Alendronic acid

Last updated

Alendronic acid
Alendronic acid.svg
Alendronate-3D-balls.png
Clinical data
Trade names Fosamax, Binosto, others
Other namesAlendronate, alendronate sodium (USAN US)
AHFS/Drugs.com Monograph
MedlinePlus a601011
License data
Pregnancy
category
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 0.6%
Metabolism excreted unchanged
Elimination half-life 126 months
Excretion Kidney
Identifiers
  • sodium [4-amino-1-hydroxy-1-(hydroxy-oxido-phosphoryl)- butyl]phosphonic acid trihydrate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.128.415 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C4H13NO7P2
Molar mass 249.096 g·mol−1
3D model (JSmol)
  • O=P(O)(O)C(O)(CCCN)P(=O)(O)O
  • InChI=1S/C4H13NO7P2/c5-3-1-2-4(6,13(7,8)9)14(10,11)12/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12) Yes check.svgY
  • Key:OGSPWJRAVKPPFI-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. [4] It is taken by mouth. [4] Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes. [4]

Contents

Common side effects (1 to 10% of patients) include constipation, abdominal pain, nausea, and acid reflux. [4] Use is not recommended during pregnancy or in those with poor kidney function. [5] Alendronic acid works by decreasing the activity of cells that break down bone. [4]

Alendronic acid was first described in 1978 and approved for medical use in the United States in 1995. [4] [6] It is available as a generic medication. In 2022, it was the 103rd most commonly prescribed medication in the United States, with more than 6 million prescriptions. [7] [8]

Medical uses

Alendronic acid is indicated for the treatment and prevention of osteoporosis in postmenopausal women; [3] the treatment to increase bone mass in men with osteoporosis; [3] the treatment of glucocorticoid-induced osteoporosis; [3] and the treatment of Paget's disease of bone. [3] [4]

Side effects

Pharmacology

Mechanism of action

Nitrogen containing bisphosphonates, which include ibandronate, pamidronate and alendronate exert their effects on osteoclasts mainly by inhibiting the synthesis of isoprenoid lipids such as isopentenyl diphosphate (IPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) via the mevalonate pathway. These isoprenoids are used in posttranslational modifcation(prenylation) of small GTPases such as Ras, Rho, and Rac. These prenylated GTPases are necessary for various cellular processes including osteoclast morphology, endosome trafficking, and apoptosis. Alendronate has also been shown to impair the function of osteclast lysosomes. [18]

Relative potency [19]
BisphosphonateRelative potency
Etidronate 1
Tiludronate 10
Pamidronate 100
Alendronate100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

Pharmacokinetics

The fraction of the drug that reaches the circulatory system intact (systemic bioavailability) after oral dosing is low, averaging only 0.6–0.7% in women and in men under fasting conditions. Intake together with meals and beverages other than water further reduces the bioavailability. The absorbed drug rapidly partitions, with approximately 50% binding to the exposed bone surface; the remainder is excreted unchanged by the kidneys. Unlike with most drugs, the strong negative charge on the two phosphonate moieties limits oral bioavailability, and, in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal elimination half-life of 10 years. [20]

Related Research Articles

<span class="mw-page-title-main">Osteoporosis</span> Skeletal disorder

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in fracture risk.

<span class="mw-page-title-main">Phossy jaw</span> Disease caused by phosphorus exposure

Phossy jaw, formally known as phosphorus necrosis of the jaw, was an occupational disease affecting those who worked with white phosphorus without proper safeguards. It is also likely to occur as the result of use of chemical weapons that contain white phosphorus. It was most commonly seen in workers in the matchstick industry in the 19th and early 20th centuries. It was caused by white phosphorus vapor, which destroys the bones of the jaw. Modern occupational hygiene practices have since eliminated the working conditions that caused this disease.

<span class="mw-page-title-main">Bisphosphonate</span> Pharmaceutical drugs for preventing bone loss

Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate groups. They are thus also called diphosphonates.

