Aldren R Comparison between Fosamax R and Aldren R for treatment of PMO : a randomized controlled trial

Problems  Disintegration of drug  Poor GI absorption ( %)  Non-metabolized  Rapid adsorption on bone surface, preferentially high turnover site  Eliminated by kidney, solely

Objectives Aldren 70 once a week (Kaspa) Fosamax 70 (MSD) for  To evaluate the anti-resorptive efficacy of Aldren 70 once a week (Kaspa) in comparison to Fosamax 70 (MSD) for treatment of PMO  To assess the side effects, drug non- responder and drug compliance

Non-Inferiority trial: Power & Sample Size Program (Vandebuilt) : Different of BTM = 0.15, SD = 0.2 AlphaPower BTM reduction diff. betw groups SD of BTM No./ group No.+20%/ group

Inclusion criteria  Post-menopausal woman  Age > 60 years old  Menopause >5 year  BP naïve  Stop any anti-osteoporotic drugs > 1 year  BMD hip: T-score at Neck/Total < -2.5 or 450 pg/ml or 450 pg/ml

Exclusion criteria  Secondary osteoporosis: GIO, DM, Hyperthyroidism, etc.  Atrial fibrillation (irregular pulse/ personal history)  CKD IV, V  History of recent PU/ GI problems  Non-communicable

Enrolled BMD hip screening 210 post-menopausal women 80 fulfilled criteria Randomized 40 cases for Aldren70 40 cases for Aldren70 40 cases for Fosamax70 40 cases for Fosamax70

Time schedule & FU interval  0 mo. CBC UA Cr LFT CTX CBC UA Cr LFT CTX Drug once a week Drug once a week + Ca 1250 & MTV ( D IU)  3 mo. CTX CTX  6 mo. CBC UA Cr LFT CTX CBC UA Cr LFT CTX Telephone remind/AE every 4 wks

Statistics  Unpaired T-test  Fisher exact’s test STATA 11.0 (StataCorp, College Station, Texas)

RCT of Fosamax 70 vs Aldren 70

Comparison of outcomes between treatment groups

The comparisons of CTX between treatment groups according to time.

The comparisons of %CTX reduction between treatment groups according to time. Note: significant clinical improvement means > 55% improvement from the baseline.

Side effects and non compliance rate between treatment groups. (N=37/37) Variables Treatmentp-value FosamaxAldren70 Side effect (%) 8 (21.6) Fever 4 (10.8)3 (8.1) Myalgia 2 (5.4) Rash 2 (5.4)0 (0) Stress 0 (0)2 (5.4) Gastritis 0 (0)2 (5.4) Constipation 2 (5.4)0 (0) Dry mouth/oral burn 1 (2.7)2 (5.4)1.000 Loss to follow-up (%) 3 (8.1)2 (5.4)1.000 Non-adherence (%) 4 (10.8)9 (24.3)0.221 Non drug response (%) (*N=35/35) 7 (18.9) 6 (16.2) CTX reduction < 55% CTX reduction < 55% - 3 months 8 (23.5)7 (20) months 8 (25.8)5 (16.7)0.534

Side effects and non compliance rate between treatment groups. (N=37/37) Variables Treatmentp-value FosamaxAldren70 Side effect (%)8 (21.6) Fever 4 (10.8)3 (8.1) Myalgia 2 (5.4) Rash 2 (5.4)0 (0) Stress 0 (0)2 (5.4) Gastritis 0 (0)2 (5.4) Constipation 2 (5.4)0 (0) Dry mouth/oral burn 1 (2.7)2 (5.4)1.000 Loss to follow-up (%) 3 (8.1)2 (5.4)1.000 Non-adherence (%) 4 (10.8)9 (24.3)0.221 Non drug response (%) (*N=35/35) 7 (18.9) 6 (16.2) CTX reduction < 55% CTX reduction < 55% - 3 months 8 (23.5)7 (20) months 8 (25.8)5 (16.7)0.534 Side effect (%) Side effect (%) FosamaxAldrenp-valueFever4 (10.8) 3 (8.1) Myalgia2 (5.4) Rash2 (5.4) 0 (0) 0.493

