CompletedNCT00106028Updated Apr 22, 2013Results posted

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

A Phase 3 interventional study of risedronate sodium (Actonel) and Placebo in Osteogenesis Imperfecta, sponsored by Warner Chilcott. Completed at 20 sites in 13 countries. Open to participants aged 4 Years to 15 Years. Per ClinicalTrials.gov, last updated 2013-04-22.

Sponsored by Warner Chilcott · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 143
Allocation: Randomized
Ages: 4 Years to 15 Years
Sex: All

Study summary

Children with Osteogenesis Imperfecta (OI) have bone pain, low bone mass and fractures. There are no approved drugs for the treatment of OI in children, even though some intravenous (IV) bisphosphonates are used off-label in some countries. In a single dose, pharmacokinetic study, data showed that risedronate was well tolerated in 28 children with OI. This three year study will test the safety and efficacy of risedronate in the treatment of children with OI. For the first year, patients will be randomized to the risedronate and placebo groups in a 2:1 ratio. For the second and third years of the study, all patients will receive risedronate.

Conditions studied

Osteogenesis Imperfecta

Browse trials for

Osteogenesis Imperfecta 85

Keywords

Primary disease: Osteogenesis Imperfecta

In context

Osteogenesis Imperfecta

85 studies on the registry are indexed under Osteogenesis Imperfecta; 20 are open to participants now.

This study's enrollment of 143 is above the median of 26 across 59 interventional studies indexed under Osteogenesis Imperfecta.

Browse Osteogenesis Imperfecta studies →

Lead sponsor

Warner Chilcott is the lead sponsor of 57 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 4 Years to 15 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

OI diagnosis
increased risk of fracture: either has a history of at least 1 radiographically confirmed, non-traumatic or low impact fracture plus low bone mineral density (BMD) or has very low BMD with or without a history of fractures.

Exclusion criteria

Exclusion Criteria:

Any bisphosphonate use within one year of enrollment

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 143 participants (actual)

Study arms

Placebo comparator
Placebo Daily
placebo tablet, once a day for one year then for two years open label risedronate
Drug: Placebo
Experimental
Risedronate Daily
risedronate tablet, once a day for one year then for two years open label risedronate once a day
Drug: risedronate sodium (Actonel)

Interventions

Drugrisedronate sodium (Actonel)
risedronate tablet once a day for one year followed by risedronate once a day for two years
DrugPlacebo
placebo tablet once a day for one year followed by risedronate once a day for two years

What researchers measure

Primary outcomes

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, 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.
Time frame: Baseline and Month 12

Secondary outcomes

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population
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
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population
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
Percent Change From Baseline in Total Body BMD at Month 12, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body BMD at Month 24, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body BMD at Month 36, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 36
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
Time frame: Baseline and Month 36
Lumbar Spine Z-score - Percent Change From Baseline to Month 12, 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".
Time frame: Baseline and Month 12
Lumbar Spine Z-score - Percent Change From Baseline to Month 24, 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".
Time frame: Baseline and Month 24
Lumbar Spine Z-score - Percent Change From Baseline to Month 36, 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".
Time frame: Baseline and Month 36
Total Body Z-score- Percent Change From Baseline to Month 12, 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".
Time frame: Baseline and Month 12
Total Body Z-score- Percent Change From Baseline to Month 24, 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".
Time frame: Baseline and Month 24
Total Body Z-score- Percent Change From Baseline to Month 36, 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".
Time frame: Baseline and Month 36
Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population
Measured by DXA.
Time frame: Baseline and Month 12
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population
Measured by DXA.
Time frame: Baseline and Month 24
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population
Measured by DXA.
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
Time frame: Baseline and Month 36
New Morphometric Vertebral Fracture at Month 12, 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.
Time frame: Baseline and Month 12
New Morphometric Vertebral Fracture at Month 36, 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.
Time frame: Baseline and Month 36
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT
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
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT
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
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population
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
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population
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
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population
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
Number of Clinical Fractures, Month 12, ITT Population
Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Time frame: 12 Months
Serum BAP - Percent Change From Baseline to Month 12, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 12 Months
Serum BAP - Percent Change From Baseline to Month 24, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 24 Months
Serum BAP - Percent Change From Baseline to Month 36, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 36 Months
Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population
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
Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population
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
Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population
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
Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, 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.
Time frame: Baseline and Month 12
Bone Age (Years), Change From Baseline to Month 12, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 12
Bone Age (Years), Change From Baseline to Month 24, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 24
Bone Age (Years), Change From Baseline to Month 36, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 36
Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population
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
Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population
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

Results

Posted Jun 28, 2010

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.

