Research Article
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Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism

Year 2021, Volume 5, Issue 9, 974 - 977, 01.09.2021
https://doi.org/10.28982/josam.958297

Abstract

Background/Aim: Anti-epileptic drugs are long-term medications; thus, side-effects are frequently seen. An important but insufficiently known side-effect is the emergence of metabolic bone diseases. The mechanism of this entity is not clearly known, but it is usually seen with the use of cytochrome P450 enzyme-inducing anti-epileptics. However, recent studies demonstrated that non-enzyme-inducing molecules also cause bone mineral impairment. The aim of this study was to shed light on the pathogenesis of anti-epileptic metabolic bone disease using bone turnover markers. Methods: This comparative, prospective case-control study included 37 patients followed-up in our outpatient clinic and 39 healthy control subjects. All the patients were female, aged over 18 years and in the premenopausal period, and had received the same anti-epileptic treatment for at least 3 months. Male patients, females who were <18 years old, pregnant, in the postmenopausal period, those with osteoporosis, gastrointestinal malabsorption, physical impairment that may prevent normal ambulation, endocrine and metabolic disease, musculoskeletal and joint disease or a history of medication use were excluded from the study. A healthy control group was formed of age-matched premenopausal women, with no disorders causing gastrointestinal malabsorption, no physical impairment preventing normal ambulation, no endocrine or metabolic disorder, or history of medication use that may affect bone turnover. The levels of serum calcium, alkaline phosphatase, 25-hydroxyvitamin D, osteoprotegerin and bone-specific alkaline phosphatase were assessed, and the results were recorded. Results: Evaluation was made of 37 female epilepsy patients with a mean age of 30.8 (8.1) years and a healthy control group of 39 age- and body mass index-matched females (P=0.69, P=0.85, respectively). The mean duration of AED use was 6.1 (5.5) years. The calcium (P=0.09), phosphate (P=0.906) and alkaline phosphatase (P=0.22) levels were similar in both groups. The levels of 25-hydroxyvitamin D (P=0.049), osteoprotegerin (P=0.025), and bone- specific alkaline phosphatase (P=0.037) were significantly lo3wer in the epilepsy group. Conclusion: Our study showed that serum levels of osteoprotegerin and bone-specific alkaline phosphatase, which are markers of increased bone formation, were lower in epilepsy patients. Probably many factors cause the bone mineral disorder seen in epilepsy patients. Antiepileptic use is one of them. These results suggest that antiepileptics may not only affect enzyme induction but also bone turnover. Neurologists should be aware of this issue and monitor patients regularly with respect to bone mineralization to enable early treatment when necessary.

References

  • 1. Artemiadis AK, Lambrinoudaki I, Voskou P, Tsivgoulis G, Safouris A, Bougea A, et al. Preliminary evidence for gender effects of levetiracetam monotherapy duration on bone health of patients with epilepsy. Epilepsy Behav. 2016 Feb;55:84-6. doi: 10.1016/j.yebeh.2015.12.025. Epub 2016 Jan 13. PMID: 26773675.
  • 2. Reynolds EH. Introduction: epilepsy in the world. Epilepsia. 2002;43 Suppl 6:1-3. doi: 10.1046/j.1528-1157.43.s.6.1.x. PMID: 12190964.
  • 3. Shen C, Chen F, Zhang Y, Guo Y, Ding M. Association between use of antiepileptic drugs and fracture risk: a systematic review and meta-analysis. Bone. 2014 Jul;64:246-53. doi: 10.1016/j.bone.2014.04.018. Epub 2014 Apr 26. PMID: 24780876.
  • 4. Andress DL, Ozuna J, Tirschwell D, Grande L, Johnson M, Jacobson AF, et al. Antiepileptic drug-induced bone loss in young male patients who have seizures. Arch Neurol. 2002 May;59(5):781-6. doi: 10.1001/archneur.59.5.781. PMID: 12020260.
  • 5. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002 May 14;58(9):1348-53. doi: 10.1212/wnl.58.9.1348. PMID: 12011279.
  • 6. Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F .Increased bone turn over in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia 2002; 43:1488–92.doi:10.1046/j.1528-1157.2002.13002.x
  • 7. Mattson RH, Gidal BE. Fractures, epilepsy, and antiepileptic drugs. Epilepsy Behav. 2004 Feb;5 Suppl 2:S36-40. doi: 10.1016/j.yebeh.2003.11.030. PMID: 15123010.
  • 8. Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert Opin Drug Saf 2011; 10:265–80.doi:10.1517/14740338.2011.534455
  • 9. Sato Y, Kondo I, Ishida S,Motooka H, Takayama K, Tomita Y,et al. Decreased bone mass and increased bone turn over with valproate therapy in adults with epilepsy. Neurology 2001; 57:445–9.doi:10.1212/WNL.57.3.445
  • 10. Boluk A, Guzelipek M, Savli H, Temel I, Ozişik HI, Kaygusuz A. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004 Jul;50(1):93-7. doi: 10.1016/j.phrs.2003.11.011. PMID: 15082034.
  • 11. Singla S, Kaushal S, Arora S, Singh G. Bone Health in Patients with Epilepsy: A Community-based Pilot Nested Case-control Study. Ann Indian Acad Neurol. 2017 Oct-Dec;20(4):367-71. doi: 10.4103/aian.AIAN_216_17. PMID: 29184339; PMCID: PMC5682740.
  • 12. Hamed SA, Moussa MM, Youssef AH, El Hameed MAA and Nasr Eldin E. Bone status in patients with epilepsy: relationship to markers of bone remodeling. Frontiers in Neurology 2014 Aug;142(5):1-7. doi: 10.3389/fneur.2014.00142. PMID: 25136330
  • 13. Simko J, Karesova I, Kremlacek J, Fekete S, Zimcikova E, Malakova J, et al. The effect of lamotrigine and phenytoin on bone turnover and bone strength: A prospective study in Wistar rats. Epilepsy research 2016;128:113-8. https:77doi.org/10.1111/j.1528-1167.2007.01176.x
  • 14. Kostenuik PJ, Shalhoub V. Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des. 2001 May;7(8):613-35. doi: 10.2174/1381612013397807. PMID: 11375772.
  • 15. Masrour Roudsari J, Mahjoub S. Quantification and comparison of bone-specific alkaline phosphatase with two methods in normal and Paget’s specimens. Caspian J Intern Med. 2012 Summer;3(3):478-83. PMID: 24009918; PMCID: PMC3755844.
  • 16. Kir HM, Garip S, Sahin D, Öztaş B. Effects of carbamazepine on serum parathormone, 25- hydroxyvitamin D, bone specific alkaline phosphatase, C-telopeptide, and osteocalcin levels in healthy rats. Bosn J Basic Med Sci. 2012 Nov;12(4):240-4. doi: 10.17305/bjbms.2012.2445. PMID: 23198939; PMCID: PMC4362499.

