Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00103740
• Collaborator: (none)
• Enrollment: 185
• Locations: 41
• Arms: 2
• Duration (Months): 108
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this core study was to show non-inferiority of zoledronic acid to risedronate, with respect to the proportion of patients who achieved therapeutic response. The extended observation period included participants of the core study who responded to treatment.

Condition or Disease	Intervention/Treatment	Phase
Paget's Disease of Bone	Drug: zoledronic acid; Drug: placebo to zoledronic acid; Drug: Risedronate; Drug: Placebo to risedronate; Drug: Calcium and vitamin D supplements	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Safety and Efficacy Trial With Intravenous Zoledronic Acid for the Treatment of Paget's Disease of Bone Using Risedronate as a Comparator, Including an Extended Observation Period
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: Dec 1, 2003
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zoledronic acid and placebo to risedronate Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Drug: zoledronic acid; 5 mg zoledronic acid in 5 mL of sterile water for infusion; Drug: Placebo to risedronate; oral capsules; Drug: Calcium and vitamin D supplements; Calcium and vitamin D supplements were supplied
Active Comparator: Risedronate and placebo to zoledronic acid Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Drug: placebo to zoledronic acid; 5 mL of sterile water for infusion; Drug: Risedronate; 30mg oral tablets overencapsulated to match the placebo capsules; Drug: Calcium and vitamin D supplements; Calcium and vitamin D supplements were supplied

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Had Therapeutic Response at 6 Months [Baseline, 6 months]

   A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months.

Secondary Outcome Measures

1. Relative Change in Serum Alkaline Phosphatase in U/L at Day 28 [Baseline and 28 days]

   The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.

2. Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10 [Baseline and day 10]

   The percent change in serum C-telopeptide from baseline to Day 10 was measured.

3. Relative Change in Urine α-CTx in ug/mmol at Day 10 [Baseline and day 10]

   The percent change in urine α-CTx from baseline to Day 10 was measured.

4. Time to First Therapeutic Response [182 days]

   Therapeutic response was defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase.

5. Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 [Day 28]

   Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Central laboratory reference ranges for serum alkaline phosphatase: 31-110 U/L (female & male 20-58 years) and 35-115 U/L (female & male >58 years).

6. Change in Pain Severity at Day 182 [Baseline and day 182]

   Change in pain severity score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.

7. Change in Pain Interference at Day 182 [Baseline and day 182]

   Change in pain interference score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.

8. Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period [8 years was the maximum]

   Extended observation period. A therapeutic response is defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess or normalization of serum alkaline phosphatase.

9. Number of Participants With a Partial Disease Relapse During the Extended Observation Period [8 years was the maximum]

   Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at Month 6 and at least 1.25 times the upper normal limit.

10. Number of Participants With a Disease Relapse During the Extended Observation Period [8 years was maximum]

    Extended observation period. A disease relapse was defined as the occurrence of a serum alkaline phosphatase level that was >= 80% of baseline serum alkaline phosphatase value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 30 years or older

• SAP 2 times ULN

• Confirmed diagnosis of Paget's disease of the bone (by x-ray, magnetic resonance imaging, computerized tomography, radioisotope imaging, etc.).

• 90 days washout calcitonin

• 180 day washout bisphosphonate

Exclusion Criteria:

