1. Date of download: 5/31/2016 From: Alendronate and Estrogen–Progestin in the Long-Term Prevention of Bone Loss: Four-Year Results from the Early Postmenopausal Intervention Cohort Study: A Randomized, Controlled Trial Ann Intern Med. 1999;131(12):935-942. doi:10.7326/0003-4819-131-12-199912210-00005 Mean percentage change (±SE) from baseline in bone mineral density at the lumbar spine, total hip, total body, and one-third distal forearm.Black triangles represent women who received 4 years of alendronate, 5 mg/d; black squares represent women who received 4 years of alendronate, 2.5 mg/d; white circles and dashes represent women who received 4 years of placebo; white diamonds represent women who received 4 years of estrogen-medroxyprogesterone acetate; black diamonds represent women who received 4 years of estradiol-norethisterone acetate; white triangles and dashes represent women who received 2 years of alendronate, 5 mg/d, followed by 2 years of placebo; and white squares and dashes represent women who received 2 years of alendronate, 2.5 mg, followed by 2 years of placebo. For graphical presentation, results from groups that received the same dosage of alendronate during the first 2 years of the study were pooled during this period for the two strata combined. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 5/31/2016 From: Alendronate and Estrogen–Progestin in the Long-Term Prevention of Bone Loss: Four-Year Results from the Early Postmenopausal Intervention Cohort Study: A Randomized, Controlled Trial Ann Intern Med. 1999;131(12):935-942. doi:10.7326/0003-4819-131-12-199912210-00005 Cumulative percentage change and corresponding least significant difference (LSD) interval at the lumbar spine, total hip, total body, and one-third distal forearm.PChanges from baseline to year 2 in the group that continuously received placebo are compared with changes in years 3 and 4 in the groups that did not continuously receive alendronate. Circles represent women who received 4 years of placebo; squares represent women who received 2 years of alendronate, 2.5 mg/d, followed by 2 years of placebo; and triangles represent women who received 2 years of alendronate, 5 mg/d, followed by 2 years of placebo. The LSD interval is approximately an 84% CI; overlapping LSD intervals imply that the value exceeds 0.05 for between-group tests. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 5/31/2016 From: Alendronate and Estrogen–Progestin in the Long-Term Prevention of Bone Loss: Four-Year Results from the Early Postmenopausal Intervention Cohort Study: A Randomized, Controlled Trial Ann Intern Med. 1999;131(12):935-942. doi:10.7326/0003-4819-131-12-199912210-00005 Mean observed change from baseline (±SE) in urineN-telopeptide cross-links of type I collagen, serum osteocalcin, and serum bone-specific alkaline phosphatase levels.BCEN(15)(16)Black triangles represent women who received 4 years of alendronate, 5 mg/d; black squares represent women who received 4 years of alendronate, 2.5 mg/d; white circles and dashes represent women who received 4 years of placebo; white diamonds represent women who received estrogen-medroxyprogesterone acetate; black diamonds represent women who received estradiol-norethisterone acetate; white triangles and dashes represent women who received 2 years of alendronate, 5 mg/d, followed by 2 years of placebo; and white squares and dashes represent women who received 2 years of alendronate, 2.5 mg/d, followed by 2 years of placebo. For graphical presentation, results from groups that received the same dosage of alendronate during the first 2 years of the study were pooled during this period for both strata combined. The mean premenopausal reference ranges (± SD) were 22.5 ± 9.4 nmol bone collagen equivalents ( )/mmol Cr for urine levels of -telopeptide cross-links of type I collagen and 8.8 ± 2.7 ng/mL for serum levels of bone-specific alkaline phosphatase. No premenopausal reference range was available for serum osteocalcin. To convert ng/mL to µg/L, multiply by 1.0. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians