Osteoporosis and Osteoporotic Fractures Problems Related to Proton Pump Inhibitors Prolonged Use
The potential negative impact on the bone with the development of osteoporosis and subsequent bone fractures is one of side effects of proton pump inhibitors administration which has been much discussed for the last decade. This review covers the latest data on the relationship between the prolonged use of proton pump inhibitors and increased risk of bone fractures. To date, three large case-control studies and one retrospective cohort study demonstrated that proton pump inhibitors treatment increases the relative risk of fractures from 1.15 (95% CI 1.10–1.20) to 1.92 (95% CI 1.16–3.18); risk of the side effect development was related to drug dose (rate of administration) and duration of exposure. New studies have further proved the existing evidence linking the use of proton pump inhibitors to development of osteoporosis. Thus, long-term use of proton pump inhibitors is recognized as an independent risk factor for osteoporotic fractures. Prolonged (more than 1 year) and high rate of administration of those drugs often results in the increased risk of fracture. However, the mechanisms of the influence remain unclear and are being studied intensively. The direct effect on the absorption of calcium or osteoblast or osteoclast function does not explain the mechanism of the effect. Suppression of the activity of vacuolar H+-ATPase during long-term treatment by high dose of proton pump inhibitors can be one of the disorders of bone metabolism mechanisms. In similar cases, such vital functions as phagocytic activity of white blood cells, bone resorption and acidification of urine can be affected. Malabsorption of vitamin B12, iron, magnesium and calcium caused by prolonged administration of proton pump inhibitors and leading to mineral deficiency might be another mechanism of osteoporosis and fractures. It is also assumed that the use of proton pump inhibitors can impede the efficiency of antiosteoporotic therapy, in particular effect of bisphosphonates thus, reducing the effectiveness of their antifracturing action. These findings suggest that physicians should better avoid the combination of proton pump inhibitors and oral bisphosphonates. Parenteral antiresorptive agents (ibandronate, zoledronic acid or denosumab) are preferable in cases of the initial pathology of the upper floors of the gastrointestinal tract or high risk for esophagitis. Currently, interaction between the intake of proton pump inhibitors and osteoporotic fractures has been identified, although the mechanisms of this association are not fully understood. Whether calcium supplements and vitamin D may reduce the risk of fractures is still unclear as well. Although an increased probability of fractures is not very high, there exists the risk of bone fractures, especially in patients who already have additional risk factors under the long and high rate of administration of proton pump inhibitors. Current studies emphasize the need for clear evidence to support this class of medicines prescription, since their long uncontrolled intake may contribute to the development of side effects, including osteoporosis and osteoporotic fractures.
Full Text:PDF (Русский)
Karateev A.E. Six knifes to the back of proton pump inhibitors. Nauchno-prakticheskaya revmatologiya. 2013; 51(3): 332–340. (Russian)
Adams A., Black M.H., Zhang J.L., et al. Proton-pump inhibitor use and hip fractures in men: a population-based case-control study. Ann Epidemiol 2014; 24:286–290; http://doi.org/10.1016/j.annepidem.2014.01.004.
Andersen B.N., Johansen P.B., Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr.Opin. Rheum. 2016; 28(4): 420-425. doi: 10.1097/BOR.0000000000000291.
Cea Soriano L, Ruigo´mez A, Johansson S, Garcı´a Rodrı´guez LA. Study of the association between hip fracture and acid-suppressive drug use in a UK primary care setting. Pharmacotherapy 2014; 34:570–581. doi: 10.1002/phar.1410.
de Vries F, van Staa TP, Leufkens HGM. Proton pump inhibitors, fracture risk and selection bias: three studies, same database, two answers. Osteopor Int. 2010; 22: 1641–1642. doi: 10.1007/s00198-010-1323-1.
Ding J., Heller D.A., Ahern F.M., Brown T.V. The Relationship between proton pump inhibitor adherence and fracture risk in the elderly. Calcif Tissue Int 2014; 94:597–607. doi: 10.1007/s00223-014-9855-6.
Freedberg D.E., Haynes K., Denburg M.R., et al. Use of proton pump inhibitors is associated with fractures in young adults: a population-based study. Osteopor Int 2015; 26:2501–2507; http://doi.org/10.1007/s00198-015-3168-0.
Gray S.L., LaCroix A.Z., Larso J., et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women. Arch Int Med. 2010; 170:765–771. doi: 10.1001/archinternmed.2010.94.
Graziani G., Badalamenti S., Como G., et al. Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload. Role of gastric acid secretion. Nephron. 2002; 91: 474–479. PMID:12119480
Graziani G., Como G., Badalamenti S., et al. Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects. Nephrol Dial Transplant. 1995;10:1376–1380. PMID: 8538929
Hansen K.E., Jones A.N., Lindstrom M.J. et al. Do Proton Pump Inhibitors Decrease Calcium Absorption? J Bone Miner Res. 2010; 25 (12): 2786–279. doi: 10.1002/jbmr.166.
Hardy P., Sechet A., Hottelart C., et al. Inhibition of gastric secretion by omeprazole and efficiency of calcium carbonate on the control of hyperphosphatemia in patients on chronic hemodialysis. Artif Organs. 1998;22:569–573. PMID: 9684693
Heidelbaugh J.J. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf. 2013; 4(3): 125–133. doi: 10.1177/2042098613482484
Hinson A.M., Wilkerson B.M., Rothman-Fitts I., et al. Hyperparathyroidism associated with long-term proton pump inhibitors independent of concurrent bisphosphonate therapy in elderly adults. J Am Geriatr Soc. 2015; 63:2070– 2073. doi: 10.1111/jgs.13661.
