Back To Search Results


Editor: Charles V. Preuss Updated: 3/24/2023 9:40:18 AM

Alendronate is FDA-approved for the treatment of postmenopausal osteoporosis, prevention of postmenopausal osteoporosis, steroid-induced osteoporosis, male osteoporosis, and Paget disease of the bone. Alendronate is an option for maintaining or increasing bone mass, although risedronate is the preferred agent in men with osteoporosis.[1]

Alendronate is not FDA-approved for use in Crohn-induced osteoporosis. Studies have evaluated the optimal treatment of Crohn-induced osteoporosis with evidence indicating the use of pamidronate infusions to avoid upper gastrointestinal (GI) adverse effects associated with oral alendronate. However, current evidence supports bisphosphonates as first-line therapy, administered orally or parenterally.[2]

Alendronate is not FDA-approved for use in osteopenia secondary to cystic fibrosis of the lung. A multicenter, randomized controlled trial with 56 participants conducted in Canada indicated alendronate therapy was well tolerated and improved bone mineral density over 12 months compared to placebo.[3] Alendronate demonstrated increased spine and femur bone mineral density in those with cystic fibrosis in an additional double-blinded trial.[4] 

Alendronate is not FDA-approved for use in fibrous dysplasia of the bone. Current data endorses the use of pamidronate in decreased bone remodeling measured through decreased serum alkaline phosphatase and urinary hydroxyproline, but no current studies support alendronate use.[5]

Alendronate is not FDA-approved for use in growth hormone deficiency. A randomized controlled trial in osteoporotic adult-onset growth hormone deficiency demonstrated that adding alendronate therapy for 12 months provided no significant difference in bone turnover, bone mineral density, or prevalence of vertebral fractures. However, participants maintained by using recombinant growth hormone in addition to alendronate indicated a significant decrease in bone turnover and an increase in bone mineral density of the lumbar spine. Further study is necessary to validate these results.[6]

Alendronate is not FDA-approved to treat hypercalcemia of malignancy. Previously, bisphosphonates were the mainstay of treatment, but intravenous calcitonin has demonstrated superior efficacy.[7] Current clinical guidelines indicate that first-line therapy is aggressive intravenous hydration, followed by calcitonin. Subsequently, administer zoledronic acid or ibandronate two to four days post calcitonin therapy initiation. Zoledronic acid is preferable to alendronate due to its superior potency. If zoledronic acid is unavailable, ibandronate or pamidronate are other options.[8]

Clinicians frequently employ alendronate in the treatment of male hypogonadism-induced osteoporosis. A randomized controlled study of 22 osteoporotic men with long-standing hypogonadism demonstrated that femoral neck bone mineral density increased with long-term alendronate administration and testosterone replacement.[9]

Rarely, alendronate is used off-label in pediatric populations with bone necrosis, hypervitaminosis D, and secondary amenorrhea. Due to the unknown teratogenic effect and the long half-life of bisphosphonates, there is not sufficient evidence to support bisphosphonate therapy in pediatric populations.[10]

Wang L. et al. conducted an in vitro study on human SW1353 chondrocytes exposed to alendronate for 12 hours and observed the expression of extracellular matrix-related genes Col2α1, COL9α2, and Acan.[11] Alendronate increased the expression of the extracellular matrix-related genes by increasing the expression of SOX-9. Alendronate was able to reverse the reduction of extracellular matrix-related genes caused by TNF-alpha. The investigators propose that alendronate could be a promising treatment for osteoarthritis by stimulating cartilage repair.

Mechanism of Action

Earn CME credit as you help guide your clinical decisions.
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed.


