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    Clinical Trial Results:
    Teriparatide and Risedronate in the Treatment of Patients with Severe Postmenopausal Osteoporosis: Comparative Effects on vertebral Fractures

    Summary
    EudraCT number
    		 2012-000123-41
    Trial protocol
    		 CZ   BE   ES   DE   AT   IT   HU   GR   PL  
    Global end of trial date
    14 Jul 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2017
    First version publication date
    30 Jul 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B3D-EW-GHDW
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01709110
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 14536, Trial Alias: B3D-EW-GHDW
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Eli Lilly and Company, Available Mon - Fri 9 AM - 5 PM EST, 1 877-285-4559,
    Scientific contact
    Eli Lilly and Company, Available Mon - Fri 9 AM - 5 PM EST, 1 877-CTLilly,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Jul 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jul 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate if teriparatide 20 μg subcutaneously once daily is superior in reducing the incidence of new vertebral fractures during 24 months of therapy, when compared with risedronate 35 mg orally once weekly, in postmenopausal women with prevalent vertebral fragility fractures.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Oct 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 118
    Country: Number of subjects enrolled
    Spain: 121
    Country: Number of subjects enrolled
    Austria: 53
    Country: Number of subjects enrolled
    Belgium: 87
    Country: Number of subjects enrolled
    Czech Republic: 136
    Country: Number of subjects enrolled
    France: 54
    Country: Number of subjects enrolled
    Germany: 68
    Country: Number of subjects enrolled
    Greece: 40
    Country: Number of subjects enrolled
    Hungary: 122
    Country: Number of subjects enrolled
    Italy: 69
    Country: Number of subjects enrolled
    Argentina: 157
    Country: Number of subjects enrolled
    United States: 122
    Country: Number of subjects enrolled
    Canada: 69
    Country: Number of subjects enrolled
    Brazil: 144
    Worldwide total number of subjects
    1360
    EEA total number of subjects
    868
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    315
    From 65 to 84 years
    970
    85 years and over
    75

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Entered

    Pre-assignment
    Screening details
    		 No Text Entered

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Teriparatide
    Arm description
    		 Teriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Teriparatide
    Investigational medicinal product code
    Other name
    LY333334, Forteo, Forsteo
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Teriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo given orally once weekly for 24 months.

    Arm title
    		 Risedronate
    Arm description
    		 Risedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Risedronate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    isedronate 35 milligram (mg) administered orally once weekly for 24 months.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo given by SC injection once daily for 24 months.

    Number of subjects in period 1
    		Teriparatide Risedronate
    Started
    680
    680
    Completed
    498
    515
    Not completed
    182
    165
         Adverse event, serious fatal
    14
    6
         Physician decision
    4
    10
         Consent withdrawn by subject
    94
    87
         Adverse event, non-fatal
    56
    48
         Caregiver decision
    1
    1
         Lost to follow-up
    7
    5
         Sponsor decision
    2
    2
         Lack of efficacy
    1
    1
         Protocol deviation
    3
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Teriparatide
    Reporting group description
    		 Teriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.

    Reporting group title
    Risedronate
    Reporting group description
    		 Risedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.

