ΔΤΑΓΓΔΛΙΑ Γ. ΚΑΚΑΝΗ ΡΔΤΜΑΣΟΛΟΓΟ Γιδάκηωρ Πανεπιζηημίοσ Αθηνών

ΔΤΑΓΓΔΛΙΑ Γ. ΚΑΚΑΝΗ ΡΔΤΜΑΣΟΛΟΓΟ Γιδάκηωρ Πανεπιζηημίοσ Αθηνών

Cumulative Incidence, % Post hoc analyses of RCTs 4 Placebo (n=1817) 3 2 59% reduction (P<.1) alendronate (n=1841) 1 * * * * 6 12 18 24 3 36 FIT = Fracture Intervention Trial *Significant cumulative difference from placebo (P<.5) Adapted from Black DM, et al. J Clin Endocrinol Metab. 2;85:4118 4124; Black DM, et al. Lancet. 1996;348:1535 1541; Black DM, et al. Int J Clin Pract Suppl. 1999;11:46 5.. Month Alendronate reduced the incidence of multiple vertebral fractures by 9% at 3 years in women with prior fractures (P<.1 vs placebo)

Cumulative Incidence, % Post hoc analyses of RCTs 3. 2. 63% reduction (P=.14) Placebo (n=1817) 1. * * * * ALENDRO NATE (n=1841) 6 12 18 24 3 36 Month A significant reduction in relative risk was evident in women with and without fractures (P<.5) at month 18 and month 36 FIT = Fracture Intervention Trial *Significant cumulative difference from placebo (P<.5) Adapted from Black DM, et al. J Clin Endocrinol Metab. 2;85:4118 4124.

3-year FIT 4-year FIT 1-year FOSIT 2 3 year phase III 2-year INPACT 2-year LTCFS Overall Favors alendronate.1.3.5 1 Relative risk Favors control 2 5 55% risk reduction across all studies (p=.8) Meta-analysis of six randomized controlled trials of alendronate to examine consistency of effect and overall effect in reducing hip fractures in postmenopausal women FIT=Fracture Intervention Trial; FOSIT=FOSAMAX International Trial; INPACT=Investigation of Postmenopausal Osteoporosis: Alendronate vs. Calcium Trial; LTCFS=Long-Term Care Facilities study Papapoulos SE, Quandt SA, Liberman UA et al. Meta-analysisof the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporos Int 25; 16:468 74.

% Μείωση κινδύνου Meta analyses of RCTs Η Αλενδρονάτη προσέφερε μεγαλύτερη προστασία κατά των ζπονδσλικών καηαγμάηφν* 5 48%** 4 36% 4% 37% 3 2 21% 1 Alendronate 8 μελέτες (n=936) Risedronate 5 μελέτες (n=264) Calcitonin 1 μελέτη (n=118) Raloxifene 1 μελέτη (n=6828) Etidronate 9 μελέτες (n=176) *Data not representative of head-to-head trials; **p<.1 vs. baseline Meta-analysis to evaluate magnitude of treatment effects on fractures and BMD based on randomized controlled trials of different osteoporosis therapies All data statistically significant vs. baseline Adapted from Cranney A et al Endocr Rev 22;23:57 578.

% Μείωση κινδύνου Meta analyses of RCTs Η Αλενδρονάτη προσέφερε μεγαλύτερη προστασία κατά των μή ζπονδσλικών καηαγμάηφν* 5 49%** 4 3 2 27%* * 2% 1 9% 1% Alendronate 6 μελέτες (n=3723) Risedronate 7 μελέτες (n=12,958) Calcitonin 1 μελέτη (n=1245) Raloxifene 2 μελέτες (n=6961) Etidronate 7 μελέτες (n=867) *Data not representative of head-to-head trials; **p<.1 vs. baseline Meta-analysis to evaluate magnitude of treatment effects on fractures and BMD based on randomized controlled trials of different osteoporosis therapies Adapted from Cranney A et al Endocr Rev 22;23:57 578.

% Μείωση κινδύνου 6 5 4 3 2 45-55% 25-36% 26-27% 1 ALENDRONATE 5 mg/day b HRT Risedronate 2.5 or 5 mg/day RR (95%CI).45 (.28,.71).64 (.49,.84).74 (.58,.94) No data were identified for Ibandronate Liberman UA, Hochberg MC, Geusens P et al. Hip and non-spine fracture risk reductions differ among antiresorptive agents: Evidence from randomised controlled trials. Int J Clin Pract 26; 6: 1394 4.