$59 per month


$599 per year

Alendronate is a bisphosphonate. Binding to hydroxyapatite crystals present in bone downregulates osteoclast-mediated bone reabsorption and decreases bone matrix breakdown. Both of these mechanisms contribute to regulating mineral reabsorption and turnover. Alendronate differs from other bone-modifying supplements as it suppresses bone formation but does not modify bone mineral accrual in endocortical or intracortical bone.[12]


  • 0.64% bioavailability in fasting women, 0.59% bioavailability in fasting men; bioavailability is reduced by up to 60% with food
  • Half-life: approximately 10 years in bone (terminal)
  • Excretion: Urine 50%, feces (unabsorbed drug)

Kendler D. et al. examined transitioning from denosumab treatment to alendronate treatment regarding its effects on bone mineral density.[13] The patients enrolled in the clinical trial were postmenopausal women (treatment-naive) with bone mineral density T-scores that ranged from -2.0 to -4.0. The investigators found that after one year of denosumab treatment, alendronate was able to maintain bone mineral density in year 2.

Mok C. et al. conducted a study to examine the effects of denosumab or alendronate treatment on bone mineral density in patients receiving long-term prednisolone treatment.[14] The investigators found that denosumab was superior to alendronate in increasing bone mineral density of the spine after 12 months of treatment. However, denosumab and alendronate had similar beneficial effects on the bone mineral density of the hip and femoral neck.

Brown J. et al. examined the effects of romosozumab vs. alendronate on lumbar spine bone mass and bone strength characteristics in postmenopausal wone with osteoporosis.[15] Romosozumab treatment was found to provide better bone mass and strength in the lumbar spine compared to alendronate treatment.

Martini C. et al. examined the in vitro effects of alendronate on adipocytes of 3T3-L1 fibroblasts, lipid characteristics and oxidative stress in mature adipocytes, and macrophage inflammatory response.[16] The investigators found that alendronate decreases the differentiation of 3T3-L1 fibroblasts to adipocytes. Alendronate decreased hydrogen peroxide-induced lipid peroxidation and decreased triglyceride content. Alendronate decreased the activation of RAW 264.7 macrophages into the pro-inflammatory M1 type. These effects of alendronate may decrease insulin resistance and adipocyte dysfunction. Viggers R. et al. conducted a clinical study on the effects of alendronate treatment on developing type 2 diabetes mellitus in patients.[17] The investigators observed that alendronate therapy decreased the risk of developing type 2 diabetes mellitus.

Ito E. et al. studied the effects of alendronate on the bone mineral density of pregnant or lactating female mice.[18] The researchers observed that temporary alendronate treatment right before or right after pregnancy or lactation decreased bone loss in the animals studied, i.e., it had a protective effect.

Zameer S. et al. researched mice exposed to d-galactose and aluminum chloride, which causes neuropathologies and cognitive decline resembling Alzheimer disease.[19] Oral treatment with alendronate reversed the observed neuropathologies and cognitive decline in the animal model for Alzheimer disease.

Alendronate is available in 5 mg, 10 mg, 35 mg, 40 mg, or 70 mg oral tablets; 70 mg tablet for solution; and 70 mg/75 mL oral solution.

Clinical indication directs dosing guidelines:

  • Postmenopausal women: 5 mg oral tablet daily or 35 mg oral tablet once weekly
  • Glucocorticoid-induced osteoporosis: 5 mg oral tablet once daily or 10 mg oral tablet once daily in women not undergoing hormone replacement therapy
  • Paget disease of the bone: 40 mg/day oral tablet for six months
  • Pediatric patients: Safety and efficacy have not been established
  • Severe renal impairment: Dosing not recommended; seek alternative treatment
  • Low-risk of fracture: Consider drug discontinuation after 3 to 5 years of use.

Alendronate was a pregnancy Category C drug under the prior FDA classification system. It is unknown whether alendronate gets excreted in the milk of lactating women; use the drug during lactation with caution.

Alendronate should be taken in the morning with a full glass of water on an empty stomach in an upright position. Individuals should remain in an upright position for 30 minutes after intake to decrease the risk of adverse reactions. Do not chew, suck, or crush the tablet.

