II. 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%

III. 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)

IV. 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. Calcium Supplementation 1200 to 1500 mg per day
      1. Does not increase bone density (but slows loss)
      2. Overdosage above 1500 mg daily weakens bone
    2. Vitamin D Supplementation 800 to 2000 IU (20-50 mcg) orally per day
      1. Increases bone density 1% per year
      2. Goal Serum 25-Hydroxy Vitamin D level: 30-100 ng/ml
      3. If Vitamin D Deficiency, then use Vitamin D Replacement protocol
      4. 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
    2. See Hip Protectors (underwear with trochanter pads)

V. 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

VI. 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

VII. Management: Vertebral spine Fracture medical management

VIII. 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]

IX. 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

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Osteoporosis (C0029456)

Definition (MEDLINEPLUS)

Osteoporosis makes your bones weak and more likely to break. Anyone can develop osteoporosis, but it is common in older women. As many as half of all women and a quarter of men older than 50 will break a bone due to osteoporosis.

Risk factors include

  • Getting older
  • Being small and thin
  • Having a family history of osteoporosis
  • Taking certain medicines
  • Being a white or Asian woman
  • Having osteopenia, which is low bone density

Osteoporosis is a silent disease. You might not know you have it until you break a bone. A bone mineral density test is the best way to check your bone health. To keep bones strong, eat a diet rich in calcium and vitamin D, exercise and do not smoke. If needed, medicines can also help.

NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Definition (MSHCZE) Časté onemocnění charakterizované úbytkem kostní hmoty, „řídnutí kostí“. Typ I je tzv. o. postmenopauzální (výrazně častější u žen, časté jsou fraktury obratlů a distálního předloktí, postižena je zejm. trabekulární kost), typ II je o. senilní (poměr žen k mužům je asi 2:1, frakturami je postižen skelet axiální i apendikulární, bývají zlomeniny krčku stehenní kosti, postižena je kost trabekulární i kortikální). Příčina není zcela jasná, vyskytuje se ve vyšším věku častěji u žen po přechodu nebo po odstranění vaječníků ještě v plodném období, bývá následkem dlouhodobé nehybnosti, delší léčby kortikoidy nebo důsledkem některých vzácnějších chorob. Vliv má kouření, nadměrná konzumace kávy aj. Projevuje se bolestmi (např. zad) a představuje vyšší riziko zlomeniny (krček stehenní kosti, kompresivní fraktura obratle). K diagnostice lze využít rentgenové vyšetření, osteodenzitometrii, biochemická vyšetření sledující kostní metabolismus. Léčba je dlouhodobá a může spíše jen zastavit další vývoj onemocnění. Uplatňují se kalcium, vitamin D, fluoridy, bisfosfonáty zejm. alendronát, kalcitonin, HRT, SERM, anabolika, symptomatická a fyzikální terapie; velký význam má rehabilitace (a přiměřené zatěžování kostí). Důležitá je prevence (dostatek vápníku, pohyb, u žen podávání pohlavních hormonů po – zejm. předčasném – přechodu, srov. HRT). (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI) A condition of reduced bone mass, with decreased cortical thickness and a decrease in the number and size of the trabeculae of cancellous bone (but normal chemical composition), resulting in increased fracture incidence. Osteoporosis is classified as primary (Type 1, postmenopausal osteoporosis; Type 2, age-associated osteoporosis; and idiopathic, which can affect juveniles, premenopausal women, and middle-aged men) and secondary osteoporosis (which results from an identifiable cause of bone mass loss).
Definition (NCI_NCI-GLOSS) A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.
Definition (NCI_CTCAE) A disorder characterized by reduced bone mass, with a decrease in cortical thickness and in the number and size of the trabeculae of cancellous bone (but normal chemical composition), resulting in increased fracture incidence.
Definition (MSH) Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.
Definition (CSP) loss of bone mass and strength due to nutritional, metabolic, or other factors, usually resulting in deformity or fracture; a major public health problem of the elderly, especially women.
Concepts Disease or Syndrome (T047)
MSH D010024
ICD9 733.00, 733.0
ICD10 M81.9 , M81.0, M81.99
SnomedCT 203428004, 156825006, 203440004, 64859006
LNC MTHU020796, LA10527-2
English Osteoporoses, Osteoporosis NOS, Osteoporosis, unspecified, osteoporosis, osteoporosis (diagnosis), OSTEOPOROSIS, Osteoporosis [Disease/Finding], Unspecified osteoporosis, site unspecified, Unspecified osteoporosis, Osteoporosis, unspecified (disorder), Osteoporosis NOS (disorder), Bone rarefaction, OP - Osteoporosis, Osteoporosis (disorder), rarefaction; bone, Osteoporosis, NOS, Osteoporosis
French OSTEOPOROSE, Ostéoporose, non précisée, Ostéoporose SAI, Ostéoporose
Portuguese OSTEOPOROSE, Osteoporose NE, Osteoporose
Spanish OSTEOPOROSIS, Osteoporosis NEOM, Osteoporosis no especificada, osteoporosis, no especificada, osteoporosis, SAI (trastorno), osteoporosis, SAI, osteoporosis, no especificada (trastorno), osteoporosis (trastorno), osteoporosis, Osteoporosis
German OSTEOPOROSE, Osteoporose, unspezifisch, Osteoporose NNB, Osteoporose, nicht naeher bezeichnet, Osteoporose
Dutch osteoporose NAO, niet-gespecificeerde osteoporose, rarefactio; bot, Osteoporose, niet gespecificeerd, osteoporose, Osteoporose, Porose, osteo-
Italian Osteoporosi non specificata, Osteoporosi NAS, Osteoporosi
Japanese 骨粗鬆症NOS, 骨粗鬆症、詳細不明, コツソショウショウNOS, コツソショウショウ, コツソショウショウショウサイフメイ, 骨多孔症-老人性, 年齢関連骨消失, 年令関連骨消失, 老人性骨粗鬆症, 老年性骨粗鬆症, 外傷後骨粗鬆症, 骨消失-年齢関連, 骨多孔症-年齢関連, 骨多孔症, オステオポロシス, 骨粗しょう症, 年齢関連骨減少, 年齢関連骨多孔症, 老年性骨多孔症, 骨粗鬆症-外傷後, 年齢関連骨粗鬆症, 年令関連骨多孔症, 老人性骨粗しょう症, 年令関連骨粗しょう症, 骨減少-年齢関連, 老人性骨多孔症, 老年性骨粗しょう症, 骨粗鬆症, オステオポローシス
Swedish Benskörhet
Czech osteoporóza, Osteoporóza NOS, Osteoporóza, Osteoporóza, blíže neurčená, řídnutí kostí
Finnish Osteoporoosi
Korean 상세불명의 골다공증
Polish Osteoporoza pourazowa, Osteoporoza starcza, Osteoporoza, Osteoporoza związana z wiekiem, Zrzeszotnienie kości
Hungarian Osteoporosis k.m.n., Osteoporosis, nem meghatározott, Osteoporosis
Norwegian Osteoporose, Benskjørhet, Beinskjørhet