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    Clinical Trial Results:
    Teriparatide (Forsteo) Treatment in Postmenopausal Women: Mechanism of Action. A two year open label single arm study of teriparatide in secondary care.

    Summary
    EudraCT number
    		 2010-021009-19
    Trial protocol
    		 GB  
    Global end of trial date
    21 Aug 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jul 2019
    First version publication date
    28 Jul 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    STH15466
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01293292
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sheffield Teaching Hospitals NHS Foundation Trust
    Sponsor organisation address
    Trust Headquarters, 8 Beech Hill Road, Sheffield, United Kingdom, S10 2SB
    Public contact
    Dr Dipak Patel, Sheffield Teaching Hospitals NHS Foundation Trust, ResearchAdministration@sth.nhs.uk
    Scientific contact
    Dr Dipak Patel, Sheffield Teaching Hospitals NHS Foundation Trust, ResearchAdministration@sth.nhs.uk
    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
    11 Jan 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Aug 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of the trial were to develop a strategy for evaluating the efficacy of anabolic therapies by: 1. Fully describing the changes in bone turnover using biochemical markers in response to anabolic therapy by: a) biochemical marker type, b) time 2. Fully describing the changes in BMD in response to anabolic therapy by: a) site, b) bone compartment, c) time
    Protection of trial subjects
    All participants were given a participant information sheet to read and consider for at least 24 hours before attending for a screening visit for the study. Participants were reviewed by a clinician, or an experienced study nurse who was delegated to this task, according to the strict inclusion and exclusion criteria. All participants give written informed consent prior to enrolment to the study. All subjects received a standard and licensed treatment for osteoporosis. Subjects were required to attend for the study visits, detailed in the study schedule, to give blood and urine samples and have DXA, HR-pQCT and QCT measurements. The volume of blood required from the study subjects was up to approximately 50 mL for the screening visit and up to approximately 25mL for the subsequent visits, the total volume of blood taken was approximately 300mL over the study period. An assessment of radiation exposure was performed by the Radiation Protection Advisor for the Sheffield Teaching Hospitals NHS Foundation Trust prior to ethical review of the project. GCP procedures were in place to ensure appropriate consent, confidentiality and privacy. Data were handled in accordance with the Data Protection Act 1998. There are no issues concerning racial and cultural diversity as we did not exclude subjects based on these criteria. Subjects received a payment to compensate for time and inconvenience.
    Background therapy
    		 To ensure that all study participants were vitamin D replete prior to administration of the teriparatide, a 100,000 IU cholecalciferol (vitamin D3) load was given orally at the end of the screening visit (-63 ± 28 days from baseline). A blood sample to assess the serum 25-hydroxyvitamin D level was then taken at baseline. If the results of the blood test revealed a serum 25-hydroxyvitamin D level <50 nmol/L, then a second loading dose was given at an extra study visit and a further blood sample was taken to assess serum 25-hydroxyvitamin D levels. A total of three 100,000 IU cholecalciferol loads were administered per individual, if required. Further 100,000 IU cholecalciferol loads were administered at six-monthly intervals throughout the study (weeks 26, 52 and 78) to ensure that all study participants remained replete. In keeping with usual clinical practice all participants also received daily calcium (600mg) and vitamin D3 (400IU) supplements as Adcal D3 (Prostrakan: Galashiels, UK) throughout the study.
    Evidence for comparator
    		 Single arm. No comparators were used
    Actual start date of recruitment
    08 Feb 2011
    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
    United Kingdom: 20
    Worldwide total number of subjects
    20
    EEA total number of subjects
    20
    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)
    9
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 We identified women with postmenopausal osteoporosis from Sheffield metabolic bone clinics, general practitioner (GP) referrals for bone densitometry and via GP mail-outs. Former research participants, who had consented to participate in future research projects, were also approached.

    Pre-assignment
    Screening details
    		 We enrolled women >5 years postmenopausal but aged <85 years, ambulatory, serum 25-hydroxyvitamin D >50 nmol/L, willing and able to give informed consent. Exclusion criteria included ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health, morbid obesity and fracture in the past year.