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 flow — Overall Study
Milestone	Placebo Daily	Risedronate Daily
Started	49	94
Month 12 completed/started open label	49	87
Completed	43	82
Not completed	6	12
Withdrew: Adverse event	3	2
Withdrew: Protocol violation	1	1
Withdrew: Withdrawal by subject	2	8
Withdrew: Lost to follow-up	0	1

Outcome measures

SecondaryPercent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population

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
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population	21.316 (17.357 to 25.275)	25.754 (22.860 to 28.648)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0625 · Mean difference (net): 4.438 · 95% CI -0.235 to 9.111LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population

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
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population	33.216 (28.191 to 38.241)	34.753 (31.076 to 38.429)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.6103 · Mean difference (net): 1.537 · 95% CI -4.424 to 7.497LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body BMD at Month 12, ITT Population

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

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMD at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMD at Month 12, ITT Population	4.252 (2.762 to 5.743)	5.806 (4.740 to 6.872)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0808 · Mean difference (net): 1.554 · 95% CI -0.193 to 3.301LS 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.

SecondaryPercent Change From Baseline in Total Body BMD at Month 24, ITT Population

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

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMD at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMD at Month 24, ITT Population	9.716 (7.897 to 11.535)	10.214 (8.899 to 11.528)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.6466 · Mean difference (net): 0.498 · 95% CI -1.648 to 2.644LS 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.

SecondaryPercent Change From Baseline in Total Body BMD at Month 36, ITT Population

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

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMD at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMD at Month 36, ITT Population	13.540 (11.204 to 15.876)	13.076 (11.374 to 14.777)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.7391 · Mean difference (net): -0.465 · 95% CI -3.224 to 2.294LS 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.

SecondaryPercent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population	17.885 (13.645 to 22.124)	28.218 (25.038 to 31.398)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = <0.0001 · Mean difference (net): 10.333 · 95% CI 5.258 to 15.408LS 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.

SecondaryPercent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population	42.367 (34.871 to 49.863)	48.407 (42.921 to 53.894)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 01789 · Mean difference (net): 6.040 · 95% CI -2.807 to 14.887LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population	68.054 (57.564 to 78.544)	68.333 (60.607 to 76.060)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.9646 · Mean difference (net): 0.280 · 95% CI -12.196 to 12.755LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body BMC at Month 12, ITT Population

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMC at Month 12, ITT Population	16.483 (13.395 to 19.570)	21.977 (19.772 to 24.181)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0030 · Mean difference (net): 5.494 · 95% CI 1.912 to 9.077LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body BMC at Month 24, ITT Population

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population	36.465 (31.582 to 41.347)	37.938 (34.406 to 41.470)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.6106 · Mean difference (net): 1.473 · 95% CI -4.245 to 7.192LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body BMC at Month 36, ITT Population

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body BMC at Month 36, ITT Population	56.211 (49.470 to 62.952)	56.526 (51.549 to 61.503)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.9372 · Mean difference (net): 0.315 · 95% CI -7.598 to 8.229LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryLumbar Spine Z-score - Percent Change From Baseline to Month 12, 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".

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Units on a Scale

Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population	-6.028 (-14.899 to 2.844)	25.648 (18.993 to 32.302)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = <0.0001 · Mean difference (net): 31.675 · 95% CI 21.051 to 42.300LS means and p-value are from ANCOVA model adjusted for baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryLumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Units on a Scale

Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population	15.608 (2.327 to 28.889)	29.637 (19.911 to 39.363)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0793 · Mean difference (net): 14.029 · 95% CI -1.667 to 29.726LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

PrimaryPercent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, 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.

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population	7.592 (5.106 to 10.078)	16.159 (14.295 to 18.024)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = <0.0001 · Mean difference (net): 8.567 · 95% CI 5.590 to 11.545LS 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.

SecondaryLumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Units on a Scale

Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population	19.325 (5.162 to 33.488)	25.640 (15.313 to 35.967)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.4575 · Mean difference (net): 6.315 · 95% CI -10.477 to 23.107LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryTotal Body Z-score- Percent Change From Baseline to Month 12, 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".

