Trial Outcomes & Findings for A Study of Once Monthly Bonviva (Ibandronate) in Prevention of Glucocorticoid-Induced Osteoporosis. (NCT NCT00545051)

Last Updated: 2016-05-12

Results Overview

Lumbar spine BMD was measured at Baseline, and Months 6 and 12 using dual-energy x-ray absorptiometry (DXA). Percent change from Baseline to Month 12 was calculated using analysis of covariance.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

140 participants

Primary outcome timeframe

Baseline and Month 12

Results posted on

2016-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	Ibandronate Participants received 150 milligram (mg) ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 International Units (IU) Vitamin D per day.	Placebo Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Overall Study STARTED	68	72
Overall Study COMPLETED	59	65
Overall Study NOT COMPLETED	9	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibandronate Participants received 150 milligram (mg) ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 International Units (IU) Vitamin D per day.	Placebo Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Overall Study Adverse Event	7	3
Overall Study Death	1	0
Overall Study Violation of inclusion/exclusion	0	2
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	1
Overall Study Administrative reasons	0	1

Baseline Characteristics

A Study of Once Monthly Bonviva (Ibandronate) in Prevention of Glucocorticoid-Induced Osteoporosis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibandronate n=68 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=72 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Total n=140 Participants Total of all reporting groups
Age, Continuous	64.4 years STANDARD_DEVIATION 7.90 • n=99 Participants	63.2 years STANDARD_DEVIATION 6.83 • n=107 Participants	63.79 years STANDARD_DEVIATION 7.39 • n=206 Participants
Sex: Female, Male Female	68 Participants n=99 Participants	72 Participants n=107 Participants	140 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: Intent-to-treat (ITT) population

Lumbar spine BMD was measured at Baseline, and Months 6 and 12 using dual-energy x-ray absorptiometry (DXA). Percent change from Baseline to Month 12 was calculated using analysis of covariance.

Outcome measures

Outcome measures
Measure	Ibandronate n=66 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=66 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at Month 12	3.2 percent change in BMD Standard Deviation 3.7	-0.1 percent change in BMD Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: ITT Population

Lumbar spine BMD was measured at Baseline and Month 6 using DXA. Percent change from Baseline to Month 6 was calculated using analysis of covariance.

Outcome measures

Outcome measures
Measure	Ibandronate n=62 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=66 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Percent Change From Baseline in Mean Lumbar Spine BMD at Month 6	2.6 percent change in BMD Standard Deviation 3.1	0.3 percent change in BMD Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline and Months 6 and 12

Population: ITT population; number (n) equals (=) number of participants analyzed at the specified visit.

Left total hip BMD was measured by DXA at Baseline, and Months 6 and 12. If there was prosthesis of left hip, the measurement of right total hip BMD was done by DXA. Percent change from Baseline to Months 6 and 12 was calculated using analysis of (co)variance for repeated measurements.

Outcome measures

Outcome measures
Measure	Ibandronate n=66 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=66 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 Month 6 (n=62,66)	0.7 percent change in BMD Standard Deviation 1.9	0.0 percent change in BMD Standard Deviation 2.1
Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 Month 12 (n=66,65)	1.2 percent change in BMD Standard Deviation 2.2	-0.7 percent change in BMD Standard Deviation 2.5

SECONDARY outcome

Timeframe: Baseline and Months 1, 6 and 12

Population: ITT population; n=number of participants analyzed at the specified visit for the given parameter.

Serum C-terminal Telopeptide of Type 1 Collagen (sCTX), Serum Procollagen Type 1 N-terminal Propeptide (P1NP) and Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP) are measures of bone resorption and are measured as nanograms per milliliter (ng/mL). Percent change from Baseline to Months 1, 6 and 12 was calculated using analysis of covariance for repeated measurements.