    Reporting group values
    		 Teriparatide Risedronate Total
    Number of subjects
    		 680 680 1360
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.6 ± 8.77 71.6 ± 8.58 -
    Gender categorical
    Units: Subjects
        Female
    		 680 680 1360
        Male
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 104 99 203
        Not Hispanic or Latino
    		 310 302 612
        Unknown or Not Reported
    		 266 279 545
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 4 8 12
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 5 15 20
        White
    		 670 653 1323
        More than one race
    		 0 3 3
        Unknown or Not Reported
    		 0 0 0
    Distribution of Stratification Factors
    A participant was considered as having a recent clinical vertebral fragility fracture if she had at least one clinical vertebral fragility fracture within the last 12 months prior to baseline. A participant was considered a recent prior bisphosphonate user if she had received a total of 6 or more months of treatment with any oral bisphosphonate within 3 years prior to baseline.
    Units: Subjects
        Vertebral Fracture with Bisphosphonate Use
    		 82 79 161
        With Vertebral Fracture without Bisphosphonate Use
    		 170 165 335
        Without Vertebral Fracture with Bisphosphonate Use
    		 184 189 373
        Without Vertebral Fracture without Bisphosphonate
    		 244 247 491
    Vertebral Fracture Status
    According to Bioclinica spine x-ray central assessment at baseline.
    Units: Subjects
        <1 Fractures
    		 0 0 0
        1 Fracture
    		 231 240 471
        2 Fractures
    		 178 174 352
        3 Fractures
    		 104 101 205
        4 Fractures
    		 60 62 122
        5 or More Fractures
    		 106 102 208
        Not Applicable
    		 1 1 2
    Bone Mineral Density (BMD) Lumbar Spine
    Low BMD is defined as a lumbar spine, total hip or femoral neck BMD ≥ 1.5 standard deviation (SD) below the average BMD for young healthy, non-Hispanic, Caucasian women. Lumbar spine, total hip and femoral neck BMD were assessed by DXA by the investigator at baseline. Any lumbar vertebrae that were not analyzed due to artifacts, fracture, osteophytes, or other abnormalities, were excluded from the analysis; the number of participants analyzed for Teriparatide arm were 644 and Risedronate arm 653.
    Units: Gram per square centimeter (g/cm2)
        arithmetic mean (standard deviation)
    		 0.858 ± 0.1541 0.856 ± 0.1473 -
    Bone Mineral Density (BMD) Femoral Neck
    Low BMD is defined as a lumbar spine, total hip or femoral neck BMD ≥ 1.5 standard deviation (SD) below the average BMD for young healthy, non-Hispanic, Caucasian women. Lumbar spine, total hip and femoral neck BMD were assessed by DXA by the investigator at baseline. Any lumbar vertebrae that were not analyzed due to artifacts, fracture, osteophytes, or other abnormalities, were excluded from the analysis; the number of participants analyzed for Teriparatide arm were 658 and Risedronate arm 656.
    Units: g/cm2
        arithmetic mean (standard deviation)
    		 0.662 ± 0.1085 0.667 ± 0.1129 -
    Bone Mineral Density (BMD) Total Hip
    Low BMD is defined as a lumbar spine, total hip or femoral neck BMD ≥ 1.5 standard deviation (SD) below the average BMD for young healthy, non-Hispanic, Caucasian women. Lumbar spine, total hip and femoral neck BMD were assessed by DXA by the investigator at baseline. Any lumbar vertebrae that were not analyzed due to artifacts, fracture, osteophytes, or other abnormalities, were excluded from the analysis; the number of participants analyzed for Teriparatide arm were 633 and Risedronate arm 640.
    Units: g/cm2
        arithmetic mean (standard deviation)
    		 0.736 ± 0.1065 0.735 ± 0.1165 -

    End points

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    End points reporting groups
    Reporting group title
    Teriparatide
    Reporting group description
    		 Teriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.

    Reporting group title
    Risedronate
    Reporting group description
    		 Risedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. All started participants received at least one dose of study drug; 683 participants were randomized.

    Primary: Proportion of Participants With New Vertebral Fractures

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    End point title
    		 Proportion of Participants With New Vertebral Fractures
    End point description
    The incidence of new vertebral fractures was assessed by quantitative vertebral morphometry measurements (QM) with qualitative visual semiquantitative grading (SQ) confirmation. A new vertebral fracture was diagnosed in a vertebra that was non-fractured at the baseline radiological examination. It was defined as a loss of vertebral body height of at least 20% and 4 mm from the baseline radiograph by vertebral QM, based upon placement of six points by a trained, central reader. Any fractures identified by QM were confirmed using SQ: if the vertebral body also had an increase of one or more severity grade, it was considered an incident vertebral fracture. Analysis Population Description: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
    End point type
    Primary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    516
    533
    Units: Participants (with at least one event)
        number (not applicable)
    28
    64
    Statistical analysis title
    		 Primary Endpoint Odds Ratio
    Comparison groups
    Risedronate v Teriparatide
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000094 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.4071
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.256
         upper limit
    		 0.647
    Notes
    [1] - Cochran-Mantel-Haenszel test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.
    Statistical analysis title
    		 Primary Endpoint Risk Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000094 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.4431
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 0.677
    Notes
    [2] - Cochran-Mantel-Haenszel test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With Pooled New and Worsening Vertebral Fractures

