Rheumatology Book

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Osteoporosis Management

Aka: Osteoporosis Management, Osteoporosis Prevention, Osteopenia Management
  1. See also
    1. Osteoporosis
    2. Osteoporosis Evaluation
    3. Osteoporosis Secondary Causes
    4. Medication Causes of Osteoporosis
  2. Indications: Treatment with Osteoporosis agents
    1. Hip Fracture or Vertebral Fracture history or
    2. Other Fracture site AND Osteopenia at femoral neck, hip or spine (T-Score -1.0 to -2.5) or
    3. Osteoporosis based on femoral neck, hip or spine BMD (T-Score <-2.5)
      1. Evaluate for Osteoporosis Secondary Causes prior to treatment
    4. Osteopenia AND high Fracture risk secondary cause (e.g. prolonged Glucocorticoid use)
    5. Osteopenia (T score -1.0 to -2.5) AND abnormal FRAX Score
      1. See Frax Calculator
        1. http://www.shef.ac.uk/FRAX/
        2. Requires hip Bone Mineral Density
      2. FRAX score (10 year Fracture probability) of Hip Fracture >3% or
      3. FRAX score for any Osteoporosis related Fracture >20%
  3. Efficacy: Number Needed to Treat (NNT) per agent
    1. Prevention of Hip Fracture over 3 years (NNT)
      1. Vitamin D 800 IU daily: NNT 45
      2. Bisphosphonates (Risedronate, Alendronate, Zoledronic acid): NNT 77-91
      3. Hormone Replacement Therapy: NNT 385
    2. Prevention of Vertebral Fracture over 3 years (NNT)
      1. Bisphosphonates (Zoledronic acid, Risedronate, Ibandronate): NNT 13-20
        1. Note that Alendronate (Fosamax) was less effective with a NNT 37
      2. Calcitonin (Miacalcin): NNT 10 (5 years)
        1. Possible increased risk of cancer
      3. Teriparatide (Forteo): NNT 11 (1.5 years)
        1. Significantly more expensive than Bisphosphonates or Calcitonin ($600/month)
  4. Management: General measures and prevention for all patients
    1. General
      1. Calcium and Vitamin D supplementation are most cost effective medications
      2. Even Alendronate (Fosamax), which is generic, costs >$50 per month
    2. Dietary Supplementation
      1. See Calcium Homeostasis
      2. Calcium Supplementation 1200 to 1500 mg per day
        1. Dosing (per NAM): 1000 mg orally daily in adults up to age 50 years (then 1200 mg orally daily)
        2. Does not increase bone density (but slows loss)
        3. Overdosage above 1500 mg daily weakens bone
      3. Vitamin D Supplementation 800 to 2000 IU (20-50 mcg) orally per day
        1. Dosing (per NAM): 600 IU orally daily from food sources in adults up to age 70 years, then 800 IU
          1. As contrasted with National Academy of Medicine (NAM), USPTF does not recommend postmenopausal supplement
        2. Increases bone density 1% per year
        3. Goal Serum 25-Hydroxy Vitamin D level: 30-100 ng/ml
        4. If Vitamin D Deficiency, then use Vitamin D Replacement protocol
        5. Postmenopausal women in community, age <75 do not appear to benefit from Vitamin D supplement
          1. Does not effect Bone Mineral Density, Muscle Strength, Fall Risk or function
          2. Hansen (2015) JAMA Intern Med 175(10): 1612-21 [PubMed]
    3. Weight bearing Exercise
      1. See Exercise in Osteoporosis
      2. Include balance training for Fall Prevention
    4. Lifestyle changes
      1. Tobacco Cessation
      2. Limit Alcohol to moderate use (2 or less drinks per day)
      3. Limit Caffeine to <250 mg per day
      4. Sunlight exposure for 30 minutes daily on at least 5 days per week
    5. Limit Proton Pump Inhibitor use (associated with higher risk of Hip Fractures)
      1. Yang (2006) JAMA 296:2947-53 [PubMed]
    6. Fall Prevention and Hip Fracture prevention
      1. See Fall Prevention in the Elderly (includes Fall Risk)
      2. See Hip Protectors (underwear with trochanter pads)
  5. Management: Osteoporosis Treatments considered effective
    1. General
      1. See Indications as above
      2. See general measures for all patients (as above)
    2. Bisphosphonates
      1. Increases bone density 5-6% per year
      2. Consider stopping oral Bisphosphonates after 5 years (and reclast after 3 years)
        1. See Bisphosphonates for protocol
      3. Preparations
        1. Alendronate (Fosamax)
          1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
          2. Oral: 10 mg daily or 70 mg weekly (half dose for prevention)
          3. Available with Cholecalciferol 2800-5600 IU (Fosamax plus D weekly)
          4. Most cost effective agent ($60/year in 2020)
        2. Risedronate (Actonel)
          1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
          2. Oral: 5 mg daily or 35 mg weekly or 150 mg monthly
          3. Available as delayed release (Atelvia) 35 mg weekly
          4. Costs $1700 per year in 2020
        3. Ibandronate (Boniva)
          1. Indicated for the prevention and treatment of Osteoporosis (Vertebral only)
          2. Oral: 2.5 mg daily or 150 mg monthly
          3. IV: 3 mg every 3 months (treatment only)
