Dr. Atef A. Mahmoud, MD, FRCP Professor of Internal Medicine
& Rheumatology Cairo Unversity Management of Refractory cases
of Osteoporosis
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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
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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
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January 2008
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March 2010
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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
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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.
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Baseline Factors Predicting Poor Response
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Investigations of Non-responders
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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 ?
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Dr. Atef A. Mahmoud, MD, FRCP Head of Rheumatology &
Rehabilitation Unit, Dr. Erfan & Bagedo Hospital Management of
Refractory cases of Osteoporosis
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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