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    End point title
    		 Proportion of Participants With Pooled New and Worsening Vertebral Fractures
    End point description
    Worsening of a pre-existing fracture was considered if the decrease in vertebral height was at least one severity grade in the semi-quantitative assessment, confirmed by a trained central reader, where vertebrae were graded as normal (SQ0) or as with mild (SQ1), moderate (SQ2), or severe (SQ3) fractures, defined as ~20 to 25% (mild), ~25 to 40% (moderate) or ~40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 to L4). Analysis Population Description: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    516
    533
    Units: Participants (with at least one event)
        number (not applicable)
    31
    69
    Statistical analysis title
    		 Risk Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000075 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.4561
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.305
         upper limit
    		 0.682
    Notes
    [3] - Cochran-Mantel-Haenszel was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.
    Statistical analysis title
    		 Odds Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000075 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.4187
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.269
         upper limit
    		 0.652
    Notes
    [4] - Cochran-Mantel-Haenszel was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures

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    End point title
    		 Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures
    End point description
    A clinical vertebral fracture was defined as a new or worsening vertebral fracture, confirmed by radiography, that was associated with signs and symptoms highly suggestive of a vertebral fracture. All non-vertebral fractures that occurred and were diagnosed between visits required the confirmation by the site investigators after evaluating the original x-ray film(s), the radiology or surgical report. For clinical vertebral fractures, the final confirmation of the diagnosis required the centralized evaluation by a trained, independent reader. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    680
    680
    Units: Participants (with at least one event)
        number (not applicable)
    30
    61
    Statistical analysis title
    		 Stratified Hazard Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000869 [5]
    Method
    		 Stratified Log Rank
    Parameter type
    		 Stratified Hazard Ratio (HR)
    Point estimate
    0.4831
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.316
         upper limit
    		 0.739
    Notes
    [5] - Stratified Log Rank test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With Non-Vertebral Fragility Fractures

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    End point title
    		 Proportion of Participants With Non-Vertebral Fragility Fractures
    End point description
    A non-vertebral fracture is a fracture at any of the following non-vertebral sites: clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, and metatarsal. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object were not considered fragility fractures but traumatic fractures. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    680
    680
    Units: Participants (with at least one event)
        number (not applicable)
    25
    38
    Statistical analysis title
    		 Stratified Hazard Ratio (HR)
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.099023 [6]
    Method
    		 Stratified Log Rank
    Parameter type
    		 Stratified Hazard Ratio (HR)
    Point estimate
    0.6553
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.101
    Notes
    [6] - Stratified Log Rank test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With Major Non-Vertebral Fragility Fractures

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    End point title
    		 Proportion of Participants With Major Non-Vertebral Fragility Fractures
    End point description
    A major non-vertebral fracture is a fracture at any of the following non-vertebral sites hip, radius, humerus, ribs, pelvis, tibia and femur. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    680
    680
    Units: Participants (with at least one event
        number (not applicable)
    18
    31
    Statistical analysis title
    		 Stratified Hazard Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.062432 [7]
    Method
    		 Stratified Log Rank
    Parameter type
    		 Stratified Hazard Ratio (HR)
    Point estimate
    0.5786
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.318
         upper limit
    		 1.052
    Notes
    [7] - Stratified Log Rank test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With New Moderate and/or Severe Vertebral Fractures

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    End point title
    		 Proportion of Participants With New Moderate and/or Severe Vertebral Fractures
    End point description
    Vertebrae were graded as moderate (SQ2), or severe (SQ3) fractures, based on ~25 to 40% (moderate) or ~40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 through L4). Analysis Population Description: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    516
    533
    Units: Participants (with at least one event)
        number (not applicable)
    26
    63
    Statistical analysis title
    		 Odds Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.3812
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.237
         upper limit
    		 0.614
    Notes
    [8] - 0.001
    Statistical analysis title
    		 Risk Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [9]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.4173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 0.646
    Notes
    [9] - Cochran-Mantel-Haenszel test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With New Multiple (2 or More) Vertebral Fractures

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    End point title
    		 Proportion of Participants With New Multiple (2 or More) Vertebral Fractures
    End point description
    Analysis Population Description: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    516
    533
    Units: Participants (with at least one event)
        number (not applicable)
    2
    12
    Statistical analysis title
    		 Odds Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007 [10]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.1593
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.035
         upper limit
    		 0.728
    Notes
    [10] - Cochran-Mantel-Haenszel test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.
    Statistical analysis title
    		 Risk Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1049
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007 [11]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.1643
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.036
         upper limit
    		 0.744
    Notes
    [11] - Cochran-Mantel-Haenszel test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures

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    End point title
    		 Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures
    End point description
    Traumatic fractures were considered if resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    680
    680
    Units: Participants (with at least one event)
        number (not applicable)
    40
    57
    Statistical analysis title
    		 Stratified Hazard Ratio
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.078 [12]
    Method
    		 Stratified Log Rank
    Parameter type
    		 Stratified Hazard Ratio (HR)
    Point estimate
    0.696
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.461
         upper limit
    		 1.05
    Notes
    [12] - Stratified Log Rank test was adjusted for the antecedent of recent clinical vertebral fractures and recent bisphosphonate use.

    Secondary: Change From Baseline to 24 Months Endpoint in Height

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    End point title
    		 Change From Baseline to 24 Months Endpoint in Height
    End point description
    Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    565
    580
    Units: Centimeter (cm)
    arithmetic mean (standard deviation)
        Baseline
    154.7 ± 7.15
    155 ± 7.4
        24 Months
    154.3 ± 7.05
    154.5 ± 7.42
    Statistical analysis title
    		 Least Square Means
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1145
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.093 [13]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Means
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [13] - Model included the following fixed effects: treatment, visit, treatment-by-visit interaction, antecedent of recent clinical vertebral fractures, recent use of bisphosphonate and baseline body height(cm).

    Secondary: Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale

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    End point title
    		 Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale
    End point description
    Participants rated the worst back pain during the 24 hours preceding the visit at baseline and each post-baseline visit. An 11-point numerical back pain rating scale (rated from 0 = no back pain to 10 = worst possible back pain) was used. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    642
    648
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    4.5 ± 2.9
    4.5 ± 2.91
        24 Months
    3.4 ± 2.95
    3.4 ± 2.89
    Statistical analysis title
    		 Least Square Means
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1290
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.585 [14]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Means
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 0.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Notes
    [14] - Model included the following fixed effects: treatment, visit, treatment-by-visit interaction, antecedent of recent clinical vertebral fractures, recent use of bisphosphonate and baseline back pain (no pain - worst pain [0-10]).

    Secondary: Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK)

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    End point title
    		 Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK)
    End point description
    The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument and was completed on five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) to measure health-related quality of life on a scale from 0-1, with the higher score indicating a better health state perceived by the participant. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the UK population-based algorithm. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    642
    647
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    0.59 ± 0.243
    0.62 ± 0.228
        24 Months
    0.65 ± 0.249
    0.68 ± 0.205
    Statistical analysis title
    		 Least Square Means
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1289
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.757 [15]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Means
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.01
    Notes
    [15] - Model included the following fixed effects: treatment, visit, treatment-by-visit interaction, antecedent of recent clinical vertebral fractures, recent use of bisphosphonate baseline EQ-5D-5L (UK).