    Period 1
    Period 1 title
    Overall trial (104 weeks) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not blinded. All participants received the same treatment

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Teriparatide treatment
    Arm description
    		 The study drug was teriparatide (Forsteo 20 mcg daily: Eli Lilly and Company, Basingstoke, UK). Participants received 104 weeks of teriparatide treatment delivered by a daily self-administered subcutaneous injection in the thigh or abdomen. The drug was supplied in pre-filled pens which administered 20 mcg doses. All participants were trained in correct injection technique.
    Arm type
    		 Single arm

    Investigational medicinal product name
    Teriparatide
    Investigational medicinal product code
    Other name
    Forsteo
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Forsteo is a recombinant human parathyroid hormone analog (1-34), [rhPTH (1-34)] indicated for treatment of (i) osteoporosis in postmenopausal women and in men at increased risk of fracture, and (ii) osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk of fracture. The recommended dose is 20 mcg subcutaneously once daily. Presentation is as 2.4ml pre-filled pens containing a solution of 600 micrograms of teriparatide (250 micrograms per ml) for injection. Each pen contains 28 doses of 20micrograms/80 microliters of teriparatide. This is administered as a subcutaneous injection into the thigh or abdominal wall. Use of the drug for more than 2 years during a patient’s lifetime is not recommended.

    Arm title
    		 Baseline pre-treatment
    Arm description
    		 Pre-treatment as advised in guidance dated - EudraCT FAQ v1.4 May 2019: Currently the system cannot accommodate this specific scenario. Hence, you can proceed with a workaround whereby the baseline is considered one group and the end data another group. By doing that you will be able to use the statistical analysis set to report analysis for a single arm.
    Arm type
    		 Baseline

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Teriparatide treatment Baseline pre-treatment
    Started
    20
    20
    Completed
    16
    16
    Not completed
    4
    4
         Lost to follow-up
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial (104 weeks)
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial (104 weeks) Total
    Number of subjects
    		 20 20
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 9 9
        From 65-84 years
    		 11 11
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 65.4 ± 5.5 -
    Gender categorical
    Postmenopausal women (n = 20, ages 65.4 ± 5.5 years) with osteoporosis, defined as an areal BMD (aBMD) T score < -2.5 at the lumbar spine or proximal femur, were enrolled into the study. We identified women with postmenopausal osteoporosis from Sheffield metabolic bone clinics, general practitioner (GP) referrals for bone densitometry and via GP mail-outs. Former research participants, who had consented to participate in future research projects, were also approached.
    Units: Subjects
        Female
    		 20 20
        Male
    		 0 0
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 161 ± 4 -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 64 ± 8.1 -
    Lumbar spine aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    		 -2.8 ± 0.3 -
    Total proximal femur aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    		 -2.2 ± 0.5 -
    femoral neck aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    		 -1.5 ± 0.6 -
    Subject analysis sets

    Subject analysis set title
    Study completers
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    We performed per-protocol analyses which only used data acquired from those participants who attended for all study visits, adhered to all study procedures and demonstrated ≥ 75% compliance with study medication; referred to as completers. A medication compliance threshold of 75% was chosen as it equated approximately to 5 injections of teriparatide per week.

    Subject analysis set title
    All enrolled
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Every participant that was enrolled into trial

    Subject analysis sets values
    		 Study completers All enrolled
    Number of subjects
    16
    20
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    8
    9
        From 65-84 years
    8
    11
        85 years and over
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    65.4 ± 5.5
    ±
    Gender categorical
    Postmenopausal women (n = 20, ages 65.4 ± 5.5 years) with osteoporosis, defined as an areal BMD (aBMD) T score < -2.5 at the lumbar spine or proximal femur, were enrolled into the study. We identified women with postmenopausal osteoporosis from Sheffield metabolic bone clinics, general practitioner (GP) referrals for bone densitometry and via GP mail-outs. Former research participants, who had consented to participate in future research projects, were also approached.
    Units: Subjects
        Female
    16
        Male
    Height
    Units: cm
        arithmetic mean (standard deviation)
    162 ± 3
    ±
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    64 ± 9
    ±
    Lumbar spine aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    -2.8 ± 0.2
    ±
    Total proximal femur aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    -1.5 ± 0.7
    ±
    femoral neck aBMD T-score
    Units: n/a
        arithmetic mean (standard deviation)
    -2.1 ± 0.5
    ±

