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Trial record 82 of 214 for:    TETRACYCLINE

Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01753856
Recruitment Status : Completed
First Posted : December 20, 2012
Results First Posted : October 8, 2015
Last Update Posted : October 8, 2015
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Osteoporosis
Interventions Drug: Teriparatide
Drug: Denosumab
Drug: Demeclocycline
Drug: Tetracycline
Drug: Calcium Supplement
Drug: Vitamin D
Enrollment 69
Recruitment Details  
Pre-assignment Details Tetracycline (TET) and demeclocycline (DEM) temporarily bind to new bone and are detected as different colors under ultraviolet light in bone biopsy samples. In this study, participants were administered DEM prior to randomization (baseline) and again with TET 22 days prior to bone biopsy obtained 3 months post first dose of study drug.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description

Teriparatide: 20-microgram (µg) subcutaneous (SC) injection once daily for 6 months.

DEM: 150-milligram (mg) tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 milligrams per day (mg/day) administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 International Units per day (IU/day) administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Period Title: Overall Study
Started 33 36
Received at Least 1 Dose of Study Drug 33 36
Completed 3-Month Bone Biopsy 31 35
Completed 30 34
Not Completed 3 2
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             0             2
Sponsor Decision             2             0
Arm/Group Title Teriparatide Denosumab Total
Hide Arm/Group Description

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Total of all reporting groups
Overall Number of Baseline Participants 33 36 69
Hide Baseline Analysis Population Description
Randomized participants who received at least 1 dose of study drug (teriparatide or denosumab).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 36 participants 69 participants
61.58  (5.84) 65.17  (8.32) 63.45  (7.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 36 participants 69 participants
Female
33
 100.0%
36
 100.0%
69
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 36 participants 69 participants
Hispanic or Latino
2
   6.1%
3
   8.3%
5
   7.2%
Not Hispanic or Latino
31
  93.9%
32
  88.9%
63
  91.3%
Unknown or Not Reported
0
   0.0%
1
   2.8%
1
   1.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 36 participants 69 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   5.6%
2
   2.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   3.0%
2
   5.6%
3
   4.3%
White
31
  93.9%
31
  86.1%
62
  89.9%
More than one race
1
   3.0%
1
   2.8%
2
   2.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 36 participants 69 participants
United States 21 27 48
Canada 12 9 21
1.Primary Outcome
Title Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies
Hide Description MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling, and calculated as the sum of the total extent of double label (DL) plus half the extent of single label (SL) divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or no label (NL) suggested varying degrees of suppression of bone formation.
Time Frame Baseline, 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the CC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BS
12.43
(7.81 to 18.97)
-2.51
(-5.08 to -1.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment group as the main effect and baseline MS/BS as a covariate.
2.Secondary Outcome
Title Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies
Hide Description [Not Specified]
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of the number of samples with specified labels in the various compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Measure Type: Number
Unit of Measure: Samples
DL and SL, in CC (n=31, 35) 31 24
DL Only, in CC (n=31, 35) 0 0
SL Only, in CC (n=31, 35) 0 9
No Label, in CC (n=31, 35) 0 2
DL and SL, in EC (n=30, 35) 30 25
DL Only, in EC (n=30, 35) 0 0
SL Only, in EC (n=30, 35) 0 6
No Label, in EC (n=30, 35) 0 4
DL and SL, in IC (n=30, 35) 30 24
DL Only, in IC (n=30, 35) 0 0
SL Only, in IC (n=30, 35) 0 10
No Label, in IC (n=30, 35) 0 1
DL and SL, in PC (n=30, 35) 10 1
DL Only, in PC (n=30, 35) 0 0
SL Only, in PC (n=30, 35) 19 4
No Label, in PC (n=30, 35) 1 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and SL, in CC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments SL Only, in CC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments No Label, in CC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments DL and SL, in EC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments SL Only, in EC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.118
Comments No Label, in EC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and SL, in IC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments SL Only, in IC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments No Label, in IC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments DL and SL, in PC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments SL Only, in PC.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No Label, in PC.
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies
Hide Description MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation.
