The Use of Zoledronic Acid to Prevent Cancer-treatment Bo... | NCT00171314

Label	Type	Description	Intervention Names
Upfront Zoledronic Acid	Experimental	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1	Drug: Zoledronic acid Drug: Letrozole
Delayed Zoledronic Acid	Experimental	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1	Drug: Zoledronic acid Drug: Letrozole

Name	Type	Description	Arm Group Labels	Other Names
Zoledronic acid	Drug	Zoledronic acid 4 mg Intravenous (IV)15 minute infusion every 6 months.	Delayed Zoledronic Acid Upfront Zoledronic Acid

Measure	Description	Time Frame
Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy	Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.	From Baseline - 12 months

Measure	Description	Time Frame
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years	Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.	From Baseline to Year 2, Year 3, Year 4, Year 5
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Buenos Aires			Argentina
Novartis Investigative Site

ID	Title	Description
FG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
FG001	Delayed Zoledronic Acid

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

Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.

For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. Participants with observations at baseline and 12 months were included in this analysis.

Posted

Mean

Standard Deviation

Percent Change

From Baseline - 12 months

ID	Title	Description
OG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
OG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Units	Counts
Participants	OG000254 OG001269

Title

Denominators

Categories

Title	Measurements
	OG0002.680± 2.8451 OG001-3.314± 3.9632

Secondary

Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.

Analysis of safety:safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. "n" in each category indicates participants with data at baseline and each corresponding timepoint.

Posted

Mean

Standard Deviation

Percent Change

From Baseline to Year 2, Year 3, Year 4, Year 5

ID	Title	Description
OG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
OG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Secondary

Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.

For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization.

Posted

Mean

Standard Deviation

Percent Change

From Baseline to Year 1, Year 2, Year 3, Year 4, Year 5

ID	Title	Description
OG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
OG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Units	Counts

Secondary

Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100.

For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. During different time points, participants with observations at that time point were included in the analysis.

Posted

Mean

Standard Deviation

Percent Change

From baseline to Year 1, Year 2, Year 3, Year 4, Year 5

ID	Title	Description
OG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
OG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Secondary

Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3

Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment.

Posted

Number

Percentage of Participants

Year 3

ID	Title	Description
OG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
OG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0011 affected269 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0013 affected269 at risk
Angina unstable	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Bundle branch block left	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Cardiac failure	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected254 at risk EG0011 affected269 at risk
Coronary artery disease	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cytotoxic cardiomyopathy	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Myocardial infarction	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0010 affected269 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Palpitations	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Pericardial effusion	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Goitre	Endocrine disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cataract	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cataract cortical	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Corneal oedema	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Abdominal strangulated hernia	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Gingival erosion	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Gingivitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Loose tooth	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Peritonitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0012 affected269 at risk
Splenic artery aneurysm	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Gait disturbance	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
General physical health deterioration	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Impaired healing	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Non-cardiac chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Sudden death	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0011 affected269 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Corneal graft rejection	Immune system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Abscess jaw	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Acanthamoeba keratitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Appendicitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0011 affected269 at risk
Breast cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Device related infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Diverticulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0012 affected269 at risk
Erysipelas	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Escherichia sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Influenza	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Lung infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Osteomyelitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Pleural infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Soft tissue infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Tooth abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0011 affected269 at risk
Tooth infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Tuberculosis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Urogenital infection bacterial	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0010 affected269 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Drug toxicity	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0013 affected269 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Post procedural discomfort	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Computerised tomogram thorax abnormal	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Weight increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Metabolic alkalosis	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0012 affected269 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Bone fistula	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0013 affected269 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0015 affected269 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected254 at risk EG0011 affected269 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Primary sequestrum	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Benign gastric neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Amnestic disorder	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Chronic inflammatory demyelinating polyradiculoneuropathy	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Monoplegia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Parkinson's disease	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Sciatica	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0012 affected269 at risk
Apathy	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0013 affected269 at risk
Mental disorder	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0011 affected269 at risk
Mutism	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Suicide attempt	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0012 affected269 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected254 at risk EG0011 affected269 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Uterine prolapse	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Vaginal discharge	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0012 affected269 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected254 at risk EG0011 affected269 at risk
Pulmonary infarction	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Vocal cord polyp	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk
Circulatory collapse	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Lymphoedema	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Vasoconstriction	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected254 at risk EG0011 affected269 at risk
Venous insufficiency	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected254 at risk EG0010 affected269 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00020 affected254 at risk EG00116 affected269 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00024 affected254 at risk EG00121 affected269 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG00026 affected254 at risk EG00136 affected269 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG00046 affected254 at risk EG00157 affected269 at risk
Influenza like illness	General disorders	MedDRA 13.1	Systematic Assessment	EG00018 affected254 at risk EG0015 affected269 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Systematic Assessment	EG00020 affected254 at risk EG00126 affected269 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG00021 affected254 at risk EG0013 affected269 at risk
Bronchitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00010 affected254 at risk EG00116 affected269 at risk
Influenza	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00014 affected254 at risk EG0019 affected269 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00012 affected254 at risk EG00114 affected269 at risk
Weight increased	Investigations	MedDRA 13.1	Systematic Assessment	EG00033 affected254 at risk EG00123 affected269 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG00024 affected254 at risk EG00133 affected269 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG000123 affected254 at risk EG001136 affected269 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00041 affected254 at risk EG00136 affected269 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00027 affected254 at risk EG00121 affected269 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0007 affected254 at risk EG00115 affected269 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00026 affected254 at risk EG00134 affected269 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00010 affected254 at risk EG00116 affected269 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00033 affected254 at risk EG00135 affected269 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00011 affected254 at risk EG00118 affected269 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00026 affected254 at risk EG00146 affected269 at risk
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG00024 affected254 at risk EG00128 affected269 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0007 affected254 at risk EG00115 affected269 at risk
Anxiety	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG00017 affected254 at risk EG00122 affected269 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG00013 affected254 at risk EG00124 affected269 at risk
Insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG00020 affected254 at risk EG00111 affected269 at risk
Vulvovaginal dryness	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG00013 affected254 at risk EG00111 affected269 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG00015 affected254 at risk EG00117 affected269 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0009 affected254 at risk EG00121 affected269 at risk
Hot flush	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG00066 affected254 at risk EG001101 affected269 at risk
Hypertension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG00032 affected254 at risk EG00125 affected269 at risk
Lymphoedema	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG00020 affected254 at risk EG00119 affected269 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D004164	Diphosphonates
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009570	Nitriles
D014230	Triazoles

ID	Title	Description
BG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
BG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Upfront Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1			47	254	225	254
EG001	Delayed Zoledronic Acid	Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.			56	269	240	269