<span class="mw-page-title-main">Paget's disease of bone</span> Disease affecting bone remodeling

Paget's disease of bone is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture or arthritis of associated joints.

<span class="mw-page-title-main">Avascular necrosis</span> Death of bone tissue due to interruption of the blood supply

Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop, which may limit the person's ability to move. Complications may include collapse of the bone or nearby joint surface.

<span class="mw-page-title-main">Zoledronic acid</span> Chemical compound

Zoledronic acid, also known as zoledronate and sold under the brand name Zometa among others, by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.

<span class="mw-page-title-main">Osteopenia</span> Abnormally low bone mineral density

Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteoporosis. In 2010, 43 million older adults in the US had osteopenia. Unlike osteoporosis, osteopenia does not usually cause symptoms, and losing bone density in itself does not cause pain.

<span class="mw-page-title-main">Pamidronic acid</span> Chemical compound

Pamidronic acid or pamidronate disodium or APD, is a nitrogen-containing bisphosphonate used to prevent osteoporosis.

<span class="mw-page-title-main">Bazedoxifene</span> Chemical compound

Bazedoxifene, used as bazedoxifene acetate, is a medication for bone problems and possibly for cancer. It is a third-generation selective estrogen receptor modulator (SERM). Since late 2013 it has had U.S. FDA approval for bazedoxifene as part of the combination drug Duavee in the prevention of postmenopausal osteoporosis. It is also being studied for possible treatment of breast cancer and pancreatic cancer.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Ibandronic acid</span> Chemical compound

Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer. It may also be used to treat hypercalcemia. It is typically formulated as its sodium salt ibandronate sodium.

<span class="mw-page-title-main">Osteonecrosis of the jaw</span> Medical condition

Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws. Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature.

<span class="mw-page-title-main">Denosumab</span> Human monoclonal antibody

Denosumab, sold under the brand names Prolia and Xgeva among others, is a human monoclonal antibody used for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

<span class="mw-page-title-main">Strontium ranelate</span> Chemical compound

Strontium ranelate, a strontium(II) salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. Studies indicate it can also slow the course of osteoarthritis of the knee. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

In enzymology, a geranyltranstransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Medication-related osteonecrosis of the jaw</span> Medical condition

Medication-related osteonecrosis of the jaw is progressive death of the jawbone in a person exposed to a medication known to increase the risk of disease, in the absence of a previous radiation treatment. It may lead to surgical complication in the form of impaired wound healing following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy.

<span class="mw-page-title-main">C-terminal telopeptide</span> Chemical compound

The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is the C-terminal telopeptide of fibrillar collagens such as collagen type I and type II. It is used as a biomarker in the serum to measure the rate of bone turnover. It can be useful in assisting clinicians to determine a patient's nonsurgical treatment response as well as evaluate a patient's risk of developing complications during healing following surgical intervention. The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to bone resorption than any other test currently available.

<span class="mw-page-title-main">Discovery and development of bisphosphonates</span> Drugs used to treat bone disorders

Bisphosphonates are an important class of drugs originally commercialised in the mid to late 20th century. They are used for the treatment of osteoporosis and other bone disorders that cause bone fragility and diseases where bone resorption is excessive. Osteoporosis is common in post-menopausal women and patients in corticosteroid treatment where biphosphonates have been proven a valuable treatment and also used successfully against Paget's disease, myeloma, bone metastases and hypercalcemia. Bisphosphonates reduce breakdown of bones by inhibiting osteoclasts, they have a long history of use and today there are a few different types of bisphosphonate drugs on the market around the world.

Parish P. Sedghizadeh is a clinician-scientist, and a clinical and surgical oral and maxillofacial pathologist. He is a Professor of Clinical Dentistry, and Section Chair of Diagnostic Sciences in the Division of Periodontology, Diagnostic Sciences & Dental Hygiene at the Herman Ostrow School of Dentistry, University of Southern California. He is also the Director of the Oral Pathology and Radiology Distance Learning Program at the University of Southern California.

