Study of the Effect of Once a Week Risedronate on the Microstructure of Tibia and Radius Using a New Scanning Method

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00386360
• Collaborator: (none)
• Enrollment: 161
• Locations: 9
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 17.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary purpose of the protocol is to evaluate the sensitivity of 3D-pQCT (3D-Peripheral Quantitative Computed Tomography) technology to detect minute changes in bone microarchitecture.

Condition or Disease	Intervention/Treatment	Phase
Osteopenia	Drug: Placebo comparator; Drug: risedronate	Phase 3

Detailed Description

The 3D-pQCT equipment allows the evaluation of changes occurring within the bone at "microarchitecture" level, without the need for invasive bone biopsies. The primary objective is to evaluate the sensitivity of the technology to detect a difference between those treated with risedronate 35mg OAW (once a week) or placebo. Early phase postmenopausal women with osteopenia have been chosen because they have a more rapid and higher level of bone loss during the first few years of the menopause.

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Non-Invasive Evaluation of Bone Microarchitecture Modification in Osteopenic Postmenopausal Women by 3D-Peripheral Quantitative Computed Tomography (3D-pQCT)
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo dose	Drug: Placebo comparator; oral weekly for one year
Experimental: Risedronate 35 mg risedronate, orally, once weekly	Drug: risedronate; 35 mg risedronate, once a week for one year

Outcome Measures

Primary Outcome Measures

1. Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12 [Baseline and Month 12]

Secondary Outcome Measures

1. Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12 [Baseline and Month 12]

2. Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12 [Baseline and Month 12]

3. Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12 [Baseline and Month 12]

4. Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 [Baseline and Month 12]

5. Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 [Baseline and Month 12]

6. Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 [Baseline and Month 12]

7. Lumbar Spine BMD, Percent Change From Baseline to Month 12 [Baseline and Month 12]

8. Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12 [Baseline and Month 12]

9. Femoral Neck BMD, Percent Change From Baseline to Month 12 [Baseline and Month 12]

10. Greater Trochanter BMD, Percent Change From Baseline to Month 12 [Baseline and Month 12]

11. Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12 [Baseline and Month 12]

    ELISA / enzyme-linked immunosorbent assay method by central lab

12. Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12 [Baseline and Month 12]

    Electrochemiluminescence assay method by central lab

13. Height, Percent Change From Baseline to Month 12 [Baseline and Month 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• cessation of menstruation (surgical or natural) between 6 and 36 months prior to study enrollment;

• osteopenic

• must have at least 1 evaluable radius and tibia, without history of fracture (traumatic or atraumatic)

• BMI (body mass index) between 18 and 28 kg/m2 inclusive;

Exclusion Criteria:

• history of any generalized bone disease, including hyperparathyroidism, Paget's disease of bone, renal osteodystrophy, or any other acquired or congenital bone disease; or any known condition that would interfere with the assessment of DXA (dual-energy X-ray absorptiometry) at either the lumbar spine (3 non-evaluable lumbar vertebrae at lumbar spine L1 - L4) or the femoral neck.

• clinical or radiological evidence of osteoporosis, such as atraumatic vertebral compression fracture (* 20% reduction in anterior-to-posterior or middle-to-posterior height ratio; or 20% reduction of the anterior, middle, and/or posterior height as compared with the adjacent vertebrae) documented by spinal X ray or a history of osteoporosis-related atraumatic fracture of the hip or of the wrist;

• glucocorticoid-induced osteopenia;

• previous bisphosphonate therapy;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Buenos Aires		Argentina	C1012AAR
2	Research Facility	Heidelberg	Victoria	Australia	3081
3	Research Facility	Toronto	Ontario	Canada	M5G 2C4
4	Research Facility	Lyon		France
5	Research Facility	Saint-Etienne		France
6	Research Facility	Toulouse		France
7	Research Facility	Berlin		Germany
8	Research Facility	Geneva		Switzerland
9	Research Facility	Cambridge		United Kingdom

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Principal Investigator: Gioacchino D'Alo, MD, P&G Pharmaceuticals, Clinical Development Europe

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00386360
• Other Study ID Numbers: 2005040
• First Posted: Oct 11, 2006
• Last Update Posted: Jan 11, 2012
• Last Verified: Oct 1, 2011

• Additional relevant MeSH terms: Bone Diseases, Metabolic; Risedronic Acid

Study Results

Participant Flow

Recruitment Details	Screening started 3 April 2006

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Period Title: Overall Study
STARTED	49	112
Intent to Treat Population (ITT)	49	110
Primary Efficacy	36	77
COMPLETED	40	95
NOT COMPLETED	9	17