Time Frame Baseline, 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 30 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BS
EC
26.12
(13.76 to 47.63)
-2.97
(-5.39 to 0.08)
IC
9.39
(4.46 to 19.31)
-6.70
(-12.80 to -3.87)
PC
2.40
(0.81 to 7.85)
-0.39
(-1.75 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
4.Secondary Outcome
Title MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug
Hide Description MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BS
CC (n=31, 35)
18.73
(11.13 to 26.64)
0.96
(0.44 to 1.93)
EC (n=30, 35)
39.50
(23.92 to 60.39)
5.42
(2.63 to 10.15)
IC (n=30, 35)
21.69
(15.61 to 30.17)
3.05
(2.03 to 7.38)
PC (n=30, 35)
4.69
(1.24 to 8.98)
0.00
(0.00 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments PC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies
Hide Description In this study, post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling-based bone formations which was determined by whether the underlying reversal line was scalloped or smooth and by the collagen fiber orientation. Percentage = (remodeling-based formation units or modeling-based formation units/ total bone formation units) * 100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling-based or modeling-based formation in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 32
Median (Inter-Quartile Range)
Unit of Measure: percentage of the total formation unit
Remodeling-Based Bone Formation in CC (n=31, 32)
89.02
(86.52 to 92.86)
90.83
(70.71 to 100.00)
Modeling-Based Bone Formation in CC (n=31, 32)
10.98
(7.14 to 13.48)
9.17
(0.00 to 29.29)
Remodeling-Based Bone Formation in EC (n=30, 29)
83.33
(65.00 to 90.00)
100.00
(80.00 to 100.00)
Modeling-Based Bone Formation in EC (n=30, 29)
16.67
(10.00 to 35.00)
0.00
(0.00 to 20.00)
Remodeling-Based Bone Formation in PC (n=29, 5)
0.00
(0.00 to 11.11)
0.00
(0.00 to 0.00)
Modeling-Based Bone Formation in PC (n=29, 5)
100.0
(88.89 to 100.00)
100.00
(100.00 to 100.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.740
Comments Remodeling-Based Bone Formation in the CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.740
Comments Modeling-Based Bone Formation in the CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments Remodeling-Based Bone Formation in the EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments Modeling-Based Bone Formation in the EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments Remodeling-Based Bone Formation in the PC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments Modeling-Based Bone Formation in the PC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies
Hide Description

The percentage of mineralizing surface where post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling based bone formation based on collagen fiber orientation and whether the underlying reversal line was scalloped or smooth.

Percentage = percentage remodeling- or modeling-based formation units * MS/BS

Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling- or modeling-based formation in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Full Range)
Unit of Measure: percentage of the total formation unit
Remodeling-Based Bone Formation in CC (n=31, 35)
16.67
(0 to 100)
0.87
(0 to 100)
Modeling-Based Bone Formation in CC (n=31, 35)
2.06
(0 to 100)
0.09
(0 to 100)
Remodeling-Based Bone Formation in EC (n=30, 35)
32.92
(0 to 100)
5.42
(0 to 100)
Modeling-Based Bone Formation in EC (n=30, 35)
6.58
(0 to 100)
0.00
(0 to 100)
Remodeling-Based Bone Formation in PC (n=30, 35)
0.00
(0 to 100)
0.00
(0 to 100)
Modeling-Based Bone Formation in PC (n=30, 35)
4.69
(0 to 100)
0.00
(0 to 100)
7.Secondary Outcome
Title Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies
Hide Description The percentage of overfilled remodeling sites in the CC, EC, and PC were defined as the percentage of observed remodeling units in which the second DL (TET) extended beyond the limits of the scalloped reversal line and into the adjacent, previously unresorbed surface of the bone. Percentage = (overfilled remodeling bone formation unit / total bone formation unit) * 100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy evaluated for overfilled remodeling sites in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 32
Median (Inter-Quartile Range)
Unit of Measure: percentage of overfilled remodeling site
CC (n=31, 32)
17.74
(10.94 to 23.85)
0.00
(0.00 to 14.29)
EC (n=30, 29)
21.98
(11.11 to 33.33)
0.00
(0.00 to 14.29)
PC (n=29, 5)
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.740
Comments PC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
Hide Description BMUs are local groups of osteoblasts and osteoclasts that act in concert to complete a single remodeling cycle. The label length is a measure of the extent of the mineralization front within each BMU in the CC, EC, IC and PC. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation.
