Literature DB >> 20226391

A review of the effect of anticonvulsant medications on bone mineral density and fracture risk.

Richard H Lee1, Kenneth W Lyles, Cathleen Colón-Emeric.   

Abstract

BACKGROUND: Osteoporosis and seizure disorders are common diagnoses in older adults and often occur concomitantly.
OBJECTIVE: The goal of this review was to discuss the current hypothesis for the pathogenesis of anticonvulsant-induced bone density loss and the evidence regarding the risk for osteoporosis and fractures in older individuals.
METHODS: A review of the literature was performed, searching in MEDLINE and CINAHL for articles published between 1990 and October 2009 with the following search terms: anticonvulsant OR antiepileptic; AND osteoporosis OR bone density OR fracture OR absorptiometry, photon. Studies within the pediatric population, cross-sectional studies, and studies whose results were published in a language other than English were excluded.
RESULTS: A search of the published literature yielded >300 results, of which 24 met the inclusion and exclusion criteria and were included in this review. Hepatic enzyme induction by certain anticonvulsant medications appears to contribute to increased metabolism of 25-hydroxyvitamin D to inactive metabolites, which results in metabolic bone disease. There is increasing evidence that anticonvulsant use is associated with a higher risk of osteoporosis and clinical fractures, especially among older agents such as phenobarbital, carbamazepine, phenytoin, and valproate. Several observational studies suggest a class effect among anticonvulsant agents, associated with clinically significant reductions in bone mineral density and fracture risk. The use of anticonvulsant medications increases the odds of fracture by 1.2 to 2.4 times. However, only 2 large-scale observational studies have specifically examined the risk among those aged >65 years. This review also identified a randomized controlled trial whose results suggest that supplementation with high-dose vitamin D may be associated with increased bone mineral density in patients taking anticonvulsant medications. However, no randomized controlled trials investigating therapeutic agents to prevent fracture in this population were identified. Consequently, there are no formal practice guidelines for the monitoring, prevention, and management of bone disease among those taking anticonvulsants.
CONCLUSIONS: Observational studies suggest an association between use of anticonvulsant medications, reduced bone mineral density, and increased fracture risk. Randomized clinical trials are needed to guide the management of bone disease among those who use anticonvulsants. Copyright 2010 Excerpta Medica Inc. All rights reserved. Published by EM Inc USA.. All rights reserved.

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Year:  2010        PMID: 20226391      PMCID: PMC3570810          DOI: 10.1016/j.amjopharm.2010.02.003

Source DB:  PubMed          Journal:  Am J Geriatr Pharmacother        ISSN: 1876-7761


  58 in total

Review 1.  Diagnosis and management of neuropathic pain.

Authors:  R Freynhagen; M I Bennett
Journal:  BMJ       Date:  2009-08-12

2.  Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy.

Authors:  P C Souverein; D J Webb; J G Weil; T P Van Staa; A C G Egberts
Journal:  Neurology       Date:  2006-05-09       Impact factor: 9.910

3.  Mortality after all major types of osteoporotic fracture in men and women: an observational study.

Authors:  J R Center; T V Nguyen; D Schneider; P N Sambrook; J A Eisman
Journal:  Lancet       Date:  1999-03-13       Impact factor: 79.321

4.  Bone density and antiepileptic drugs: a case-controlled study.

Authors:  L J Stephen; A R McLellan; J H Harrison; D Shapiro; M H Dominiczak; G J Sills; M J Brodie
Journal:  Seizure       Date:  1999-09       Impact factor: 3.184

5.  Risk of extremity fractures in adult outpatients with epilepsy.

Authors:  Hakan B I Persson; K A Alberts; B Y Farahmand; T Tomson
Journal:  Epilepsia       Date:  2002-07       Impact factor: 5.864

6.  Osteomalacia with long-term anticonvulsant therapy in epilepsy.

Authors:  C E Dent; A Richens; D J Rowe; T C Stamp
Journal:  Br Med J       Date:  1970-10-10

7.  Fractures and handicap in an adult population: A clinical study.

Authors:  Guillaume Chevrel; Anne Limouzin; Patrick Garnero; Caroline de Montalivet; Dominique Loubier
Journal:  Joint Bone Spine       Date:  2007-08-15       Impact factor: 4.929

8.  Reduced bone mass and increased bone turnover in postmenopausal women with epilepsy using antiepileptic drug monotherapy.