Patients taking human parathyroid hormone should avoid taking alendronate. This combination can reduce calcium-sparing effects, thus impacting serum calcium concentrations unfavorably. 

Iles B. et al. created an experimental dosage form of alendronate nanoparticles that caused fewer gastric lesions in Wistar rats and demonstrated no toxicity in murine osteoblastic cells.[20]

The most common adverse events include transient hypocalcemia, transient hypophosphatemia, and GI symptoms (e.g., abdominal pain, heartburn, nausea, constipation, diarrhea, flatulence, and esophagitis). Additional adverse events are myalgia, joint pain, headache, dizziness, peripheral edema, back pain, and weakness.

Rare but reported adverse events include toxic epidermal necrosis and oropharyngeal ulceration.[21]

Post-marketing reports include rare occurrences of osteonecrosis of the jaw, generally associated with tooth extraction or local infection with delayed healing; esophageal erosions/esophagitis/esophageal ulcers; and hypersensitivity reactions.[22]

Papamitsou T. et al. researched the effects of alendronate treatment on Wistar rat’s stomach and liver.[23] The researcher observed microscopic inflammation of the stomach and mild hepatotoxicity. 

Bautista-Villanueva S. et al. report on a patient who developed pustular skin reactions on both calves because of alendronate therapy.[24] The patient was a 55-year-old man with a history of ulcerative colitis and osteoporosis. The patient had previous allergic reactions to mesalamine and golimumab treatments.

Zhang C. et al. examined the effects of alendronate treatment on bone healing in ovariectomized 3-month-old female rats.[25] The investigators created an osteoporotic calvarial defect animal model. Alendronate treatment decreased the healing of the calvarial lesion in the animal model.

Naganathar N. et al. conducted a retrospective clinical study of the effects of alendronate therapy on renal function in patients (with osteoporosis, age > 65 years old) with decreased renal function (creatinine clearance < 35 ml/min).[26] The investigators found that alendronate therapy did not significantly reduce renal function from the patient’s baseline renal function.

Contraindications to alendronate include patients with known hypersensitivity, esophageal abnormalities, delayed esophageal emptying, or achalasia. Severe risk of esophageal morbidity indicates avoidance in patients who are unable to sit or stand upright for at least 30 minutes. Avoid alendronate in patients with hypocalcemia.[21]

Baseline concentrations of calcium and bone mineral density should be established before therapy begins, with follow-up testing at 6 to 12 months post-therapy. Calcium at baseline and continual monitoring are needed if hypocalcemia risk is recurring. The clinician should decrease the dose or discontinue therapy if hypocalcemia occurs during treatment. Magnesium and phosphorus require monitoring at regular intervals.[27]

The physician should offer some form of a drug holiday to patients on alendronate therapy. The accumulation of alendronate in the kidney allows for persistent anti-fracture benefits even after cessation of treatment. Current recommendations suggest tailoring the drug holiday length to individual patients. The average drug holiday in low-risk patients is 3 to 5 years. It also bears mentioning that alendronate is an extremely safe drug, and the benefits of continued therapy often outweigh the benefits of a drug holiday.[28]


No known toxicities have been reported with alendronate to date, and alendronate has no FDA boxed warning.

Some post-marketing reports indicated an association with significant esophageal and gastric mucosal toxicity; however, studies have since concluded alendronate does not cause predictable mucosal damage when used as directed.[29]

Enhancing Healthcare Team Outcomes

Alendronate is a frequently used agent to manage osteoporosis and several other bone disorders, often prescribed in combination with vitamin D. Besides the clinician, the nurse and pharmacist must be fully aware of the therapeutic uses and adverse reactions of this agent. The most feared complication is osteonecrosis of the jaw, which is most likely to occur when dental work has taken place.[30] Thus, the patient must receive education about this drug and the need to see a healthcare provider before any oral cavity procedure.

