Trial Outcomes & Findings for The Effect of Protein Supplementation on Bone Health in Healthy Older Men and Women (NCT NCT00421408)

Last Updated: 2020-04-09

Results Overview

There is no absolute normative range for bone mineral density. Population norms have been established for specific races and men and women for the hip based on data collected by National Health Examination Nutrition Surveys (NHANES) and for the spine based largely on data collected by individual manufacturers. Values within 1 standard deviation of the population mean are generally considered normal. Values below 1 standard deviation from the population mean are generally considered to reflect reduced bone mass.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

208 participants

Primary outcome timeframe

Measured at baseline and 18 months

Results posted on

2020-04-09

Participant Flow

Recruitment started in June 2007 and the last participant was screened in October 2010. Subjects were recruited to the Yale Center for Clinical Investigation in New Haven, CT or the University of Connecticut Health Center in Farmington, CT.

Subjects were randomized 1 month after screening if they were found eligible after screening. Between screening and randomization their calcium and vitamin D intake was stabilized for baseline measurements.

Participant milestones

Participant milestones
Measure	Placebo Carbohydrate 40 g Daily for 18 Months Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Overall Study STARTED	102	106
Overall Study COMPLETED	60	61
Overall Study NOT COMPLETED	42	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Carbohydrate 40 g Daily for 18 Months Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Overall Study Lost to Follow-up	30	20
Overall Study Discountinued from treatment/ f/u cont.	12	25

Baseline Characteristics

The Effect of Protein Supplementation on Bone Health in Healthy Older Men and Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=102 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=106 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months	Total n=208 Participants Total of all reporting groups
Age, Continuous	70.5 years STANDARD_DEVIATION 6.4 • n=5 Participants	69.9 years STANDARD_DEVIATION 6.1 • n=7 Participants	70.2 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	89 Participants n=5 Participants	89 Participants n=7 Participants	178 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	102 participants n=5 Participants	106 participants n=7 Participants	208 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at baseline and 18 months

Population: Only participants with data at the baseline and 18 month timeframe were used in the analysis.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=79 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=92 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Change in Anterior-posterior Spine Bone Mass Density Measured by Dual Energy X-ray Absorptiometry (DXA) Compared to Baseline	0.51 percentage change Standard Error 0.38	0.51 percentage change Standard Error 0.38

PRIMARY outcome

Timeframe: Measured at baseline and 18 months

Population: Only participants with data at the baseline and 18 month timeframe were used in the analysis. Only half of the study partipants were randomized to receive Quantitative Computed Tomography testing.

There is no normative data for quantitative computed tomography it is based on local experience.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=30 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=30 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Change in Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) Compared to Baseline	-0.07 percent change Standard Error 1.08	-2.64 percent change Standard Error 1.81

PRIMARY outcome

Timeframe: Measured at 0 months

Population: All participants were analyzed using the mixed models method.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=102 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=106 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at Baseline	1.10 g/cm^2 Standard Error 0.01	1.13 g/cm^2 Standard Error 0.01

PRIMARY outcome

Timeframe: Measured at 9 months

Population: All participants were analyzed using the mixed models method.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=102 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=106 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 9 Months	1.14 g/cm^2 Standard Error 0.02	1.12 g/cm^2 Standard Error 0.01

PRIMARY outcome

Timeframe: Measured at 18 months

Population: All participants were analyzed using the mixed models method.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=102 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=106 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Anterior-posterior Spine Bone Mineral Density Measured by Dual Energy X-ray Absorptiometry (DXA) at 18 Months	1.14 g/cm^2 Standard Error 0.02	1.12 g/cm^2 Standard Error 0.01

PRIMARY outcome

Timeframe: Measured at 0 months

Population: All participants were analyzed using the mixed models method. For the Quantitative Computed Tomography (QCT) test only half of the participants were randomized to receive it.

There is no normative data for quantitative computed tomography it is based on local experience.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=44 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=45 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at Baseline	106 mg/cm^3 Standard Error 3.72	103 mg/cm^3 Standard Error 4.51

PRIMARY outcome

Timeframe: Measured at 18 months

Population: All participants were analyzed using the mixed models method. For the Quantitative Computed Tomography (QCT) test only half of the participants were randomized to receive it.

