Tools
Alendronate
Indications
FDA-Approved Indications
Alendronate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis, steroid-induced osteoporosis, and male osteoporosis, as well as for the management of Paget disease of bone. Alendronate belongs to the class of bisphosphonate medications, which aids in the prevention of bone resorption and the promotion of bone density, making it a valuable treatment for osteoporosis and various other bone-related conditions. Alendronate is an option for maintaining or increasing bone mass, whereas risedronate is preferred in men with osteoporosis.[1]
Off-Label Uses
Alendronate is used as an off-label medication for the below-mentioned conditions.
Crohn-induced osteoporosis: Although alendronate is used as an off-label medication for Crohn-induced osteoporosis, studies have shown that pamidronate infusions are the optimal treatment option for this condition. Pamidronate infusions can help mitigate upper gastrointestinal (GI) adverse effects associated with oral alendronate. However, current evidence underscores bisphosphonates as the preferred first-line therapy, whether administered orally or via parenteral routes.[2]
Osteopenia with cystic fibrosis: Alendronate is used as an off-label medication for treating osteopenia secondary to cystic fibrosis of the lung. However, a multicenter, randomized controlled trial in Canada with 56 participants demonstrated that alendronate therapy was well-tolerated and significantly improved bone mineral density over 12 months compared to a placebo.[3] In an additional double-blinded trial, alendronate exhibited a notable increase in spine and femur bone mineral density in individuals with cystic fibrosis.[4]
Fibrous dysplasia: Alendronate is used as an off-label medication for treating fibrous dysplasia of the bone. Current data supports the utilization of pamidronate, as it demonstrates a reduction in bone remodeling, as indicated by decreased serum alkaline phosphatase and urinary hydroxyproline. However, current research does not support using alendronate for this purpose.[5]
Growth hormone deficiency: Alendronate is used as an off-label medication for managing growth hormone deficiency in individuals. In a randomized controlled trial involving adults with osteoporotic adult-onset growth hormone deficiency, adding alendronate therapy for 12 months yielded no significant differences in bone turnover, bone mineral density, or the prevalence of vertebral fractures. However, participants concurrently treated with recombinant growth hormone and alendronate demonstrated a significant reduction in bone turnover and a substantial increase in bone mineral density, specifically in the lumbar spine. Further research is required to confirm and validate these findings.[6]
Hypercalcemia of malignancy: Alendronate is used as an off-label medication to treat hypercalcemia of malignancy. Although, in the past, bisphosphonates were used as the primary treatment for this condition, current research demonstrates a superior efficacy in intravenous calcitonin in addressing this condition.[7] Current clinical guidelines indicate that first-line therapy involves aggressive intravenous hydration, followed by the administration of calcitonin. Subsequently, 2 to 4 days after initiating calcitonin therapy, zoledronic acid or ibandronate is recommended. Zoledronic acid is the preferred choice over alendronate due to its superior potency. If zoledronic acid is unavailable, ibandronate or pamidronate can be considered alternative options.[8]
Alendronate is often utilized by clinicians in the management of osteoporosis induced by male hypogonadism. A randomized controlled study involving 22 men with osteoporosis and long-standing hypogonadism revealed that long-term treatment with alendronate, in conjunction with testosterone replacement, increased femoral neck bone mineral density.[9]
Rarely, alendronate is used off-label in pediatric populations to address conditions such as bone necrosis, hypervitaminosis D, and secondary amenorrhea. Due to the unknown teratogenic effects and the extended half-life of bisphosphonates, there is insufficient evidence to endorse bisphosphonate therapy for pediatric populations.[10]
Wang et al conducted an in vitro study involving human SW1353 chondrocytes exposed to alendronate for 12 hours, during which they monitored the expression of extracellular matrix–related genes, including Col2α1, COL9α2, and Acan.[11] Alendronate increased the expression of the extracellular matrix–related genes by upregulating the expression of SOX-9. Notably, alendronate successfully reversed the reduction of extracellular matrix–related genes caused by tumor necrosis factor-alpha (TNF-α). The study suggests that alendronate may be a promising treatment for osteoarthritis by promoting cartilage repair.
Mechanism of Action
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Mechanism of Action
Alendronate belongs to the class of bisphosphonate medications and is used to treat osteoporosis and other bone-related conditions. By binding to hydroxyapatite crystals within bone, alendronate downregulates osteoclast-mediated bone reabsorption, thereby leading to a reduction in bone matrix breakdown. Both of these mechanisms collectively contribute to regulating the reabsorption and turnover of minerals. Alendronate differs from other bone-modifying supplements by its ability to suppress bone formation without modifying bone mineral accrual in endocortical or intracortical bone.[12]
Pharmacokinetics
The pharmacokinetic profile of alendronate is provided below.
Bioavailability: The bioavailability of alendronate is limited to 0.64% in fasting women and 0.59% in fasting men. However, this bioavailability diminishes by as much as 60% when the drug is taken with food.
Half-life: Alendronate exhibits a notably protracted terminal half-life of approximately 10 years within bone tissues.
Excretion: Alendronate is primarily excreted through urine, accounting for 50% of elimination, with unabsorbed drugs appearing in the feces.