Baseline Characteristics

Arm/Group Title	Placebo	Risedronate	Total
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day	Total of all reporting groups
Overall Participants	49	112	161
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (2.2)	52.6 (1.8)	52.6 (2.0)
Sex: Female, Male (Count of Participants)
Female	49 100%	112 100%	161 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian (Oriental)	1 2%	0 0%	1 0.6%
Caucasian	48 98%	107 95.5%	155 96.3%
Hispanic	0 0%	2 1.8%	2 1.2%
Multi-Racial	0 0%	1 0.9%	1 0.6%
Region of Enrollment (participants) [Number]
France	9 18.4%	24 21.4%	33 20.5%
Germany	23 46.9%	46 41.1%	69 42.9%
United Kingdom	6 12.2%	12 10.7%	18 11.2%
Switzerland	3 6.1%	7 6.3%	10 6.2%
Argentina	6 12.2%	15 13.4%	21 13%
Australia	0 0%	2 1.8%	2 1.2%
Canada	2 4.1%	6 5.4%	8 5%

Outcome Measures

1. Primary Outcome

Title	Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population - all patients in ITT population who had no major protocol violations and had an evaluable distal radius BV/TV (trabecular bone volume to tissue volume) at baseline and Month 12.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	49	110
Least Squares Mean (95% Confidence Interval) [Percent Change]	-1.486	-1.255

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7096
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.231
	Confidence Interval	(2-Sided) 95%; -0.995 to 1.458
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) Population - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-2.121	-1.578

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2973
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.543
	Confidence Interval	(2-Sided) 95%; -0.485 to 1.571
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.786	-0.301

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1275
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.485
	Confidence Interval	(2-Sided) 95%; -0.141 to 1.110
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-1.820	-1.156

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3360
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.664
	Confidence Interval	(2-Sided) 95%; -0.697 to 2.025
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.440	-0.106

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4565
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.334
	Confidence Interval	(2-Sided) 95%; -0.551 to 1.219
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.784	-0.173

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0614
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.611
	Confidence Interval	(2-Sided) 95%; -0.030 to 1.252
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	0.785	0.725

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9212
	Comments
	Method	ANOVA
	Comments	LS means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.060
	Confidence Interval	(2-Sided) 95%; -1.258 to 1.138
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Lumbar Spine BMD, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-1.797	1.473

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.270
	Confidence Interval	(2-Sided) 95%; 2.231 to 4.310
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.976	0.468

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.444
	Confidence Interval	(2-Sided) 95%; 0.748 to 2.140
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Femoral Neck BMD, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-1.422	-0.014

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.408
	Confidence Interval	(2-Sided) 95%; 0.469 to 2.348
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Greater Trochanter BMD, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.462	0.996

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0087
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.458
	Confidence Interval	(2-Sided) 95%; 0.375 to 2.541
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12
Description	ELISA / enzyme-linked immunosorbent assay method by central lab
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	1.537	-38.002

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-39.540
	Confidence Interval	(2-Sided) 95%; -59.957 to -19.123
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12
Description	Electrochemiluminescence assay method by central lab
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-5.762	-46.031

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-40.269
	Confidence Interval	(2-Sided) 95%; -51.300 to -29.238
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Height, Percent Change From Baseline to Month 12
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

PP - all patients in ITT population who had no major protocol violations.

Arm/Group Title	Placebo	Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day	35 mg risedronate tablet, orally, once weekly on the same day
Measure Participants	41	89
Least Squares Mean (95% Confidence Interval) [Percent Change]	-0.163	-0.071