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Units on a Scale

Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population	-20.661 (-47.090 to 5.769)	16.933 (-1.793 to 35.660)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0172 · Mean difference (net): 37.594 · 95% CI 6.801 to 68.386LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryTotal Body Z-score- Percent Change From Baseline to Month 24, ITT Population

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Units on a Scale

Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population	8.371 (-22.631 to 39.373)	7.879 (-14.273 to 30.032)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.9786 · Mean difference (net): -0.492 · 95% CI -36.807 to 35.824LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryTotal Body Z-score- Percent Change From Baseline to Month 36, ITT Population

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Units on a Scale

Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population	7.146 (-20.474 to 34.766)	-1.494 (-21.400 to 18.411)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.5971 · Mean difference (net): -8.640 · 95% CI -40.952 to 23.672LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population

Measured by DXA.

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population	8.803 (6.751 to 10.856)	9.817 (8.278 to 11.356)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.4154 · Mean difference (net): 1.014 · 95% CI -1.442 to 3.470LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population

Measured by DXA.

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population	16.381 (13.214 to 19.549)	17.266 (14.945 to 19.586)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.6404 · Mean difference (net): 0.884 · 95% CI -2.855 to 4.623LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population

Measured by DXA.

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population	24.952 (20.877 to 29.027)	23.292 (20.296 to 26.289)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.4978 · Mean difference (net): -1.660 · 95% CI -6.499 to 3.179LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body Bone Area Month 12, ITT Population

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population	11.405 (8.708 to 14.101)	14.939 (13.028 to 16.850)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0270 · Mean difference (net): 3.534 · 95% CI 0.410 to 6.658LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body Bone Area Month 24, ITT Population

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population	24.051 (20.684 to 27.417)	25.116 (22.699 to 27.533)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.5925 · Mean difference (net): 1.065 · 95% CI -2.868 to 4.998LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryPercent Change From Baseline in Total Body Bone Area Month 36, ITT Population

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Percent Change

Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population	37.109 (32.144 to 42.074)	38.303 (34.674 to 41.931)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.6840 · Mean difference (net): 1.193 · 95% CI -4.604 to 6.991LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryNew Morphometric Vertebral Fracture at Month 12, 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.

Time frame:: Baseline and Month 12
Reported as:: Number · Participants

New Morphometric Vertebral Fracture at Month 12, ITT Population
Participants	Placebo Daily	Risedronate Daily
At Least One New Fracture Vertebra	8	28
No New Fractured Vertebra	40	60

Statistical analysis

Placebo Daily vs Risedronate Daily · Fisher Exact · p = 0.0680

SecondaryNew Morphometric Vertebral Fracture at Month 36, 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.

Time frame:: Baseline and Month 36
Reported as:: Number · Participants

New Morphometric Vertebral Fracture at Month 36, ITT Population
Participants	Placebo Daily	Risedronate Daily
At Least One New Fracture Vertebra	14	20
No New Fractured Vertebra	31	62

Statistical analysis

Placebo Daily vs Risedronate Daily · Fisher Exact · p = 0.4121

SecondaryCategorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT

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
Reported as:: Number · Participants

Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT
Participants	Placebo Daily	Risedronate Daily
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

Placebo Daily vs Risedronate Daily · Savage Exact Test · p = 0.3658

SecondaryCategorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT

Time frame:: Baseline and Month 36
Reported as:: Number · Participants

Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT
Participants	Placebo Daily	Risedronate Daily
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

Placebo Daily vs Risedronate Daily · Savage Exact Test · p = 0.3408

SecondaryIncidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population

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
Reported as:: Number · Participants

Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population
Participants	Placebo Daily	Risedronate Daily
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

SecondaryIncidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population

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
Reported as:: Number · Participants

Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population
Participants	Placebo Daily	Risedronate Daily
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

SecondaryProbability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population

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
Reported as:: Number · Probability of Fractures

Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population
Probability of Fractures	Placebo Daily	Risedronate Daily
Number Patients All Fractures	24 ± 29	29
All Fractures/Kaplan-Meier Cumulative Incidence	0.5043 ± .0740	0.314 ± .0484
Number Patients Vertebral Fractures	0	0
Vertebral Fractures/Kaplan-Meier Cumulative Incid.	0 ± 0	0 ± 0
Number Patients Non-Vertebral Fractures	24	29
Non-Vertebral Fractures/Kaplan-Meier Cum. Incid.	0.5043 ± 0.0740	0.314 ± 0.0484
Number Patients Long Bone Non-Vertebral Fractures	17	18
Long Bone Non-Vertebral Fractures/Kaplan-Meier Cum	0.3618 ± 0.0714	0.1954 ± 0.0413
Number Patients Other Non-Vertebral Fractures	10	12
Other Non-Vertebral Fractures/Kaplan-Meier Cum.	0.204 ± 0.0576	0.1311 ± 0.0353

