1. What is the evidence for benefits and harms of treating osteoarthritis with oral medication(s)? How do these benefits and harms change with dosage and duration of treatment, and what is the evidence that alternative dosage strategies, such as intermittent dosing and drug holidays, affect the benefits and harms of oral medication use?
2. Are there clinically important differences in the harms and benefits of oral treatments for osteoarthritis for certain demographic and clinical subgroups? (Demographic subgroups include age, sex, and race; Co-existing diseases include hypertension, edema, ischemic heart disease, heart failure; PUD; history of previous bleeding due to NSAIDS; Concomitant medication use includes anticoagulants).
3. What is the evidence that the gastrointestinal harms of NSAID use are reduced by co-prescribing of H2-antagonists, misoprostol, or proton pump inhibitors?
4. What are the benefits and safety of treating osteoarthritis with oral medications as compared with topical preparations?