2) 250 (81.4) 264 (85.7) Serious adverse events 31 (10.1) 32 (10.4) 32 (10.4) Deaths 1 (0.3) 1 (0.3) 0 (0.0) Withdrawn due to an adverse event 28 (9.1) 37 (12.1) 25 (8.1) Most common adverse events associated with withdrawal  Gastrointestinal disorder 13 (4.2) 21 (6.8) 14 (4.5) Most common adverse events  Arthralgia 33 (10.7) 29 (9.4) 27 (8.8)  Back pain 27 (8.8) 29 (9.4) 29 (9.4)  Nasopharyngitis

24 (7.8) 32 (10.4) 38 (12.3)  Influenza 23 (7.5) 27 (8.8) 25 (8.1)  Urinary tract infection 20 (6.5) 21 (6.8) 22 (7.1)  Diarrhea 19 (6.2) 30 (9.8) 21 (6.8)  Upper abdominal pain 8 (2.6) 11 (3.6) 26 (8.4) Adverse events SBE-��-CD ic50 of special interest  Clinical vertebral fracture see more 1 (0.3) 0 (0.0) 3 (1.0)  Clinical nonvertebral fracture 15 (4.9) 13 (4.2) 20 (6.5)  Upper gastrointestinal tract adverse events 56 (18.2) 59 (19.2) 69 (22.4)  Selected musculoskeletal adverse eventsa 66 (22.1) 67 (21.8) 77 (25.0)  Adverse events potentially associated with acute phase reactionb 4 (1.3) 7 (2.3) 4 (1.3) aIncludes arthralgia, back pain, bone pain, musculoskeletal pain, musculoskeletal

discomfort, myalgia, and neck pain bIncludes symptoms of influenza-like illness or pyrexia with a start date within the first 3 days after the first dose of study drug and duration of 7 days or less Adverse events of special interest for bisphosphonates include clinical fractures, musculoskeletal adverse events, acute phase reactions, and osteonecrosis of the jaw (ONJ). Clinical fractures are defined as all non-vertebral fractures and symptomatic, Autophagy Compound Library cell assay radiographically confirmed vertebral fractures that occurred after randomization and were reported as adverse events. Acute phase reactions are defined as influenza-like illness and/or pyrexia starting within 3 days following the first dose of study drug and having duration of 7 days or Meloxicam less. Clinical fracture and musculoskeletal adverse events were reported by similar proportions of

subjects across treatment groups (Table 1). No cases of acute phase reaction or ONJ were reported. Other than the expected small, transient, and asymptomatic decreases in serum calcium seen within the first few weeks of treatment, no clinically important differences or trends were seen across groups for any laboratory parameter measured, including measures of hepatic and renal function, and electrocardiograms during the 2-year study. No histological abnormalities were observed in any of the biopsy specimens, and double tetracycline label was detected in all 45 biopsies. Static and dynamic histomorphometric measurements and bone mineralization parameters were similar across treatment groups (Table 2).