Time Frame Baseline, 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label lengths measured in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 30 25
Median (Inter-Quartile Range)
Unit of Measure: millimeters (mm)
CC (n=30, 24)
0.19
(0.13 to 0.22)
0.05
(0.00 to 0.12)
EC (n=28, 25)
0.25
(0.08 to 0.31)
0.03
(-0.04 to 0.18)
IC (n=30, 24)
0.18
(0.16 to 0.25)
0.02
(-0.07 to 0.11)
PC (n=4, 1)
0.12
(-0.02 to 0.60)
0.10
(0.10 to 0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.850
Comments PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
9.Secondary Outcome
Title Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
Hide Description MAR is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between 2 consecutive labels divided by the time interval. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation. SL cases were imputed to a value of 0.3 micrometers per day (µm/day) or counted as missing. NL cases were reported as missing.
Time Frame Baseline, 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an evaluation of MAR in the CC, EC, IC and PC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 34
Median (Inter-Quartile Range)
Unit of Measure: mcm/day
DL Only, in CC (n=30, 24)
0.00
(-0.02 to 0.04)
-0.04
(-0.11 to 0.01)
DL and Imputed SL, in CC (n=31, 33)
0.01
(-0.02 to 0.06)
-0.06
(-0.15 to -0.00)
DL Only, in EC (n=28, 25)
0.03
(-0.03 to 0.08)
-0.07
(-0.12 to 0.01)
DL and Imputed SL, in EC (n=29, 31)
0.03
(-0.03 to 0.08)
-0.09
(-0.16 to 0.00)
DL Only, in IC (n=30, 24)
0.20
(0.09 to 0.34)
-0.18
(-0.28 to -0.10)
DL and Imputed SL, in IC (n=30, 34)
0.20
(0.09 to 0.34)
-0.22
(-0.33 to -0.12)
DL Only, in PC (n=4, 1)
0.05
(-0.14 to 0.11)
-0.04
(-0.04 to -0.04)
DL and Imputed SL, in PC (n=19, 4)
0.00
(-0.03 to 0.08)
-0.04
(-0.07 to -0.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments DL Only, in CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in the CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.931
Comments DL Only, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.549
Comments DL and Imputed SL, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
10.Secondary Outcome
Title Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
Hide Description BFR/BS is the volume of mineralized bone formed per unit surface of bone per unit of time [mm cubed per mm squared per year (mm³/mm²/year)]. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicates active bone formation, a SL or NL suggests suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 mcm/day or counted as missing. NL cases were assigned a value of zero.
Time Frame Baseline, 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with BFR/BS assessments in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: mm³/mm²/year
DL Only, in CC (n=30, 26)
0.0280
(0.0173 to 0.0426)
-0.0056
(-0.0093 to -0.0021)
DL and Imputed SL, in CC (n=31, 35)
0.0275
(0.0143 to 0.0426)
-0.0055
(-0.0094 to -0.0021)
DL Only, in EC (n=29, 28)
0.0509
(0.0300 to 0.1105)
-0.0069
(-0.0118 to 0.0002)
DL and Imputed SL, in EC (n=30, 35)
0.0501
(0.0300 to 0.1105)
-0.0069
(-0.0123 to -0.0016)
DL Only, in IC (n=30, 25)
0.0455
(0.0208 to 0.0654)
-0.0184
(-0.0290 to -0.0103)
DL and Imputed SL, in IC (n=30, 35)
0.0455
(0.0208 to 0.0654)
-0.0184
(-0.0290 to -0.0103)
DL Only, in PC (n=6, 16)
0.0231
(0.0058 to 0.0369)
0.0000
(-0.0019 to 0.0000)
DL and Imputed SL, in PC (n=30, 35)
0.0015
(0.0008 to 0.0101)
-0.0005
(-0.0019 to 0.0000)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
11.Secondary Outcome
Title Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
Hide Description At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. Percentage = (Single or double TET labels / BS) *100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label surface measured in the specified compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of TET label
sLS/BS, in CC (n=31, 35)
15.44
(10.16 to 18.53)
1.28
(0.66 to 2.62)
dLS/BS, in CC (n=31, 35)
10.44
(6.00 to 15.41)
0.22
(0.00 to 0.79)
sLS/BS, in EC (n=30, 35)
24.24
(14.65 to 30.32)
7.18
(4.13 to 10.58)
dLS/BS, in EC (n=30, 35)
28.84
(12.83 to 43.96)
1.68
(0.00 to 5.08)
sLS/BS, in IC (n=30, 35)
15.28
(11.17 to 17.26)
4.66
(2.54 to 9.57)
dLS/BS, in IC (n=30, 35)
14.96
(10.55 to 19.69)
0.83
(0.00 to 1.87)
sLS/BS, in PC (n=30, 35)
9.37
(2.47 to 13.92)
0.00
(0.00 to 0.00)
dLS/BS, in PC (n=30, 35)
0.00
(0.00 to 0.62)
0.00
(0.00 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments sLS/BS, in CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments dLS/BS, in CC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments sLS/BS, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments dLS/BS, in EC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments sLS/BS, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments dLS/BS, in IC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments sLS/BS, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments dLS/BS, in PC.