Variables Treatmentp-value FosamaxAldren70 Side effect (%) 8 (21.6) Fever 4 (10.8)3 (8.1) Myalgia 2 (5.4) Rash 2 (5.4)0 (0) Stress 0 (0)2 (5.4) Gastritis 0 (0)2 (5.4) Constipation 2 (5.4)0 (0) Dry mouth/oral burn 1 (2.7)2 (5.4)1.000 Loss to follow-up (%) 3 (8.1)2 (5.4)1.000 Non-adherence (%) 4 (10.8)9 (24.3)0.221 Non drug response (%) (*N=35/35) 7 (18.9) 6 (16.2) CTX reduction < 55% CTX reduction < 55% - 3 months 8 (23.5)7 (20) months 8 (25.8)5 (16.7)0.534 Side effect (%) Side effect (%) FosamaxAldrenp-value Gastritis0 (0) 2 (5.4) Constipation2 (5.4) 0 (0) Dry mouth/oral burn1 (2.7) 2 (5.4) Side effects and non compliance rate between treatment groups. (N=37/37)

Variables Treatmentp-value FosamaxAldren70 Side effect (%) 8 (21.6) Fever 4 (10.8)3 (8.1) Myalgia 2 (5.4) Rash 2 (5.4)0 (0) Stress 0 (0)2 (5.4) Gastritis 0 (0)2 (5.4) Constipation 2 (5.4)0 (0) Dry mouth/oral burn 1 (2.7)2 (5.4)1.000 Loss to follow-up (%) 3 (8.1)2 (5.4)1.000 Non-adherence (%) 4 (10.8)9 (24.3)0.221 Non drug response (%) (*N=35/35) 7 (18.9) 6 (16.2) CTX reduction < 55% - 3 months 8 (23.5)7 (20) months 8 (25.8)5 (16.7)0.534 Non-responder Treatmentp-valueFosamaxAldren70 CTX reduction < 55% CTX reduction < 55% - 3 months 8 (23.5) 7 (20.0) months 8 (25.8) 5 (16.7) Side effects and non compliance rate between treatment groups. (N=37/37)

Variables Treatmentp-value FosamaxAldren70 Side effect (%) 8 (21.6) Fever 4 (10.8)3 (8.1) Myalgia 2 (5.4) Rash 2 (5.4)0 (0) Stress 0 (0)2 (5.4) Gastritis 0 (0)2 (5.4) Constipation 2 (5.4)0 (0) Dry mouth/oral burn 1 (2.7)2 (5.4)1.000 Loss to follow-up (%) 3 (8.1)2 (5.4)1.000 Non-adherence (%)4 (10.8)9 (24.3)0.221 Non drug response (%) (*N=35/35) 7 (18.9) 6 (16.2) CTX reduction < 55% CTX reduction < 55% - 3 months 8 (23.5)7 (20) months 8 (25.8)5 (16.7)0.534 Treatmentp-valueFosamaxAldren70 Non-adherence (%) 4 (10.8) 4 (10.8) 9 (24.3) 9 (24.3) Side effects and non compliance rate between treatment groups. (N=37/37)

High suppression Treatmentp-value FosamaxAldren70 CTX < 150 pg/ml - 3 months18 (52.9) 19 (54.3) months18 (58.1) 22 (73.3) CTX < 100 pg/ml - 3 months9 (26.5) 12 (34.3) months15 (48.4) 13 (43.3) 0.799

Number of patients at each interval of follow-up FosamaxAldren Start drug(0 mo.) mo.35 6 mo.3229

Number of drug non-responders and non-compliance FosamaxAldren Start drug(0 mo.) mo.7/35 (20%) 6 mo.+1/32+3/29

Conclusion 1. EfficacyAldren & Fosamax 1. Efficacy between Aldren & Fosamax has no statistical difference (by Bone resorption marker measurement, CTX). 2. Side effects (AE/SAE) Aldren & Fosamax 2. Side effects (AE/SAE) between Aldren & Fosamax has no statistical difference. 3. Non-responder to oral BP is 20% (in both groups by BTM) 4. Non-compliance of BP once a week is 17% in 3 mo. and 26% in 6 months.

Quiz 1 BP non-responder, sCTX should be lower than.. A. -30% B. -40% C. -50% D. -55% E. -60%

Quiz 2 The non-responder to BP(Alendronate) in Thai, by BTM monitoring is …… A. 5% B. 10% C. 15% D. 20% E. 30%

Quiz 3 The non-adherence to BP once a week in Thai, at 6 months is …… A. 5% B. 7% C. 17% D. 26%

Quiz 4 High turnover OP is determined by … A. BMD < 1.5 %/year B. BMD < 5 %/year C. BTM, CTX > 2.0 SD D. BTM, CTX > 2.5 SD

Quiz 5 Who is NOT a candidate for BP treatment? A. Low turnover osteoporoisis B. Prior vertebral fracture C. Steroid induced ostetoporosis D. Osteoporosis in malignancy