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Bisphosphonates

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Bisphosphonates, Alendronate, Fosamax, Etidronate, Didronel, Tiludronate, Skelid, Risedronate, Actonel, Pamidronate, Aredia, Ibandronate, Boniva, Binosto

  • Indications
  1. Osteoporosis
  2. Metabolic bone disease (e.g. Paget's Disease of Bone)
  • Contraindications
  1. Hypocalcemia
  2. Chronic Kidney Disease with GFR <35 ml/min
  3. Oral Bisphosphonates (may use IV Bisphosphonates instead)
    1. Delayed Gastric Emptying
    2. Esophageal disorders
    3. Gastric Bypass or other gastrointestinal malabsorption
  • Efficacy
  1. Decreases rate of bone resorption
  2. Reduces risk of Vertebral Fracture: 8.8%
  3. Reduces risk of non-Vertebral Fracture (5.6%)
  4. Reference
    1. Black (1996) 348:1535-41 [PubMed]
  1. Prevention of Hip Fracture over 3 years (NNT)
    1. Risedronate (Actonel): 77
    2. Alendronate (Fosamax): 91
    3. Zoledronic Acid (Reclast): 91
    4. Compare to Vitamin D 800 IU daily: 45
    5. Compare to Hormone Replacement Therapy: 385
  2. Prevention of Vertebral Fracture over 3 years (NNT)
    1. Zoledronic Acid (Reclast): 13
    2. Risedronate (Actonel): 15
    3. Ibandronate (Boniva): 20
    4. Alendronate (Fosamax): 37
    5. Compare to Calcitonin (Miacalcin) or Teriparatide (Forteo): 10-11
  • Precautions
  • Drug Holiday
  1. Adverse effect risk increases with cummulative use
  2. Stopping bisphosphonate (start of drug holiday)
    1. Consider stopping oral Bisphosphonates after 5 years (or 8-10 years if multiple Vertebral Fractures)
    2. Consider stopping Reclast after 3 years (or 6 years if multiple Vertebral Fractures)
    3. Consider stopping especially if no history of osteoporotic Fracture
  3. Restarting bisphosphonate
    1. Consider repeat DEXA Scan every 2 years for monitoring
    2. Biomarkers (Serum Ctx and Alkaline Phosphatase)
      1. Not typically helpful in making decision to restart bisphosphonate
      2. Markers often return conflicting results
    3. Primary prevention (Osteopenia and risk)
      1. Restart after fixed interval 3 year period or
      2. Restart at 1-5 years based on patient factors or Bone Mineral Density
    4. Osteoporosis (e.g. Fracture history)
      1. Restart after fixed interval or
      2. Restart after 2-4% Bone Mineral Density reduction
  4. References
    1. Kennel (2012) Mayo POIM Conference, Rochester
  • Adverse effects
  1. Osteonecrosis of the jaw
    1. Marx (2005) J Oral Maxillofac Surg 63:1567–1575 [PubMed]
  2. Bone, joint or Muscle pain
    1. Consider stopping medication if persists
  3. Significant Gastrointestinal risks
    1. Esophageal erosions or Esophageal ulcers
      1. Appears to occur more with Alendronate
    2. Take with over 8 ounces water
    3. Stay upright for at least 30 minutes after dose
    4. Take at least 60 minutes before breakfast
  4. Atypical Subtrochanteric Fractures (rare)
  • Pharmacokinetics
  • Absorption inhibited if taken with food
  1. Wait 1-2 hours before eating
  1. See Adverse effects for Patient Instructions
  2. Alendronate (Fosamax, Fosamax plus D or Binosto)
    1. Background
      1. Fosamax is generic and low cost (less than $10/month) in United States
      2. Binosto is Alendronate effervescent tab (marketed in 2013)
        1. Less gastrointestinal side effects (unproven) and costs over $140/month
        2. Hodges (2012) Int J Pharm 432:57-62 [PubMed]
    2. Osteoporosis
      1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
      2. Prophylaxis: 5 mg orally daily or 35 mg orally Weekly
      3. Treatment: 10 mg orally daily or 70 mg orally Weekly
    3. Paget's Disease
      1. Dose: 40 mg orally daily for 6 months
  3. Risedronate (Actonel)
    1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
    2. Osteoporosis: 5 mg orally daily or 35 mg orally weekly or 75 mg monthly
    3. Paget's Disease: 30 mg orally daily for 2 months
  4. Ibandronate (Boniva)
    1. Indicated for the prevention and treatment of Osteoporosis (Vertebral only) and Paget's Disease
    2. Oral: 2.5 mg daily or 150 mg monthly
    3. IV: 3 mg every 3 months (treatment only)
    4. Monthly: 150 mg orally (same cost as for daily)
    5. Chestnut (2004) J Bone Miner Res 19:1241-9 [PubMed]
  5. Zoledronic Acid (Reclast)
    1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral) and Paget's Disease
    2. IV: 5 mg yearly infused over 15 minutes (every 2 years for prevention)
    3. Contraindicated in Hypocalcemia and GFR <35 ml/min
    4. Adverse effects: Acute phase reaction with fever, myalgias, Headache
    5. Black (2007) N Engl J Med 356(18): 1809-22 [PubMed]
  • Preparations
  • Metabolic bone disease
  1. Etidronate (Didronel)
    1. Paget's Disease: 5-10 mg/kg orally daily for 6 months
    2. Hypercalcemia: 7.5 mg/kg in 250 cc NS IV daily for 3 days
      1. Given slowly over >2 hours
  2. Tiludronate (Skelid)
    1. S-Containing agent
    2. No effect on Fracture risk
    3. Indicated for Paget's Disease of Bone
    4. Dose: 40 mg PO qd
  3. Pamidronate (Aredia)
    1. Dose: 40-80 mg IV slowly over >2 hours every 4 months
    2. Indications
      1. Paget's Disease of Bone
      2. Hypercalcemia of Malignancy
      3. Osteolytic bone lesions (e.g. Multiple Myeloma)
  • References
  1. Greenspan (2000) Am Fam Physician 61(9):2371-6 [PubMed]