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline as a covariate.
12.Secondary Outcome
Title Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH)
Hide Description PTH regulates calcium and phosphate metabolism in bone and kidney, and is typically measured in serum using the intact PTH assay. Percentage = (PTH value at specified time points - PTH value at baseline) / PTH value at baseline * 100.
Time Frame Baseline, 1, 3, and 6 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had serum PTH assessed at baseline and the specified time points.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 28 34
Median (Inter-Quartile Range)
Unit of Measure: percentage change in PTH
1 month (n=28, 34)
-26.89
(-52.28 to -12.81)
72.24
(29.87 to 119.53)
3 months (n=18, 28)
-32.16
(-38.80 to -10.17)
46.68
(0.21 to 78.87)
6 months (n=27, 33)
-40.18
(-63.29 to -10.14)
30.40
(0.00 to 60.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 1 month.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 3 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 6 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
13.Secondary Outcome
Title Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP)
Hide Description P1NP is a marker of bone turnover and is a measure of bone formation. Percentage = (P1NP value at specified time points - P1NP value at baseline) / P1NP value at baseline * 100.
Time Frame Baseline, 1, 3, and 6 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had serum P1NP measurements at baseline and the specified time points.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 33 34
Median (Inter-Quartile Range)
Unit of Measure: percentage change in P1NP
1 month (n=33, 34)
134.38
(93.77 to 194.96)
-11.56
(-26.87 to -0.73)
3 months (n=22, 29)
213.15
(104.94 to 325.78)
-66.64
(-73.46 to -59.26)
6 months (n=31, 32)
284.22
(180.86 to 536.92)
-68.24
(-75.31 to -55.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 1 month.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 3 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 6 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Secondary Outcome
Title Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin
Hide Description Osteocalcin is a marker of bone turnover and a measure of osteoblast function. Percentage = (osteocalcin value at specified time points - osteocalcin value at baseline) / (osteocalcin value at baseline) * 100.
Time Frame Baseline, 1, 3, and 6 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had serum osteocalcin measured at baseline and the specified time points.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 33
Median (Inter-Quartile Range)
Unit of Measure: percentage change in osteocalcin
1 month (n=31, 33)
90.53
(61.19 to 127.56)
-6.56
(-16.83 to 7.34)
3 months (n=20, 29)
123.66
(83.20 to 174.59)
-45.70
(-52.20 to -38.60)
6 months (n=29, 31)
187.29
(131.24 to 290.30)
-50.53
(-59.89 to -37.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 1 month.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 3 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 6 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Secondary Outcome
Title Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX)
Hide Description CTX is a marker of bone turnover and is a measure of bone resorption. Percentage = (CTX value at specified time points - CTX value at baseline) / (CTX value at baseline) * 100.