• Allergic reaction to bisphosphonates

• History of upper GI disorders

• History of iritis, uveitis

• Calculated creatinine clearance < 30 ml/min at baseline

• Evidence of vitamin D deficiency

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative site	Tucson	Arizona	United States	85732
2	Novartis Investigative Site	Colorado Springs	Colorado	United States	80901
3	Novartis Investigative Site	Indianapolis	Indiana	United States	46202
4	Novartis Investigative Site	New Orleans	Louisiana	United States	70121
5	Novartis Investigative Site	Boston	Massachusetts	United States	02114
6	Novartis Investigative Site	Syracuse	New York	United States	13210
7	Novartis Investigative Site	Cleveland	Ohio	United States	44195
8	Novartis Investigative Site	Medford	Oregon	United States	97504
9	Novartis Investigative Site	Columbia	South Carolina	United States	29209
10	Novartis Investigative Site	Madison	Wisconsin	United States	53592
11	Novartis Investigative Site	Fitzroy		Australia
12	Novartis Investigative Site	Kogarah		Australia
13	Novartis Investigative site	Newcastle		Australia
14	Novartis Investigative Site	Parkville		Australia
15	Novartis Investigative site	St. Leonards		Australia
16	Novartis Investigative site	Brussels		Belgium
17	Novartis Investigative Site	Gent		Belgium
18	Novartis Investigative Site	Montreal		Canada
19	Novartis Investigative Site	Angers		France
20	Novartis Investigative Site	Dreux Cedex		France
21	Novartis Investigative Site	Marseille		France
22	Novartis Investigative Site	Nice Cedex		France
23	Novartis Investigative Site	Paris Cedex		France
24	Novartis Investigative Site	Rouen Cedex		France
25	Novartis Investigative Site	Toulouse		France
26	Novartis Investigative Site	Berlin		Germany
27	Novartis Investigative Site	Frankfurt		Germany
28	Novartis Investigative Site	Leipzig		Germany
29	Novartis Investigative Site	Leverkusen		Germany
30	Novartis Investigative Site	Wirzburg		Germany
31	Novartis Investigative site	Christchurch		New Zealand
32	Novartis Investigative site	Cape Town		South Africa
33	Novartis Investigative site	Barcelona		Spain
34	Novartis Investigative site	Madrid		Spain
35	Novartis Investigative Site	Malaga		Spain
36	Novartis Investigative Site	Salamanca		Spain
37	Novartis Investigative site	Santiago de Compostela		Spain
38	Novartis Investigative Site	Valencia		Spain
39	Novartis Investigative Site	Liverpool		United Kingdom
40	Novartis Investigative Site	London		United Kingdom
41	Novartis Investigative site	Oxford		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00103740
• Other Study ID Numbers: CZOL446H2305; ZOL446K2305; NCT00051649
• First Posted: Feb 15, 2005
• Last Update Posted: Jun 4, 2012
• Last Verified: May 1, 2012

• Keywords provided by Novartis Pharmaceuticals: Zoledronic acid, risedronate, Paget's disease of bone
• Additional relevant MeSH terms: Bone Diseases; Osteitis Deformans; Vitamin D; Zoledronic Acid; Risedronic Acid; Etidronic Acid; Calcium

Study Results

Participant Flow

Pre-assignment Detail	371 patients were screened. 185 patients were randomized.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Period Title: Period 1 - Core
STARTED	92	93
COMPLETED	85	89
NOT COMPLETED	7	4
Period Title: Period 1 - Core
STARTED	78	63
COMPLETED	9	27
NOT COMPLETED	69	36

Baseline Characteristics

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid	Total
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Total of all reporting groups
Overall Participants	92	93	185
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.3 (9.42)	68.2 (11.15)	69.8 (10.41)
Sex: Female, Male (Count of Participants)
Female	30 32.6%	36 38.7%	66 35.7%
Male	62 67.4%	57 61.3%	119 64.3%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Had Therapeutic Response at 6 Months
Description	A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

Modified intent to treat population: all randomized patients with both baseline and at least one post-baseline serum alkaline phosphatase measurement. Missing values at 6 months were imputed using the last post-baseline measurement prior to 6 months.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	88	89
Number [participants]	84 91.3%	67 72%

2. Secondary Outcome

Title	Relative Change in Serum Alkaline Phosphatase in U/L at Day 28
Description	The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.
Time Frame	Baseline and 28 days

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at baseline and 28 days were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	79	85
Mean (Standard Deviation) [percent change]	-49.1 (14.55)	-24.3 (18.19)

3. Secondary Outcome

Title	Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
Description	The percent change in serum C-telopeptide from baseline to Day 10 was measured.
Time Frame	Baseline and day 10

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 10 were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	60	70
Mean (Standard Deviation) [percent change]	-74.2 (123.73)	-40.1 (34.70)

4. Secondary Outcome

Title	Relative Change in Urine α-CTx in ug/mmol at Day 10
Description	The percent change in urine α-CTx from baseline to Day 10 was measured.
Time Frame	Baseline and day 10

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 10 were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	67	70
Mean (Standard Deviation) [percent change]	-87.5 (39.33)	-28.7 (68.22)

