Study Evaluating Bazedoxifene Acetate In Osteoporosis In Postmenopausal Women

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether bazedoxifene acetate is safe and effective in the treatment of osteoporosis in postmenopausal women.

Official Title
-----------------
Fracture Incidence Reduction And Safety Of TSE-424 (Bazedoxifene Acetate) Compared To Placebo And Raloxifene In Osteoporotic Postmenopausal Women

Conditions
-----------------
Osteoporosis

Intervention / Treatment
-----------------
* Drug: Bazedoxifene Acetate
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be at least 2 years postmenopausal Osteoporotic subjects without vertebral fracture who meet BMD criteria, or Osteoporotic subjects with vertebral fracture Exclusion Criteria: Diseases that may affect bone metabolism Vasomotor symptoms requiring treatment Known history or suspected cancer of the breast Active or past history of venous thromboembolic events

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: Bazedoxifene Acetate<br>* BZA 20mg, daily, oral<br>|
| Placebo Comparator: B<br> | Other: Placebo<br>* Placebo, daily, oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With New Vertebral Fractures Through Month 36 | New vertebral fracture: decrease in anterior, mid, or posterior vertebral (vt) height of approximately 20% and 4 millimeter (mm) or more from baseline (base) to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from fourth thoracic to fourth lumbar vertebra (T4 to L4), provided vertebra was not fractured at base. Participant was counted only once irrespective of how many new vt fractures were diagnosed. Stratification factor was base fracture status, categorized as no prevalent fracture and at least 1 prevalent fracture. | Baseline through Month 36 | 
| Percentage of Participants With New Vertebral Fractures Through Month 60 | New vertebral fracture: decrease in anterior, mid, or posterior vt height of approximately 20% and 4 millimeter (mm) or more from baseline (base) to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from fourth thoracic to fourth lumbar vertebra (T4 to L4), provided vertebra was not fractured at base. Participant was counted only once irrespective of how many new vt fractures were diagnosed. Stratification factor was base fracture status, categorized as no prevalent fracture and at least 1 prevalent fracture. | Baseline through Month 60 | 
| Percentage of Participants With New Vertebral Fractures Through Month 84 | New vertebral fracture: decrease in anterior, mid, or posterior vt height of approximately 20% and 4 millimeter (mm) or more from baseline (base) to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from fourth thoracic to fourth lumbar vertebra (T4 to L4), provided vertebra was not fractured at base. Participant was counted only once irrespective of how many new vt fractures were diagnosed. Stratification factor was base fracture status, categorized as no prevalent fracture and at least 1 prevalent fracture. | Baseline through Month 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Breast Cancer Through Month 36 | Incidence of breast cancer was defined as the number of participants with breast cancer diagnosis by the time point of interest divided by the number of participants included in the analysis. The reported rate was rescaled to reflect average follow-up time per 1000 women (1000 multiplied by number of cases divided by total follow-up time). | Baseline through Month 36 | 
| Incidence of Breast Cancer Through Month 60 | Incidence of breast cancer was defined as the number of participants with breast cancer diagnosis by the time point of interest divided by the number of participants included in the analysis. The reported rate was rescaled to reflect average follow-up time per 1000 women (1000 multiplied by number of cases divided by total follow-up time). | Baseline through Month 60 | 
| Incidence of Breast Cancer Through Month 84 | Incidence of breast cancer was defined as the number of participants with breast cancer diagnosis by the time point of interest divided by the number of participants included in the analysis. The reported rate was rescaled to reflect average follow-up time per 1000 women (1000 multiplied by number of cases divided by total follow-up time). | Baseline through Month 84 | 
| Percentage of Participants With New Clinical Vertebral Fractures Through Month 36 | A new clinical vertebral fracture was defined as a new fracture found at any time because of back pain suggestive of fracture(s). New Clinical vertebral fractures were verified with radiographic assessment using both semi-quantitative and quantitative morphometric assessment: decrease in anterior, mid, or posterior vt height of approximately 20% and 4 mm or more from base to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from T4 to L4, provided vertebra was not fractured at base. | Baseline through Month 36 | 