Time Frame Baseline, 1, 3, and 6 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and serum CTX measured at baseline and the specified time points.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 33
Median (Inter-Quartile Range)
Unit of Measure: percentage change in CTX
1 month (n=31, 33)
6.09
(-21.35 to 43.75)
-90.70
(-92.11 to -87.50)
3 months (n=21, 29)
73.04
(33.33 to 140.00)
-90.77
(-92.59 to -85.92)
6 months (n=29, 33)
89.13
(50.00 to 220.29)
-82.50
(-86.96 to -60.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 1 month.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 3 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 6 months.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest
Hide Description Ac.f is the probability of new remodeling cycles initiated on the BS per year. Ac.f = (BFR/BS) / wall thickness. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were assigned a value of zero.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Ac.f assessments in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: new cycles per year
DL Only, in CC (n=31, 26)
1.41
(0.88 to 2.02)
0.10
(0.04 to 0.20)
DL and Imputed SL, in CC (n=31, 35)
1.41
(0.88 to 2.02)
0.06
(0.02 to 0.14)
DL Only, in EC (n=30, 29)
2.77
(1.48 to 4.31)
0.35
(0.19 to 0.62)
DL and Imputed SL, in EC (n=30, 35)
2.77
(1.48 to 4.31)
0.34
(0.09 to 0.59)
DL Only, in IC (n=30, 25)
1.88
(1.13 to 2.48)
0.17
(0.11 to 0.36)
DL and Imputed SL, in IC (n=30, 35)
1.88
(1.13 to 2.48)
0.12
(0.06 to 0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest
Hide Description Aj.AR is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were counted as missing.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Aj.AR assessments in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 33
Median (Inter-Quartile Range)
Unit of Measure: µm/day
DL Only, in CC (n=31, 24)
0.58
(0.46 to 0.67)
0.21
(0.09 to 0.48)
DL and Imputed SL, in CC (n=31, 33)
0.58
(0.46 to 0.67)
0.14
(0.08 to 0.33)
DL Only, in EC (n=30, 25)
0.76
(0.56 to 0.88)
0.65
(0.41 to 0.82)
DL and Imputed SL, in EC (n=30, 30)
0.76
(0.56 to 0.88)
0.58
(0.22 to 0.81)
DL Only, in IC (n=30, 24)
1.03
(0.88 to 1.18)
0.58
(0.26 to 0.83)
DL and Imputed SL, in IC (n=30, 33)
1.03
(0.88 to 1.18)
0.35
(0.19 to 0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments DL Only, in CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.214
Comments DL Only, in EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments DL and Imputed SL, in EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL Only, in IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments DL and Imputed SL, in IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest
Hide Description OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) *100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of OV/BV in the CC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BV
2.58
(1.67 to 3.51)
0.39
(0.17 to 0.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
19.Secondary Outcome
Title Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest
Hide Description OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) *100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the assessment of OS/BS in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BS
CC (n=31, 35)
20.51
(12.50 to 24.13)
3.46
(2.05 to 5.40)
EC (n=30, 35)
30.85
(21.47 to 48.02)
6.95
(2.82 to 10.88)
IC (n=30, 35)
17.81
(11.89 to 22.50)
4.34
(2.07 to 6.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
20.Secondary Outcome
Title Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest
Hide Description O.Th is a measure of the average thickness of osteoid seams.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an O.Th assessment in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-mcg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: micrometers (mcm)
CC (n= 31, 35)
6.12
(5.52 to 6.71)
3.78
(3.49 to 4.18)
EC (n= 30, 35)
6.99
(5.61 to 7.99)
4.33
(3.49 to 4.78)
IC (n= 30, 35)
7.08
(6.15 to 7.92)
4.68
(3.68 to 5.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
21.Secondary Outcome
Title Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest
Hide Description W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with a W. Th assessment in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: µm
CC (n=31, 35)
26.29
(25.58 to 27.84)
24.03
(22.79 to 25.23)
EC (n=30, 35)
31.88
(29.75 to 32.99)
30.08
(27.61 to 32.03)
IC (n=30, 35)
38.25
(33.87 to 39.84)
37.80
(34.61 to 40.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments EC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.678
Comments IC.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
22.Secondary Outcome
Title Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest
Hide Description ES/BS is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption. Percentage = (ES/BS) *100.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with ES/BS assessed in the CC, EC and IC of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 35
Median (Inter-Quartile Range)
Unit of Measure: percentage of BS
CC (n=31, 35)
3.73
(2.95 to 6.05)
1.52
(0.92 to 2.87)
EC (n=30, 35)
3.79
(2.79 to 6.25)
1.65
(0.78 to 2.47)
IC (n=30, 35)
11.19
(7.37 to 13.71)
1.27
(0.90 to 3.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments CC
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments EC
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments IC
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
23.Other Pre-specified Outcome
Title Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest
Hide Description The length of TET DLs is a measure of the extent of bone formation in each compartment within individual remodeling units and is measured in mm. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation.
Time Frame 3 months post first dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of DL length in the various compartments of the iliac crest.