    End points

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    End points reporting groups
    Reporting group title
    Teriparatide treatment
    Reporting group description
    		 The study drug was teriparatide (Forsteo 20 mcg daily: Eli Lilly and Company, Basingstoke, UK). Participants received 104 weeks of teriparatide treatment delivered by a daily self-administered subcutaneous injection in the thigh or abdomen. The drug was supplied in pre-filled pens which administered 20 mcg doses. All participants were trained in correct injection technique.

    Reporting group title
    Baseline pre-treatment
    Reporting group description
    		 Pre-treatment as advised in guidance dated - EudraCT FAQ v1.4 May 2019: Currently the system cannot accommodate this specific scenario. Hence, you can proceed with a workaround whereby the baseline is considered one group and the end data another group. By doing that you will be able to use the statistical analysis set to report analysis for a single arm.

    Subject analysis set title
    Study completers
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    We performed per-protocol analyses which only used data acquired from those participants who attended for all study visits, adhered to all study procedures and demonstrated ≥ 75% compliance with study medication; referred to as completers. A medication compliance threshold of 75% was chosen as it equated approximately to 5 injections of teriparatide per week.

    Subject analysis set title
    All enrolled
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Every participant that was enrolled into trial

    Primary: Percent change in L1-L3 trabecular volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in L1-L3 trabecular volumetric bone mineral density (vBMD)
    End point description
    End point type
    Primary
    End point timeframe
    Baseline to 104 weeks
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [1]
    Units: percent
        arithmetic mean (standard error)
    28.5 ± 19.4
    0 ± 0
    28.5 ± 19.4
    Notes
    [1] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in L1-L3 trabecular vBMD
    Statistical analysis description
    Percent change in L1-L3 trabecular vBMD from baseline to week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    28.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.2
         upper limit
    		 38.8
    Variability estimate
    Standard deviation
    Dispersion value
    19.4

    Secondary: Percent change in total body areal bone mineral content (aBMC)

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    End point title
    		 Percent change in total body areal bone mineral content (aBMC)
    End point description
    Percent change in total body aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [2]
    Units: percent
        arithmetic mean (standard error)
    -1.17 ± 0.94
    0 ± 0
    -1.17 ± 0.94
    Notes
    [2] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in total body aBMC
    Statistical analysis description
    Percent change in total body aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.17
         upper limit
    		 0.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.94

    Secondary: Percent change in sub-total body areal bone mineral content (aBMC)

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    End point title
    		 Percent change in sub-total body areal bone mineral content (aBMC)
    End point description
    Percent change in sub-total body aBMC between baseline and week 104. Sub-total body aBMC = total body aBMC minus skull aBMC.
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [3]
    Units: percent
        arithmetic mean (standard error)
    -0.04 ± 0.90
    0 ± 0
    -0.04 ± 0.90
    Notes
    [3] - Per-protocol analysis of completers
    Statistical analysis title
    		 Percent change in sub-total body aBMC
    Statistical analysis description
    Percent change in sub-total body aBMC between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.96
         upper limit
    		 1.88
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.9

    Secondary: Percent change in skull areal bone mineral content (aBMC)

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    End point title
    		 Percent change in skull areal bone mineral content (aBMC)
    End point description
    Percent change in skull aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [4]
    Units: percent
        arithmetic mean (standard error)
    -4.96 ± 1.87
    0 ± 0
    -4.96 ± 1.87
    Notes
    [4] - Per-protocol analysis of completers
    Statistical analysis title
    		 Percent change in skull aBMC
    Statistical analysis description
    Percent change in skull aBMC between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.02
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.94
         upper limit
    		 -0.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.87

    Secondary: Percent change in arms areal bone mineral density (aBMC)

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    End point title
    		 Percent change in arms areal bone mineral density (aBMC)
    End point description
    Percent change in arms aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [5]
    Units: percent
        arithmetic mean (standard error)
    -5.12 ± 1.08
    0 ± 0
    -5.12 ± 1.08
    Notes
    [5] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in arms aBMC
    Statistical analysis description
    Percentage change in arms aBMC between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0003
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -5.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.43
         upper limit
    		 -2.81
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.08

