Osteoporosis : The Silent Thief <ul><li>OSTEOPOROSIS  has been defined as a systemic skeletal disease characterized by low...
Osteoporotic bone remodelling O STEO F OS
Bone Remodelling With Alendronate O STEO F OS
Mode Of Action <ul><li>Gets preferentially bound under osteoclasts. Osteoclasts ingest the attached alendronate. Released ...
Mode Of Action  (Contd.) <ul><li>Inhibits cytokine production by osteoblasts </li></ul><ul><li>Supports the osteoblast med...
Design of the FIT Trial Screening Visits *  BMD ( <  0.68 g/cm 2 ) *  Other eligibility *  Vertebral X-ray Vertebral Defor...
FIT Trial - Increase in BMD at Femoral Neck 4.1% increase in BMD with Alendronate p<0.001 % of patients Lancet, 348, 1996 ...
FIT TRIAL  -  Summary of Fracture Results <ul><li>Type of fracture % incidence P value reduction </li></ul><ul><li>At leas...
Alendronate plus Hormone Replacement Therapy (HRT) 428 postmenopausal women receiving HRT (average duration of treatment 9...
Alendronate plus Hormone Replacement Therapy (HRT) Bone mass HRT alone group Combination therapy group (alendronate + HRT)...
Steroid-induced Osteoporosis <ul><li>Majority of bone loss occurs in the beginning (10-20%) </li></ul><ul><li>25% may expe...
Alendronate in Steroid-Induced Osteoporosis (Patients receiving 7.5 mg Prednisone) Age : 17-83 year NEJM 1998; 339: 292-9....
Early Postmenopausal Intervention Cohort Study (EPIC) NEJM 1998; 338(8): 485-492. 1609 postmenopausal women (aged 45 to 59...
Hip Bone Mineral Density NEJM 1998; 338(8): 485-492. 0% 20% 40% 60% 80% 100% Placebo 2.5 mg of alendronate 5 mg of alendro...
Early Postmenopausal Intervention Cohort Study (EPIC) <ul><li>Results of US Cohort :  Percentage increase in BMD at end of...
Alendronate Osteoporosis Prevention Study Group Annals of Internal Medicine, 1998; 128  : 253-261 447 women < age 40 to 59...
Alendronate Osteoporosis Prevention Study Group  (Contd.) Annals of Internal Medicine, 1998; 128  : 253-261 Mean changes f...
Alendronate in Men with Primary Osteoporosis – Interim Results (12 months) of an Ongoing Study * BMD Inpharma 1999; No. 11...
<ul><li>Dosage </li></ul><ul><li>Prevention of postmenopausal osteoporosis 5 mg/day </li></ul><ul><li>Treatment of postmen...
Contraindications <ul><li>Abnormalities of the esophagus such as stricture or achalasia </li></ul><ul><li>Inability to sta...
Upcoming SlideShare
Loading in …5
×

Osteoporosis : The Silent Thief Osteoporosis : The Silent Thief

2,230 views

Published on

Published in: Health & Medicine
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,230
On SlideShare
0
From Embeds
0
Number of Embeds
23
Actions
Shares
0
Downloads
219
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