Statistical analysis

Placebo Daily vs Risedronate Daily · Cox proportional hazards · p = 0.0253 (All Fractures) · Hazard ratio (hr): 0.534 · 95% CI 0.310 to 0.922Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Cox Proportional Hazard · p = 0.0253 (All Non-Vertebral Fractures) · Hazard ratio (hr): 0.534 · 95% CI 0.310 to 0.922Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Cox Proportional Hazards · p = 0.0501 (Long Bone Non-Vertebral Fracture) · Hazard ratio (hr): 0.487 · 95% CI 0.250 to 0.950Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Cox Proportional Hazard · p = 0.2141 (Other Non-Vertebral Fracture) · Hazard ratio (hr): 0.608 · 95% CI 0.262 to 1.410Hazard Ratio and 95% CI based on Cox proportional hazards model stratified by age group with treatment and pooled-country as covariates.

SecondaryNumber of Clinical Fractures, Month 12, ITT Population

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

Time frame:: 12 Months
Reported as:: Number · Participants

Number of Clinical Fractures, Month 12, ITT Population
Participants	Placebo Daily	Risedronate Daily
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

Placebo Daily vs Risedronate Daily · Wald test · p = 0.0416 (All Fractures) · Hazard ratio (hr): 0.584 · 95% CI 0.348 to 0.980Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Wald Test · p = 0.0416 (Non-Vertebral Fracture) · Hazard ratio (hr): 0.584 · 95% CI 0.348 to 0.980Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Wald Test · p = 0.0799 (Long Bone Non-Vertebral Fracture) · Hazard ratio (hr): 0.543 · 95% CI 0.274 to 1.076Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.
Placebo Daily vs Risedronate Daily · Wald Test · p = 0.682 (Other Non-Vertebral Fracture) · Hazard ratio (hr): 0.682 · 95% CI 0.304 to 1.532Hazard Ratio and 95% CI based on Anderson-Gill mean intensity model stratified by age group with treatment and pooled-country as covariates.

SecondarySerum BAP - Percent Change From Baseline to Month 12, ITT Population

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

Time frame:: Baseline and 12 Months
Reported as:: Least squares mean · Percent Change

Serum BAP - Percent Change From Baseline to Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Serum BAP - Percent Change From Baseline to Month 12, ITT Population	6.783 (-2.107 to 15.674)	-4.895 (-11.509 to 1.719)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.0318 · Mean difference (net): -11.678 · 95% CI -22.325 to -1.031LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondarySerum BAP - Percent Change From Baseline to Month 24, ITT Population

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

Time frame:: Baseline and 24 Months
Reported as:: Least squares mean · Percent Change

Serum BAP - Percent Change From Baseline to Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Serum BAP - Percent Change From Baseline to Month 24, ITT Population	-11.196 (-20.748 to -1.643)	-11.128 (-18.286 to -3.971)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.9907 · Mean difference (net): 0.067 · 95% CI -11.401 to 11.536LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondarySerum BAP - Percent Change From Baseline to Month 36, ITT Population

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

Time frame:: Baseline and 36 Months
Reported as:: Least squares mean · Percent Change

Serum BAP - Percent Change From Baseline to Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Serum BAP - Percent Change From Baseline to Month 36, ITT Population	-19.884 (-28.658 to -11.109)	-24.570 (-31.304 to -17.836)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.3826 · Mean difference (net): -4.686 · 95% CI -15.276 to 5.903LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryUrine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population

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
Reported as:: Least squares mean · Percent Change

Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population	-14.556 (-24.218 to -4.894)	-41.185 (-48.625 to -33.745)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = <0.0001 · Mean difference (net): -26.629 · 95% CI -38.089 to -15.169LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryUrine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population

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
Reported as:: Least squares mean · Percent Change

Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population	-40.358 (-54.722 to -25.994)	-31.318 (-42.478 to -20.158)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.3075 · Mean difference (net): 9.040 · 95% CI -8.433 to 26.512LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryUrine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population

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
Reported as:: Least squares mean · Percent Change

Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population
Percent Change	Placebo Daily	Risedronate Daily
Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population	-47.570 (-57.317 to -37.823)	-52.609 (-60.203 to -45.015)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.3998 · Mean difference (net): -5.039 · 95% CI -16.849 to 6.772LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryWong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, 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.

