zoledronate (Zometa, Reclast)
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Indications
- hypercalcemia of malignancy (treatment of choice)[20]
- osteoporosis (quarterly-yearly)*
- secondary prevention of hip fracture[9]
- increase in bone mineral density at the lumbar spine & femoral neck[13]
- osteolytic bone lesions of multiple myeloma[16]
- Paget's disease of bone[5]
* yearly IV zoledronate generally approved by Medicare only if contraindications to oral bisphosphates (dysphagia, esophageal stricture, GERD requiring daily PPI)[20]
* zoledronate administered at baseline in early postmenopausal women (age 50-60 years) & 5 years later was effective in preventing morphometric vertebral fracture at 10 years[27]
Contraindications
- creatinine clearance < 35 ml/min
- renal failure or worsening renal function*
- radiographic evidence of tooth abscess[25]
- vitamin D deficiency (osteoporosis)
* see notes
Benefit/risk
- 1 dose of IV zoledronate in frail elderly women in nursing homes or assisted living with osteoporosis[18]
- improves bone mineral density
- non-significant increase in bone fractures & mortality
- lowers risk for fragility fractures in postmenopausal women with osteopenia ((22 vs 39 per 1000 person-years)[23]
- NNT: 15 women for 6 years to prevent one fragility fracture
- zoledronate every other year reduced overall fractures in elderly women, but not hip fractures[23]
Dosage
- 0.25-5 mg IV, given over 15 minutes
- osteoporosis: 4-5 mg/year divided quarterly to yearly
- duration of therapy 3 years for most patients[15]
- reassess fracture risk after 3 years*
- risk of vertebral fracture may be diminished with therapy continued longer than 3 years[15]
- Paget's disease: 5 mg IV once, every 6 months?[5]
* dental examination prior to administration
* correct vitamin D deficiency prior to administration for osteoporosis
* risk for subsequent osteoporotic fracture during the following 3 years is low if Z score > -2.5, no recent fracture & no more than 1 risk factor[17]
Dosage adjustment in renal failure
- monitor serum creatinine before each dose[3]
- measure serum cystatin C/creatine ratio if frailty/sarcopenia (not directly affected by muscle mass)
| eGFR | Dosage |
|---|---|
| > 60 mL/min | 4.0 mg |
| 55-60 mL/min | 3.5 mg |
| 40-49 mL/min | 3.3 mg |
| 35-39 mL/min | 3.0 mg |
Pharmacokinetics
- eliminated in the urine
Adverse effects
- nausea
- myalgia
- fever
- osteonecrosis of the jaw*
- serious atrial fibrillation (1%)[8]
- reports of acute renal failure[12][14]
- transient hypocalcemia may occur, treat vitamin D deficiency
- pyrexia & myalgias may occur after the 1st dose, but does not usually recur[26]
*dental consultation
- no active oral infection
- biannual dental care for
- teeth cleaning
- minizing periodontal inflammation
- addressing caries
- endodontic care for non restorable teeth
Mechanism of action
- inhibits bone resorption
- may reduce bone pain & fractures in patients with bone metastases
- more effective than pamidronate
- as effective as residronate[11]
- diminishes risk of hip fractures, vertebral fractures & other factures[19]
Notes
- cost $1000/dose 2007
- GRS9 describes 69 yo man with weight loss of 9 kg due to lung cancer with hypercalcemia of malignancy, serum creatinine of 1.9 mg/dL, no weight given; if his weight was 60 kg (132 lbs) calculated creatinine clearance would be 31 mL/min & zoledronate would be contraindicated according to the standard above; yet zoledronate was recommended (GRS9)[20]
More general terms
Additional terms
References
- ↑ Prescriber's Letter 8(9):53 2001
- ↑ Journal Watch 22(7):53, 2002 Reid et al, N Engl J Med 346:653, 2002
- ↑ Jump up to: 3.0 3.1 FDA Safteywatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Zometa
- ↑ FDA Safteywatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#zometa2
- ↑ Jump up to: 5.0 5.1 5.2 Reid IR et al, Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med 2005 Sep 1; 353:898-908 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16135834
- ↑ Prescriber's Letter 14(6): 2007 New Developments With Bisphosphonate Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230613&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 14(9): 2007 Once-yearly Osteoporosis Treatment and Other Bisphosphonate Developments PATIENT HANDOUT: Bisphosphonates and Jaw Bone Damage INFORMATION FOR DENTISTS: American Dental Association recommendations for patients taking oral bisphosphonates RECLAST FOR OSTEOPOROSIS Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230902&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 8.0 8.1 Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17476007
