Trial Outcomes & Findings for Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children (NCT NCT00106028)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

143 participants

Primary outcome timeframe

Baseline and Month 12

Results posted on

2013-04-22

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Daily placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Study Month 12 Completed/Started Open Label	49	87
Overall Study COMPLETED	43	82
Overall Study NOT COMPLETED	6	12
Overall Study STARTED	49	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Daily placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily risedronate tablet, once a day for one year then for two years open label risedronate once a day
Overall Study Adverse Event	3	2
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	2	8
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day	Total n=143 Participants Total of all reporting groups
Age, Categorical <=18 years	49 Participants n=5 Participants	94 Participants n=7 Participants	143.0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0.0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0.0 Participants n=5 Participants
Age Continuous	8.6 years STANDARD_DEVIATION 3.1 • n=5 Participants	8.9 years STANDARD_DEVIATION 3.4 • n=7 Participants	8.825 years STANDARD_DEVIATION 3.313 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	49 Participants n=7 Participants	71.0 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	45 Participants n=7 Participants	72.0 Participants n=5 Participants
Region of Enrollment Australia	8 participants n=5 Participants	16 participants n=7 Participants	24.0 participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	1 participants n=7 Participants	2.0 participants n=5 Participants
Region of Enrollment Chile	4 participants n=5 Participants	9 participants n=7 Participants	13.0 participants n=5 Participants
Region of Enrollment Czech Republic	1 participants n=5 Participants	4 participants n=7 Participants	5.0 participants n=5 Participants
Region of Enrollment Finland	5 participants n=5 Participants	7 participants n=7 Participants	12.0 participants n=5 Participants
Region of Enrollment Germany	5 participants n=5 Participants	8 participants n=7 Participants	13.0 participants n=5 Participants
Region of Enrollment Hungary	2 participants n=5 Participants	2 participants n=7 Participants	4.0 participants n=5 Participants
Region of Enrollment Italy	1 participants n=5 Participants	2 participants n=7 Participants	3.0 participants n=5 Participants
Region of Enrollment Poland	5 participants n=5 Participants	9 participants n=7 Participants	14.0 participants n=5 Participants
Region of Enrollment South Africa	0 participants n=5 Participants	1 participants n=7 Participants	1.0 participants n=5 Participants
Region of Enrollment Spain	1 participants n=5 Participants	1 participants n=7 Participants	2.0 participants n=5 Participants
Region of Enrollment United Kingdom	9 participants n=5 Participants	21 participants n=7 Participants	30.0 participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	13 participants n=7 Participants	20.0 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population	7.592 Percent Change Interval 5.106 to 10.078	16.159 Percent Change Interval 14.295 to 18.024

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population	21.316 Percent Change Interval 17.357 to 25.275	25.754 Percent Change Interval 22.86 to 28.648

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population	33.216 Percent Change Interval 28.191 to 38.241	34.753 Percent Change Interval 31.076 to 38.429

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population.

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMD at Month 12, ITT Population	4.252 Percent Change Interval 2.762 to 5.743	5.806 Percent Change Interval 4.74 to 6.872

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population.

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMD at Month 24, ITT Population	9.716 Percent Change Interval 7.897 to 11.535	10.214 Percent Change Interval 8.899 to 11.528

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population.

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMD at Month 36, ITT Population	13.540 Percent Change Interval 11.204 to 15.876	13.076 Percent Change Interval 11.374 to 14.777

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population	17.885 Percent Change Interval 13.645 to 22.124	28.218 Percent Change Interval 25.038 to 31.398

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population	42.367 Percent Change Interval 34.871 to 49.863	48.407 Percent Change Interval 42.921 to 53.894

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population	68.054 Percent Change Interval 57.564 to 78.544	68.333 Percent Change Interval 60.607 to 76.06

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMC at Month 12, ITT Population	16.483 Percent Change Interval 13.395 to 19.57	21.977 Percent Change Interval 19.772 to 24.181

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population	36.465 Percent Change Interval 31.582 to 41.347	37.938 Percent Change Interval 34.406 to 41.47

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body BMC at Month 36, ITT Population	56.211 Percent Change Interval 49.47 to 62.952	56.526 Percent Change Interval 51.549 to 61.503

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population	-6.028 Units on a Scale Interval -14.899 to 2.844	25.648 Units on a Scale Interval 18.993 to 32.302

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population	15.608 Units on a Scale Interval 2.327 to 28.889	29.637 Units on a Scale Interval 19.911 to 39.363

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population	19.325 Units on a Scale Interval 5.162 to 33.488	25.640 Units on a Scale Interval 15.313 to 35.967

SECONDARY outcome

Timeframe: Baseline and Month 12

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

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population	-20.661 Units on a Scale Interval -47.09 to 5.769	16.933 Units on a Scale Interval -1.793 to 35.66

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population	8.371 Units on a Scale Interval -22.631 to 39.373	7.879 Units on a Scale Interval -14.273 to 30.032

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

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".

