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| ID | Type | Description | Link |
|---|---|---|---|
| B3D-US-GHDV | Other Identifier | Eli Lilly and Company |
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The purpose of this study is to determine how teriparatide or denosumab affects the bone of postmenopausal women with osteoporosis after 3 months of treatment, as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Teriparatide | Experimental | 20 micrograms (µg) teriparatide administered subcutaneously (SC) once every day for 6 months. Demeclocycline (DEM): Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligrams (mg) DEM will be taken orally every 6 hours; Days 4 to15: DEM will not be administered. Tetracycline (TET): Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 milligrams per day (mg/day) administered orally. Vitamin D: Approximately 800 to 1200 International Units per day (IU/day) administered orally. |
|
| Denosumab | Active Comparator | 60 mg denosumab administered SC once in 6 months. DEM: Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 mg DEM will be taken orally every 6 hours; Days 4 to 15: DEM will not be administered. TET: Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 mg/day administered orally. Vitamin D: Approximately 800 to 1200 IU/day administered orally. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Teriparatide | Drug | Administered SC |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies | 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. | Baseline, 3 months post first dose of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 3 months post first dose of study drug | |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lakewood | Colorado | 80227 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29024120 | Derived | Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, Melby TE, Ruff VA. Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab: A Longitudinal Analysis From Baseline to 3 Months in the AVA Study. J Bone Miner Res. 2018 Feb;33(2):298-306. doi: 10.1002/jbmr.3309. Epub 2017 Nov 15. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Teriparatide | 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:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| FG001 | Denosumab | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Randomized participants who received at least 1 dose of study drug (teriparatide or denosumab).
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| ID | Title | Description |
|---|---|---|
| BG000 | Teriparatide | 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:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of BS | Baseline, 3 months post first dose of study drug |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Teriparatide | 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:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest pain | General disorders | MedRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymph node pain | Blood and lymphatic system disorders | MedRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D019379 | Teriparatide |
| D000069448 | Denosumab |
| D003707 | Demeclocycline |
| D013752 | Tetracycline |
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D010281 | Parathyroid Hormone |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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| Denosumab | Drug | Administered SC |
|
| Demeclocycline | Drug | Administered orally |
|
| Tetracycline | Drug | Administered orally |
|
| Calcium Supplement | Drug | Administered orally |
|
| Vitamin D | Drug | Administered orally |
|
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. |
| Baseline, 3 months post first dose of study drug |
| MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug | 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. | 3 months post first dose of study drug |
| Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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. | 3 months post first dose of study drug |
| Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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 | 3 months post first dose of study drug |
| Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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. | 3 months post first dose of study drug |
| 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 | 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. | Baseline, 3 months post first dose of study drug |
| Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies | 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. | Baseline, 3 months post first dose of study drug |
| 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 | 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. | Baseline, 3 months post first dose of study drug |
| 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 | 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. | 3 months post first dose of study drug |
| Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) | 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. | Baseline, 1, 3, and 6 months post first dose of study drug |
| Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) | 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. | Baseline, 1, 3, and 6 months post first dose of study drug |
| Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin | 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. | Baseline, 1, 3, and 6 months post first dose of study drug |
| Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) | 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. | Baseline, 1, 3, and 6 months post first dose of study drug |
| Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest | 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. | 3 months post first dose of study drug |
| Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest | 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. | 3 months post first dose of study drug |
| Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest | OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) *100. | 3 months post first dose of study drug |
| Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest | OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) *100. | 3 months post first dose of study drug |
| Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest | O.Th is a measure of the average thickness of osteoid seams. | 3 months post first dose of study drug |
| Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest | W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets. | 3 months post first dose of study drug |
| Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest | 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. | 3 months post first dose of study drug |
| 3 months post first dose of study drug |
| United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gainesville | Georgia | 30501 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Detroit | Michigan | 48202 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Omaha | Nebraska | 68131 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vancouver | British Columbia | V5Z 4E1 | Canada |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sainte-Foy | Quebec | G1V 3M7 | Canada |
| Sponsor Decision |
|
| BG001 | Denosumab | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Teriparatide | 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:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
| OG001 | Denosumab | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. |
|
|
|
| Secondary | 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 | 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. | Posted | Number | Samples | 3 months post first dose of study drug |
|
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of BS | Baseline, 3 months post first dose of study drug |
|
|
|
|
| Secondary | MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of BS | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of the total formation unit | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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 | 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. | Posted | Median | Full Range | percentage of the total formation unit | 3 months post first dose of study drug |
|
|
|
| Secondary | Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of overfilled remodeling site | 3 months post first dose of study drug |
|
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Median | Inter-Quartile Range | millimeters (mm) | Baseline, 3 months post first dose of study drug |
|
|
|
|
| Secondary | Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies | 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. | 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. | Posted | Median | Inter-Quartile Range | mcm/day | Baseline, 3 months post first dose of study drug |
|
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Median | Inter-Quartile Range | mm³/mm²/year | Baseline, 3 months post first dose of study drug |
|
|
|
|
| Secondary | 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 | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of TET label | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) | 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. | Randomized participants who received at least 1 dose of study drug and had serum PTH assessed at baseline and the specified time points. | Posted | Median | Inter-Quartile Range | percentage change in PTH | Baseline, 1, 3, and 6 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) | 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. | Randomized participants who received at least 1 dose of study drug and had serum P1NP measurements at baseline and the specified time points. | Posted | Median | Inter-Quartile Range | percentage change in P1NP | Baseline, 1, 3, and 6 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin | 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. | Randomized participants who received at least 1 dose of study drug and had serum osteocalcin measured at baseline and the specified time points. | Posted | Median | Inter-Quartile Range | percentage change in osteocalcin | Baseline, 1, 3, and 6 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) | 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. | Randomized participants who received at least 1 dose of study drug and serum CTX measured at baseline and the specified time points. | Posted | Median | Inter-Quartile Range | percentage change in CTX | Baseline, 1, 3, and 6 months post first dose of study drug |
|
|
|
|
| Secondary | Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest | 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. | 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. | Posted | Median | Inter-Quartile Range | new cycles per year | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest | 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. | 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. | Posted | Median | Inter-Quartile Range | µm/day | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest | OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) *100. | 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. | Posted | Median | Inter-Quartile Range | percentage of BV | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest | OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) *100. | 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. | Posted | Median | Inter-Quartile Range | percentage of BS | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest | O.Th is a measure of the average thickness of osteoid seams. | 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. | Posted | Median | Inter-Quartile Range | micrometers (mcm) | 3 months post first dose of study drug |