- ↑ Jump up to: 9.0 9.1 Lyles KW et al, Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007 357:[ePub] http://dx.doi.org/10.1056/NEJMoa74941 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17878149
- ↑ Prescriber's Letter 14(11): 2007 Zoledronic Acid (Reclast) After an Initial Hip Fracture Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=231114&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 11.0 11.1 Reid DM et al, Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial Lancet 2009 373:1253-1263, 11 April 2009 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19362675
- ↑ Jump up to: 12.0 12.1 FDA Drug Safety Newsletter - Volume 2, Number 2, 2009 http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm167843.htm
- ↑ Jump up to: 13.0 13.1 McClung M et al. Zoledronic acid for the prevention of bone loss in postmenopausal women with low bone mass: A randomized controlled trial. Obstet Gynecol 2009 Nov; 114:999. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20168099
- ↑ Jump up to: 14.0 14.1 FDA MedWatch 09/01/11 Reclast (zoledronic acid): Drug Safety Communication - New Contraindication and Updated Warning on Kidney Impairment http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270464.htm
- ↑ Jump up to: 15.0 15.1 15.2 Whitaker M et al Bisphosphonates for Osteoporosis - Where Do We Go from Here? N Engl J Med 2012 May 9, <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22571168 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1202619
Black DM et al Continuing Bisphosphonate Treatment for Osteoporosis - For Whom and for How Long? N Engl J Med 2012 May 9, <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22571169 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1202623 - ↑ Jump up to: 16.0 16.1 Deprecated Reference
- ↑ Jump up to: 17.0 17.1 Cosman F et al. Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: When is it reasonable to discontinue treatment? J Clin Endocrinol Metab 2014 Dec; 99:4546 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25215556
- ↑ Jump up to: 18.0 18.1 Greenspan SL et al Efficacy and Safety of Single-Dose Zoledronic Acid for Osteoporosis in Frail Elderly WomenA Randomized Clinical Trial. JAMA Intern Med. Published online April 13, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25867538 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2247163
Lindsay R Osteoporosis Treatment and Fracture Outcomes. JAMA Intern Med. Published online April 13, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25866943 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2247159 - ↑ Jump up to: 19.0 19.1 Reid IR Efficacy, effectiveness and side effects of medications used to prevent fractures. J Intern Med. 2015 Jun;277(6):690-706 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25495429
- ↑ Jump up to: 20.0 20.1 20.2 20.3 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
- ↑ Maricic M. Intravenous zoledronic acid: what are the indications for male osteoporosis? Curr Osteoporos Rep. 2010 Mar;8(1):4-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20425084
- ↑ Maricic M. The role of zoledronic acid in the management of osteoporosis. Clin Rheumatol. 2010 Oct;29(10):1079-84. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20544246
- ↑ Jump up to: 23.0 23.1 23.2 Reid IR, Horne AM, Mihov B et al Fracture Prevention with Zoledronate in Older Women with Osteopenia. N Engl J Med 2018;379:2407-2416. Oct 1, 2018 Not indexed in PubMed. Published Online. https://www.nejm.org/doi/full/10.1056/NEJMoa1808082
Rosen CJ A Not-So-New Treatment for Old Bones. N Engl J Med. Oct 1, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30273092 DOI: Free full text https://www.nejm.org/doi/full/10.1056/NEJMe1812434 - ↑ Kaur U, Chakrabarti SS, Gambhir IS. Zoledronate Induced Hypocalcemia and Hypophosphatemia in Osteoporosis: A Cause of Concern. Curr Drug Saf. 2016;11(3):267-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27113952
- ↑ Jump up to: 25.0 25.1 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ Jump up to: 26.0 26.1 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
- ↑ Jump up to: 27.0 27.1 Bolland MJ, Nisa Z, Mellar A et al Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. N Engl J Med. 2025 Jan 16;392(3):239-248. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39813642 Clinical Trial. https://www.nejm.org/doi/full/10.1056/NEJMoa2407031