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population	7.146 Units on a Scale Interval -20.474 to 34.766	-1.494 Units on a Scale Interval -21.4 to 18.411

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

Measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population	8.803 Percent Change Interval 6.751 to 10.856	9.817 Percent Change Interval 8.278 to 11.356

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population	16.381 Percent Change Interval 13.214 to 19.549	17.266 Percent Change Interval 14.945 to 19.586

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Measured by DXA.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population	24.952 Percent Change Interval 20.877 to 29.027	23.292 Percent Change Interval 20.296 to 26.289

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population	11.405 Percent Change Interval 8.708 to 14.101	14.939 Percent Change Interval 13.028 to 16.85

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population	24.051 Percent Change Interval 20.684 to 27.417	25.116 Percent Change Interval 22.699 to 27.533

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population	37.109 Percent Change Interval 32.144 to 42.074	38.303 Percent Change Interval 34.674 to 41.931

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
New Morphometric Vertebral Fracture at Month 12, ITT Population At Least One New Fracture Vertebra	8 Participants	28 Participants
New Morphometric Vertebral Fracture at Month 12, ITT Population No New Fractured Vertebra	40 Participants	60 Participants

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
New Morphometric Vertebral Fracture at Month 36, ITT Population At Least One New Fracture Vertebra	14 Participants	20 Participants
New Morphometric Vertebral Fracture at Month 36, ITT Population No New Fractured Vertebra	31 Participants	62 Participants

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT No New Fractured Vertebra	40 Participants	60 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT One Fractured Vertebra	3 Participants	17 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT Two Fractured Vertebra	2 Participants	8 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT Three or more Fractured Vertebra	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT No New Fractured Vertebra	31 Participants	62 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT One Fractured Vertebra	6 Participants	10 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT Two Fractured Vertebra	5 Participants	7 Participants
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT Three or more Fractured Vertebra	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Month 12

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

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=28 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=53 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population Number Patients with New Vertebral Fractures	7 Participants	19 Participants
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population Number of New Vertebral Fractures	19 Participants	32 Participants
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population Number Patients New Fractures & Mild SQ Score	7 Participants	17 Participants
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population Number Patients New Fractures & Mod/Sev SQ Score	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Month 12

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

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=21 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=41 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population Number Patients with New Vertebral Fractures	1 Participants	10 Participants
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population Number of New Vertebral Fractures	1 Participants	13 Participants
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population Number Patients New Fractures & Mild SQ Score	1 Participants	10 Participants
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population Number Patients New Fractures & Mod/Sev SQ Score	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Time to First Event (days) up to 12 Months

Population: ITT Population

Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Number Patients All Fractures	24 Probability of Fractures 29	29 Probability of Fractures
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population All Fractures/Kaplan-Meier Cumulative Incidence	0.5043 Probability of Fractures .0740	0.314 Probability of Fractures .0484
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Number Patients Vertebral Fractures	0 Probability of Fractures	0 Probability of Fractures
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Vertebral Fractures/Kaplan-Meier Cumulative Incid.	0 Probability of Fractures 0	0 Probability of Fractures 0
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Number Patients Non-Vertebral Fractures	24 Probability of Fractures	29 Probability of Fractures
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Non-Vertebral Fractures/Kaplan-Meier Cum. Incid.	0.5043 Probability of Fractures 0.0740	0.314 Probability of Fractures 0.0484
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Number Patients Long Bone Non-Vertebral Fractures	17 Probability of Fractures	18 Probability of Fractures
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Long Bone Non-Vertebral Fractures/Kaplan-Meier Cum	0.3618 Probability of Fractures 0.0714	0.1954 Probability of Fractures 0.0413
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Number Patients Other Non-Vertebral Fractures	10 Probability of Fractures	12 Probability of Fractures
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Other Non-Vertebral Fractures/Kaplan-Meier Cum.	0.204 Probability of Fractures 0.0576	0.1311 Probability of Fractures 0.0353

SECONDARY outcome

Timeframe: 12 Months

Population: ITT Population

Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Number of Clinical Fractures, Month 12, ITT Population Number of Fractures	38 Participants	42 Participants
Number of Clinical Fractures, Month 12, ITT Population Number of Patients with Fractures	24 Participants	29 Participants
Number of Clinical Fractures, Month 12, ITT Population Number of Vertebral Fractures	0 Participants	0 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Patients with Vertebral Fractures	0 Participants	0 Participants
Number of Clinical Fractures, Month 12, ITT Population Number of Non-Vertebral Fractures	38 Participants	42 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Patients with Non-Vertebral Fractures	24 Participants	29 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Long-Bone Non-Vertebral Fractures	27 Participants	28 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Patients Long-Bone Non-Vertebral Fractures	17 Participants	18 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Other Non-Vertebral Fractures	11 Participants	14 Participants
Number of Clinical Fractures, Month 12, ITT Population Number Patients with Other Non-Vertebral Fractures	10 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline and 12 Months

Population: ITT Population

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Serum BAP - Percent Change From Baseline to Month 12, ITT Population	6.783 Percent Change Interval -2.107 to 15.674	-4.895 Percent Change Interval -11.509 to 1.719