Outcome measures

Outcome measures
Measure	Ibandronate n=68 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=68 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 sCTX Month 1 (n=68,68)	-44.7 percent change in bone turnover markers Standard Deviation 36.5	-3.8 percent change in bone turnover markers Standard Deviation 33.3
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 sCTX Month 6 (n=62,66)	-53.3 percent change in bone turnover markers Standard Deviation 24.3	-3.5 percent change in bone turnover markers Standard Deviation 48.0
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 sCTX Month 12 (n=65,65)	-42.0 percent change in bone turnover markers Standard Deviation 27.9	11.6 percent change in bone turnover markers Standard Deviation 82.4
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 P1NP Month 1 (n=68,68)	-23.8 percent change in bone turnover markers Standard Deviation 17.2	-2.3 percent change in bone turnover markers Standard Deviation 22.5
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 P1NP Month 6 (n=60,66)	-62.5 percent change in bone turnover markers Standard Deviation 16.3	-3.7 percent change in bone turnover markers Standard Deviation 44.5
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 P1NP Month 12 (n=64,67)	-48.8 percent change in bone turnover markers Standard Deviation 37.2	12.5 percent change in bone turnover markers Standard Deviation 54.6
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 TRACP Month 1 (n=68,68)	-31.3 percent change in bone turnover markers Standard Deviation 12.0	-7.3 percent change in bone turnover markers Standard Deviation 11.9
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 TRACP Month 6 (n=62,66)	-32.9 percent change in bone turnover markers Standard Deviation 14.8	-7.1 percent change in bone turnover markers Standard Deviation 17.0
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 TRACP Month 12 (n=65,67)	-27.4 percent change in bone turnover markers Standard Deviation 16.5	-6.3 percent change in bone turnover markers Standard Deviation 18.0

SECONDARY outcome

Timeframe: Month 6

Population: ITT population

Worsening in BMD was defined as BMD T-score at any site less than or equal to (≤) - 2.5 standard deviations and/or worsening in BMD of at least 7% at any site.

Outcome measures

Outcome measures
Measure	Ibandronate n=62 Participants Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=66 Participants Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Percentage of Participants Withdrawn Due to Worsening in BMD at 6 Months and/or Worsening in BMD at Least 7 Percent (%) at Any Site at 6 Months	0.0 percentage of participants	0.0 percentage of participants

Adverse Events

Ibandronate

Serious events: 10 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ibandronate n=70 participants at risk Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=70 participants at risk Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Gastrointestinal disorders Diarrhoea	4.3% 3/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	7.1% 5/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Gastrointestinal disorders Dyspepsia	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	7.1% 5/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Gastrointestinal disorders Nausea	2.9% 2/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Influenza	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	2.9% 2/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Musculoskeletal and connective tissue disorders Arthralgia	11.4% 8/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Musculoskeletal and connective tissue disorders Back pain	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	5.7% 4/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	4.3% 3/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Nervous system disorders Headache	2.9% 2/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	10.0% 7/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.

Additional Information

Medical Communications

Hoffmannb-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ibandronate n=70 participants at risk Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.	Placebo n=70 participants at risk Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day.
Blood and lymphatic system disorders Agranulocytosis	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Blood and lymphatic system disorders Anaemia due to gastrointestinal bleeding	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Acute pancreatitis	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Erysipelas	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Pneumonia	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Acute pyelonephritis	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Infections and infestations Sepsis	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
General disorders Concussion	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Investigations Poisoning	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Follicle centre lymphoma	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant tongue neoplasm	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Nervous system disorders Headache	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	2.9% 2/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Nervous system disorders Transient ischaemic attack	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.
Blood and lymphatic system disorders Deep vein thrombosis	2.9% 2/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.	0.00% 0/70 • Adverse events were collected from the date of randomization until 15 days after the end of study at 12 months. The safety population included all participants who had at least one dose of the trial medication, whether withdrawn prematurely or not, and at least one follow-up data point. Two participants received both treatments and were allocated to the ibandronate group for all assessments of safety.