Rheumatology Book

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Bisphosphonates

Aka: Bisphosphonates, Alendronate, Fosamax, Etidronate, Didronel, Tiludronate, Skelid, Risedronate, Actonel, Pamidronate, Aredia, Ibandronate, Boniva
  1. Indications
    1. Osteoporosis
    2. Metabolic bone disease (e.g. Paget's Disease of Bone)
  2. Contraindications
    1. Delayed gastric emptying
  3. 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
  4. Efficacy: Number Needed to Treat (NNT) per agent
    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
  5. Precautions
    1. Adverse effect risk increases with cummulative use
    2. Consider stopping for one year after 5 years of use if no history of osteoporotic Fracture
  6. Adverse effects
    1. Osteonecrosis of the jaw
      1. Marx (2005) J Oral Maxillofac Surg 63:1567–1575
    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)
  7. Pharmacokinetics: Absorption inhibited if taken with food
    1. Wait 1-2 hours before eating
  8. Agents: Osteoporosis and Metabolic Bone Disease
    1. See Adverse effects for patient instructions
    2. Alendronate (Fosamax or Fosamax plus D)
      1. Osteoporosis
        1. Prophylaxis: 5 mg orally daily or 35 mg orally Weekly
        2. Treatment: 10 mg orally daily or 70 mg orally Weekly
      2. Paget's Disease: 40 mg orally daily for 6 months
    3. Risedronate (Actonel)
      1. Osteoporosis: 5 mg orally daily or 35 mg orally Weekly
      2. Paget's Disease: 30 mg orally daily for 2 months
    4. Ibandronate (Boniva) for Osteoporosis
      1. Daily: 2.5 mg orally
      2. Monthly: 150 mg orally (same cost as for daily)
      3. Chestnut (2004) J Bone Miner Res 19:1241-9
    5. Zoledronic Acid (Reclast)
      1. Approved for Post-menopausal Osteoporosis and Paget's Disease
      2. Contraindicated in Hypocalcemia or where GFR <35 ml/min
      3. Adverse effects: Acute phase reaction with fever, myalgias, Headache
      4. Dosing: 5 mg IV infused over 15 minutes once yearly
      5. Black (2007) N Engl J Med 356(18): 1809-22
  9. Agents: 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)
  10. References
    1. Greenspan (2000) Am Fam Physician 61(9):2371-6

Risedronate (C0246719)

Definition (NCI) A substance that is being studied in the prevention and treatment of osteoporosis. It belongs to the family of drugs called bone resorption inhibitors.
Definition (PDQ) A synthetic pyridinyl bisphosphonate agent. Risedronate binds to hydroxyapatite crystals in bone and inhibits osteoclast-dependent bone resorption Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=256445&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=256445&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1528" NCI Thesaurus)
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C073008
SnomedCT 96289004, 387582001
English 2-(3-pyridinyl)-1-hydroxyethylidenebisphosphonate, RISEDRONATE, Risedronate (product), Risedronate, Risedronate (substance), RISE, risedronate, 2-(3-pyridinyl)-1-hydroxyethylidene-bisphosphonate
Spanish risedronato (producto), risedronato (sustancia), risedronato
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Boniva (C1541222)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C073007
English Boniva
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Ibandronate (C0379199)

Definition (NCI) A drug that is used to prevent and treat osteoporosis, and is being studied in the treatment of cancer that has spread to the bones. It belongs to the family of drugs called bisphosphonates.
Definition (PDQ) A synthetic nitrogen-containing bisphosphonate. Ibandronate inhibits farnesyl pyrophosphate synthase, resulting in a reduction in geranylgeranyl GTPase signaling proteins and apoptosis of osteoclasts. This agent increases bone mineral density, decreases bone remodeling, inhibits osteoclast-mediated bone resorption, and reduces metastases-related and corticosteroid-related bone pain. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=365963&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=365963&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1670" NCI Thesaurus)
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C073007
SnomedCT 96287002
English 1-hydroxy-3-(methylpentylamino)propylidenebisphosphonate, (1-hydroxy-3-(methylpentylamino)propylidene)bisphosphonate, Ibandronate (substance), Ibandronate, ibandronate, IBANDRONATE
Spanish ibandronato (sustancia), ibandronato
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Actonel brand of risedronate sodium (C0718248)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C073008
English actonel, Actonel brand of risedronate sodium, Actonel, Aventis brand of risedronic acid, monosodium salt, Procter & Gamble Pharmaceuticals brand of risedronic acid, monosodium salt, Procter & Gamble brand of risedronic acid, monosodium salt
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Skelid (C0592793)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C058651
English Skelid
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Alendronate (C0102118)