    Secondary: Percent change in thoracic spine areal bone mineral content (aBMC)

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    End point title
    		 Percent change in thoracic spine areal bone mineral content (aBMC)
    End point description
    Percent change in thoracic spine aBMC from baseline to week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [6]
    Units: percent
        arithmetic mean (standard error)
    7.20 ± 3.97
    0 ± 0
    7.20 ± 3.97
    Notes
    [6] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in thoracic spine aBMC
    Statistical analysis description
    Percentage change in thoracic spine aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.09
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    7.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.26
         upper limit
    		 15.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.97

    Secondary: Percent change in lumbar spine areal bone mineral content (aBMC)

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    End point title
    		 Percent change in lumbar spine areal bone mineral content (aBMC)
    End point description
    Percent change in lumbar spine aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [7]
    Units: percent
        arithmetic mean (standard error)
    23.49 ± 4.34
    0 ± 0
    23.49 ± 4.34
    Notes
    [7] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in lumbar spine aBMC
    Statistical analysis description
    Percent change in lumbar spine aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    23.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.24
         upper limit
    		 32.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.34

    Secondary: Percent change in ribs areal bone mineral content (aBMC)

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    End point title
    		 Percent change in ribs areal bone mineral content (aBMC)
    End point description
    Percent change in ribs aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [8]
    Units: percent
        arithmetic mean (standard error)
    3.07 ± 3.42
    0 ± 0
    3.07 ± 3.42
    Notes
    [8] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in ribs aBMC
    Statistical analysis description
    Percent change in ribs aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.24
         upper limit
    		 10.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.42

    Secondary: Percent change in pelvis areal bone mineral content (aBMC)

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    End point title
    		 Percent change in pelvis areal bone mineral content (aBMC)
    End point description
    Percent change in pelvis aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [9]
    Units: percent
        arithmetic mean (standard error)
    9.29 ± 2.09
    0 ± 0
    9.29 ± 2.09
    Notes
    [9] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in pelvis aBMC
    Statistical analysis description
    Percent change in pelvis aBMC between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment v Study completers
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0005
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    9.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.38
         upper limit
    		 13.75
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.09

    Secondary: Percent change in legs areal bone mineral content (aBMC)

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    End point title
    		 Percent change in legs areal bone mineral content (aBMC)
    End point description
    Percent change in legs aBMC between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [10]
    Units: percent
        arithmetic mean (standard error)
    -2.94 ± 1.07
    0 ± 0
    -2.94 ± 1.07
    Notes
    [10] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in legs aBMC
    Statistical analysis description
    Percent change in legs aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.01
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.21
         upper limit
    		 -0.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.07

    Secondary: Percent change in central total body areal bone mineral content (aBMC)

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    End point title
    		 Percent change in central total body areal bone mineral content (aBMC)
    End point description
    Percent change in central total body aBMC including ribs, pelvis, thoracic spine and lumbar spine.
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [11]
    Units: percent
        arithmetic mean (standard error)
    8.52 ± 1.57
    0 ± 0
    8.52 ± 1.57
    Notes
    [11] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in central total body aBMC
    Statistical analysis description
    Percent change in central total body aBMC between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    8.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.16
         upper limit
    		 11.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.57

    Secondary: Percent change in peripheral total body areal bone mineral content (aBMC)

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    End point title
    		 Percent change in peripheral total body areal bone mineral content (aBMC)
    End point description
    Percent change in peripheral total body aBMC. This includes arms, legs and skull aBMC.
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [12]
    Units: percent
        arithmetic mean (standard error)
    -4.09 ± 1.08
    0 ± 0
    -4.09 ± 1.08
    Notes
    [12] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in peripheral total body aBMC
    Statistical analysis description
    Percent change in peripheral total body aBMC between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.39
         upper limit
    		 -1.79
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.08

    Secondary: Percent change in total lumbar spine areal bone mineral density (aBMD)