Insogma K.L. The effect of proton pump-inhibiting drugs on mineral metabolism. Am J Gastroenterol. 2009; 104, Suppl 2: S2-4. doi: 10.1038/ajg.2009.44.
Ito T., Jensen R.T. Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium. Curr Gastroenterol Rep. 2010; 12(6): 448–457. doi:10.1007/s11894-010-0141-0.
Jo Y., Park E., Ahn S.B., et al. A proton pump inhibitor’s effect on bone metabolism mediated by osteoclast action in old age: a prospective randomized study. Gut Liver. 2015; 9: 1–8. doi: 10.5009/gnl14135.
Lau Y., Ahmed N. Fracture risk and bone mineral density reduction associated with proton pump inhibitors. Pharmacotherapy 2012; 32: 67–79. doi: 10.1002/PHAR.1007.
Lewis J.R., Barre D., Zhu K. et al. Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study. J Bone Miner Res. 2014; 29(11): 2489-2497. doi: 10.1002/jbmr.2279
McCarthy D. M. Adverse effects of proton pump inhibitor drugs: clues and conclusions. Current Opinion in Gastroenterology. 2010; 26: 624–631. doi: 10.1097/MOG.0b013e32833ea9d9.
Moberg L.M.E., Nilsson P.M., Samsioe G., Borgfeldt C. Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study. Maturitas. 2014; 78:310–315. doi: 10.1016/j.maturitas.2014.05.019.
Ngamruengphong S., Leontiadis G., Radhi S. et al. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209–1218. doi: 10.1038/ajg.2011.113.
O’Connell M.B., Madden D.M., Murray A.M. et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am. J. Med. 2005; 118: 778–781. Doi: 10.1016/j.amjmed.2005.02.007
O'Neill L. W., Culpepper B. L., Galdo J.A. Long-term Consequences of Chronic Proton Pump Inhibitor Use. US Pharmacist. 2013; 38(12): 38-42.
Prause M., Seeliger C., Unger M., et al. Pantoprazole decreases cell viability and function of human osteoclasts. Mediators Inflamm. 2015; 2015: 413097. doi: 10.1155/2015/413097.
Prause M., Seeliger C., Unger M., et al. Pantoprazole increases cell viability and function of primary human osteoblasts in vitro. Injury. 2014; 45:1156–1164. doi: 10.1016/j.injury.2014.05.005.
Prieto-Alhambra D., Page`s-Castella` A., Wallace G., et al. Predictors of fracture while on treatment with oral bisphosphonates: a population-based cohort study. J Bone Miner Res. 2013; 29: 268–274. doi: 10.1002/jbmr.2011.
Ranchon F., Vantard N., Gouraud A. et al. Suspicion of drug-drug interaction between high-dose methotrexate and proton pump inhibitors: a case report – should the practice be changed? Chemotherapy 2011;57:225–229. doi: 10.1159/000327372.
Recker R.R. Calcium absorption and achlorhydria. N Engl J Med. 1985; 313: 70–73. PMID: 4000241
Roux C., Goldstein J., Zhou X. et al. Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors. Osteoporos Int. 2012; 23: 277–284. doi: 10.1007/s00198-011-1574-5.
Serfaty-Lacrosniere C., Wood R.J., Voytko D. et al. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J. Am. Coll. Nutr. 1995; 14: 364–368. PMID: 8568113
Suzuki M., Suzuki H., Hibi T. Proton pump inhibitors and gastritis. J Clin Biochem. Nutr. 2008;42:71–75. doi: 10.3164/jcbn.2008012.
Targownik L., Leslie W., Davison K. et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol. 2012; 107: 1361–1369. doi: 10.1038/ajg.2012.200.
Targownik L.E., Lix L.M., Leung S., Leslie W.D. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology 2010; 138: 896-904. DOI: http://dx.doi.org/10.1053/j.gastro.2009.11.014
Targownik L.E., Lix L.M., Metge C.J., Prior H.J., et al. Use of proton pump inhibitors and risk of osteoporotic fractures. CMAJ. 2008; 179:319–326. doi: 10.1503/cmaj.071330.
US Food and Drug Administration FDA (2010) Possible fracture risk with high dose, long-term use of proton pump inhibitors. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed 28 May 2010.
van der Hoorn M.M.C., Tett S.E., de Vries O.J., et al. The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: a prospective cohort study. Bone 2015; 81:1–23. doi: 10.1016/j.bone.2015.08.024.
Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006; 79:76–83. DOI: 10.1007/s00223-006-0021-7
Yang YX, Lewis JD, Epstein S, Metz DC, et al. Long-term proton pump inhibitor therapy and the risk of hip fracture. JAMA. 2006; 296:2947–2953. DOI: 10.1001/jama.296.24.2947
Yu E.W., Blackwell T., Ensrud K.E., et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008; 83: 251–259. doi: 10.1007/s00223-008-9170-1.
- There are currently no refbacks.
Copyright (c) 2016 TRAUMA
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2018