Year 2021, Volume 5, Issue 9, 974 - 977, 01.09.2021
https://doi.org/10.28982/josam.958297

Abstract

References

  • 1. Artemiadis AK, Lambrinoudaki I, Voskou P, Tsivgoulis G, Safouris A, Bougea A, et al. Preliminary evidence for gender effects of levetiracetam monotherapy duration on bone health of patients with epilepsy. Epilepsy Behav. 2016 Feb;55:84-6. doi: 10.1016/j.yebeh.2015.12.025. Epub 2016 Jan 13. PMID: 26773675.
  • 2. Reynolds EH. Introduction: epilepsy in the world. Epilepsia. 2002;43 Suppl 6:1-3. doi: 10.1046/j.1528-1157.43.s.6.1.x. PMID: 12190964.
  • 3. Shen C, Chen F, Zhang Y, Guo Y, Ding M. Association between use of antiepileptic drugs and fracture risk: a systematic review and meta-analysis. Bone. 2014 Jul;64:246-53. doi: 10.1016/j.bone.2014.04.018. Epub 2014 Apr 26. PMID: 24780876.
  • 4. Andress DL, Ozuna J, Tirschwell D, Grande L, Johnson M, Jacobson AF, et al. Antiepileptic drug-induced bone loss in young male patients who have seizures. Arch Neurol. 2002 May;59(5):781-6. doi: 10.1001/archneur.59.5.781. PMID: 12020260.
  • 5. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002 May 14;58(9):1348-53. doi: 10.1212/wnl.58.9.1348. PMID: 12011279.
  • 6. Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F .Increased bone turn over in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia 2002; 43:1488–92.doi:10.1046/j.1528-1157.2002.13002.x
  • 7. Mattson RH, Gidal BE. Fractures, epilepsy, and antiepileptic drugs. Epilepsy Behav. 2004 Feb;5 Suppl 2:S36-40. doi: 10.1016/j.yebeh.2003.11.030. PMID: 15123010.
  • 8. Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert Opin Drug Saf 2011; 10:265–80.doi:10.1517/14740338.2011.534455
  • 9. Sato Y, Kondo I, Ishida S,Motooka H, Takayama K, Tomita Y,et al. Decreased bone mass and increased bone turn over with valproate therapy in adults with epilepsy. Neurology 2001; 57:445–9.doi:10.1212/WNL.57.3.445
  • 10. Boluk A, Guzelipek M, Savli H, Temel I, Ozişik HI, Kaygusuz A. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004 Jul;50(1):93-7. doi: 10.1016/j.phrs.2003.11.011. PMID: 15082034.
  • 11. Singla S, Kaushal S, Arora S, Singh G. Bone Health in Patients with Epilepsy: A Community-based Pilot Nested Case-control Study. Ann Indian Acad Neurol. 2017 Oct-Dec;20(4):367-71. doi: 10.4103/aian.AIAN_216_17. PMID: 29184339; PMCID: PMC5682740.
  • 12. Hamed SA, Moussa MM, Youssef AH, El Hameed MAA and Nasr Eldin E. Bone status in patients with epilepsy: relationship to markers of bone remodeling. Frontiers in Neurology 2014 Aug;142(5):1-7. doi: 10.3389/fneur.2014.00142. PMID: 25136330
  • 13. Simko J, Karesova I, Kremlacek J, Fekete S, Zimcikova E, Malakova J, et al. The effect of lamotrigine and phenytoin on bone turnover and bone strength: A prospective study in Wistar rats. Epilepsy research 2016;128:113-8. https:77doi.org/10.1111/j.1528-1167.2007.01176.x
  • 14. Kostenuik PJ, Shalhoub V. Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des. 2001 May;7(8):613-35. doi: 10.2174/1381612013397807. PMID: 11375772.
  • 15. Masrour Roudsari J, Mahjoub S. Quantification and comparison of bone-specific alkaline phosphatase with two methods in normal and Paget’s specimens. Caspian J Intern Med. 2012 Summer;3(3):478-83. PMID: 24009918; PMCID: PMC3755844.
  • 16. Kir HM, Garip S, Sahin D, Öztaş B. Effects of carbamazepine on serum parathormone, 25- hydroxyvitamin D, bone specific alkaline phosphatase, C-telopeptide, and osteocalcin levels in healthy rats. Bosn J Basic Med Sci. 2012 Nov;12(4):240-4. doi: 10.17305/bjbms.2012.2445. PMID: 23198939; PMCID: PMC4362499.

