The Focus on Increased Risk of Fractures in their Prolonged Use

DOI: 10.47026/2413-4864-2024-1-93-100

UDC: 615.065
BBC: 53.52

Trukhan D.I., Tarasova L.V., Stepashina T.E.

The Focus on Increased Risk of Fractures in their Prolonged Use

Keywords: proton pump inhibitors, drug safety, osteoporosis, hypocalcemia, hip fracture, wrist fracture, vertebral fracture

Proton pump inhibitors are the most effective drugs for the treatment of acid-dependent diseases. For a long time, proton pump inhibitors have been considered to be completely safe drugs both for short-term and long-term use. A number of modern clinical studies note that when prescribing proton pump inhibitors in high doses for a long time, the possibility of side effects should be taken into account. The purpose of the review is to study the effect of prolonged use of proton pump inhibitors on the condition of bone tissue and the risk of osteoporotic fractures. Materials and methods. A search was conducted in the PubMed and Scopus information databases for publications on the safety of using proton pump inhibitors, including sources published before December 1, 2023, with an emphasis on the influence of proton pump inhibitors on bone tissue and the possible risk of fractures. Results. According to numerous studies, prolonged use of proton pump inhibitors is associated with an increased risk of fractures of the hip, vertebrae and the wrist. An increased risk of fractures may be associated with hypergastrinemia and hypochlorhydria (due to inhibition of acid secretion by proton pump inhibitors), and electrolyte disorders (hypocalcemia). Conclusions. All the pros and cons of prescribing proton pump inhibitors in patients with a history of fractures associated with osteoporosis should be carefully considered. In the curation of comorbid/multimorbid patients, proton pump inhibitors should be used if medically required for as short duration as possible and at the minimum effective dose to relieve symptoms.