| Percentage of Participants With New Clinical Vertebral Fractures Through Month 60 | A new clinical vertebral fracture was defined as a new fracture found at any time because of back pain suggestive of fracture(s). New Clinical vertebral fractures were verified with radiographic assessment using both semi-quantitative and quantitative morphometric assessment: decrease in anterior, mid, or posterior vt height of approximately 20% and 4 mm or more from base to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from T4 to L4, provided vertebra was not fractured at base. | Baseline through Month 60 | 
| Percentage of Participants With New Clinical Vertebral Fractures Through Month 84 | A new clinical vertebral fracture was defined as a new fracture found at any time because of back pain suggestive of fracture(s). New Clinical vertebral fractures were verified with radiographic assessment using both semi-quantitative and quantitative morphometric assessment: decrease in anterior, mid, or posterior vt height of approximately 20% and 4 mm or more from base to end of study confirmed by measurement of involved vt body, a semi-quantitative grade change of 1 from base for any vertebra from T4 to L4, provided vertebra was not fractured at base. | Baseline through Month 84 | 
| Number of Participants With Worsening Vertebral Fractures Through Month 36 | A worsening vertebral fracture was defined as a decrease in anterior, mid, or posterior vertebral height of at least 20% and at least 4 mm as evaluated by quantitative morphometric assessment, and a grade change of at least 1 as rated by a radiologist using the semi-quantitative rating scale. It can occur only in a vertebra that was fractured at baseline. | Baseline through Month 36 | 
| Number of Participants With Worsening Vertebral Fractures Through Month 60 | A worsening vertebral fracture was defined as a decrease in anterior, mid, or posterior vertebral height of at least 20% and at least 4 mm as evaluated by quantitative morphometric assessment, and a grade change of at least 1 as rated by a radiologist using the semi-quantitative rating scale. It can occur only in a vertebra that was fractured at baseline. | Baseline through Month 60 | 
| Number of Participants With Worsening Vertebral Fractures Through Month 84 | A worsening vertebral fracture was defined as a decrease in anterior, mid, or posterior vertebral height of at least 20% and at least 4 mm as evaluated by quantitative morphometric assessment, and a grade change of at least 1 as rated by a radiologist using the semi-quantitative rating scale. It can occur only in a vertebra that was fractured at baseline. | Baseline through Month 84 | 
| Percentage of Participants With Non-vertebral Fractures Through Month 36 | Non-vertebral fractures were determined by direct questioning at each clinic visit after medication therapy begins. Osteoporosis-related, hip and wrist fractures were summarized. | Baseline through Month 36 | 
| Percentage of Participants With Non-vertebral Fractures Through Month 60 | Non-vertebral fractures were determined by direct questioning at each clinic visit after medication therapy begins. Osteoporosis-related, hip and wrist fractures were summarized. | Baseline through Month 60 | 
| Percentage of Participants With Non-vertebral Fractures Through Month 84 | Non-vertebral fractures were determined by direct questioning at each clinic visit after medication therapy begins. Osteoporosis-related, hip and wrist fractures were summarized. | Baseline through Month 84 | 
| Change From Baseline in Height at Month 36 | Height was measured 3 times using standardized Harpenden stadiometer (height based on the middle stadiometer reading was recorded). | Baseline, Month 36 | 
| Change From Baseline in Height at Month 60 | Height was measured 3 times using standardized Harpenden stadiometer (height based on the middle stadiometer reading was recorded). | Baseline, Month 60 | 
| Change From Baseline in Height at Month 84 | Height (cm) was measured 3 times using standardized Harpenden stadiometer (height based on the middle stadiometer reading was recorded). | Baseline, Month 84 | 
| Percent Change From Baseline in Bone Mineral Density (BMD) at Month 6, 12, 18, 24 and 36 | BMD of lumbar spine (Lu Sp) and hip (total hip [Tl Hp], femoral neck [Fe Ne] and femur trochanter [Fe Tr]) was evaluated by dual-energy x-ray absorptiometry (DXA). The left hip was evaluated unless prevented by pathology, in which case the right hip was evaluated throughout the study. Results were scored as T score, defined as BMD at the site when compared to the young normal reference mean. Normal BMD is a T-score of -1.0 or higher. | Baseline, Months 6, 12, 18, 24, 36 | 