There is no normative data for quantitative computed tomography it is based on local experience.

Outcome measures

Outcome measures
Measure	Placebo Carbohydrate 40 g Daily for 18 Months n=44 Participants Participants will receive a placebo supplement daily (40 g maltodextrin). Placebo : Placebo supplement daily for 18 months	Protein Powder 40 g Daily for 18 Months n=45 Participants Participants will receive a protein supplement daily (40 g whey protein supplement). Whey protein supplement : 40-g whey protein supplement daily for 18 months
Spine Bone Mineral Density Measured by Quantitative Computed Tomography (QCT) at 18 Months	106 mg/cm^3 Standard Error 4.07	99.3 mg/cm^3 Standard Error 4.29

Adverse Events

Placebo Carbohydrate Powder 40 g Daily

Serious events: 14 serious events

Other events: 46 other events

Deaths: 0 deaths

Protein Powder 40 g Daily

Serious events: 4 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Karl Insogna

Yale University

Phone: 203-737-2871

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo Carbohydrate Powder 40 g Daily n=102 participants at risk	Protein Powder 40 g Daily n=106 participants at risk
Musculoskeletal and connective tissue disorders spinal fusion	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Respiratory, thoracic and mediastinal disorders pneumonia	2.9% 3/102 • Number of events 3 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Endocrine disorders surgery for thyroid tumor	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Back surgery	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Hepatobiliary disorders Liver cancer	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Nervous system disorders Stroke	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders pyelonephritis	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Vascular disorders Severe nose bleed	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Cardiac disorders Dramatic drop in blood pressure	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Vascular disorders Bleed	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Hernia surgery	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Surgical and medical procedures Colon resection	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Hepatobiliary disorders Acute pancreatitits	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Hip replacement	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.

Measure	Placebo Carbohydrate Powder 40 g Daily n=102 participants at risk	Protein Powder 40 g Daily n=106 participants at risk
Gastrointestinal disorders Mild to moderate gastro-intestinal upset	17.6% 18/102 • Number of events 18 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	29.2% 31/106 • Number of events 31 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Musculo-skeletal surgery	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Ear and labyrinth disorders Vertigo	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	1.9% 2/106 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Skin and subcutaneous tissue disorders Skin disorders	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	1.9% 2/106 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Infections and infestations Infections	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Investigations Incidental findings on QCT	3.9% 4/102 • Number of events 4 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Gastrointestinal disorders Diagnosed with Barret's esophagus	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders Decrease in glomerular filtration rate	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Investigations Burning tongue syndrome	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Cardiac disorders High blood pressure	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Blood and lymphatic system disorders Anemia	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Injury, poisoning and procedural complications Bike accident	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders Bladder tumor	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders Attenuating mass in left kidney	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Ruptured baker's cyst in knee while walking	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Nervous system disorders restlessness	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mouth cancer	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Cardiac disorders Difficult breathing due to atrial fibrillation	0.98% 1/102 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.00% 0/106 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders Kidney stone	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Cardiac disorders Fluid retention	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Renal and urinary disorders Acute renal failure following cardiac cath procedure	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Infections and infestations Shingles	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	1.9% 2/106 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Metabolism and nutrition disorders Elevated cholesterol	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Gastrointestinal disorders Pain in lower left quadrant	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Surgical and medical procedures Outpatient hernia surgery	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Cardiac disorders Increased duration of heart palpitations	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Injury, poisoning and procedural complications Car accident	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Endocrine disorders Hyperglycemia	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Respiratory, thoracic and mediastinal disorders Dry mouth	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal squamous cells removed from right cheek	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Bursa removed from right knee	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Injury, poisoning and procedural complications Bruise and bleeding post blood draw	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Respiratory, thoracic and mediastinal disorders Asthmatic bronchitis	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Arthritis	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	1.9% 2/106 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Pain	2.0% 2/102 • Number of events 2 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.
Musculoskeletal and connective tissue disorders Broken bone	0.00% 0/102 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.	0.94% 1/106 • Number of events 1 • AE data was collected from July 2007 to May 2012 Gastrointestinal adverse events were assessed at times as part of a group of events.