    Secondary: Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US)

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    End point title
    		 Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US)
    End point description
    The same EQ-5D-5L results were converted into a weighted health-state Index Score according to the USA population-based algorithm. Analysis Population Description: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 Months
    End point values
    		 Teriparatide Risedronate
    Number of subjects analysed
    642
    647
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    0.7 ± 0.167
    0.72 ± 0.159
        24 Months
    0.74 ± 0.176
    0.76 ± 0.145
    Statistical analysis title
    		 Least Square Means
    Comparison groups
    Teriparatide v Risedronate
    Number of subjects included in analysis
    1289
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.694 [16]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Means
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.01
    Notes
    [16] - Model included the following fixed effects: treatment, visit, treatment-by-visit interaction, antecedent of recent clinical vertebral fractures, recent use of bisphosphonate baseline EQ-5D-5L (US).

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All randomized participants
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Teriparatide
    Reporting group description
    		 Teriparatide 20 microgram administered by subcutaneous injection once daily for 24 months. Placebo given orally once weekly for 24 months.

    Reporting group title
    Risedronate
    Reporting group description
    		 Risedronate 35 milligram administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months.

    Serious adverse events
    		 Teriparatide Risedronate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    138 / 683 (20.20%)
    117 / 683 (17.13%)
         number of deaths (all causes)
    15
    7
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 683 (0.15%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    3 / 683 (0.44%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast neoplasm
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondrosarcoma
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystadenocarcinoma ovary
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypergammaglobulinaemia benign monoclonal
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 683 (0.29%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 683 (0.15%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial disorder
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 683 (0.29%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Granulomatosis with polyangiitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 683 (0.15%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    4 / 683 (0.59%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery occlusion
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Oedema peripheral
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Reproductive system and breast disorders
    Female genital tract fistula
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 683 (0.15%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 683 (0.15%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngospasm
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 683 (0.44%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood pressure increased
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbohydrate antigen 19-9 increased
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Fall
         subjects affected / exposed
    15 / 683 (2.20%)
    19 / 683 (2.78%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 21
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    4 / 683 (0.59%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    3 / 683 (0.44%)
    6 / 683 (0.88%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Forearm fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    5 / 683 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    3 / 683 (0.44%)
    5 / 683 (0.73%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    3 / 683 (0.44%)
    6 / 683 (0.88%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural stroke
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural nausea
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural vomiting
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 683 (0.29%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    3 / 683 (0.44%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    2 / 683 (0.29%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Left ventricle outflow tract obstruction
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    3 / 683 (0.44%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    5 / 683 (0.73%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Atrioventricular block
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    2 / 683 (0.29%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cardiac failure congestive
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Pericarditis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar ischaemia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral artery embolism
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intercostal neuralgia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 683 (0.29%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radicular pain
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    2 / 683 (0.29%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 683 (0.44%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 683 (0.29%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pernicious anaemia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 683 (0.29%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 683 (0.00%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    2 / 683 (0.29%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral hernia, obstructive
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal achalasia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Regurgitation
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic lupus erythematosus rash
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Renal impairment
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 683 (0.44%)
    5 / 683 (0.73%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kyphosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 683 (0.44%)
    4 / 683 (0.59%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periostitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    2 / 683 (0.29%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon disorder
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 683 (0.44%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia pyelonephritis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 683 (0.29%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 683 (0.44%)
    3 / 683 (0.44%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Postoperative wound infection
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 683 (0.15%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Urinary tract infection
         subjects affected / exposed
    2 / 683 (0.29%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 683 (0.15%)
    0 / 683 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 683 (0.00%)
    1 / 683 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 683 (0.00%)
    2 / 683 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Teriparatide Risedronate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    130 / 683 (19.03%)
    130 / 683 (19.03%)
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    44 / 683 (6.44%)
    51 / 683 (7.47%)
         occurrences all number
    54
    63
    Back pain
         subjects affected / exposed
    73 / 683 (10.69%)
    79 / 683 (11.57%)
         occurrences all number
    77
    89
    Pain in extremit
         subjects affected / exposed
    37 / 683 (5.42%)
    0 / 683 (0.00%)
         occurrences all number
    45
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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