| Percent Change From Baseline in Bone Mineral Density (BMD) at Months 48, 60 | BMD of lumbar spine (Lu Sp) and hip (total hip [Tl Hp], femoral neck [Fe Ne] and femur trochanter [Fe Tr]) was evaluated by dual-energy x-ray absorptiometry (DXA). The left hip was evaluated unless prevented by pathology, in which case the right hip was evaluated throughout the study. Results were scored as T score, defined as BMD at the site when compared to the young normal reference mean. Normal BMD is a T-score of -1.0 or higher. | Baseline, Month 48, 60 | 
| Percent Change From Baseline in Bone Mineral Density (BMD) at Months 72 and 84 | BMD of lumbar spine (Lu Sp) and hip (total hip [Tl Hp], femoral neck [Fe Ne] and femur trochanter [Fe Tr]) was evaluated by dual-energy x-ray absorptiometry (DXA). The left hip was evaluated unless prevented by pathology, in which case the right hip was evaluated throughout the study. Results were scored as T score, defined as BMD at the site when compared to the young normal reference mean. Normal BMD is a T-score of -1.0 or higher. | Baseline, Month 72, 84 | 
| Percent Change From Baseline in Osteocalcin at Month 3, 6 and 12 | Osteocalcin is a biochemical marker of bone formation. Blood samples were collected to evaluate osteocalcin levels. | Baseline, Months 3, 6, 12 | 
| Percent Change From Baseline in Osteocalcin at Months 36 and 60 | Osteocalcin is a biochemical marker of bone formation. Blood samples were collected to evaluate osteocalcin levels. | Baseline, Months 36, 60 | 
| Percent Change From Baseline in Osteocalcin at Months 72 and 84 | Osteocalcin is a biochemical marker of bone formation. Blood samples were collected to evaluate osteocalcin levels. | Baseline, Months 72, 84 | 
| Percent Change From Baseline in C-telopeptide (CTx) at Month 3, 6 and 12 | C-telopeptide is a biochemical marker of bone formation. Blood samples were collected to evaluate C-telopeptide levels. | Baseline, Months 3, 6, 12 | 
| Percent Change From Baseline in C-telopeptide (CTx) at Months 36 and 60 | C-telopeptide is a biochemical marker of bone formation. Blood samples were collected to evaluate C-telopeptide levels. | Baseline, Months 36, 60 | 
| Percent Change From Baseline in C-telopeptide (CTx) at Months 72 and 84 | C-telopeptide is a biochemical marker of bone formation. Blood samples were collected to evaluate C-telopeptide levels. | Baseline, Months 72, 84 | 
| Percent Change From Baseline in Lipid Parameters at Months 6, 12, 24 and 36 | Lipid parameters evaluated included total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), high-density lipoprotein fraction 2 (HDL2) and high-density lipoprotein fraction 3 (HDL3). | Baseline, Months 6, 12, 24, 36 | 
| Bone Histomorphometric Indices at Month 36: BV, OV, OS, OcS, ObS, MS, ES, OMS, CP | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Percentage of following indices (volume,surface,porosity) was calculated:Bone Volume(BV), Osteoid Volume(OV), Osteoid Surface(OS), Osteoclast Surface(OcS), Osteoblast Surface(ObS), Mineralizing surface(MS), Eroded Surface(ES), Osteoid Mineralizing surface(OMS), Cortical porosity(CP). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: BV, OV, OS, OcS, ObS, MS, ES, OMS, CP | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Percentage of following indices (volume,surface,porosity) was calculated:Bone Volume(BV), Osteoid Volume(OV), Osteoid Surface(OS), Osteoclast Surface(OcS), Osteoblast Surface(ObS), Mineralizing surface(MS), Eroded Surface(ES), Osteoid Mineralizing surface(OMS), Cortical porosity(CP). | Month 60 | 
| Bone Histomorphometric Indices at Month 36: WTh, OTh, TbTh, TbSp and CTh | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: Wall Thickness (WTh), Osteoid Thickness (OTh), Trabecular Thickness (TbTh), Trabecular Separation (TbSp) and Cortical thickness (CTh). Trabecular separation defined as the thickness of the spaces as defined by binarization within the volume of interest. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: WTh, OTh, TbTh, TbSp and CTh | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: WTh, OTh, TbTh, TbSp and CTh. Trabecular separation defined as the thickness of the spaces as defined by binarization within the volume of interest. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: Total Surface (Goldner Slide) [TSG] | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: Total Surface (Goldner Slide) [TSG]. All specimens were demineralized and subjected to staining procedures (Goldner's staining). Slides were analyzed using light microscopy for total surface area, the surface area that consisted of bone and the surface area that consisted of graft material (all in mm^2 and expressed as percent (%) of the total surface. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: TSG | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: Total Surface (Goldner Slide) [TSG]. All specimens were demineralized and subjected to staining procedures (Goldner's staining). Slides were analyzed using light microscopy for total surface area, the surface area that consisted of bone and the surface area that consisted of graft material (all in mm^2 and expressed as percent (%) of the total surface. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: TtAr | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated variable: Tissue Area (TtAr). Tissue area comprised of the porous calcified substance from which bones were made. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: TtAr | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated variable: Tissue Area (TtAr). Tissue area comprised of the porous calcified substance from which bones were made. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: BFP, RP and RmP | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: Bone Formation Period (BFP), Resorption Period (RP), Remodeling Period (RmP). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: BFP, RP and RmP | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD. Calculated indices included: Bone Formation Period (BFP), Resorption Period (RP), Remodeling Period (RmP). | Month 60 | 
| Bone Histomorphometric Indices at Month 36: SuD | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Surface Density (SuD). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: SuD | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Surface Density (SuD). | Month 60 | 
| Bone Histomorphometric Indices at Month 36: BFRTS | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Bone Form Rate (BFR)-Total Surface Reference (BFRTS). BFR accounts the bone surface which is actively mineralizing, which depends on the number of osteoblasts that are active. BFR= Fraction of mineralizing surface and bone surface multiplied by mineralization apposition rate (MAR). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: BFRTS | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Bone Form Rate (BFR)-Total Surface Reference (BFRTS). BFR accounts the bone surface which is actively mineralizing, which depends on the number of osteoblasts that are active. BFR= Fraction of mineralizing surface and bone surface multiplied by mineralization apposition rate (MAR). | Month 60 | 
| Bone Histomorphometric Indices at Month 36: ACF | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Activation Frequency (ACF). The total period (TP) is the duration between the beginning of one formation period (FP) and the beginning of the next FP. The number of times per year that this spot begins the FP is the activation frequency (ACF). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: ACF | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Activation Frequency (ACF). The total period (TP) is the duration between the beginning of one formation period (FP) and the beginning of the next FP. The number of times per year that this spot begins the FP is the activation frequency (ACF). | Month 60 | 
| Bone Histomorphometric Indices at Month 36: Mlt | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Mineralization Lag Time (Mlt). Mineralization lag time was the lag between the time osteoid was formed and the mineral was added. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: Mlt | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Mineralization Lag Time (Mlt). Mineralization lag time was the lag between the time osteoid was formed and the mineral was added. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: MAR | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Mineral Apposition Rate (MAR). MAR is the area of new bone formed during the label interval. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: MAR | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Mineral Apposition Rate (MAR). MAR is the area of new bone formed during the label interval. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: TbN | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Trabecular Number (TbN). TbN= Ratio of bone volume to tissue volume divided by trabecular thickness. | Month 36 | 
| Bone Histomorphometric Indices at Month 60: TbN | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Trabecular Number (TbN). TbN= Ratio of bone volume to tissue volume divided by trabecular thickness. | Month 60 | 
| Bone Histomorphometric Indices at Month 36: BFRBV | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Bone Formation Rate (BFR)-Bone Volume Reference (BFRBV). BFR accounts the bone volume which is actively mineralizing, which depends on the number of osteoblasts that are active. BFR= Fraction of mineralizing volume and bone volume multiplied by mineralization apposition rate (MAR). | Month 36 | 