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    End point title
    		 Percent change in total lumbar spine areal bone mineral density (aBMD)
    End point description
    Percent change in total lumbar spine aBMD between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [13]
    Units: percent
        arithmetic mean (standard deviation)
    11.8 ± 5.8
    0 ± 0
    11.8 ± 5.8
    Notes
    [13] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in total lumbar spine aBMD
    Statistical analysis description
    Percent change in total lumbar spine aBMD between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.7
         upper limit
    		 14.9
    Variability estimate
    Standard deviation
    Dispersion value
    5.8

    Secondary: Percent change in radius total volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in radius total volumetric bone mineral density (vBMD)
    End point description
    Percentage change in radius total vBMD between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [14]
    Units: percent
        arithmetic mean (standard deviation)
    -2.8 ± 6.7
    0 ± 0
    -2.8 ± 6.7
    Notes
    [14] - Pre-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius total vBMD
    Statistical analysis description
    Percent change in radius total vBMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.03
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 0.8
    Variability estimate
    Standard deviation
    Dispersion value
    6.7

    Secondary: Percent change in tibia total volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in tibia total volumetric bone mineral density (vBMD)
    End point description
    Percent change in tibia total (vBMD) between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to 104 weeks
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [15]
    Units: percent
        arithmetic mean (standard deviation)
    -2.5 ± 5.5
    0 ± 0
    -2.5 ± 5.5
    Notes
    [15] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia total vBMD
    Statistical analysis description
    Percent change in tibia total vBMD between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.008
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 0.4
    Variability estimate
    Standard deviation
    Dispersion value
    5.5

    Secondary: Percent change in tibia trabecular volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in tibia trabecular volumetric bone mineral density (vBMD)
    End point description
    Percent change in tibia trabecular vBMD between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [16]
    Units: percent
        arithmetic mean (standard deviation)
    -1.4 ± 6.4
    0 ± 0
    -1.4 ± 6.4
    Notes
    [16] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia trabecular vBMD
    Statistical analysis description
    Percent change in tibia trabecular vBMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 2
    Variability estimate
    Standard deviation
    Dispersion value
    6.4

    Secondary: Percent change in radius trabecular number

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    End point title
    		 Percent change in radius trabecular number
    End point description
    Percent change in radius trabecular number between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [17]
    Units: percent
        arithmetic mean (standard deviation)
    -3.5 ± 7.6
    0 ± 0
    -3.5 ± 7.6
    Notes
    [17] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius trabecular number
    Statistical analysis description
    Percent change in radius trabecular number between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 0.5
    Variability estimate
    Standard deviation
    Dispersion value
    7.6

    Secondary: Percent change in tibia trabecular number

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    End point title
    		 Percent change in tibia trabecular number
    End point description
    Percent change in tibia trabecular number between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [18]
    Units: percent
        arithmetic mean (standard deviation)
    -1.0 ± 9.3
    0 ± 0
    -1.0 ± 9.3
    Notes
    [18] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia trabecular number
    Statistical analysis description
    Percent change in tibia trabecular number between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.06
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 4
    Variability estimate
    Standard deviation
    Dispersion value
    9.3

    Secondary: Percent change in radius trabecular thickness

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    End point title
    		 Percent change in radius trabecular thickness
    End point description
    Percent change in radius trabecular thickness between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [19]
    Units: percent
        arithmetic mean (standard deviation)
    2.7 ± 8.0
    0 ± 0
    2.7 ± 8.0
    Notes
    [19] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius trabecular thickness
    Statistical analysis description
    Percent change in radius trabecular thickness between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 7
    Variability estimate
    Standard deviation
    Dispersion value
    8

    Secondary: Percent change in tibia trabecular thickness

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    End point title
    		 Percent change in tibia trabecular thickness
    End point description
    Percent change in tibia trabecular thickness between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [20]
    Units: percent
        arithmetic mean (standard deviation)
    -0.2 ± 9.2
    0 ± 0
    -0.2 ± 9.2
    Notes
    [20] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia trabecular thickness
    Statistical analysis description
    Percent change in tibia trabecular thickness between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.05
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 4.7
    Variability estimate
    Standard deviation
    Dispersion value
    9.2

