Alendronate


Article Author:
Lyndie Wilkins Parker


Article Editor:
Charles Preuss


Editors In Chief:
Sherri Murrell


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Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
9/1/2019 11:03:40 PM

Indications

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 when 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 addition of alendronate therapy for 12 months provided no significant difference in bone turnover, bone mineral density, or prevalence of vertebral fractures. However, participants maintained on 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 first-line therapy is aggressive intravenous hydration, followed by calcitonin. Two to four days post calcitonin therapy initiation, zoledronic acid, or ibandronate should be administered. Zoledronic acid is preferable to alendronate due to 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 administration of alendronate along with 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]

Mechanism of Action

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 contributes to regulating mineral reabsorption and turnover. Alendronate differs from other bone-modifying supplements as it suppresses bone formation, but it does not modify bone mineral accrual in endocortical or intracortical bone.[11]

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

Administration

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: 5mg oral tablet once daily or 10 mg oral tablet once daily in women not undergoing hormone replacement therapy
  • Paget disease of the bone: 40mg/day oral tablet for 6 months
  • Pediatric patients: Safety and efficacy have not been established
  • Severe renal impairment: Dosing is 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 it is excreted in the milk of women who are lactating, use 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. It is recombinant due to the reduction in calcium-sparing effects, thus impacts serum calcium levels unfavorably. 

Adverse Effects

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.[12]

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.[13]

Contraindications

Contraindicaitons 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. Alendronate should be avoided in patients with hypocalcemia.[12]

Monitoring

Baseline levels 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 is needed if hypocalcemia risk is recurring. The dose should be decreased or therapy discontinued if hypocalcemia occurs during therapy. Magnesium and phosphorus require monitoring at regular intervals.[14]

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 therapy. Current recommendations suggest tailoring the drug holiday length to the individual patients. The average drug-holiday in low-risk patients is 3 to 5 years. It also bears mention that alendronate is an extremely safe drug, and the benefits of continued therapy often outweigh the benefits of a drug holiday.[15]

Toxicity

There are no known toxicities reported at this time.

Alendronate has no FDA box 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.[16]

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 physician, 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 there has been dental work carried out. Thus, the patient must receive education about this drug and the need to see a healthcare provider before any type of oral cavity procedure. Also, 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 or nurse. All patients on alendronate close monitoring for side effects, which can be serious; this is where nursing staff needs to be informed on the drug so they can counsel patients and make a direct inquiry about potential adverse effects, and notify the doctor of any issues.[17] Alendronate therapy requires interprofessional teamwork and coordination to ensure optimal patient outcomes. [Level V]


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Alendronate - Questions

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A 65-year-old female presents to discuss the results of her dual-energy x-ray absorptiometry (DEXA) bone scan. She has been postmenopausal for 7 years and denies any use of hormone replacement therapy. The DEXA bone scan T-score is -3.5. The patient indicates that she is interested in preserving bone-mineral density and she would prefer tablet therapy over an IV solution. What is the mechanism of action of the most appropriate drug?



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A fair-skinned 65-year-old woman, at risk for osteoporosis, is prescribed alendronate. What is the most reported side effect when taking a drug in this class of medications?



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Which of the following brand named drugs is effective in treating postmenopausal induced osteoporosis?



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A 65-year-old woman is following up with her primary care provider following a hemiarthroplasty for an intracapsular hip fracture. She is able to ambulate without any pain and is scheduled to undergo physical therapy this week. The provider orders a few standard tests and a dual-energy x-ray absorptiometry scan to assess bone health. Her report show calcium of 5.6 mEq/L, phosphate of 2.5 mEq/L and a T score less than -2.5 for the lumbar and wrist regions. In addition to dietary modification, she is started on a couple of different medications to improve her bone quality. She asks for counsel on the medication when she arrives to pick up the prescription. Which of the following is the most appropriate counseling point?



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A 65-year-old postmenopausal female presents for follow-up after a fall and subsequent distal radial fracture at a family barbeque 1 week ago. Emergency department (ED) labs demonstrate a calcium level of 5.6 mg/dL, vitamin D level of 50 nanograms/mL, and parathyroid level of 50 picograms/mL. The patient states she was given some fluids and medications in the ED but does not know what she was given. She currently takes enalapril and atorvastatin for blood pressure control and hypercholesterolemia. Which of the following is the best course of action if this patient's dual-energy x-ray absorptiometry (DEXA) scan T-score is -2.5?



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Which of the following is an appropriate indication for alendronate use?



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Which of the following is a risk factor for a rare but significant adverse effect of alendronate that can lead to severe ulcerations in some patients?



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What is the most common adverse effect of the first-line drug to treat osteoporosis in postmenopausal women?



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A 34-year-old male presents to his primary care provider complaining of bone pain and hearing loss. The patient states he feels as though his ears are plugged, and he cannot hear as well as he did 6-months ago. Lab values reveal an increased serum alkaline phosphatase, normal calcium, normal parathyroid hormone, and normal CBC. An x-ray reveals a mosaic pattern of woven and lamellar bone. What is the mechanism of action of the first line of therapy for this patient's diagnosis?



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Alendronate - References

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     [PubMed]
Compston J, Osteoporosis in inflammatory bowel disease. Gut. 2003 Jan     [PubMed]
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     [PubMed]
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     [PubMed]
Liens D,Delmas PD,Meunier PJ, Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet (London, England). 1994 Apr 16     [PubMed]
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     [PubMed]
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     [PubMed]
Mirrakhimov AE, Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. North American journal of medical sciences. 2015 Nov     [PubMed]
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     [PubMed]
Eghbali-Fatourechi G, Bisphosphonate therapy in pediatric patients. Journal of diabetes and metabolic disorders. 2014     [PubMed]
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     [PubMed]
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     [PubMed]
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     [PubMed]
Lowe CE,Depew WT,Vanner SJ,Paterson WG,Meddings JB, Upper gastrointestinal toxicity of alendronate. The American journal of gastroenterology. 2000 Mar     [PubMed]
Diab DL,Watts NB, Bisphosphonate drug holiday: who, when and how long. Therapeutic advances in musculoskeletal disease. 2013 Jun     [PubMed]
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. 2018 Apr 12     [PubMed]
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     [PubMed]

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