References

Lazebnik L.B., Tkachenkol E.I. et al. VI Natsional’nye rekomendatsii po diagnostike i lecheniyu kislotozavisimykh i assotsiirovannykh s Helicobacter pylori zabolevanii (VI Moskovskie soglasheniya) [VI National recommendations for the diagnosis and treatment of acid-dependent and Helicobacter pylori-associated diseases (VI Moscow Agreements)]. Eksperimental’naya i klinicheskaya gastroenterologiya, 2017, no. 2, pp. 3-–
Ivashkin V.T., Maev I.V. et al. Rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii po diagnostike i lecheniyu gastroezofageal’noi reflyuksnoi bolezni [Recommendations of the Russian Gastroenterological Association for the diagnosis and treatment of gastroesophageal reflux disease]. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii, 2020, no. 30(4), pp. 70–97. DOI: 10.22416/1382-4376-2020-30-4-70-97.
Tarasova L.V., Trukhan D.I. Lekarstvennaya bezopasnost’ v gastroenterologii [Drug safety in gastroenterology]. Eksperimental’naya i klinicheskaya gastroenterologiya, 2013, no. 4, pp. 81–
Trukhan D.I. Ratsional’naya farmakoterapiya v real’noi klinicheskoi praktike skvoz’ prizmu mul’timorbidnosti i lekarstvennoi bezopasnosti [Rational pharmacotherapy in real clinical practice through the prism of multimorbidity and drug safety]. Klinicheskii razbor v obshchei meditsine, 2020, no. 2, pp.29– DOI: 10.47407/kr2020.1.2.00015.
Trukhan D.I., Konshu N.V. Ratsional’naya farmakoterapiya v klinike vnutrennikh boleznei skvoz’ prizmu mul’timorbidnosti i lekarstvennoi bezopasnosti [Rational pharmacotherapy in the clinic of internal diseases through the prism of multimorbidity and drug safety]. Handbook of a polyclinic doctor, 2019, no. 2, pp. 10–18.
Al Ali H.S., Jabbar A.S., Neamah N.F., Ibrahim N.K. Long-Term Use of Omeprazole: Effect on Haematological and Biochemical Parameters. Acta Med Indones. 2022, vol. 54(4), pp. 585–
Arj A., Razavi Zade M. et al. Proton pump inhibitors use and change in bone mineral density. Int J Rheum Dis., 2016, vol. 19(9), pp. 864–868. DOI: 10.1111/1756-185X.12866.
Bhargavi V. Desai, Misbah N. Qadri, Bhavin A. Vyas. Proton pump inhibitors and osteoporosis risk: exploring the role of TRPM7 channel. Eur J Clin Pharmacol., 2022, vol. 78(1), pp.35– DOI: 10.1007/s00228-021-03237-3.
Cheng Z., Liu Y. et al. Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways. Mol Med., 2022, vol. 28(1), p. 21. DOI: 10.1186/s10020-022-00448-x.
Chinzon D., Domingues G., Tosetto N., Perrotti M. Safety of long-term proton pump inhibitors: facts and myths. Arq Gastroenterol. 2022, vol. 59(2), pp. 219–225 DOI: 10.1590/S0004-2803.202202000-40.
Freedberg D.E., Kim L.S., Yang Y.X. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017, vol. 152(4), pp. 706–715. DOI: 10.1053/j.gastro.2017.01.031.
Haastrup P.F., Jarbøl D.E. et al. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol. 2021, vol. 8, e000563. DOI: 10.1136/bmjgast-2020-000563.
Hussain M.S., Mazumder T. Long-term use of proton pump inhibitors adversely affects minerals and vitamin metabolism, bone turnover, bone mass, and bone strength. J Basic Clin Physiol Pharmacol., 2021, vol. 33(5), pp. 567–579. DOI: 10.1515/jbcpp-2021-0203.
Insogna K.L. The effect of proton pump-inhibiting drugs on mineral metabolism. Am J Gastroenterol., 2009, vol. 104(2), pp. S2–4. DOI: 10.1038/ajg.2009.44.
Kinoshita Y., Ishimura N., Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil., 2018, vol. 24, pp. 182–196. DOI: 10.5056/jnm18001.
Lespessailles E., Toumi H. Proton Pump Inhibitors and Bone Health: An Update Narrative Review. Int J Mol Sci., 2022, vol. 23(18), 10733. DOI: 10.3390/ijms231810733.
Liamis G., Milionis H.J., Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab., 2009, vol. 27(6), pp. 635–642. DOI: 10.1007/s00774-009-0119-x.
Lin S.M., Yang S.H., Liang C.C., Huang H.K. Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients: a population-based cohort study. Osteoporos Int., 2018, vol. 29(1), pp. 153–162. DOI: 10.1007/s00198-017-4262-2.
Liu J., Li X., Fan L. et al. Proton pump inhibitors therapy and risk of bone diseases: An update meta-analysis. Life Sci., 2019, vol. 218, pp. 213–223. DOI: 10.1016/j.lfs.2018.12.058.
Maideen N.M.P. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J., 2023, vol. 59(2), pp. 115–127. DOI: 10.4068/cmj.2023.59.2.115.