5. Secondary Outcome

Title	Time to First Therapeutic Response
Description	Therapeutic response was defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase.
Time Frame	182 days

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	92	93
Median (Inter-Quartile Range) [days]	64	91

6. Secondary Outcome

Title	Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28
Description	Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Central laboratory reference ranges for serum alkaline phosphatase: 31-110 U/L (female & male 20-58 years) and 35-115 U/L (female & male >58 years).
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at day 28 were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	88	88
Number [participants]	8 8.7%	1 1.1%

7. Secondary Outcome

Title	Change in Pain Severity at Day 182
Description	Change in pain severity score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.
Time Frame	Baseline and day 182

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 182 were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	50	46
Mean (Standard Deviation) [units on a scale]	-0.5 (1.74)	-0.1 (2.02)

8. Secondary Outcome

Title	Change in Pain Interference at Day 182
Description	Change in pain interference score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.
Time Frame	Baseline and day 182

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 182 were included in this analysis.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	49	45
Mean (Standard Deviation) [units on a scale]	-0.5 (1.97)	0.0 (1.89)

9. Secondary Outcome

Title	Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period
Description	Extended observation period. A therapeutic response is defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess or normalization of serum alkaline phosphatase.
Time Frame	8 years was the maximum

Outcome Measure Data

Analysis Population Description

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	78	63
Number [participants]	10 10.9%	42 45.2%

10. Secondary Outcome

Title	Number of Participants With a Partial Disease Relapse During the Extended Observation Period
Description	Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at Month 6 and at least 1.25 times the upper normal limit.
Time Frame	8 years was the maximum

Outcome Measure Data

Analysis Population Description

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	78	63
Number [participants]	9 9.8%	37 39.8%

11. Secondary Outcome

Title	Number of Participants With a Disease Relapse During the Extended Observation Period
Description	Extended observation period. A disease relapse was defined as the occurrence of a serum alkaline phosphatase level that was >= 80% of baseline serum alkaline phosphatase value.
Time Frame	8 years was maximum

Outcome Measure Data

Analysis Population Description

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Arm/Group Title	Zoledronic Acid and Placebo to Risedronate	Risedronate and Placebo to Zoledronic Acid
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
Measure Participants	78	63
Number [participants]	0 0%	15 16.1%

Adverse Events

Adverse Event Reporting Description	The safety population consisted of all randomized patients who were exposed to study drug.
Arm/Group Title	Zoledronic Acid		Risedronate
Arm/Group Description	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.		Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
All Cause Mortality
	Zoledronic Acid		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zoledronic Acid		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/88 (4.5%)		3/90 (3.3%)
General disorders
Chest pain	0/88 (0%)		1/90 (1.1%)
Infections and infestations
Enterobacter sepsis	1/88 (1.1%)		0/90 (0%)
Escherichia infection	1/88 (1.1%)		0/90 (0%)
Injury, poisoning and procedural complications
Femur fracture	1/88 (1.1%)		0/90 (0%)
Humerus fracture	0/88 (0%)		1/90 (1.1%)
Spinal fracture	1/88 (1.1%)		0/90 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/88 (1.1%)		0/90 (0%)
Nervous system disorders
Cerebrovascular accident	1/88 (1.1%)		0/90 (0%)
Reproductive system and breast disorders
Endometrial hyperplasia	0/88 (0%)		1/90 (1.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/88 (1.1%)		0/90 (0%)
Dyspnoea	1/88 (1.1%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Zoledronic Acid		Risedronate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/88 (45.5%)		28/90 (31.1%)
Gastrointestinal disorders
Constipation	5/88 (5.7%)		2/90 (2.2%)
Diarrhoea	6/88 (6.8%)		7/90 (7.8%)
Nausea	6/88 (6.8%)		3/90 (3.3%)
General disorders
Fatigue	6/88 (6.8%)		2/90 (2.2%)
Influenza like illness	13/88 (14.8%)		6/90 (6.7%)
Infections and infestations
Influenza	5/88 (5.7%)		2/90 (2.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/88 (5.7%)		4/90 (4.4%)
Bone pain	6/88 (6.8%)		2/90 (2.2%)
Nervous system disorders
Dizziness	5/88 (5.7%)		4/90 (4.4%)
Headache	9/88 (10.2%)		6/90 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.