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Units on a Scale

Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population
Units on a Scale	Placebo Daily	Risedronate Daily
Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population	-0.056 (-0.471 to 0.358)	-0.409 (-0.712 to -0.106)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANCOVA · p = 0.1592 · Mean difference (net): -0.352 · 95% CI -0.845 to 0.140LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryBone Age (Years), Change From Baseline to Month 12, ITT Population

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

Time frame:: Baseline and Month 12
Reported as:: Least squares mean · Years

Bone Age (Years), Change From Baseline to Month 12, ITT Population
Years	Placebo Daily	Risedronate Daily
Bone Age (Years), Change From Baseline to Month 12, ITT Population	0.956 (0.756 to 1.155)	1.083 (0.935 to 1.231)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANOVA · p = 0.2917 · Mean difference (net): 0.127 · 95% CI -0.111 to 0.365LS means and p-value are from ANOVA model with fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryBone Age (Years), Change From Baseline to Month 24, ITT Population

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

Time frame:: Baseline and Month 24
Reported as:: Least squares mean · Years

Bone Age (Years), Change From Baseline to Month 24, ITT Population
Years	Placebo Daily	Risedronate Daily
Bone Age (Years), Change From Baseline to Month 24, ITT Population	2.147 (1.888 to 2.407)	2.155 (1.962 to 2.347)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANOVA · p = 0.9622 · Mean difference (net): 0.007 · 95% CI -0.304 to 0.319LS mean and p-value are from ANOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryBone Age (Years), Change From Baseline to Month 36, ITT Population

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

Time frame:: Baseline and Month 36
Reported as:: Least squares mean · Years

Bone Age (Years), Change From Baseline to Month 36, ITT Population
Years	Placebo Daily	Risedronate Daily
Bone Age (Years), Change From Baseline to Month 36, ITT Population	3.087 (2.800 to 3.374)	3.096 (2.879 to 3.312)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANOVA · p = 0.9596 · Mean difference (net): 0.009 · 95% CI -0.336 to 0.354LS means and p-value are from ANOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryAnnualized Growth Velocity - Change From Baseline to Month 12, ITT Population

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
Reported as:: Least squares mean · Change in Annualized Growth Velocity

Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population
Change in Annualized Growth Velocity	Placebo Daily	Risedronate Daily
Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population	0.895 (0.709 to 1.080)	1.002 (0.865 to 1.138)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANOVA · p = 0.3400 · Mean difference (net): 0.107 · 95% CI -0.114 to 0.328LS means and p-value are from ANOVA model with fixed effects for age group, treatment and pooled center for post-baseline.

SecondaryAnnualized Growth Velocity - Change From Baseline to Month 36, ITT Population

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
Reported as:: Least squares mean · Change in Annualized Growth Velocity

Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population
Change in Annualized Growth Velocity	Placebo Daily	Risedronate Daily
Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population	0.982 (0.886 to 1.077)	1.011 (0.941 to 1.081)

Statistical analysis

Placebo Daily vs Risedronate Daily · ANOVA · p = 0.6218 · Mean difference (net): 0.029 · 95% CI -0.084 to 0.142LS means and p-value are from ANCOVA model adjusted by baseline and fixed effects for age group, treatment and pooled center for post-baseline.

Adverse events

Collected over 36 months: One year double-blind treatment, 2 years open-label risedronate treatment. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo Daily	—	8/49 (16.3%)	47/49 (95.9%)
Risedronate Daily	—	11/94 (11.7%)	86/94 (91.5%)
Years 2 & 3 Placebo-Risedronate	—	13/49 (26.5%)	46/49 (93.9%)
Years 2 & 3 Risedronate	—	16/87 (18.4%)	79/87 (90.8%)

Most frequent serious events

Showing 10 of 30

Most frequent serious events
Event	Placebo Daily	Risedronate Daily	Years 2 & 3 Placebo-Risedronate	Years 2 & 3 Risedronate
Femur fractureInjury, poisoning and procedural complications	7/49	4/94	6/49	3/87
Tibia fractureInjury, poisoning and procedural complications	2/49	2/94	1/49	2/87
Ulna fractureInjury, poisoning and procedural complications	2/49	1/94	2/49	2/87
Radius fractureInjury, poisoning and procedural complications	2/49	0/94	2/49	0/87
Forearm fractureInjury, poisoning and procedural complications	0/49	2/94	1/49	1/87
Fibula fractureInjury, poisoning and procedural complications	1/49	1/94	1/49	1/87
Lower limb fractureInjury, poisoning and procedural complications	1/49	0/94	0/49	0/87
Wrist fractureInjury, poisoning and procedural complications	1/49	0/94	0/49	0/87
CellulitisInfections and infestations	0/49	1/94	1/49	0/87
Cervical Vertebral FractureInjury, poisoning and procedural complications	0/49	0/94	1/49	0/87

