A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate)

Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. It is measured in units of nanograms (ng) per milliliter (mL). The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX time point- sCTX Baseline) / (sCTX Baseline) \* 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1.

Time frame: Baseline (Visit 1) and Day 3

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication.

Overall minimum and maximum relative percent change in sCTX concentrations from Baseline were calculated for all participants over D7, D14, D21 and D28 of Month 6 and the difference between it was analyzed.

Time frame: Day (D)7, D14, D21 and D28 of Month 6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication.

An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.

Time frame: Up to 7 months

Population: The Safety Analysis Population was a subset of the ITT Population consisting of participants with at least 1 post-baseline safety assessment.

Marked laboratory abnormalities are those which exceed the marked abnormality range (i.e., greater or less than the Roche defined marked abnormality range; i.e Low or High) and which also represents a clinically relevant change from Baseline of at least a designated amount. The indicated abnormal laboratory parameters (along with their marked reference range) are as follows : Hematocrit (0.31- 0.56 fraction), hemoglobin (110 - 200 g/L), platelets (100 - 550 \*10\^9/L), white blood cell (WBC) (3.0 - 18.0 \*10\^9/L), alanine aminotransferase (ALT) (0 - 110 U/L), creatinine (0 - 154 µmol/L), chloride (95 - 115 mmol/L), phosphate (0.75 - 1.60 mmol/L ). Creatinine clearance was calculated using the Cockroft-Gault formula.

Time frame: Up to 7 months

Population: The Safety analysis Population was a subset of the ITT Population consisting of participants with at least 1 post-baseline safety assessment. 'n' denotes the number of participants who received the indicated study drug for each arm.

Percentage of participants whose sCTX concentration was between 0.011 and 0.321 ng/mL (Mean -2 to + 0 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL.

Time frame: Baseline (Visit 1), Day (D)3 of M1, and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication. 'n' denotes number of participants who received the indicated study drug for each arm.

Percentage of participants whose sCTX concentration was between 0.011 and 0.476 ng/mL (Mean -2 to + 1 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL. Baseline visit was defined as Visit 1.

Time frame: Baseline (Visit 1) and Day (D)3 of M1 and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication. 'n' denotes number of participants who received the indicated study drug for each arm.

The Cochran-Mantel Haenszel test stratified by Baseline sCTX category was used to compare the 2 treatment groups for proportion of participants whose sCTX concentration was between 0.011 and 0.631 ng/mL (premenopausal normal range mean +/- 2 SD) who achieved a decrease in sCTX of at least 8% from Baseline. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD=0.155 ng/mL. Baseline visit was defined as Visit 1.

Time frame: Baseline (Visit 1) and Day (D)3 of Month (M)1 and; D7, D14, D21, D28 of each M1, M2, M3, M4, M5, and M6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication. 'n' denotes number of participants who received the indicated study drug for each arm.

BSAP is a biochemical marker of bone formation and measured in units per litre (U/L). The relative percent change in BSAP was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (BSAP time point- BSAP Baseline) / (BSAP Baseline) \* 100. The greater the percent decrease from Baseline, the greater the response to therapy. Baseline visit was defined as Visit 1.

Time frame: Baseline (Visit 1), Day (D) 7 and D 28 of Month (M)1, M2, M3, M4, M5, M6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication. 'n' denotes number of participants who received the indicated study drug for each arm.

Parathyroid hormone (PTH) regulates calcium and phosphate metabolism in bone and kidney, and is measured in picogram/milliliter (pg/mL). The relative percent change in PTH was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (PTH time point- PTH Baseline) / (PTH Baseline) \* 100. Post treatment assessments were done at Baseline, Month (M)1 Day (D)7, and M6D7

Time frame: Baseline (Visit 1), Month (M)1 Day (D)7, and M6D7

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication.

sCTX is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX Time point- sCTX Baseline) / (sCTX Baseline) \* 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1.

Time frame: Baseline (Visit 1), Day (D) 3, D7, D14, D21, D28 of Month (M)1, M2, M3, M4, M5, M6

Population: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication. n denotes number of participants who received the indicated study drug for each arm.