|
|
|
|
| Other Pre-specified | Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest | 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. | 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. | Posted | Mean | Standard Deviation | mm | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest | W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets. | 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. | Posted | Median | Inter-Quartile Range | µm | 3 months post first dose of study drug |
|
|
|
|
| Secondary | Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest | 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. | 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. | Posted | Median | Inter-Quartile Range | percentage of BS | 3 months post first dose of study drug |
|
|
|
|
| 2 |
| 33 |
| 27 |
| 33 |
| EG001 | Denosumab | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:
TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:
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. | 2 | 36 | 23 | 36 |
| Appendicitis | Infections and infestations | MedRA 17.0 | Systematic Assessment |
|
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedRA 17.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedRA 17.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedRA 17.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedRA 17.0 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedRA 17.0 | Systematic Assessment |
|
| Local swelling | General disorders | MedRA 17.0 | Systematic Assessment |
|
| Thirst | General disorders | MedRA 17.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedRA 17.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedRA 17.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedRA 17.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedRA 17.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedRA 17.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedRA 17.0 | Systematic Assessment |
|
| Post procedural discomfort | Injury, poisoning and procedural complications | MedRA 17.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedRA 17.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Foot deformity | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Tendon disorder | Musculoskeletal and connective tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedRA 17.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedRA 17.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedRA 17.0 | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedRA 17.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedRA 17.0 | Systematic Assessment |
|
| Bladder spasm | Renal and urinary disorders | MedRA 17.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedRA 17.0 | Systematic Assessment |
|
| Urine abnormality | Renal and urinary disorders | MedRA 17.0 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedRA 17.0 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedRA 17.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Skin induration | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedRA 17.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedRA 17.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedRA 17.0 | Systematic Assessment |
|
| Spider vein | Vascular disorders | MedRA 17.0 | Systematic Assessment |
|
Not provided
| D009750 |
| Nutritional and Metabolic Diseases |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| SL Only, in CC (n=31, 35) |
|
| No Label, in CC (n=31, 35) |
|
| DL and SL, in EC (n=30, 35) |
|
| DL Only, in EC (n=30, 35) |
|
| SL Only, in EC (n=30, 35) |
|
| No Label, in EC (n=30, 35) |
|
| DL and SL, in IC (n=30, 35) |
|
| DL Only, in IC (n=30, 35) |
|
| SL Only, in IC (n=30, 35) |
|
| No Label, in IC (n=30, 35) |
|
| DL and SL, in PC (n=30, 35) |
|
| DL Only, in PC (n=30, 35) |
|
| SL Only, in PC (n=30, 35) |
|
| No Label, in PC (n=30, 35) |
|
SL Only, in CC. |
| 2-Sided |
| No |
| Superiority or Other |
| Fisher Exact | 0.494 | No Label, in CC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | 0.001 | DL and SL, in EC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | 0.027 | SL Only, in EC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | 0.118 | No Label, in EC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | <0.001 | DL and SL, in IC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | 0.001 | SL Only, in IC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | >0.999 | No Label, in IC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | 0.002 | DL and SL, in PC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | <0.001 | SL Only, in PC. | 2-Sided | No | Superiority or Other |
| Fisher Exact | <0.001 | No Label, in PC. | 2-Sided | No | Superiority or Other |
| PC |
|
ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. |
| <0.001 |
IC. |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | <0.001 | PC. | 2-Sided | No | Superiority or Other |
| IC (n=30, 35) |
|
| PC (n=30, 35) |
|
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | IC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | PC. | 2-Sided | No | Superiority or Other |
| Remodeling-Based Bone Formation in EC (n=30, 29) |
|
| Modeling-Based Bone Formation in EC (n=30, 29) |
|
| Remodeling-Based Bone Formation in PC (n=29, 5) |
|
| Modeling-Based Bone Formation in PC (n=29, 5) |
|
| 0.740 |