The pharmacist should educate the patient on potential drug interactions with alendronate and perform an overall medication reconciliation to check for drug interactions, reporting any concerns to the physician and nurse. All patients on alendronate require close monitoring for side effects, which can be serious; this is where the nurse needs to monitor the drug, counsel the patient, make a direct inquiry about potential adverse effects, and notify the healthcare team of any issues.[31] Alendronate therapy requires interprofessional teamwork and coordination, with open communication channels between various team members, to ensure optimal patient outcomes. [Level 5]

Chen Y et al. conducted a population-based cohort study on patient adherence to alendronate therapy in preventing a second hip fracture.[32] The investigators found that the alendronate medication possession ratio (MPR, a measure of medication adherence) of greater than or equal to 50% for the year reduces the risk of a second hip fracture.



León Vázquez F, Herrero Hernández S, Cuerpo Triguero C, Andrés Prado MJ, Cabello Ballesteros L. Prescription of alendronate and risedronate in men: off-label use in a health area. Reumatologia clinica. 2015 Mar-Apr:11(2):64-7. doi: 10.1016/j.reuma.2014.05.003. Epub 2014 Aug 6     [PubMed PMID: 25107345]


Compston J. Osteoporosis in inflammatory bowel disease. Gut. 2003 Jan:52(1):63-4     [PubMed PMID: 12477761]


Papaioannou A, Kennedy CC, Freitag A, Ioannidis G, O'Neill J, Webber C, Pui M, Berthiaume Y, Rabin HR, Paterson N, Jeanneret A, Matouk E, Villeneuve J, Nixon M, Adachi JD. Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). Chest. 2008 Oct:134(4):794-800. doi: 10.1378/chest.08-0608. Epub 2008 Jul 18     [PubMed PMID: 18641106]


Aris RM, Lester GE, Caminiti M, Blackwood AD, Hensler M, Lark RK, Hecker TM, Renner JB, Guillen U, Brown SA, Neuringer IP, Chalermskulrat W, Ontjes DA. Efficacy of alendronate in adults with cystic fibrosis with low bone density. American journal of respiratory and critical care medicine. 2004 Jan 1:169(1):77-82     [PubMed PMID: 14563654]


Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet (London, England). 1994 Apr 16:343(8903):953-4     [PubMed PMID: 7909013]


Biermasz NR, Hamdy NA, Janssen YJ, Roelfsema F. Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial. The Journal of clinical endocrinology and metabolism. 2001 Jul:86(7):3079-85     [PubMed PMID: 11443170]

Level 1 (high-level) evidence


Diskin CJ, Stokes TJ, Dansby LM, Radcliff L, Carter TB. Malignancy-related hypercalcemia developing on a bisphosphonate but responding to calcitonin. Clinical lung cancer. 2007 Jul:8(7):434-5     [PubMed PMID: 17681097]


Mirrakhimov AE. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. North American journal of medical sciences. 2015 Nov:7(11):483-93. doi: 10.4103/1947-2714.170600. Epub     [PubMed PMID: 26713296]


Shimon I, Eshed V, Doolman R, Sela BA, Karasik A, Vered I. Alendronate for osteoporosis in men with androgen-repleted hypogonadism. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005 Dec:16(12):1591-6     [PubMed PMID: 16362147]


Eghbali-Fatourechi G. Bisphosphonate therapy in pediatric patients. Journal of diabetes and metabolic disorders. 2014:13(1):109. doi: 10.1186/s40200-014-0109-y. Epub 2014 Dec 17     [PubMed PMID: 25551100]


Wang L, Mi B, Zhang Y, Yan H, Zhu H. Alendronate promotes the gene expression of extracellular matrix mediated by SP-1/SOX-9. Human & experimental toxicology. 2021 Jul:40(7):1173-1182. doi: 10.1177/0960327120988875. Epub 2021 Feb 1     [PubMed PMID: 33522294]