Makunts T., Cohen I.V., Awdishu L., Abagyan R. Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis. Sci Rep., 2019, vol. 9, 2282. DOI: 10.1038/s41598-019-39335-7.
Morris C., Pillans P. Proton pump inhibitor-associated hypomagnesaemia and hypocalcaemia. Aust Prescr., 2017, vol. 40(2), pp. 79–80. DOI: 10.18773/austprescr.2017.019.
Ngamruengphong S., Leontiadis G.I., Radhi S., et al. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol., 2011, vol. 106, pp. 1209–1218. DOI: 10.1038/ajg.2011.113.
Novotny M., Klimova B., Valis M. PPI Long Term Use: Risk of Neurological Adverse Events? Front Neurol., 2019, vol. 9, 1142. DOI: 10.3389/fneur.2018.01142.
Park J.H., Lee J., Yu S.Y. et al. Comparing proton pump inhibitors with histamin-2 receptor blockers regarding the risk of osteoporotic fractures: a nested case-control study of more than 350,000 Korean patients with GERD and peptic ulcer disease. BMC Geriatr., 2020, vol. 20(1), p. 407. DOI: 10.1186/s12877-020-01794-3.
Poly T.N., Islam M.M., Yang H.C. et. al. Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporos Int. 2019, vol. 30(1), pp. 103-114. DOI: 10.1007/s00198-018-4788-y.
Salvo E.M., Ferko N.C., Cash S.B. et al. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther., 2021, vol. 54(2), pp. 129–143. DOI: 10.1111/apt.16407.
Sobel R.E., Bate A., Marshall J. et al. Do FDA label changes work? Assessment of the 2010 class label change for proton pump inhibitors using the Sentinel System’s analytic tools // Pharmacoepidemiol Drug Saf., 2018, vol. 27(3), pp. 332–339. DOI: 10.1002/pds.4392.
Sugiyama T. Proton pump inhibitor use and fracture risk: an update of drug safety communication needed? Am J Gastroenterol., 2019, vol. 114, pp. 360–361. DOI: 10.14309/ajg.0000000000000053.
Tagboto S. Severe Electrolyte Disturbances Due to Proton Pump Inhibitor Therapy: An Underrecognized Problem with Potentially Severe Sequelae. Am J Case Rep., 2022, vol. 23, e936893. DOI: 10.12659/AJCR.936893.
Targownik L.E., Fisher D.A., Saini S.D. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterol., 2022, vol. 162, pp. 1334–1342. DOI: 10.1053/j.gas tro.2021.12.247.
Targownik L.E., Leslie W.D., Davison K.S. et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol., 2012, vol. 107(9), pp. 1361–1369. DOI: 10.1038/ajg.2012.200.
Thong B.K.S., Ima-Nirwana S., Chin K.Y. Proton pump inhibitors and fracture risk: a review of current evidence and mechanisms involved. Int J Environ Res Public Health., 2019, vol. 16, p. 1571. DOI: 10.3390/ijerph16091571.
Thurber K.M., Otto A.O., Stricker S.L. Proton pump inhibitors: Understanding the associated risks and benefits of long-term use. Am J Health Syst Pharm., 2023, vol. 80(8), pp. 487–494. DOI: 10.1093/ajhp/zxad009.
Yu E.W., Bauer S.R., Bain P.A., Bauer D.C. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med., 2011, vol. 124, pp. 519–526. DOI: 10.1016/amj med.2011.01.007.
Zhang X., Adebayo A.S., Wang D. et al. PPI-Induced Changes in Plasma Metabolite Levels Influence Total Hip Bone Mineral Density in a UK Cohort. J Bone Miner Res., 2023, vol. 38(2), pp. 326–334. DOI: 10.1002/jbmr.4754.
Zhou B., Huang Y., Li H. et al. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016, vol. 27, pp. 339–347. DOI: 10.1007/s00198-015-3365-x.

About authors

Trukhan Dmitry I.: Doctor of Medical Sciences, Professor, Department of Polyclinic Therapy and Internal Diseases, Omsk State Medical University, Russia, Omsk (dmitry_trukhan@mail.ru; ORCID: https://orcid.org/0000-0002-1597-1876)

Tarasova Larisa V.: Doctor of Medical Sciences, Head of the Department of Hospital Therapy, Chuvash State University, Russia, Cheboksary (tlarisagast18@mail.ru; ORCID: https://orcid.org/0000-0003-1496-0689)

Stepashina Tatyana E.: Senior Lecturer, Department of Hospital Therapy, Chuvash State University, Russia, Cheboksary (stepashina.t@mail.ru; )

Article link

Trukhan D.I., Tarasova L.V., Stepashina T.E. The Focus on Increased Risk of Fractures in their Prolonged Use [Electronic resource] // Acta medica Eurasica. – 2024. – №1. P. 93-100. – URL: https://acta-medica-eurasica.ru/en/single/2024/1/10/. DOI: 10.47026/2413-4864-2024-1-93-100.

Single article

Trukhan D.I., Tarasova L.V., Stepashina T.E.