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risedronate
	Comments	In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1385
	Comments
	Method	ANOVA
	Comments	LS Means are least squares (adjusted) means from ANOVA model with fixed effects for treatment and pooled center.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.092
	Confidence Interval	(2-Sided) 95%; -0.030 to 0.213
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Twelve Months
Arm/Group Title	Placebo		Risedronate
Arm/Group Description	Placebo, 1 tablet weekly on the same day		35 mg risedronate tablet, orally, once weekly on the same day
All Cause Mortality
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/49 (10.2%)		7/110 (6.4%)
Ear and labyrinth disorders
Vertigo Positional	1/49 (2%)	1	0/110 (0%)	0
Gastrointestinal disorders
Gastrointestinal Disorder	0/49 (0%)	0	1/110 (0.9%)	1
Infections and infestations
Appendicitis	0/49 (0%)	0	1/110 (0.9%)	1
Cholera	1/49 (2%)	1	0/110 (0%)	0
Vestibuar Neuronitis	1/49 (2%)	1	0/110 (0%)	0
Injury, poisoning and procedural complications
Radius Fracture	0/49 (0%)	0	1/110 (0.9%)	1
Skeletal Injury	0/49 (0%)	0	1/110 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/49 (2%)	1	0/110 (0%)	0
Nervous system disorders
Cervical Root Pain	0/49 (0%)	0	1/110 (0.9%)	1
Psychiatric disorders
Depression	0/49 (0%)	0	1/110 (0.9%)	1
Panic Reaction	0/49 (0%)	0	1/110 (0.9%)	1
Renal and urinary disorders
Urinary Bladder Polyp	0/49 (0%)	0	1/110 (0.9%)	1
Reproductive system and breast disorders
Ovarian Cyst	1/49 (2%)	1	0/110 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/49 (77.6%)		76/110 (69.1%)
Blood and lymphatic system disorders
Anaemia	0/49 (0%)	0	3/110 (2.7%)	4
Cardiac disorders
Angina	1/49 (2%)	1	0/110 (0%)	0
Tachycardia	1/49 (2%)	1	0/110 (0%)	0
Ear and labyrinth disorders
Ear Pain	1/49 (2%)	1	0/110 (0%)	0
Vertigo	1/49 (2%)	1	0/110 (0%)	0
Vertigo Positional	1/49 (2%)	1	0/110 (0%)	0
Gastrointestinal disorders
Abdominal Pain Upper	1/49 (2%)	1	4/110 (3.6%)	4
Periodontitis	0/49 (0%)	0	4/110 (3.6%)	4
Constipation	1/49 (2%)	1	3/110 (2.7%)	3
Dental Caries	0/49 (0%)	0	3/110 (2.7%)	3
Dyspepsia	0/49 (0%)	0	3/110 (2.7%)	4
Abdominal Pain	1/49 (2%)	1	2/110 (1.8%)	2
Diarrhoea	2/49 (4.1%)	2	1/110 (0.9%)	2
Gastritis	2/49 (4.1%)	2	1/110 (0.9%)	2
Glossodynia	1/49 (2%)	1	0/110 (0%)	0
General disorders
Drug Intolerance	1/49 (2%)	1	0/110 (0%)	0
Irritability	1/49 (2%)	1	0/110 (0%)	0
Oedema Peripheral	1/49 (2%)	1	0/110 (0%)	0
Sensation of Foreign Body	1/49 (2%)	1	0/110 (0%)	0
Temperature Intolerance	1/49 (2%)	1	0/110 (0%)	0
Infections and infestations
Nasopharyngitis	5/49 (10.2%)	5	10/110 (9.1%)	11
Bronchitis	3/49 (6.1%)	3	7/110 (6.4%)	7
Gastroenteritis	2/49 (4.1%)	2	4/110 (3.6%)	4
Influenza	4/49 (8.2%)	4	4/110 (3.6%)	4
Cholera	1/49 (2%)	1	0/110 (0%)	0
Tonsillitis	1/49 (2%)	1	0/110 (0%)	0
Vestibular Neuronitis	1/49 (2%)	1	0/110 (0%)	0
Injury, poisoning and procedural complications
Fall	0/49 (0%)	0	4/110 (3.6%)	4
Contusion	0/49 (0%)	0	3/110 (2.7%)	3
Radius Fracture	1/49 (2%)	1	1/110 (0.9%)	1
Back Injury	1/49 (2%)	1	0/110 (0%)	0
Joint Sprain	1/49 (2%)	1	0/110 (0%)	0
Limb Injury	1/49 (2%)	1	0/110 (0%)	0
Investigations
Weight Decreased	1/49 (2%)	1	1/110 (0.9%)	1
Weight Increased	1/49 (2%)	1	0/110 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/49 (4.1%)	2	8/110 (7.3%)	11
Back Pain	5/49 (10.2%)	5	3/110 (2.7%)	4
Bone Pain	1/49 (2%)	1	3/110 (2.7%)	3
Neck Pain	0/49 (0%)	0	3/110 (2.7%)	3
Osteoarthritis	3/49 (6.1%)	3	3/110 (2.7%)	3
Intervertebral Disc Protrusion	2/49 (4.1%)	2	2/110 (1.8%)	2
Chondropathy	1/49 (2%)	1	1/110 (0.9%)	1
Pain in Extremity	1/49 (2%)	2	1/110 (0.9%)	1
Bursitis	1/49 (2%)	1	0/110 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/49 (2%)	1	0/110 (0%)	0
Nervous system disorders
Headache	2/49 (4.1%)	2	3/110 (2.7%)	3
Cervicobrachial Syndrome	1/49 (2%)	1	0/110 (0%)	0
Hypoaesthesia	1/49 (2%)	1	0/110 (0%)	0
Paraesthesia	1/49 (2%)	2	0/110 (0%)	0
Psychiatric disorders
Depression	1/49 (2%)	1	2/110 (1.8%)	2
Reproductive system and breast disorders
Endometriosis	1/49 (2%)	1	0/110 (0%)	0
Ovarian Cyst	1/49 (2%)	1	0/110 (0%)	0
Vulvovaginal Dryness	1/49 (2%)	1	0/110 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/49 (2%)	1	1/110 (0.9%)	1
Asthma	1/49 (2%)	1	0/110 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/49 (2%)	1	0/110 (0%)	0
Dermatitis	1/49 (2%)	1	0/110 (0%)	0
Onchoclasis	1/49 (2%)	1	0/110 (0%)	0
Rash	1/49 (2%)	1	0/110 (0%)	0
Vascular disorders
Hypertension	1/49 (2%)	1	5/110 (4.5%)	5
Hot Flush	1/49 (2%)	1	3/110 (2.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.