Vrahnas C, Buenzli PR, Pearson TA, Pennypacker BL, Tobin MJ, Bambery KR, Duong LT, Sims NA. Differing Effects of Parathyroid Hormone, Alendronate, and Odanacatib on Bone Formation and on the Mineralization Process in Intracortical and Endocortical Bone of Ovariectomized Rabbits. Calcified tissue international. 2018 Dec:103(6):625-637. doi: 10.1007/s00223-018-0455-8. Epub 2018 Jul 17     [PubMed PMID: 30019315]


Kendler D, Chines A, Clark P, Ebeling PR, McClung M, Rhee Y, Huang S, Stad RK. Bone Mineral Density After Transitioning From Denosumab to Alendronate. The Journal of clinical endocrinology and metabolism. 2020 Mar 1:105(3):e255-64. doi: 10.1210/clinem/dgz095. Epub     [PubMed PMID: 31665314]


Mok CC, Ho LY, Leung SMT, Cheung HN, Chen SPL, Ma KM. Denosumab versus alendronate in long-term glucocorticoid users: A 12-month randomized controlled trial. Bone. 2021 May:146():115902. doi: 10.1016/j.bone.2021.115902. Epub 2021 Feb 23     [PubMed PMID: 33631355]

Level 1 (high-level) evidence


Brown JP, Engelke K, Keaveny TM, Chines A, Chapurlat R, Foldes AJ, Nogues X, Civitelli R, De Villiers T, Massari F, Zerbini CAF, Wang Z, Oates MK, Recknor C, Libanati C. Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2021 Nov:36(11):2139-2152. doi: 10.1002/jbmr.4409. Epub 2021 Aug 10     [PubMed PMID: 34190361]


Martini C, Sosa FN, Malvicini R, Pacienza N, Yannarelli G, Del C Vila M. Alendronate inhibits triglyceride accumulation and oxidative stress in adipocytes and the inflammatory response of macrophages which are associated with adipose tissue dysfunction. Journal of physiology and biochemistry. 2021 Nov:77(4):601-611. doi: 10.1007/s13105-021-00826-9. Epub 2021 Jul 24     [PubMed PMID: 34302624]


Viggers R, Al-Mashhadi Z, Starup-Linde J, Vestergaard P. Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study. Frontiers in endocrinology. 2021:12():771426. doi: 10.3389/fendo.2021.771426. Epub 2021 Nov 19     [PubMed PMID: 34867816]

Level 2 (mid-level) evidence


Ito E, Sato Y, Kobayashi T, Soma T, Matsumoto T, Kimura A, Miyamoto K, Matsumoto H, Matsumoto M, Nakamura M, Sato K, Miyamoto T. Transient alendronate administration to pregnant or lactating mothers prevents bone loss in mice without adverse effects on offspring. Bone. 2021 Dec:153():116133. doi: 10.1016/j.bone.2021.116133. Epub 2021 Jul 28     [PubMed PMID: 34329815]


Zameer S, Hussain S, Vohora D, Kalam Najmi A, Ali J, Akhtar M. Alendronate reduces the cognitive and neurological disturbances induced by combined doses of d-galactose and aluminum chloride in mice. Journal of applied toxicology : JAT. 2021 Nov:41(11):1779-1793. doi: 10.1002/jat.4160. Epub 2021 Mar 10     [PubMed PMID: 33694194]


Iles B, Ribeiro de Sá Guimarães Nolêto I, Dourado FF, de Oliveira Silva Ribeiro F, de Araújo AR, de Oliveira TM, Souza JMT, Barros AB, Sousa GC, de Jesus Oliveira AC, da Silva Martins C, de Oliveira Viana Veras M, de Carvalho Leitão RF, de Souza de Almeida Leite JR, da Silva DA, Medeiros JVR. Alendronate sodium-polymeric nanoparticles display low toxicity in gastric mucosal of rats and Ofcol II cells. NanoImpact. 2021 Oct:24():100355. doi: 10.1016/j.impact.2021.100355. Epub 2021 Aug 27     [PubMed PMID: 35559814]