Kendler et al conducted a study investigating the transition from denosumab treatment to alendronate treatment and its impact on bone mineral density.[13] The clinical trial included postmenopausal women who were treatment-naive, with bone mineral density T-scores ranging from -2.0 to -4.0. The study results revealed that after 1 year of denosumab treatment, alendronate effectively preserved bone mineral density into the second year of the trial.
Mok 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 study revealed that after 12 months of treatment, denosumab outperformed alendronate in increasing bone mineral density in the spine. However, both denosumab and alendronate also exhibited similar positive effects on bone mineral density in the hip and femoral neck.
Brown et al investigated the impact of romosozumab compared to alendronate on lumbar spine bone mass and bone strength characteristics in postmenopausal women with osteoporosis.[15] The study determined that romosozumab treatment resulted in superior bone mass and strength in the lumbar spine when compared to alendronate treatment.
Martini et al examined the in vitro effects of alendronate on 3T3-L1 fibroblast-derived adipocytes, focusing on lipid characteristics and oxidative stress in mature adipocytes, as well as the inflammatory response of macrophages.[16] The study revealed that alendronate reduced the differentiation of 3T3-L1 fibroblasts into adipocytes. Furthermore, it decreased hydrogen peroxide-induced lipid peroxidation and lowered triglyceride content. Alendronate also inhibited the activation of RAW 264.7 macrophages, shifting them away from the pro-inflammatory M1 type. These effects of alendronate can potentially decrease insulin resistance and adipocyte dysfunction.
Viggers et al conducted a clinical study to examine the influence of alendronate treatment on the incidence of type 2 diabetes in patients and whether alendronate had any effect on the development of this condition.[17] The study revealed that alendronate therapy reduced the risk of developing type 2 diabetes.
Ito et al studied the effects of alendronate on the bone mineral density of pregnant or lactating female mice.[18] The conclusions derived from the animal studies research demonstrated that temporary alendronate treatment immediately before or after pregnancy or during lactation effectively mitigated bone loss, thereby indicating a protective effect.
Zameer et al conducted research on mice exposed to d-galactose and aluminum chloride—a combination known to induce neuropathologies and cognitive decline resembling Alzheimer disease.[19] Oral administration of alendronate effectively reversed the neuropathologies and cognitive decline observed in the animal model for Alzheimer disease.
Administration
Available Dosage Forms and Strengths
Alendronate is available in various forms, including oral tablets in 5 mg, 10 mg, 35 mg, 40 mg, and 70 mg strengths; a 70 mg tablet for solution; and a 70 mg/75 mL oral solution.
Dosage Regimens
For optimal effectiveness, alendronate should be taken in the morning with a full glass of water while standing or sitting upright and on an empty stomach. Individuals should maintain an upright position for 30 minutes after taking the medication to minimize the risk of adverse reactions and avoid chewing, sucking, or crushing the tablet.
The dosing guidelines for alendronate are determined based on the patient's specific clinical indications, risk factors, and individual needs. Dosing guidelines are determined by the clinical indications, which are listed below.
Postmenopausal women: The recommended dosage options for postmenopausal women include an oral tablet of 5 mg daily or 35 mg once weekly.
Glucocorticoid-induced osteoporosis: The recommended dosages for individuals with glucocorticoid-induced osteoporosis are 5 mg oral tablet once daily or 10 mg oral tablet once daily for women not undergoing hormone replacement therapy.
Paget disease of bone: The recommended dosing regimen for individuals with this condition includes an oral tablet of 40 mg administered daily for a duration of 6 months.
Severe renal impairment: Healthcare providers advise against using this medication for individuals with severe renal problems and suggest exploring alternative treatment options instead.
Low-risk of fracture: In situations where there is a low risk of fracture, it is prudent to contemplate discontinuing the medication after 3 to 5 years of use.
Pediatric patients: The safety and efficacy of this medication have not been established in pediatric populations.
Pregnancy and breastfeeding: Alendronate was classified as a pregnancy category C drug in the previous FDA pregnancy category system. As the excretion of alendronate in the milk of lactating women is not well understood, it is recommended to exercise caution when using the drug during lactation.
Individuals prescribed human parathyroid hormone should refrain from using alendronate simultaneously. This combination may diminish calcium-sparing effects, potentially resulting in unfavorable changes in serum calcium concentrations.
Iles et al developed an experimental dosage form of alendronate nanoparticles, which resulted in fewer gastric lesions in Wistar rats and exhibited no toxicity in murine osteoblastic cells.[20]
Adverse Effects
The most common adverse effects of alendronate include transient hypocalcemia, transient hypophosphatemia, and GI symptoms, such as abdominal pain, heartburn, nausea, constipation, diarrhea, flatulence, and esophagitis. Other reported adverse events include myalgia, joint pain, headache, dizziness, peripheral edema, back pain, and weakness. Although infrequent, additionally reported adverse effects of alendronate encompass toxic epidermal necrolysis and oropharyngeal ulceration.[21]
Post-marketing reports have indicated rare instances of osteonecrosis of the jaw, typically associated with tooth extraction or local infection with delayed healing. In addition, reports include esophageal erosions, esophagitis, esophageal ulcers, and hypersensitivity reactions.[22]
Papamitsou et al conducted a study to investigate the effects of alendronate treatment on the stomach and liver of Wistar rats.[23] The study revealed microscopic inflammation of the stomach and mild hepatotoxicity.