        4. Zoledronic Acid (Reclast)
          1. Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
          2. IV: 5 mg yearly (every 2 years for prevention)
          3. Costs $270 per year (in addition to infusion cost)
          4. Contraindicated in Hypocalcemia or GFR <35 ml/min
    3. Estrogen Replacement Therapy (ERT or HRT) in women
      1. Benefits may not outweigh risks of CVA, VTE, CAD, Breast Cancer
        1. Cauley (2003) JAMA 290(13): 1729-38 [PubMed]
      2. Standard Dosing
        1. Minimum preventive plasma Estradiol level: 60 pg/ml
        2. Maximal effect requires Premarin 0.625
        3. Increases bone density 3-4% per year
      3. Alternative Estrogen dosing
        1. Some effect seen at 0.3 mg or Transdermal Estrogen
        2. 17-beta-Estradiol 0.25 mg increases BMD
          1. Prestwood (2003) JAMA 290:1042-8 [PubMed]
      4. Fracture protection lost 5 years after stopping ERT
        1. Yates (2004) Obstet Gynecol 103:440-6 [PubMed]
    4. Selective Estrogen Receptor Modulator (e.g. Raloxifene) in women
      1. Similar benefit to Estrogen Replacement with the risks of VTE, but not Breast Cancer, CVA, CAD
      2. Indicated if unable to take Estrogen Replacement, and only for Vertebral Fracture prevention and treatment
      3. Raloxifene (Evista) 60 mg orally daily
    5. Testosterone Replacement in men
      1. Increases bone density
      2. Unclear if prevents osteoporotic Fractures
      3. Consider in men with symptomatic Hypogonadism
        1. Example: Low Testosterone and low libido
  6. Management: Osteoporosis Treatments for high risk patients
    1. Indications: High risk Osteoporosis patients
      1. History of osteoporotic Fracture
      2. Multiple Fracture risk factors
      3. Intollerance to or contraindication of other medications
    2. Recombinant Parathyroid Hormone Analog: Teriparatide (Forteo), Abaloparatide (Tymlos)
      1. Indicated for Osteoporosis treatment (Vertebral, non-Vertebral, hip) and Vertebral spine Fractures
      2. Daily Subcutaneous Injection (20 mcg SQ daily for Forteo, 80 mcg SQ daily for Tymlos)
      3. Precautions: Do not use with bisphosphonate and do not use longer than 2 years (Osteosarcoma risk)
      4. Very expensive ($20,000 to 46,000 per year in 2020)
      5. Efficacy: Reduced risk for osteoporotic Vertebral Fractures
        1. Neer (2001) N Engl J Med 344:1434-41 [PubMed]
    3. Romosozumab (Evenity) Injection
      1. SQ Injectable Monoclonal Antibody, sclerositin inhibitor
      2. Increases bone growth and decreases bone breakdown
      3. Indicated for high risk women with Fractures despite bisphosphonate or multiple Vertebral Fractures
      4. Contraindicated if MI or CVA in last year (associated with increased cardiovascular risk)
      5. Limit to one year of use (effects wane after this) and then switch to bisphosphonate
      6. Costs $22,000 per year in 2019 (covered under Medicare Part B)
      7. (2019) Presc Lett 26(6)
    4. Denosumab (Prolia) Injection
      1. Indicated for Osteoporosis treatment (Vertebral, non-Vertebral) and Vertebral spine Fractures
      2. Monoclonal Antibody blocks Osteoclasts (nuclear factor kappa B Ligand activator receptor)
      3. Dose: 60 mg SQ every 6 months
      4. Increased risk of infection
      5. Risk of rebound Vertebral Fractures when stopped or dose delayed
        1. Switch to bisphosphonate when course completed
      6. Consider in men with high Fracture risk secondary to androgen deprivation therapy (for Prostate Cancer)
      7. Cost $2600 per year in 2020
  7. Management: Vertebral spine Fracture medical management
    1. See Vertebral Compression Fracture
  8. Management: Agents under investigation for possible benefit in Osteoporosis
    1. HMG-CoA Reductase Inhibitor (Statin drugs)
    2. Thiazide Diuretics (e.g. Hydrochlorothiazide)
      1. Decreases urinary Calcium loss
      2. Reduction in Hip Fracture if used >10 years
      3. Consider in hypertensive patients
      4. LaCroix (2000) Ann Intern Med 133:516-26 [PubMed]
    3. Dietary Magnesium 600 mg/day or more
    4. Dietary Soy Protein 40 grams/day or more
      1. Scheiber (1999) Menopause 6:233-41 [PubMed]
  9. Management: Agents no longer recommended for Osteoporosis treatment
    1. Fluoride Supplementation
      1. Initial studies showed increased bone density 10% per year
      2. However, unclear whether bone strength was increased
  10. References
    1. (2020) presc lett 27(10): 58-9
    2. (2021) Obstet Gynecol 138(3):494-506 +PMID: 34412075 [PubMed]
    3. Andrews (1998) Postgrad Med 104(4): 89-97 [PubMed]
    4. Campion (2003) Am Fam Physician 67(7):1521-6 [PubMed]
    5. Jeremiah (2015) Am Fam Physician 92(4): 261-8 [PubMed]
    6. Lindsay (1984) Obstet Gynecol 63:759-63 [PubMed]
    7. South-Paul (2001) Am Fam Physician 63(6):1121-8 [PubMed]
    8. Taxel (1998) Geriatrics 53(8): 22-3 [PubMed]

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