SECONDARY outcome

Timeframe: Baseline and 24 Months

Population: ITT Population

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Serum BAP - Percent Change From Baseline to Month 24, ITT Population	-11.196 Percent Change Interval -20.748 to -1.643	-11.128 Percent Change Interval -18.286 to -3.971

SECONDARY outcome

Timeframe: Baseline and 36 Months

Population: ITT Population

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Serum BAP - Percent Change From Baseline to Month 36, ITT Population	-19.884 Percent Change Interval -28.658 to -11.109	-24.570 Percent Change Interval -31.304 to -17.836

SECONDARY outcome

Timeframe: Baseline and Endpoint / Month 12

Population: ITT Population

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population	-14.556 Percent Change Interval -24.218 to -4.894	-41.185 Percent Change Interval -48.625 to -33.745

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population	-40.358 Percent Change Interval -54.722 to -25.994	-31.318 Percent Change Interval -42.478 to -20.158

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population	-47.570 Percent Change Interval -57.317 to -37.823	-52.609 Percent Change Interval -60.203 to -45.015

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population	-0.056 Units on a Scale Interval -0.471 to 0.358	-0.409 Units on a Scale Interval -0.712 to -0.106

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: ITT Population

Bone Age determined by visual assessment of hand / wrist radiographs.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Bone Age (Years), Change From Baseline to Month 12, ITT Population	0.956 Years Interval 0.756 to 1.155	1.083 Years Interval 0.935 to 1.231

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT Population

Bone Age determined by visual assessment of hand / wrist radiographs.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Bone Age (Years), Change From Baseline to Month 24, ITT Population	2.147 Years Interval 1.888 to 2.407	2.155 Years Interval 1.962 to 2.347

SECONDARY outcome

Timeframe: Baseline and Month 36

Population: ITT Population

Bone Age determined by visual assessment of hand / wrist radiographs.

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Bone Age (Years), Change From Baseline to Month 36, ITT Population	3.087 Years Interval 2.8 to 3.374	3.096 Years Interval 2.879 to 3.312

SECONDARY outcome

Timeframe: Baseline and Month 12

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

Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population	0.895 Change in Annualized Growth Velocity Interval 0.709 to 1.08	1.002 Change in Annualized Growth Velocity Interval 0.865 to 1.138

SECONDARY outcome

Timeframe: Baseline and Month 36

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

Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]

Outcome measures

Outcome measures
Measure	Placebo Daily n=49 Participants placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 Participants risedronate tablet, once a day for one year then for two years open label risedronate once a day
Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population	0.982 Change in Annualized Growth Velocity Interval 0.886 to 1.077	1.011 Change in Annualized Growth Velocity Interval 0.941 to 1.081

Adverse Events

Placebo Daily

Serious events: 8 serious events

Other events: 47 other events

Deaths: 0 deaths

Risedronate Daily

Serious events: 11 serious events

Other events: 86 other events

Deaths: 0 deaths

Years 2 & 3 Placebo-Risedronate

Serious events: 13 serious events

Other events: 46 other events

Deaths: 0 deaths

Years 2 & 3 Risedronate

Serious events: 16 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Grexan Wulff, Manager Regulatory Affairs

Warner Chilcott

Phone: 973-442-3376

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Daily n=49 participants at risk placebo tablet, once a day for one year then for two years open label risedronate	Risedronate Daily n=94 participants at risk risedronate tablet, once a day for one year then for two years open label risedronate once a day	Years 2 & 3 Placebo-Risedronate n=49 participants at risk Year 1 Placebo Double-Blind, Years 2 \& 3 Open-Label Risedronate	Years 2 & 3 Risedronate n=87 participants at risk Years 1-3 Risedronate, Double-Blind Year 1, Open-Label Years 2 \& 3
Injury, poisoning and procedural complications Femur fracture	14.3% 7/49 • Number of events 8 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	4.3% 4/94 • Number of events 7 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	12.2% 6/49 • Number of events 7 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	3.4% 3/87 • Number of events 5 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.1% 2/94 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Tibia fracture	4.1% 2/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.1% 2/94 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.3% 2/87 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Fibula fracture	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Ulna fracture	4.1% 2/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	4.1% 2/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.3% 2/87 • Number of events 3 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Lower limb fracture	2.0% 1/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Radius fracture	4.1% 2/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	4.1% 2/49 • Number of events 2 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Wrist fracture	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Gastrointestinal disorders Crohn's disease	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Gastrointestinal disorders Gastritis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Infections and infestations Cellulitis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Infections and infestations Mastoiditis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/94 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Infections and infestations Gastroenteritis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Infections and infestations Pneumonia	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Infections and infestations Tonsillitis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Concussion	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Ilium Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Pelvic Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Cervical Vertebral Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Injury, poisoning and procedural complications Patella Fracture	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Ear and labyrinth disorders Tympanic Membrane Perforation	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
General disorders Device Failure	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	1.1% 1/87 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Cardiac disorders Palpitations	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign Bone Neoplasm	0.00% 0/49 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/94 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	2.0% 1/49 • Number of events 1 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment	0.00% 0/87 • 36 months: One year double-blind treatment, 2 years open-label risedronate treatment