Μέση μεταβολή % (±SE) Long-term extension analyses Ten years experience with alendronate for osteoporosis in postmenopausal women 14 12 1 8 6 4 OΜΣΣ 13.7% (p<.1) Τροχαντήρας 1.2% (p<.1) Ολικό Ιζσίο 6.7% (p<.1) Αυχένας Μηριαίου 5.5% (p<.1) 2 1 2 3 4 5 6 7 8 9 1 Adapted from Bone HG et al N Engl J Med 24;35:1189 1199. Χρόνια Η Αλενδρονάτη προσέφερε σταθερή βελτίωση της Οζηικήρ Πςκνόηηηαρ για 1 χρόνια με καλή ανεκτικότητα The discontinuation of alendronate resulted in a gradual loss of effect, asmeasured by bone density and biochemical markers of bone remodeling N=86

nmol BCE/mmol Cr µg/l 1 25 9 8 7 NTx ούρφν (μέζη ηιμή) 2 Οζηική Αλκαλική Φφζθαηάζη (μέζη ηιμή) 6 15 5 4 1 3 2 5 1 12 24 36 48 6 72 84 96 18 12 Μήνας 12 24 36 48 6 72 84 96 18 12 Μήνας Bone HG et al N Engl J Med 24;35(12):1189 1199;

Από βιοψίες οστών η αλενδρονάτη Βεληιώνει ηη μικποαπσιηεκηονική ζηο ζπογγώδερ οζηούν Αςξάνει ομοιογενώρ ηην επιμεηάλλωζη ζηο ζπογγώδερ και θλοιώδερ και μειώνει ηην ποποηικόηηηα Φςζιολογικό οζηούν μεηά και από δέκα έηη Από μελέηη ανάλςζηρ παπαμέηπων απσιηεκηονικήρ ηος ιζσίος [Hip structure analysis (HAS)] η Αλενδπονάηη Βεληιώνει ηιρ γεωμεηπικέρ παπαμέηποςρ ηηρ δομήρ ηος ιζσίος (cortical thickness, cross-sectional area, section modulus, and buckling ratio in the narrow neck, intertrochanteric region, and femoral shaft) Boivin GY et al 2. Bone.;27:687 94. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Hochberg MC, J Clin Endocrinol Metab. 22;87:1586 92. Recker R et al Curr Med Res Opin 25;21:185 194 JAMA, December 27, 26 Vol 296, No. 24 Greenspan et al 25 J Bone Miner Res. 25;2:1525 32. Effect of hormone replacement, alendronate, or combination therapy on hip structural geometry: a 3-year, double-blind, placebo-controlled clinical trial.

LS Mean (95% CI) Change From Baseline, ng/ml ALN+D56 Βεληίωζη ηων επιπέδων ηης βιηαμίνης - D ζηις 39 εβδομάδες 1 9 8 7 6 5 4 3 2 1 6.1 (95% CI: 5.2, 7.) ALENDRONATE +D56 IU (n=321) Week 39 4. (95% CI: 3.1, 4.8) ALENDRONATE +D28 IU (n=32) LS = least squares; CI = confidence interval

Βεληίωζη όλων ηων βιοσημικών παπαμέηπων Το ποζοζηό ηων αζθενών με ςπεπαζβεζηιοςπία ήηαν σαμηλό Bone 44 (29) 639-647

Rheumatol Int 29 DOI 1.17/s296-9-94-5 123

BMC Musculoskelet Disord 21 Apr 14;11(1):68. Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study. Grima DT, Papaioannou A, Airia P, Ioannidis G, Adachi JD A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 25 to the Canadian market.

Bone HG et al N Engl J Med 24;35(12):1189 1199;

Ανηικαηαγμαηική δράζη και ανηικαηαγμαηική δράζη ζηο ιζτίο επιβεβαιφμένη από κλινικές μελέηες, μεηαναλύζεις και ζσγκριηικές μελέηες Εσνοική επίδραζη ζηην ποιόηηηα ηοσ ζπογγώδοσς οζηού από βιουίες (έωρ 1 έηη) αλλά και θλοιώδοσς από βιουίες και μελέηη ανάλσζης παραμέηρφν αρτιηεκηονικής ηοσ ιζτίοσ [Hip structure analysis (HAS)] Μακροτρόνια (έφς 1 έηη) αποηελεζμαηικόηηηα και αζθάλεια