Details

Primary Language English
Subjects Clinical Neurology
Journal Section Research article
Authors

Buket TUĞAN YILDIZ (Primary Author)
Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi
0000-0001-6783-2336
Türkiye


Tuba Tülay KOCA
KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0002-4596-858X
Türkiye


Muhammed SEYİTHANOĞLU
KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0002-8027-7549
Türkiye


Duygun ALTINTAŞ AYKAN
KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0001-8224-4006
Türkiye

Publication Date September 1, 2021
Published in Issue Year 2021, Volume 5, Issue 9

Cite

Bibtex @research article { josam958297, journal = {Journal of Surgery and Medicine}, issn = {}, eissn = {2602-2079}, address = {jsurgmed@gmail.com}, publisher = {Fatih BAŞAK}, year = {2021}, volume = {5}, pages = {974 - 977}, doi = {10.28982/josam.958297}, title = {Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism}, key = {cite}, author = {Tuğan Yıldız, Buket and Koca, Tuba Tülay and Seyithanoğlu, Muhammed and Altıntaş Aykan, Duygun} }
APA Tuğan Yıldız, B. , Koca, T. T. , Seyithanoğlu, M. & Altıntaş Aykan, D. (2021). Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism . Journal of Surgery and Medicine , 5 (9) , 974-977 . DOI: 10.28982/josam.958297
MLA Tuğan Yıldız, B. , Koca, T. T. , Seyithanoğlu, M. , Altıntaş Aykan, D. "Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism" . Journal of Surgery and Medicine 5 (2021 ): 974-977 <http://jsurgmed.com/en/pub/issue/64812/958297>
Chicago Tuğan Yıldız, B. , Koca, T. T. , Seyithanoğlu, M. , Altıntaş Aykan, D. "Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism". Journal of Surgery and Medicine 5 (2021 ): 974-977
RIS TY - JOUR T1 - Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism AU - Buket Tuğan Yıldız , Tuba Tülay Koca , Muhammed Seyithanoğlu , Duygun Altıntaş Aykan Y1 - 2021 PY - 2021 N1 - doi: 10.28982/josam.958297 DO - 10.28982/josam.958297 T2 - Journal of Surgery and Medicine JF - Journal JO - JOR SP - 974 EP - 977 VL - 5 IS - 9 SN - -2602-2079 M3 - doi: 10.28982/josam.958297 UR - https://doi.org/10.28982/josam.958297 Y2 - 2021 ER -
EndNote %0 Journal of Surgery and Medicine Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism %A Buket Tuğan Yıldız , Tuba Tülay Koca , Muhammed Seyithanoğlu , Duygun Altıntaş Aykan %T Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism %D 2021 %J Journal of Surgery and Medicine %P -2602-2079 %V 5 %N 9 %R doi: 10.28982/josam.958297 %U 10.28982/josam.958297
ISNAD Tuğan Yıldız, Buket , Koca, Tuba Tülay , Seyithanoğlu, Muhammed , Altıntaş Aykan, Duygun . "Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism". Journal of Surgery and Medicine 5 / 9 (September 2021): 974-977 . https://doi.org/10.28982/josam.958297
AMA Tuğan Yıldız B. , Koca T. T. , Seyithanoğlu M. , Altıntaş Aykan D. Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism. J Surg Med. 2021; 5(9): 974-977.
Vancouver Tuğan Yıldız B. , Koca T. T. , Seyithanoğlu M. , Altıntaş Aykan D. Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism. Journal of Surgery and Medicine. 2021; 5(9): 974-977.
IEEE B. Tuğan Yıldız , T. T. Koca , M. Seyithanoğlu and D. Altıntaş Aykan , "Investigation of the effect of anti-epileptic drugs on bone metabolism using osteoprotegerin and bone-specific alkaline phosphatase: The direct effects of antiepileptic drugs on bone metabolism", Journal of Surgery and Medicine, vol. 5, no. 9, pp. 974-977, Sep. 2021, doi:10.28982/josam.958297

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