 (14.29%)	7	11/87 (12.64%)	23
Back pain † 1	5/49 (10.20%)	5	16/94 (17.02%)	20	7/49 (14.29%)	7	13/87 (14.94%)	20
Bone pain † 1	2/49 (4.08%)	2	9/94 (9.57%)	11	2/49 (4.08%)	2	3/87 (3.45%)	4
Arthralgia † 1	7/49 (14.29%)	11	8/94 (8.51%)	11	8/49 (16.33%)	11	5/87 (5.75%)	11
Musculoskeletal pain † 1	2/49 (4.08%)	3	5/94 (5.32%)	5	4/49 (8.16%)	4	2/87 (2.30%)	3
Nervous system disorders
Headache † 1	4/49 (8.16%)	4	19/94 (20.21%)	25	4/49 (8.16%)	5	8/87 (9.20%)	13
Psychiatric disorders
Psychiatric Disorders † 1	1/49 (2.04%)	1	2/94 (2.13%)	2	3/49 (6.12%)	3	2/87 (2.30%)	2
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/49 (6.12%)	3	9/94 (9.57%)	17	4/49 (8.16%)	5	8/87 (9.20%)	18
Oropharyngeal pain † 1	4/49 (8.16%)	4	5/94 (5.32%)	5	4/49 (8.16%)	4	2/87 (2.30%)	7
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders † 1	4/49 (8.16%)	4	9/94 (9.57%)	9	6/49 (12.24%)	9	12/87 (13.79%)	14
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (12.1)

Limitations and Caveats

The clinical meaningfulness of new fractures in the thoracic spine scored as Genant Grade I is unclear, thus the morphometric vertebral fracture data are evaluated further.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.

The findings of the study may be published in a scientific journal or presented at a scientific meeting. Before submitting the results of the study for publication or presentation, the Investigator will allow the Sponsor 30 days in which to review and comment on the manuscript.

Results Point of Contact

• Name/Title: Grexan Wulff, Manager Regulatory Affairs
• Organization: Warner Chilcott
• Phone: 973-442-3376
• EMail: gwulff@wcrx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bishop N, Adami S, Ahmed SF, Anton J, Arundel P, Burren CP, Devogelaer JP, Hangartner T, Hosszu E, Lane JM, Lorenc R, Makitie O, Munns CF, Paredes A, Pavlov H, Plotkin H, Raggio CL, Reyes ML, Schoenau E, Semler O, Sillence DO, Steiner RD. Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Oct 26;382(9902):1424-32. doi: 10.1016/S0140-6736(13)61091-0. Epub 2013 Aug 6.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00106028
• Other Study ID Numbers: 2003100; HMR4003I/3001
• First Submitted: March 18, 2005
• First Posted: March 21, 2005
• Results First Submitted: April 15, 2009
• Results First Posted: June 28, 2010
• Last Update Posted: April 22, 2013