Alendronic acid/colecalciferol, sold under the brand name Fosamax Plus D among others, is a medication for the treatment of osteoporosis in men or in postmenopausal women.

References

  1. "Alendronate Use During Pregnancy". Drugs.com. 22 August 2019. Retrieved 17 May 2020.
  2. "Product monograph brand safety updates". Health Canada . 7 July 2016. Retrieved 3 April 2024.
  3. 1 2 3 4 5 "Fosamax- alendronate sodium tablet". DailyMed. 16 April 2024. Retrieved 30 September 2024.
  4. 1 2 3 4 5 6 7 "Fosamax Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 2 February 2019.
  5. British National Formulary : BNF 76 (76 ed.). Pharmaceutical Pres s. 2018. pp. 710–711. ISBN   978-0-85711-338-2.
  6. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 523. ISBN   978-3-527-60749-5.
  7. "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  8. "Alendronate Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  9. Sun K, Liu JM, Sun HX, Lu N, Ning G (January 2013). "Bisphosphonate treatment and risk of esophageal cancer: a meta-analysis of observational studies". Osteoporosis International. 24 (1): 279–286. doi:10.1007/s00198-012-2158-8. PMID   23052941. S2CID   12625687.
  10. Haber SL, McNatty D (March 2012). "An evaluation of the use of oral bisphosphonates and risk of esophageal cancer". The Annals of Pharmacotherapy. 46 (3): 419–423. doi:10.1345/aph.1Q482. PMID   22333262. S2CID   38417272.
  11. "Severe Pain with Osteoporosis Drugs". FDA Patient Safety News. March 2008. Archived from the original on 15 April 2014.
  12. "Fosamax product description" (PDF). Merck & Co.
  13. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P (August 2007). "A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics". Clinical Therapeutics. 29 (8): 1548–1558. doi:10.1016/j.clinthera.2007.08.008. PMID   17919538.
  14. Carini F, Barbano L, Saggese V, Monai D, Porcaro G (April 2012). "Multiple systemic diseases complicated by bisphosphonate osteonecrosis: a case report". Annali di Stomatologia. 3 (2 Suppl): 32–36. PMC   3512552 . PMID   23285320.
  15. Lenart BA, Lorich DG, Lane JM (March 2008). "Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate". The New England Journal of Medicine. 358 (12): 1304–1306. doi: 10.1056/NEJMc0707493 . PMID   18354114. S2CID   26968573.
  16. Weinstein RS, Roberson PK, Manolagas SC (January 2009). "Giant osteoclast formation and long-term oral bisphosphonate therapy". The New England Journal of Medicine. 360 (1): 53–62. doi:10.1056/NEJMoa0802633. PMC   2866022 . PMID   19118304.
  17. Kwek EB, Goh SK, Koh JS, Png MA, Howe TS (February 2008). "An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy?". Injury. 39 (2): 224–231. doi:10.1016/j.injury.2007.08.036. PMID   18222447.
  18. Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, et al. (June 2000). "Cellular and molecular mechanisms of action of bisphosphonates". Cancer. 88 (12 Suppl): 2961–2978. doi:10.1002/1097-0142(20000615)88:12+<2961::aid-cncr12>3.3.co;2-c. PMID   10898340.
  19. Tripathi DK (30 September 2013). Essentials of medical pharmacology (Seventh ed.). New Delhi. ISBN   978-9-350-25937-5. OCLC   868299888.{{cite book}}: CS1 maint: location missing publisher (link)
  20. Shinkai I, Ohta Y (January 1996). "New drugs--reports of new drugs recently approved by the FDA. Alendronate". Bioorganic & Medicinal Chemistry. 4 (1): 3–4. doi:10.1016/0968-0896(96)00042-9. PMID   8689235.