    Secondary: Percent change in radius trabecular separation

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    End point title
    		 Percent change in radius trabecular separation
    End point description
    Percent change in radius trabecular separation between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [21]
    Units: percent
        arithmetic mean (standard deviation)
    4.2 ± 8.3
    0 ± 0
    4.2 ± 8.3
    Notes
    [21] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius trabecular separation
    Statistical analysis description
    Percent change in radius trabecular separation between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 8.6
    Variability estimate
    Standard deviation
    Dispersion value
    8.3

    Secondary: Percent change in tibia trabecular separation

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    End point title
    		 Percent change in tibia trabecular separation
    End point description
    Percent change in tibia trabecular separation baseline to week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [22]
    Units: percent
        arithmetic mean (standard deviation)
    1.9 ± 9.8
    0 ± 0
    1.9 ± 9.8
    Notes
    [22] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia trabecular separation
    Statistical analysis description
    Percent change in tibia trabecular separation between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.06
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 7.1
    Variability estimate
    Standard deviation
    Dispersion value
    9.8

    Secondary: Percent change in radius cortical volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in radius cortical volumetric bone mineral density (vBMD)
    End point description
    Percent change in radius cortical volumetric bone mineral density (vBMD) between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [23]
    Units: percent
        arithmetic mean (standard deviation)
    -3.3 ± 5.8
    0 ± 0
    -3.3 ± 5.8
    Notes
    [23] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius cortical vBMD
    Statistical analysis description
    Percent change in radius cortical vBMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 -0.2
    Variability estimate
    Standard deviation
    Dispersion value
    5.8

    Secondary: Percent change in tibia cortical volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in tibia cortical volumetric bone mineral density (vBMD)
    End point description
    Percent change in tibia cortical vBMD between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [24]
    Units: percent
        arithmetic mean (standard deviation)
    -3.4 ± 3.7
    0 ± 0
    -3.4 ± 3.7
    Notes
    [24] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia cortical vBMD
    Statistical analysis description
    Percent change in tibia cortical vBMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 -1.4
    Variability estimate
    Standard deviation
    Dispersion value
    3.7

    Secondary: Percent change in radius cortical thickness

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    End point title
    		 Percent change in radius cortical thickness
    End point description
    Percent change in radius cortical thickness between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [25]
    Units: percent
        arithmetic mean (standard deviation)
    -4.7 ± 12.3
    0 ± 0
    -4.7 ± 12.3
    Notes
    [25] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius cortical thickness
    Statistical analysis description
    Percent change in radius cortical thickness between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.08
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.3
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.3

    Secondary: Percent change in tibia cortical thickness

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    End point title
    		 Percent change in tibia cortical thickness
    End point description
    Percent change in tibia cortical thickness between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [26]
    Units: percent
        arithmetic mean (standard deviation)
    -3.1 ± 8.9
    0 ± 0
    -3.1 ± 8.9
    Notes
    [26] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia cortical thickness
    Statistical analysis description
    Percent change in tibia cortical thickness between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.8
         upper limit
    		 1.6
    Variability estimate
    Standard deviation
    Dispersion value
    8.9

    Secondary: Percent change in radius cortical porosity

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    End point title
    		 Percent change in radius cortical porosity
    End point description
    Percent change in radius cortical porosity between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [27]
    Units: percent
        arithmetic mean (standard deviation)
    21.2 ± 20.7
    0 ± 0
    21.2 ± 20.7
    Notes
    [27] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius cortical porosity
    Statistical analysis description
    Percent change in radius cortical porosity between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    21.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.2
         upper limit
    		 32.2
    Variability estimate
    Standard deviation
    Dispersion value
    20.7

    Secondary: Percent change in tibia cortical porosity

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    End point title
    		 Percent change in tibia cortical porosity
    End point description
    Percent change in tibia cortical porosity between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [28]
    Units: percent
        arithmetic mean (standard deviation)
    10.3 ± 17.5
    0 ± 0
    10.3 ± 17.5
    Notes
    [28] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia cortical porosity
    Statistical analysis description
    Percent change in tibia cortical porosity between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0002
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 19.6
    Variability estimate
    Standard deviation
    Dispersion value
    17.5

