Osteoporosis : The Silent Thief Osteoporosis : The Silent Thief

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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

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