Slide 1

Dr. Atef A. Mahmoud, MD, FRCP Professor of Internal Medicine & Rheumatology Cairo Unversity Management of Refractory cases of Osteoporosis

Slide 2

Case Study F.M.A,84 years old Egyptian F., MRN 707962 Rheumatology OPD: (December 1977, 67yrs old) LBP, Hip and Knee pain lumbar spond., OA No H. of chronic medical diseaes, no fx. nor FH of fx. December 1998 BMD LS T 1.5 FN T-1.5 Calcium 1000mg + Cholecalciferol 400 u/d

Slide 3

June 2000 Graves disease, started on Neomercazol 30 mg/d controlled, dose reduced Hypertension, AF on coumadin INR 2.7 Dyslipidaemia on Atrovastatin 10 mg/d Repeat BMD, Auguest 2000 Lumbar sp. T -1.65 FU -3.1% FN T -1.51 FU -3.7% Start Alendronate Sodium 10 mg/d

Slide 4

Repeat BMD, January 2004 Osteopoenia, LS + 17.8%, FN + 15.8% December 2006, still on Fosamax, no Fx. Repeat BMD in 2006 very satisfactory Drug holiday for 2yrs.,continue Cal. & vit. D BMD repeated in january 2008 and March 2010 almost normal

Slide 5

January 2008

Slide 6

Slide 7

Slide 8

March 2010

Slide 9

Slide 10

Slide 11

Alendronate 70 mg Once Weekly is Therapeutically Equivalent to Alendronate 10 mg daily 11 FOSAMAX Increased Lumbar Spine BMD More Than Placebo As seen in FLEX, FLEX = FIT Long-term EXtension study; BMD = bone mineral density; FIT = Fracture Intervention Trial a Pooled 5-mg and 10-mg groups; b Error bars indicate 95% confidence interval; c Measured in clinical fracture arm only Adapted from Black DM et al. JAMA. 2006;296:29272938. FOSAMAX (alendronate sodium) is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. FOSAMAX/FOSAMAX a FOSAMAX/placebo 0 2 4 12 14 16 01234 BMD Change From FIT Baseline, Mean % b Year FITFLEX 6 8 10 0 2 4 12 14 16 01234 Year 6 8 10 5 Number FOSAMAX/FOSAMAX648648647645449 c 646595553 FOSAMAX/placebo 431429430426293 c 429402365 3.7% P

Compliance Issues Ca and VtD RaloxifenAlend Daily Alend weekly Resid Daily Within 6 mo 14.39.19.85.911.8 6-12 mo5.45.36.60.94.7 >12 mo2.91.94.50.12.5 Total22.716.320.96.919

Slide 49

Low compliance leads to low efficacy Fracture risk at 24 months Compliance to bisphosphonates (MPR) 50% Below efficacy zone 80% Protective effect of bisphosphonates (35 537 patients) starts >50 % compliance optimal >80% compliance 1/2 patients 3.5% in BMD in 2 yr at any one of the skeletal sites measured, despite documented continuous prescription of an AR agent in the preceding 24 moths.

Slide 52

Baseline Factors Predicting Poor Response

Slide 53

Slide 54

Investigations of Non-responders

Slide 55

Management of Poor Responders The use of other anti-osteoporosis agent Optimal intake of Ca and Vitamin D Treatment of underlying causes of secondary osteoporosis ( 30% of PM women and 40% in osteoporotic men) Role of other new therapies and anabolic agents ?

Slide 56

Slide 57

Dr. Atef A. Mahmoud, MD, FRCP Head of Rheumatology & Rehabilitation Unit, Dr. Erfan & Bagedo Hospital Management of Refractory cases of Osteoporosis

Slide 58

Alendronate 70 mg Once Weekly is Therapeutically Equivalent to Alendronate 10 mg daily 58 Continuous Increases in Lumbar Spine BMD with Alendronate 10 mg over 10 Years 012345678910 0 2 4 6 8 12 14 Year Mean Percent Change (SE) ALN 5 mg (n=78) ALN 10 mg (n=86) ALN 20 mg/ALN 5 mg/Placebo (n=83) Adapted from Bone HG et al N Engl J Med 2004;350:11891199. The mean percent change from baseline to year 10 appears in parentheses following each treatment group. (9.3%) p