    Secondary: Percent change radius cortical tissue mineral density (TMD)

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    End point title
    		 Percent change radius cortical tissue mineral density (TMD)
    End point description
    Percent change radius cortical tissue mineral density (TMD) between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [29]
    Units: percent
        arithmetic mean (standard deviation)
    -3.2 ± 4.2
    0 ± 0
    -3.2 ± 4.2
    Notes
    [29] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius cortical TMD
    Statistical analysis description
    Percent chang in radius cortical TMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 -1
    Variability estimate
    Standard deviation
    Dispersion value
    4.2

    Secondary: Percent change in tibia cortical tissue mineral density (TMD)

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    End point title
    		 Percent change in tibia cortical tissue mineral density (TMD)
    End point description
    Percent change in tibia cortical tissue mineral density (TMD) between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [30]
    Units: percent
        arithmetic mean (standard deviation)
    -3.8 ± 3.6
    0 ± 0
    -3.8 ± 3.6
    Notes
    [30] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia cortical TMD
    Statistical analysis description
    Percent change in tibia cortical TMD between baseline and week 104
    Comparison groups
    Baseline pre-treatment v Teriparatide treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 -1.9
    Variability estimate
    Standard deviation
    Dispersion value
    3.6

    Secondary: Percent change in tibia stiffness

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    End point title
    		 Percent change in tibia stiffness
    End point description
    Percent change in tibia stiffness between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [31]
    Units: percent
        arithmetic mean (standard deviation)
    -5.6 ± 23.1
    0 ± 0
    -5.6 ± 23.1
    Notes
    [31] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia stiffness
    Statistical analysis description
    Percent change in tibia stiffness between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.9
         upper limit
    		 6.7
    Variability estimate
    Standard deviation
    Dispersion value
    23.1

    Secondary: Percent change in radius failure load

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    End point title
    		 Percent change in radius failure load
    End point description
    Percent change in radius failure load between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [32]
    Units: percent
        arithmetic mean (standard deviation)
    0.6 ± 7.0
    0 ± 0
    0.6 ± 7.0
    Notes
    [32] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius failure load
    Statistical analysis description
    Percent change in radius failure load between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 4.3
    Variability estimate
    Standard deviation
    Dispersion value
    7

    Secondary: Percent change in tibia failure load

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    End point title
    		 Percent change in tibia failure load
    End point description
    Percent change in tibia failure load between baseline and week 104
    End point type
    Secondary
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [33]
    Units: percent
        arithmetic mean (standard deviation)
    0.2 ± 4.4
    0 ± 0
    0.2 ± 4.4
    Notes
    [33] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in tibia failure load
    Statistical analysis description
    Percent change in tibia failure load between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.04
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 2.5
    Variability estimate
    Standard deviation
    Dispersion value
    4.4

    Other pre-specified: Percent change in radius trabecular volumetric bone mineral density (vBMD)

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    End point title
    		 Percent change in radius trabecular volumetric bone mineral density (vBMD)
    End point description
    Percent change in radius trabecular vBMD between baseline and week 104
    End point type
    Other pre-specified
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [34]
    Units: percent
        arithmetic mean (standard deviation)
    -1.4 ± 6.3
    0 ± 0
    -1.4 ± 6.3
    Notes
    [34] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius trabecular vBMD
    Statistical analysis description
    Percent change in radius trabecular vBMD between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 2
    Variability estimate
    Standard deviation
    Dispersion value
    6.3

