II. Indications
- Osteoporosis
- Metabolic bone disease (e.g. Paget's Disease of Bone)
III. Contraindications
- Hypocalcemia
- Chronic Kidney Disease with GFR <35 ml/min
- Oral Bisphosphonates (may use IV Bisphosphonates instead)
- Delayed Gastric Emptying
- Esophageal disorders
- Gastric Bypass or other gastrointestinal malabsorption
IV. Efficacy
V. Efficacy: Number Needed to Treat (NNT) per agent
- Prevention of Hip Fracture over 3 years (NNT)
- Risedronate (Actonel): 77
- Alendronate (Fosamax): 91
- Zoledronic Acid (Reclast): 91
- Compare to Vitamin D 800 IU daily: 45
- Compare to Hormone Replacement Therapy: 385
- Prevention of Vertebral Fracture over 3 years (NNT)
- Zoledronic Acid (Reclast): 13
- Risedronate (Actonel): 15
- Ibandronate (Boniva): 20
- Alendronate (Fosamax): 37
- Compare to Calcitonin (Miacalcin) or Teriparatide (Forteo): 10-11
VI. Precautions: Drug Holiday
- Adverse effect risk increases with cummulative use
- Stopping bisphosphonate (start of drug holiday)
- Restarting bisphosphonate
- Consider repeat DEXA Scan every 2 years for monitoring
- Biomarkers (Serum Ctx and Alkaline Phosphatase)
- Not typically helpful in making decision to restart bisphosphonate
- Markers often return conflicting results
- Primary prevention (Osteopenia and risk)
- Restart after fixed interval 3 year period or
- Restart at 1-5 years based on patient factors or Bone Mineral Density
- Osteoporosis (e.g. Fracture history)
- Restart after fixed interval or
- Restart after 2-4% Bone Mineral Density reduction
- References
- Kennel (2012) Mayo POIM Conference, Rochester
VII. Adverse effects
- Osteonecrosis of the jaw
- Bone, joint or Muscle pain
- Consider stopping medication if persists
- Significant Gastrointestinal risks
- Esophageal erosions or Esophageal ulcers
- Appears to occur more with Alendronate
- Take with over 8 ounces water
- Stay upright for at least 30 minutes after dose
- Take at least 60 minutes before breakfast
- Esophageal erosions or Esophageal ulcers
- Atypical Subtrochanteric Fractures (rare)
VIII. Pharmacokinetics: Absorption inhibited if taken with food
- Wait 1-2 hours before eating
IX. Preparations: Osteoporosis and Metabolic Bone Disease
- See Adverse effects for Patient Instructions
- Alendronate (Fosamax, Fosamax plus D or Binosto)
- Background
- Fosamax is generic and low cost (less than $10/month) in United States
- Binosto is Alendronate effervescent tab (marketed in 2013)
- Less gastrointestinal side effects (unproven) and costs over $140/month
- Hodges (2012) Int J Pharm 432:57-62 [PubMed]
- Osteoporosis
- Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
- Prophylaxis: 5 mg orally daily or 35 mg orally Weekly
- Treatment: 10 mg orally daily or 70 mg orally Weekly
- Paget's Disease
- Dose: 40 mg orally daily for 6 months
- Background
- Risedronate (Actonel)
- Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral)
- Osteoporosis: 5 mg orally daily or 35 mg orally weekly or 75 mg monthly
- Paget's Disease: 30 mg orally daily for 2 months
- Ibandronate (Boniva)
- Indicated for the prevention and treatment of Osteoporosis (Vertebral only) and Paget's Disease
- Oral: 2.5 mg daily or 150 mg monthly
- IV: 3 mg every 3 months (treatment only)
- Monthly: 150 mg orally (same cost as for daily)
- Chestnut (2004) J Bone Miner Res 19:1241-9 [PubMed]
- Zoledronic Acid (Reclast)
- Indicated for the prevention and treatment of Osteoporosis (hip, Vertebral, non-Vertebral) and Paget's Disease
- IV: 5 mg yearly infused over 15 minutes (every 2 years for prevention)
- Contraindicated in Hypocalcemia and GFR <35 ml/min
- Adverse effects: Acute phase reaction with fever, myalgias, Headache
- Black (2007) N Engl J Med 356(18): 1809-22 [PubMed]
X. Preparations: Metabolic bone disease
- Etidronate (Didronel)
- Paget's Disease: 5-10 mg/kg orally daily for 6 months
- Hypercalcemia: 7.5 mg/kg in 250 cc NS IV daily for 3 days
- Given slowly over >2 hours
- Tiludronate (Skelid)
- S-Containing agent
- No effect on Fracture risk
- Indicated for Paget's Disease of Bone
- Dose: 40 mg PO qd
- Pamidronate (Aredia)
- Dose: 40-80 mg IV slowly over >2 hours every 4 months