| Bone Histomorphometric Indices at Month 60: BFRBV | Bone histomorphometry verified rate of bone remodeling. Anterior iliac crest bone biopsy done to exclude presence of osteomalacia or more subtle defects in mineralization; investigated qualitative aspects of bone. Also assessed decrease in rate of bone turnover, investigated mechanism for observed increase in BMD Calculated indices included: Bone Formation Rate (BFR)-Bone Volume Reference (BFRBV). BFR accounts the bone volume which is actively mineralizing, which depends on the number of osteoblasts that are active. BFR= Fraction of mineralizing volume and bone volume multiplied by mineralization apposition rate (MAR). | Month 60 | 
| Women's Health Questionnaire (WHQ) | WHQ is a measure of mid-aged women's emotional and physical health. Consists of 36-item assessing nine domains of physical and emotional health: Depressed mood; Somatic symptoms; Anxiety/fears; Vasomotor symptoms; Sleep problems; Sexual behavior; Menstrual symptoms; Memory/concentration; and Attractiveness. Each item scored on a 4 point scale (yes definitely, yes sometimes, not much, no not at all) reduced to binary option as 0 (no) and 1 (yes). Domain subscale score was calculated as sum of domain items score divided by number of domain items. Total score was calculated as the sum of individual domain subscale score divided by number of domains. Total score range from 0 (absent) to 1 (present), with higher scores indicating more pronounced distress and dysfunction. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline | 
| Change From Baseline in Women's Health Questionnaire (WHQ) at Month 12, 24 and 36 | WHQ is a measure of mid-aged women's emotional and physical health. Consists of 36-item assessing nine domains of physical and emotional health: Depressed mood; Somatic symptoms; Anxiety/fears; Vasomotor symptoms; Sleep problems; Sexual behavior; Menstrual symptoms; Memory/concentration; and Attractiveness. Each item scored on a 4 point scale (yes definitely, yes sometimes, not much, no not at all) reduced to binary option as 0 (no) and 1 (yes). Domain subscale score was calculated as sum of domain items score divided by number of domain items. Total score was calculated as the sum of individual domain subscale score divided by number of domains. Total score range from 0 (absent) to 1 (present), with higher scores indicating more pronounced distress and dysfunction.Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline, Months 12, 24, 36 | 
| European Foundation for Osteoporosis Quality of Life Questionnaire (QUALEFFO) | QUALEFFO is an osteoporosis-specific health instrument developed specifically for participants with vertebral deformities used to evaluate the effect of back pain and treatment on quality of life. The QUALEFFO questionnaire includes 41 items in 5 domains: pain, physical function, social function, general health perception, and mental function. The total score is calculated according to the scoring algorithm developed by the International Osteoporosis Foundation. Total scores are reported from 0 to 100, with lower scores corresponding to better quality of life. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline | 
| Change From Baseline in European Foundation for Osteoporosis Quality of Life Questionnaire (QUALEFFO) at Month 12, 24 and 36 | QUALEFFO is an osteoporosis-specific health instrument developed specifically for participants with vertebral deformities used to evaluate the effect of back pain and treatment on quality of life. The QUALEFFO questionnaire includes 41 items in 5 domains: pain, physical function, social function, general health perception, and mental function. The total score is calculated according to the scoring algorithm developed by the International Osteoporosis Foundation. Total scores are reported from 0 to 100, with lower scores corresponding to better quality of life. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline, Months 12, 24, 36 | 
| Euro Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline | 
| Change From Baseline in Euro Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Month 12, 24 and 36 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline, Months 12, 24, 36 | 
| Euro Quality of Life-5 Dimensions (EQ-5D)- Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline | 
| Change From Baseline in Euro Quality of Life-5 Dimensions (EQ-5D)- Health State Profile Utility Score at Month 12, 24 and 36 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Baseline values at different time points were considered only for the participants who were evaluable at those time points. | Baseline, Months 12, 24, 36 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Osteoporosis, Postmenopause