Modeling-Based Bone Formation in the CC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.008 | Remodeling-Based Bone Formation in the EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.008 | Modeling-Based Bone Formation in the EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.661 | Remodeling-Based Bone Formation in the PC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.661 | Modeling-Based Bone Formation in the PC. | 2-Sided | No | Superiority or Other |
| Remodeling-Based Bone Formation in EC (n=30, 35) |
|
| Modeling-Based Bone Formation in EC (n=30, 35) |
|
| Remodeling-Based Bone Formation in PC (n=30, 35) |
|
| Modeling-Based Bone Formation in PC (n=30, 35) |
|
| PC (n=29, 5) |
|
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.740 | PC. | 2-Sided | No | Superiority or Other |
| IC (n=30, 24) |
|
| PC (n=4, 1) |
|
ANCOVA model with treatment group as the main effect and baseline as a covariate. |
| 0.004 |
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | 0.850 | PC. | 2-Sided | No | Superiority or Other |
| DL Only, in EC (n=28, 25) |
|
| DL and Imputed SL, in EC (n=29, 31) |
|
| DL Only, in IC (n=30, 24) |
|
| DL and Imputed SL, in IC (n=30, 34) |
|
| DL Only, in PC (n=4, 1) |
|
| DL and Imputed SL, in PC (n=19, 4) |
|
ANCOVA model with treatment group as the main effect and baseline as a covariate. |
| <0.001 |
DL and Imputed SL, in the CC. |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL Only, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL and Imputed SL, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL Only, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL and Imputed SL, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | 0.931 | DL Only, in PC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | 0.549 | DL and Imputed SL, in PC. | 2-Sided | No | Superiority or Other |
| DL Only, in EC (n=29, 28) |
|
| DL and Imputed SL, in EC (n=30, 35) |
|
| DL Only, in IC (n=30, 25) |
|
| DL and Imputed SL, in IC (n=30, 35) |
|
| DL Only, in PC (n=6, 16) |
|
| DL and Imputed SL, in PC (n=30, 35) |
|
ANCOVA model with treatment group as the main effect and baseline as a covariate. |
| <0.001 |
DL and Imputed SL, in CC. |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL Only, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL and Imputed SL, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL Only, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL and Imputed SL, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL Only, in PC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | DL and Imputed SL, in PC. | 2-Sided | No | Superiority or Other |
| sLS/BS, in EC (n=30, 35) |
|
| dLS/BS, in EC (n=30, 35) |
|
| sLS/BS, in IC (n=30, 35) |
|
| dLS/BS, in IC (n=30, 35) |
|
| sLS/BS, in PC (n=30, 35) |
|
| dLS/BS, in PC (n=30, 35) |
|
ANCOVA model with treatment group as the main effect and baseline as a covariate. |
| <0.001 |
dLS/BS, in CC. |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | sLS/BS, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | dLS/BS, in EC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | sLS/BS, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | dLS/BS, in IC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | <0.001 | sLS/BS, in PC. | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline as a covariate. | 0.028 | dLS/BS, in PC. | 2-Sided | No | Superiority or Other |
| 6 months (n=27, 33) |
|
3 months. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | 6 months. | 2-Sided | No | Superiority or Other |
| 6 months (n=31, 32) |
|
3 months. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | 6 months. | 2-Sided | No | Superiority or Other |
| 6 months (n=29, 31) |
|
3 months. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | 6 months. | 2-Sided | No | Superiority or Other |
| 6 months (n=29, 33) |
|
3 months. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | 6 months. | 2-Sided | No | Superiority or Other |
| DL Only, in EC (n=30, 29) |
|
| DL and Imputed SL, in EC (n=30, 35) |
|
| DL Only, in IC (n=30, 25) |
|
| DL and Imputed SL, in IC (n=30, 35) |
|
DL and Imputed SL, in CC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL Only, in EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL and Imputed SL, in EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL Only, in IC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL and Imputed SL, in IC. | 2-Sided | No | Superiority or Other |
| DL Only, in EC (n=30, 25) |
|
| DL and Imputed SL, in EC (n=30, 30) |
|
| DL Only, in IC (n=30, 24) |
|
| DL and Imputed SL, in IC (n=30, 33) |
|
DL and Imputed SL, in CC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.214 | DL Only, in EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.031 | DL and Imputed SL, in EC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL Only, in IC. | 2-Sided | No | Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | DL and Imputed SL, in IC. | 2-Sided | No | Superiority or Other |
| IC (n=30, 35) |
|
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | IC. | 2-Sided | No | Superiority or Other |
| IC (n= 30, 35) |
|
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | IC. | 2-Sided | No | Superiority or Other |
| DL, in IC (n=30, 24) |
|
| DL, in PC (n=10, 1) |
|
ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. |
| 0.004 |
Average length of double labels in EC |
| 2-Sided |
| No |
| Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | <0.001 | Average length of double labels in IC | 2-Sided | No | Superiority or Other |
| ANCOVA | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | 0.850 | Average length of double labels in the PC | 2-Sided | No | Superiority or Other |
| IC (n=30, 35) |
|
EC. |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 0.678 | IC. | 2-Sided | No | Superiority or Other |
| IC (n=30, 35) |
|
EC |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | <0.001 | IC | 2-Sided | No | Superiority or Other |