- Indications
- Paget's Disease of Bone
- Hypercalcemia of Malignancy
- Osteolytic bone lesions (e.g. Multiple Myeloma)
XI. References
Images: Related links to external sites (from Bing)
Related Studies
alendronate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ALENDRONATE SODIUM 10 MG TAB | Generic | $0.13 each |
ALENDRONATE SODIUM 35 MG TAB | Generic | $0.34 each |
ALENDRONATE SODIUM 70 MG TAB | Generic | $0.29 each |
risedronate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
RISEDRONATE SOD DR 35 MG TAB | Generic | $25.30 each |
RISEDRONATE SODIUM 150 MG TAB | Generic | $14.15 each |
RISEDRONATE SODIUM 35 MG TAB | Generic | $2.46 each |
RISEDRONATE SODIUM 35 MG TABLET | Generic | $2.46 each |
ibandronate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
IBANDRONATE SODIUM 150 MG TAB | Generic | $4.48 each |
Ontology: pamidronate (C0043603)
Definition (NCI_NCI-GLOSS) | 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) | 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. |
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) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C019248 |
SnomedCT | 420481001, 96288007 |
English | (3-amino-1-hydroxypropylidene)-1,1-biphosphonate, (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate, amino-1-hydroxypropane-1,1-diphosphonate, aminohydroxypropylidene diphosphonate, aminopropanehydroxydiphosphonate, APD, amidronate, Pamidronic Acid, 1-hydroxy-3-aminopropane-1,1-diphosphonic acid, pamidronate [Chemical/Ingredient], apd, apds, AHPrBP, PAMIDRONIC ACID, Pamidronate, Pamidronate (substance), PAMIDRONATE, pamidronate |
Spanish | ácido pamidrónico, ácido pamidrónico (producto), ácido pamidrónico (sustancia), pamidronato (sustancia), pamidronato |
Ontology: 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. |
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-RETIRADO- (concepto no activo), etidronato-RETIRADO-, etidronato (sustancia), etidronato, EHDP, Etanohidroxidifosfonato |
German | Etidronat, EHDP, Ethanhydroxydiphosphonat |
French | Étidronate |
Ontology: 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 | Pharmacologic Substance (T121) , Organophosphorus Compound (T115) |
MSH | D019386 |
SnomedCT | 96290008 |
LNC | LP171384-3 |
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 |
German | Alendronat |
Italian | Alendronato |
Portuguese | Alendronato |
Ontology: Aredia (C0104018)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C019248 |
English | Novartis brand of pamidronate disodium salt, Aredia, aredia |
Ontology: Tiludronate (C0145942)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
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 |
Ontology: Risedronate (C0246719)
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 | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C073008 |
SnomedCT | 96289004, 387582001 |
LNC | LP171635-8 |
English | 2-(3-pyridinyl)-1-hydroxyethylidenebisphosphonate, RISEDRONATE, Risedronate (product), RISEDRONATE SODIUM ANHYDROUS, Risedronate, Risedronate (substance), RISE, risedronate, 2-(3-pyridinyl)-1-hydroxyethylidene-bisphosphonate |
Spanish | risedronato (producto), risedronato (sustancia), risedronato |
Ontology: Fosamax (C0376569)
Concepts | Pharmacologic Substance (T121) , Organophosphorus Compound (T115) |
MSH | D019386 |
French | Fosamax |
English | fosamax, Fosamax |
Ontology: Ibandronate (C0379199)
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 | Pharmacologic Substance (T121) , Organic Chemical (T109) |
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 |
Ontology: Didronel (C0591373)
Concepts | Pharmacologic Substance (T121) , Organophosphorus Compound (T115) |
MSH | D012968 |
English | didronel, Didronel |
Ontology: Skelid (C0592793)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C058651 |
English | Skelid |
Ontology: Actonel brand of risedronate sodium (C0718248)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
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 |
Ontology: Boniva (C1541222)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C073007 |
English | Boniva |