Most frequent other events

Showing 10 of 47

Most frequent other events
Event	Placebo Daily	Risedronate Daily	Years 2 & 3 Placebo-Risedronate	Years 2 & 3 Risedronate
FallInjury, poisoning and procedural complications	14/49	19/94	22/49	36/87
Hand fractureInjury, poisoning and procedural complications	3/49	5/94	11/49	12/87
Pain in extremityMusculoskeletal and connective tissue disorders	8/49	20/94	7/49	11/87
HeadacheNervous system disorders	4/49	19/94	4/49	8/87
Femur fractureInjury, poisoning and procedural complications	8/49	9/94	9/49	4/87
Back painMusculoskeletal and connective tissue disorders	5/49	16/94	7/49	13/87
ArthralgiaMusculoskeletal and connective tissue disorders	7/49	8/94	8/49	5/87
VomitingGastrointestinal disorders	3/49	14/94	5/49	5/87
PainGeneral disorders	5/49	14/94	1/49	3/87
Tibia fractureInjury, poisoning and procedural complications	2/49	5/94	7/49	7/87

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Placebo Daily	Risedronate Daily	Total
<=18 years	49	94	143.0
Between 18 and 65 years	0	0	0.0
>=65 years	0	0	0.0

Age Continuous
Age Continuous(years)	Placebo Daily	Risedronate Daily	Total
Mean	8.6 ± 3.1	8.9 ± 3.4	8.825 ± 3.313

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo Daily	Risedronate Daily	Total
Female	22	49	71.0
Male	27	45	72.0

Region of Enrollment
Region of Enrollment(participants)	Placebo Daily	Risedronate Daily	Total
Australia	8	16	24.0
Belgium	1	1	2.0
Chile	4	9	13.0
Czech Republic	1	4	5.0
Finland	5	7	12.0
Germany	5	8	13.0
Hungary	2	2	4.0
Italy	1	2	3.0
Poland	5	9	14.0
South Africa	0	1	1.0
Spain	1	1	2.0
United Kingdom	9	21	30.0
United States	7	13	20.0

Study locations

20 sites

Miami Children's Hospital
Miami, Florida 33155, United States
University of Nebraska Medical Center, Children's Hospital
Omaha, Nebraska 68114, United States
Hospital for Special Surgery
New York, New York 10021, United States
Wright State University BioMedical Imaging Laboratory and Miami Valley Hospital
Dayton, Ohio 45409, United States
Oregon Health & Science University
Portland, Oregon 97239, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Princess Margaret Hospital for Children
Perth, Australia
Cliniques Universitaires Saint Luc
Bruxelles, Belgium
Pontificia Universidad Catolica de Chile
Santiago, Chile
Osteocentrum, II. Interní klinika, Fakultní nemocnice Plzeň-Bory
Plzen, Czech Republic
Hospital for Children and Adolescents
Helsinki, Finland
Klinikum und Poliklinik für Kinderheilkunde der Universität zu Köln
Koln, Germany
2nd Department of Pediatrics, Semmelwies University, Faculty of Medicine
Budapest, Hungary
Rheumatologic Rehabilitation Unit of the University of Verona
Valeggio sul Mincio, Italy
Zaklad Biochemii i Medycyny Doswiadczalnej (Biochemisty Dept, Institute "Monument-Children Health Centre"
Warzawa-Międzylesie, Poland
Little Company of Mary Hospital
Pretoria, Gauteng, South Africa
Hospital Sant Joan de Deu
Barcelona, Spain
Bristol Royal Hospital for Children,
Bristol, United Kingdom
Royal Hospital for Sick Children
Glasgow, G3 8SJ, United Kingdom
Sheffield Children's Hospital
Sheffield, S210 2TH, United Kingdom

References and documents

Publications

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. PubMed 23927913 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 22, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00106028
Lead sponsor: Warner Chilcott
Responsible party: Sponsor
First posted: Mar 21, 2005
Start date: Nov 2004
Primary completion: Apr 2008
Completion: Mar 2010
Results posted: Jun 28, 2010
Last update: Apr 22, 2013

Study contacts

Dietrich H Wenderoth, MD

study director · Procter and Gamble

Oversight

Data monitoring committee: No

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This study is completed, as verified in Apr 2013. You cannot join it, but the record below documents what was studied.

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