Osteoporosis : The Silent Thief Osteoporosis : The Silent Thief

  1. 1. Osteoporosis : The Silent Thief <ul><li>OSTEOPOROSIS has been defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of the bone tissue, with a consequent increase in bone fragility and susceptibility to fracture </li></ul>O STEO F OS Amount of bone resorbed >>> Amount of bone formed by osteoclasts by osteoblasts ¯ BONE LOSS
  2. 2. Osteoporotic bone remodelling O STEO F OS
  3. 3. Bone Remodelling With Alendronate O STEO F OS
  4. 4. Mode Of Action <ul><li>Gets preferentially bound under osteoclasts. Osteoclasts ingest the attached alendronate. Released alendronate inactivates the osteoclasts. Bone resorption inhibited. </li></ul><ul><li>Alendronate may reduce the number of remodelling sites </li></ul>O STEO F OS
  5. 5. Mode Of Action (Contd.) <ul><li>Inhibits cytokine production by osteoblasts </li></ul><ul><li>Supports the osteoblast mediated bone formation </li></ul><ul><li>Induces the osteoblasts to synthesize a substance which may directly inhibit the osteoclastic resorption </li></ul><ul><li>Alendronate inhibits the osteoclastic bone resorption </li></ul><ul><li>without inhibiting the osteoblastic bone formation – </li></ul><ul><li>increase in bone mass </li></ul>O STEO F OS
  6. 6. Design of the FIT Trial Screening Visits * BMD ( < 0.68 g/cm 2 ) * Other eligibility * Vertebral X-ray Vertebral Deformity Present Vertebral Deformity Absent Vertebral Deformity Study Randomize (N=2027) 3 years Prim. Endpoint New Vertebral Deformity Sec. Endpoint All Clinical Fractures Clinical Fracture Study Randomize (N=4434) 4.25 years Prim. Endpoint Any Clinical Fracture Sec. Vertebral Deformity O STEO F OS
  7. 7. FIT Trial - Increase in BMD at Femoral Neck 4.1% increase in BMD with Alendronate p<0.001 % of patients Lancet, 348, 1996 Months alendronate placebo O STEO F OS
  8. 8. FIT TRIAL - Summary of Fracture Results <ul><li>Type of fracture % incidence P value reduction </li></ul><ul><li>At least one new vertebral fracture 47 <0.001 </li></ul><ul><li>Multiple ( > 2) new vertebral fractures 90 <0.001 </li></ul><ul><li>Clinical (symptomatic) vertebral fracture 55 <0.001 </li></ul><ul><li>Hip fracture 51 0.047 </li></ul><ul><li>Wrist fracture 48 0.013 </li></ul>Lancet, 348, 1996 O STEO F OS
  9. 9. Alendronate plus Hormone Replacement Therapy (HRT) 428 postmenopausal women receiving HRT (average duration of treatment 9.5 years) Bone mass : > 2 SD below normal Average age : 62 years Average duration of menopause : 15 years 214 women continued on HRT for one year 214 women received alendronate 10 mg/day along with HRT for one year Inpharma 26 Sept’ 1998, No. 1156: 18
  10. 10. Alendronate plus Hormone Replacement Therapy (HRT) Bone mass HRT alone group Combination therapy group (alendronate + HRT) Percentage increases in bone mass from baseline after 1 year’s treatment Inpharma 26 Sept’ 1998, No. 1156: 18 Addition of Alendronate to Hormone Replacement Therapy (HRT) results in 2 to 5 times greater increase in Bone Mineral Density (BMD) than HRT alone
  11. 11. Steroid-induced Osteoporosis <ul><li>Majority of bone loss occurs in the beginning (10-20%) </li></ul><ul><li>25% may experience a fracture </li></ul><ul><li>4 fold increase in all fractures </li></ul><ul><li>Usually affects vertebrae, ribs, hip </li></ul><ul><li>Risk higher in patients with higher dose, taking longer, low BMD etc </li></ul>Cause  Calcium  Urinary Calcium  Osteoblast absorption excretion formation and function
  12. 12. Alendronate in Steroid-Induced Osteoporosis (Patients receiving 7.5 mg Prednisone) Age : 17-83 year NEJM 1998; 339: 292-9. 4 2 0 -2 12 24 36 48 Lumbar Spine M e a n ( S E ) P e r c e n t C h a n g e i n B o n e M i n e r a l D e n s i t y + Week Placebo n=159 5 mg of alendronate n=161 10 mg of alendronate n=157
  13. 13. Early Postmenopausal Intervention Cohort Study (EPIC) NEJM 1998; 338(8): 485-492. 1609 postmenopausal women (aged 45 to 59 years) Study Centres : US and Europe Placebo n = 502 Alendronate 2.5 mg/day n = 499 Alendronate 5 mg/day n = 498 Estrogenprogestin n = 110
  14. 14. Hip Bone Mineral Density NEJM 1998; 338(8): 485-492. 0% 20% 40% 60% 80% 100% Placebo 2.5 mg of alendronate 5 mg of alendronate Estrogen- progestin >2% gain  2% change >2% loss Women (%)
  15. 15. Early Postmenopausal Intervention Cohort Study (EPIC) <ul><li>Results of US Cohort : Percentage increase in BMD at end of 2 years </li></ul><ul><li>Alendronate HRT P </li></ul><ul><li>Hip bone 1.3 + 0.3 1.8 + 0.3 P = 0.21 </li></ul><ul><li>Lumber Spine 2.9 + 0.5 4.0 + 0.3 P = 0.06 </li></ul><ul><li>Total body 0.8 + 0.3 1.2 + 0.2 P = 0.29 </li></ul>NEJM 1998; 338(8): 485-492.
  16. 16. Alendronate Osteoporosis Prevention Study Group Annals of Internal Medicine, 1998; 128 : 253-261 447 women < age 40 to 59 years > Duration of menopause : 6 to 36 months before study entry Duration of trial : 3 years Placebo n = 90 Alendronate 1 mg/day n = 92 Alendronate 5 mg/day n = 88 Alendronate 10 mg/day n = 88 Alendronate 20/0 mg/day n = 89
  17. 17. Alendronate Osteoporosis Prevention Study Group (Contd.) Annals of Internal Medicine, 1998; 128 : 253-261 Mean changes from baseline in Bone Mineral Density 0 -3 -3 -2 -1 0 1 2 3 4 5 6 12 18 Month Mean change in Trochanter Bone Mineral Density, Percentage Points 24 30 36 0 -3 -2 -1 0 1 2 6 12 18 Month Mean change in Total Body Bone Mineral Density, Percentage Points 24 30 36 Placebo 1 mg/d 5 mg/d 10 mg/d 20/0 mg/d
  18. 18. Alendronate in Men with Primary Osteoporosis – Interim Results (12 months) of an Ongoing Study * BMD Inpharma 1999; No. 1196: Pg 13–14 Lumbar Spine *p<0.001 * Femoral Neck *p<0.04 *
  19. 19. <ul><li>Dosage </li></ul><ul><li>Prevention of postmenopausal osteoporosis 5 mg/day </li></ul><ul><li>Treatment of postmenopausal osteoporosis </li></ul><ul><li>10 mg/d </li></ul><ul><li>Administration </li></ul><ul><li>Once-a-day with a full glass of plain water (200 ml) only, on an empty stomach </li></ul><ul><li>Patient should not lie down for half an hour after administration </li></ul><ul><li>Patient should not eat food for half an hour after administration </li></ul>Dosage and Administration
  20. 20. Contraindications <ul><li>Abnormalities of the esophagus such as stricture or achalasia </li></ul><ul><li>Inability to stand or sit upright for at least 30 minutes </li></ul><ul><li>Hypersensitivity to any of the components of this product </li></ul><ul><li>Hypocalcemia </li></ul>O STEO F OS

×