Bautista-Villanueva et al reported a case of a patient who developed pustular skin reactions on both calves as a result of alendronate therapy.[24] The male patient, aged 55, had a history of ulcerative colitis and osteoporosis and also experienced allergic reactions to mesalamine and golimumab.
Zhang et al examined the effects of alendronate treatment on bone healing in 3-month-old female rats subjected to ovariectomy.[25] The researchers developed an animal model with osteoporotic calvarial defects. Notably, alendronate treatment was found to impede the healing of the calvarial lesion in this animal model.
Naganathar et al conducted a retrospective clinical study to investigate the effects of alendronate therapy on renal function in patients with osteoporosis, aged 65 and older, and experiencing reduced renal function (creatinine clearance <35 mL/min).[26] The study indicated that alendronate therapy did not cause a significant reduction in the patient's baseline renal function.
Contraindications
Contraindications to alendronate include patients with known hypersensitivity to the drug, as well as those with esophageal abnormalities, delayed esophageal emptying, or achalasia. To mitigate the substantial risk of esophageal morbidity, it is advisable to refrain from administering the medication to patients who cannot maintain an upright sitting or standing position for a minimum of 30 minutes. In addition, alendronate should be avoided in patients with hypocalcemia.[21]
Box Warning
Alendronate has no FDA-boxed warnings.
Monitoring
Baseline concentrations of calcium and bone mineral density should be established before initiating alendronate therapy, with subsequent follow-up assessments at 6 to 12 months after commencing treatment. In cases with a recurring risk of hypocalcemia, it is essential to conduct baseline calcium measurements and maintain continuous monitoring. If hypocalcemia arises during treatment, the clinician should consider reducing the dose or discontinuing therapy. Furthermore, it is necessary to monitor magnesium and phosphorus levels at regular intervals.[27]
Physicians should consider providing patients on alendronate therapy with intermittent breaks from the medication, also known as a drug holiday. The accumulation of alendronate in the kidney allows for persistent anti-fracture benefits even after the discontinuation of treatment. Current recommendations suggest tailoring the duration of the drug holiday based on individual patient needs. Typically, low-risk patients may benefit from a drug holiday lasting 3 to 5 years. Notably, alendronate is widely regarded as a highly safe medication, and the benefits of continued therapy often outweigh the benefits of a drug holiday.[28]
Toxicity
To date, there have been no reported toxicities associated with the use of alendronate. Although certain post-marketing reports indicated an association with significant esophageal and gastric mucosal toxicity, subsequent studies have established that alendronate does not cause predictable mucosal damage when used as directed.[29]
Enhancing Healthcare Team Outcomes
Alendronate is a commonly prescribed medication for the management of osteoporosis and various other bone disorders, and it is often administered alongside vitamin D. A team of interprofessional healthcare providers comprising clinicians, nurses, and pharmacists must possess a comprehensive understanding of the therapeutic uses and potential adverse reactions of alendronate. The most concerning complication is osteonecrosis of the jaw, with the highest likelihood of occurrence following dental procedures.[30] As a result, patients must be educated about the medication and the importance of consulting a healthcare provider before any oral cavity procedure.
Pharmacists should take the initiative to educate patients about potential drug interactions involving alendronate. Furthermore, they should conduct a comprehensive medication reconciliation to identify and assess any possible drug interactions and promptly communicate any concerns to the patient's physician and nurse. All patients undergoing alendronate treatment necessitate vigilant monitoring for severe adverse effects. Nurses are responsible for overseeing the medication, providing patient counseling, actively inquiring about potential adverse effects, and promptly informing the healthcare team of any concerns.[31] The successful management of alendronate therapy necessitates effective interprofessional teamwork and coordination, featuring open communication channels and shared decision-making among patients and various team members, to achieve the best possible patient outcomes
Chen et al conducted a population-based cohort study examining patient adherence to alendronate therapy to prevent a second hip fracture.[32] The study indicated that having a medication possession ratio (MPR), which measures medication adherence, of 50% or higher for alendronate over a year reduces the risk of a second hip fracture.
References
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]
Level 2 (mid-level) evidenceCompston J. Osteoporosis in inflammatory bowel disease. Gut. 2003 Jan:52(1):63-4 [PubMed PMID: 12477761]
Level 1 (high-level) evidencePapaioannou 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]
Level 2 (mid-level) evidenceAris 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]
Level 1 (high-level) evidenceLiens 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) evidenceDiskin 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]
Level 3 (low-level) evidenceMirrakhimov 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]
Level 1 (high-level) evidenceEghbali-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) evidenceBrown 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) evidenceIto 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) evidencede 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]
Level 3 (low-level) evidencePapamitsou 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) evidenceBautista-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]
Level 1 (high-level) evidenceDiab 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) evidenceLowe 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]
Level 1 (high-level) evidenceCummings 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]