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description:

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Overall Number of Participants Analyzed 31 25
Mean (Standard Deviation)
Unit of Measure: mm
DL, in CC (n=31, 24) 0.40  (0.08) 0.31  (0.10)
DL, in EC (n=30, 25) 0.48  (0.15) 0.35  (0.20)
DL, in IC (n=30, 24) 0.43  (0.11) 0.27  (0.12)
DL, in PC (n=10, 1) 0.38  (0.41) 0.32 [1]   (NA)
[1]
n=1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Average length of DLs in the CC
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments Average length of double labels in EC
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Average length of double labels in IC
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Teriparatide, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.850
Comments Average length of double labels in the PC
Method ANCOVA
Comments ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Teriparatide Denosumab
Hide Arm/Group Description

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

All-Cause Mortality
Teriparatide Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Teriparatide Denosumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/33 (6.06%)      2/36 (5.56%)    
General disorders     
Chest pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Infections and infestations     
Appendicitis  1  0/33 (0.00%)  0 1/36 (2.78%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung adenocarcinoma  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  0/33 (0.00%)  0 1/36 (2.78%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Teriparatide Denosumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/33 (81.82%)      23/36 (63.89%)    
Blood and lymphatic system disorders     
Lymph node pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Eye disorders     
Dry eye  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Abdominal pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Abdominal pain lower  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Constipation  1  1/33 (3.03%)  1 4/36 (11.11%)  4
Diarrhoea  1  1/33 (3.03%)  1 1/36 (2.78%)  1
Gastrooesophageal reflux disease  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Nausea  1  4/33 (12.12%)  4 0/36 (0.00%)  0
General disorders     
Fatigue  1  4/33 (12.12%)  5 1/36 (2.78%)  1
Injection site erythema  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Local swelling  1  2/33 (6.06%)  2 0/36 (0.00%)  0
Thirst  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Infections and infestations     
Bronchitis  1  3/33 (9.09%)  3 1/36 (2.78%)  1
Ear infection  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Gastroenteritis  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Nasopharyngitis  1  1/33 (3.03%)  1 2/36 (5.56%)  2
Injury, poisoning and procedural complications     
Contusion  1  10/33 (30.30%)  10 4/36 (11.11%)  4
Fall  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Post procedural discomfort  1  1/33 (3.03%)  1 4/36 (11.11%)  4
Metabolism and nutrition disorders     
Hypokalaemia  1  2/33 (6.06%)  2 1/36 (2.78%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/33 (15.15%)  6 1/36 (2.78%)  1
Bone pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Foot deformity  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Groin pain  1  1/33 (3.03%)  1 1/36 (2.78%)  1
Joint stiffness  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Joint swelling  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Muscular weakness  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Pain in extremity  1  3/33 (9.09%)  5 1/36 (2.78%)  1
Sensation of heaviness  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Tendon disorder  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/33 (3.03%)  2 0/36 (0.00%)  0
Dysgeusia  1  2/33 (6.06%)  2 0/36 (0.00%)  0
Headache  1  4/33 (12.12%)  6 0/36 (0.00%)  0
Loss of consciousness  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Tremor  1  1/33 (3.03%)  1 1/36 (2.78%)  1
Renal and urinary disorders     
Bladder spasm  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Nephrolithiasis  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Urine abnormality  1  2/33 (6.06%)  2 0/36 (0.00%)  0
Reproductive system and breast disorders     
Vaginal discharge  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Cough  1  3/33 (9.09%)  3 1/36 (2.78%)  1
Oropharyngeal pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Sneezing  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Hyperhidrosis  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Onychoclasis  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Pruritus  1  1/33 (3.03%)  2 1/36 (2.78%)  1
Rash  1  2/33 (6.06%)  2 2/36 (5.56%)  2
Skin induration  1  1/33 (3.03%)  1 1/36 (2.78%)  1
Swelling face  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Urticaria  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Vascular disorders     
Haematoma  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Hypotension  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Spider vein  1  1/33 (3.03%)  1 0/36 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01753856     History of Changes
Other Study ID Numbers: 14592
B3D-US-GHDV ( Other Identifier: Eli Lilly and Company )
First Submitted: December 18, 2012
First Posted: December 20, 2012
Results First Submitted: June 9, 2015
Results First Posted: October 8, 2015
Last Update Posted: October 8, 2015