Authors:  Merete Alice Lyngstad-Brechan; Erik Taubøll; Karl Otto Nakken; Leif Gjerstad; Kristin Godang; Rune Jemtland; Jens Bollerslev
Journal:  Scand J Clin Lab Invest       Date:  2008       Impact factor: 1.713

9.  Prevalence of epilepsy in Rochester, Minnesota: 1940-1980.

Authors:  W A Hauser; J F Annegers; L T Kurland
Journal:  Epilepsia       Date:  1991 Jul-Aug       Impact factor: 5.864

10.  Effects of phenytoin and carbamazepine on calcium transport in Caco-2 cells.

Authors:  Melinda von Borstel Smith; Kristi Crofoot; Rosita Rodriguez-Proteau; Theresa M Filtz
Journal:  Toxicol In Vitro       Date:  2007-02-27       Impact factor: 3.500

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  39 in total

1.  Osteomalacia: a forgotten cause of fractures in the elderly.

Authors:  Z Rokan; W D Kealey
Journal:  BMJ Case Rep       Date:  2015-02-09

2.  Low vitamin D levels are common in patients with epilepsy.

Authors:  Diane L Teagarden; Kimford J Meador; David W Loring
Journal:  Epilepsy Res       Date:  2014-07-06       Impact factor: 3.045

Review 3.  Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis.

Authors:  Ying Zhang; Yu-xin Zheng; Jun-ming Zhu; Jian-min Zhang; Zhe Zheng
Journal:  J Zhejiang Univ Sci B       Date:  2015-07       Impact factor: 3.066

4.  Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial.

Authors:  Peter L Havens; Charles B Stephensen; Rohan Hazra; Patricia M Flynn; Craig M Wilson; Brandy Rutledge; James Bethel; Cynthia G Pan; Leslie R Woodhouse; Marta D Van Loan; Nancy Liu; Jorge Lujan-Zilbermann; Alyne Baker; Bill G Kapogiannis; Kathleen Mulligan
Journal:  Clin Infect Dis       Date:  2012-01-19       Impact factor: 9.079

5.  Research summit III proceedings on dosing in children with an injured brain or cerebral palsy: executive summary.

Authors:  Thubi H A Kolobe; Jennifer Braswell Christy; Mary E Gannotti; Jill C Heathcock; Diane L Damiano; Edward Taub; Michael J Majsak; Andrew M Gordon; Robyn K Fuchs; Margaret E O'Neil; Vincent J Caiozzo
Journal:  Phys Ther       Date:  2014-02-13

Review 6.  Adverse bone effects of medications used to treat non-skeletal disorders.

Authors:  N B Watts
Journal:  Osteoporos Int       Date:  2017-07-27       Impact factor: 4.507

Review 7.  Breast cancer survivorship: a comprehensive review of long-term medical issues and lifestyle recommendations.

Authors:  Balazs I Bodai; Phillip Tuso
Journal:  Perm J       Date:  2015

Review 8.  Vitamin D Metabolism and Guidelines for Vitamin D Supplementation.

Authors:  Indra Ramasamy
Journal:  Clin Biochem Rev       Date:  2020-12

9.  Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia.

Authors:  Zhican Wang; Yvonne S Lin; Leslie J Dickmann; Emma-Jane Poulton; David L Eaton; Johanna W Lampe; Danny D Shen; Connie L Davis; Margaret C Shuhart; Kenneth E Thummel
Journal:  J Bone Miner Res       Date:  2013-05       Impact factor: 6.741

Review 10.  Brains, bones, and aging: psychotropic medications and bone health among older adults.

Authors:  Monique J Brown; Briana Mezuk
Journal:  Curr Osteoporos Rep       Date:  2012-12       Impact factor: 5.096

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