Definition (CHV) a drug used to prevent or treat osteoporosis
Definition (CSP) bone resorption inhibitor.
Definition (MSH) A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.
Concepts Organophosphorus Compound (T115) , Pharmacologic Substance (T121)
MSH D019386
SnomedCT 96290008
English alendronate, Alendronate, Aminohydroxybutane Bisphosphonate, Bisphosphonate, Aminohydroxybutane, AHBUTBP, (4-Amino-1-hydroxybutylidene)bisphosphonic Acid, Alendronate [Chemical/Ingredient], 4 Amino 1 Hydroxybutylidene 1,1 Biphosphonate, 4-Amino-1-Hydroxybutylidene 1,1-Biphosphonate, Alendronate (substance), ALENDRONATE
Swedish Alendronat
Czech alendronát
Finnish Alendronaatti
Russian ALENDRONAT, АЛЕНДРОНАТ
Japanese アレンドロン酸, アレンドロナート, アレンドロネート
Polish Alendronian
Spanish alendronato (sustancia), alendronato, Alendronato
French Alendronate, (4-amino-1-hydroxybutylidène) bisphosphonate monosodique, 4-Amino-1-hydroxybutylidène 1,1-biphosphonate, Bisphosphonate d'aminohydroxybutane
German Alendronat
Italian Alendronato
Portuguese Alendronato
Sources
Derived from the NIH UMLS (Unified Medical Language System)


pamidronate (C0043603)

Definition (NCI) A drug that is used to treat hypercalcemia (too much calcium in the blood) and cancer that has spread to the bones. It belongs to the family of drugs called bisphosphonates.
Definition (NCI) A drug that is used to treat hypercalcemia (too much calcium in the blood) and cancer that has spread to the bones. It belongs to the family of drugs called bisphosphonates.
Definition (PDQ) A synthetic bisphosphonate agent. Although its mechanism of action is not completely understood, pamidronate appears to adsorb to calcium phosphate crystals in bone, blocking their dissolution by inhibiting osteoclast-mediated bone resorption. This agent does not inhibit bone mineralization and formation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39149&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39149&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1345" NCI Thesaurus)
Definition (NCI) An amino- bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Pamidronic acid binds to and adsorbs onto hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoid metabolites that are substrates for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, pamidronic acid decreases bone turnover rate, stabilizes the bone matrix and reduces hypercalcemia.
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C019248
SnomedCT 420481001, 420442001, 96288007
English (3-amino-1-hydroxypropylidene)-1,1-biphosphonate, (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate, 1-hydroxy-3-aminopropane-1,1-diphosphonic acid, amino-1-hydroxypropane-1,1-diphosphonate, aminohydroxypropylidene diphosphonate, aminopropanehydroxydiphosphonate, APD, amidronate, Pamidronic Acid, Pamidronic acid (product), Pamidronic acid (substance), Pamidronic acid, PAMIDRONIC ACID, pamidronate [Chemical/Ingredient], apd, apds, AHPrBP, Pamidronate, Pamidronate (substance), PAMIDRONATE, pamidronate
Spanish ácido pamidrónico, ácido pamidrónico (producto), ácido pamidrónico (sustancia), pamidronato (sustancia), pamidronato
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Tiludronate (C0145942)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C058651
SnomedCT 422263009, 96286006
English (chloro-4-phenyl)thiomethylene biphosphonate, (chloro-4-phenyl)thiomethylene bisphosphonate, TILUDRONATE, Tiludronate, Tiludronate (substance), tiludronate
Japanese チルドロン酸
Spanish tiludronato (sustancia), tiludronato
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Didronel (C0591373)

Concepts Organophosphorus Compound (T115) , Pharmacologic Substance (T121)
MSH D012968
English didronel, Didronel
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Etidronate (C0086268)

Definition (CSP) ethane-1-hydroxy-1,1-diphosphonate; a diphosphonate compound that affects calcium metabolism and inhibits the resorption and deposition of hydroxyapatite crystals in bone.
Definition (NCI) A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases).
Concepts Organophosphorus Compound (T115) , Pharmacologic Substance (T121)
MSH D012968
SnomedCT 49791005, 96284009, 372908005
English 1 Hydroxyethane 1,1 Diphosphonate, 1 Hydroxyethylidene 1,1 Bisphosphonate, 1-Hydroxyethane-1,1-Diphosphonate, 1-Hydroxyethylidene-1,1-Bisphosphonate, EHDP, Ethanehydroxydiphosphonate, Ethanehydroxyphosphate, Etidronate, HEDP, Hydroxyethanediphosphonate, 1,1-hydroxyethylenediphosphonate, etidronate, Etidronate (product), Etidronate [Chemical/Ingredient], ehdp, 1,1 hydroxyethylenediphosphonate, Etidronate (substance), Etidronate -RETIRED-, ETIDRONATE
Czech EHDP, etidronát, ethanhydroxydifosfonát
Portuguese Etidronato, EHDP, Etanoidroxidifosfonato
Spanish Etidronato, etidronato (producto), etidronato (sustancia), etidronato-RETIRADO- (concepto no activo), etidronato-RETIRADO-, etidronato, EHDP, Etanohidroxidifosfonato
German Etidronat, EHDP, Ethanhydroxydiphosphonat
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Fosamax (C0376569)

Concepts Organophosphorus Compound (T115) , Pharmacologic Substance (T121)
MSH D019386
French Fosamax
English fosamax, Fosamax
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Aredia (C0104018)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C019248
English Novartis brand of pamidronate disodium salt, Aredia, aredias, aredia
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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