Musette P, Kaufman JM, Rizzoli R, Cacoub P, Brandi ML, Reginster JY. Cutaneous side effects of antiosteoporosis treatments. Therapeutic advances in musculoskeletal disease. 2011 Feb:3(1):31-41. doi: 10.1177/1759720X10387202. Epub     [PubMed PMID: 22870464]

Level 3 (low-level) evidence


de Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK. Esophagitis associated with the use of alendronate. The New England journal of medicine. 1996 Oct 3:335(14):1016-21     [PubMed PMID: 8793925]


Papamitsou T, Sotiriou S, Papakoulas A, Toskas A, Kamperis D, Karachrysafi S, Dietrich EM, Lialiaris S, Sioga A. Alendronate effect in esophagus, stomach and liver: an animal based pathological study. Histology and histopathology. 2020 Apr:35(4):417-422. doi: 10.14670/HH-18-161. Epub 2019 Sep 10     [PubMed PMID: 31502656]

Level 3 (low-level) evidence


Bautista-Villanueva S, Galleani C, Barranco R, Bellón T, Blanco M, García-Moguel I. Acute Localized Exanthematous Pustulosis Due to Alendronate. Journal of investigational allergology & clinical immunology. 2021 Feb 21:32(1):69-70. doi: 10.18176/jiaci.0709. Epub 2021 May 28     [PubMed PMID: 34045177]


Zhang C, Zhu J, Jia J, Guan Z, Sun T, Zhang W, Yuan W, Wang H, Song C. Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model. Journal of bone and mineral metabolism. 2021 Nov:39(6):925-933. doi: 10.1007/s00774-021-01235-0. Epub 2021 Jun 6     [PubMed PMID: 34091742]


Naganathar N, Yau W-, Mok ZH, Tan ZYF, Chew STH. Alendronate use in older patients with reduced renal function: challenges and opportunities in clinical practice. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2021 Oct:32(10):1981-1988. doi: 10.1007/s00198-021-05907-5. Epub 2021 Mar 15     [PubMed PMID: 33721033]


Braga de Castro Machado A, Hannon R, Eastell R. Monitoring alendronate therapy for osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1999 Apr:14(4):602-8     [PubMed PMID: 10234582]


Diab DL, Watts NB. Bisphosphonate drug holiday: who, when and how long. Therapeutic advances in musculoskeletal disease. 2013 Jun:5(3):107-11. doi: 10.1177/1759720X13477714. Epub     [PubMed PMID: 23858334]

Level 3 (low-level) evidence


Lowe CE, Depew WT, Vanner SJ, Paterson WG, Meddings JB. Upper gastrointestinal toxicity of alendronate. The American journal of gastroenterology. 2000 Mar:95(3):634-40     [PubMed PMID: 10710050]


Cummings SR, Santora AC, Black DM, Russell RGG. History of alendronate. Bone. 2020 Aug:137():115411. doi: 10.1016/j.bone.2020.115411. Epub 2020 May 11     [PubMed PMID: 32437874]


Carter M. Prevention of Glucocorticoid-Induced Osteoporosis: Clinical audit to evaluate the implementation of National Osteoporosis Guideline Group 2017 guidelines in a primary care setting. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2019 Jan-Mar:22(1):25-30. doi: 10.1016/j.jocd.2018.03.009. Epub 2018 Apr 12     [PubMed PMID: 29729949]


Chen YJ, Kung PT, Chou WY, Tsai WC. Alendronate medication possession ratio and the risk of second hip fracture: an 11-year population-based cohort study in Taiwan. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2020 Aug:31(8):1555-1563. doi: 10.1007/s00198-020-05399-9. Epub 2020 Mar 27     [PubMed PMID: 32221674]