    Post-hoc: Percent change in radius stiffness

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    End point title
    		 Percent change in radius stiffness
    End point description
    Percent change in radius stiffness between baseline and week 104
    End point type
    Post-hoc
    End point timeframe
    Baseline to week 104
    End point values
    		 Teriparatide treatment Baseline pre-treatment Study completers
    Number of subjects analysed
    16
    16
    16 [35]
    Units: percent
        arithmetic mean (standard deviation)
    0.7 ± 8.1
    0 ± 0
    0.7 ± 8.1
    Notes
    [35] - Per-protocol analysis for completers
    Statistical analysis title
    		 Percent change in radius stiffness
    Statistical analysis description
    Percent change in radius stiffness between baseline and week 104
    Comparison groups
    Teriparatide treatment v Baseline pre-treatment
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 5
    Variability estimate
    Standard deviation
    Dispersion value
    8.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Weeks: 0, 1, 2, 4, 12, 26, 39, 52, 65, 78, 91, 104
    Adverse event reporting additional description
    Adverse event information including dates of event (including onset and resolution), event diagnosis and description, severity, assessment of relatedness to Forsteo or calcium/vitamin D supplements or vitamin D dosing and action taken was collected at visit 2 (baseline) and at each study visit thereafter.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Teriparatide (Forsteo) 20 mcg subcutaneous injection
    Reporting group description
    		 Teriparatide (Forsteo) 20 mcg subcutaneous injection once daily. Duration 104 weeks. This is a single arm study.

    Serious adverse events
    		 Teriparatide (Forsteo) 20 mcg subcutaneous injection
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 20 (15.00%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast lump
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver metastases
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Surgical and medical procedures
    Cystocele repair
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Teriparatide (Forsteo) 20 mcg subcutaneous injection
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 20 (95.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenal adenoma
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Haemangioma of liver
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Hepatic cyst
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Vascular disorders
    Blood pressure high
         subjects affected / exposed
    2 / 20 (10.00%)
         occurrences all number
    2
    Hot flushes
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Sweating
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Surgical and medical procedures
    Dental fillings
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Dupuytren's contracture operation
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Mole excision
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Rodent ulcer excision
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Inflammation at site of injection
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Injection site bruising
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Chest infection
         subjects affected / exposed
    2 / 20 (10.00%)
         occurrences all number
    5
    Emphysema
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Shortness of breath
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Ankle injury
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Back pain
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Broken ankle
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Dislocated patella
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Cardiac disorders
    Generall unwell
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Palpitations
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    2
    Nervous system disorders
    Benign essential tremor
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Dizziness
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Fuzzy head
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Headache
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Pain in spine
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    TIA
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Gastrointestinal disorders
    Acid reflux (oesophageal)
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Constipation
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Diverticulitis
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Epidemic vomiting and diarrhoea
         subjects affected / exposed
    3 / 20 (15.00%)
         occurrences all number
    3
    Indigestion
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    2 / 20 (10.00%)
         occurrences all number
    2
    Stomach pain
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Stomach upset
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    2
    Vomiting
         subjects affected / exposed
    2 / 20 (10.00%)
         occurrences all number
    2
    Skin and subcutaneous tissue disorders
    Itchy legs
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Rash both legs
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Rash on face
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Rash trunk
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Bursitis
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Leg pain
         subjects affected / exposed
    2 / 20 (10.00%)
         occurrences all number
    2
    Plantar fasciitis
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Infections and infestations
    Common cold
         subjects affected / exposed
    10 / 20 (50.00%)
         occurrences all number
    14
    Cough
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Dental abscess
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Head cold
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Leg infection
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Lethargy
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Sore throat
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Tonsillitis
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Viral sore throat
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    High cholesterol
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jan 2011
    Substantial Amendment 01 [SA01] SA01 was submitted to the MHRA - to change the procedures required for testing, loading and retesting vitabin D levels. - reschedule a whole body DXA scan - add additional exclusion criteria to the sub-study protocol These changes were to ensure that only participants that meet the full eligibility criteria undertake research protocol procedures at visit 2. At the point of approval of this amendment, no participants had entered the study
    16 Oct 2014
    Substantial Amendment 05 [SA05] This amendment was to update the Reference Safety Information for the IMP Forsteo. An updated SmPC was submitted to the MHRA (SmPC Forsteo dated 25 April 2014). The Chief Investigator confirmed that the update RSI did not change the risk benefit assessment of the study, therefore no change to the protocol or other documents was made.

    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.
    This was an open-label study with no control group. Inclusion of a control group of postmenopausal women with osteoporosis was deemed to be unethical, and we assumed that the open-label design would not influence the study outcomes.
    For support, Contact us.
    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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