Methotrexate osteopathy in rheumatoid arthritis: A case from clinical practice
M. V. Kozyreva,
A. V. Sukhinina,
D. M. Kudinsky,
A. Yu. Feklistov,
T. A. Korotkova,
N. V. Toroptsova https://doi.org/10.47360/1995-4484-2026-208-213
Abstract
Methotrexate (МТX) is one of the most widely used medication as a basic anti-inflammatory therapy in the treatment of rheumatic diseases (RD). It is prescribed to rheumatological patients in doses not exceeding 25 mg per week. As it was used in clinical practice, data appeared on a possible side effect on bone tissue – osteopathy associated with its long-term use, which is rare in patients with RD. Methotrexate osteopathy is characterized by the presence of three signs: bone pain in weight-bearing limbs; atraumatic fractures localized in various bones of the lower extremities; the presence of osteoporosis on the X-ray image.
The article describes a case of osteopathy after long-term treatment with МТX in a postmenopausal patient with RA and osteoporosis who had multiple atraumatic stress fractures of both distal femurs, proximal and distal part of both tibias, as well as the talus of the left foot.
About the Authors
M. V. Kozyreva
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Maria V. Kozyreva
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
A. V. Sukhinina
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Anastasiia V. Sukhinina
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
D. M. Kudinsky
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Danil M. Kudinsky
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
A. Yu. Feklistov
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Alexey Yu. Feklistov
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
T. A. Korotkova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Tatiana A. Korotkova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
N. V. Toroptsova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Competing Interests:
Russian Federation
Natalia V. Toroptsova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
none
References
1. Ragab AH, Frech RS, Vietti TJ. Osteoporotic fractures secondary to methotrexate therapy of acute leukemia in remission. Cancer. 1970;25(3):580-585. doi: 10.1002/1097-0142(197003)25:3<580::aidcncr2820250313>3.0.co;2-m
2. Stanisavljevic S, Babcock AL. Fractures in children treated with methotrexate for leukemia. Clin Orthop Relat Res. 1977;(125):139-144.
3. Ansell G, Evans S, Jackson CT, Lewis-Jones S. Cytotoxic drugs for non-neoplastic disease. Br Med J (Clin Res Ed). 1983;287(6394):762. doi: 10.1136/bmj.287.6394.762-a
4. Semba CP, Mitchell MJ, Sartoris DJ, Resnick D. Multiple stress fractures in the hindfoot in rheumatoid arthritis. J Rheumatol. 1989;16(5):671-676.
5. Wijnands M, Burgers A. Stress fracture in long term methotrexate treatment for psoriatic arthritis. Ann Rheum Dis. 2001;60(8):736739. doi: 10.1136/ard.60.8.736
6. Singwe M, Le Gars L, Karneff A, Prier A, Kaplan G. Multiple stress fractures in a scleroderma patient on methotrexate therapy. Rev Rhum Engl Ed. 1998;65(7-9):508-510.
7. Rudler M, Pouchot J, Paycha F, Gentelle S, Grasland A, Vinceneux P. Low dose methotrexate osteopathy in a patient with polyarticular juvenile idiopathic arthritis. Ann Rheum Dis. 2003;62(6):588-589. doi: 10.1136/ard.62.6.588
8. Rolvien T, Creutzfeldt AM, Lohse AW, Amling M. Stress fractures in systemic lupus erythematosus after long-term МТ use successfully treated by МТ discontinuation and individualized bone-specific therapy. Lupus. 2019;28(6):790-793. doi: 10.1177/0961203319841434
9. Rolvien T, Jandl NM, Stürznickel J, Beil FT, Kötter I, Oheim R, et al. Clinical and radiological characterization of patients with immobilizing and progressive stress fractures in methotrexate osteopathy. Calcif Tissue Int. 2021;108(2):219-230. doi: 10.1007/s00223-020-00765-5
10. May KP, Mercill D, McDermott MT, West SG. The effect of methotrexate on mouse bone cells in culture. Arthritis Rheum. 1996;39(3):489-494. doi: 10.1002/art.1780390317
11. Olsen NJ, Spurlock CF 3rd, Aune TM. Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther. 2014;16(1):R17. doi: 10.1186/ar4444
12. Nowińska B, Cegieła U, Folwarczna J, Sliwiński L, Kaczmarczyk-Sedlak I, Pytlik M, et al. Effects of raloxifene on development of the methotrexate-induced changes in bone mechanical properties of male rats. Pharmacol Rep. 2007;59(3):359-364.
13. King TJ, Georgiou KR, Cool JC, Scherer MA, Ang ES, Foster BK, et al. Methotrexate chemotherapy promotes osteoclast formation in the long bone of rats via increased pro-inflammatory cytokines and enhanced NF-κB activation. Am J Pathol. 2012;181(1):121-129. doi: 10.1016/j.ajpath.2012.03.037
14. Stevens H, Jacobs JW, Van Rijk PP, De Klerk JM. Methotrexate osteopathy demonstrated by Technetium-99m HDP bone scintigraphy. Clin Nucl Med. 2001;26(5):389-391. doi: 10.1097/00003072200105000-00002
15. Robin F, Cadiou S, Albert JD, Bart G, Coiffier G, Guggenbuhl P. Methotrexate osteopathy: Five cases and systematic literature review. Osteoporos Int. 2021;32(2):225-232. doi: 10.1007/s00198-020-05664-x
16. Ruffer N, Krusche M, Beil FT, Amling M, Kötter I, Rolvien T. Clinical features of methotrexate osteopathy in rheumatic musculoskeletal disease: A systematic review. Semin Arthritis Rheum. 2022;52:151952. doi: 10.1016/j.semarthrit.2022.151952
17. von Brackel FN, Grambeck J, Barvencik F, Amling M, Oheim R. МТ osteopathy versus osteoporosis including response to treatment data – A retrospective single center study including 172 patients. Calcif Tissue Int. 2024;115(5):599-610. doi: 10.1007/s00223-02401290-5
18. Giusti A, Hamdy NA, Papapoulos SE. Bone. Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies. 2010;47(2):169-180. doi: 10.1016/j.bone.2010.05.019
19. Anderson PA, Kates SL, Watts NB. Update on atypical femoral fractures. J Bone Joint Surg Am. 2024;106(19):1819-1828. doi: 10.2106/JBJS.23.01439
20. Carbone L, Vasan S, Elam R, Gupta S, Tolaymat O, Crandall C, et al. The association of methotrexate, sulfasalazine, and hydroxychloroquine use with fracture in postmenopausal women with rheumatoid arthritis: Findings from the Women’s Health Initiative. JBMR Plus. 2020;4(10):e10393. doi: 10.1002/jbm4.10393
21. Hauser B, Merriman A, Foley J, Golla J, McRorie E, Ralston SH. Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures. Ann Rheum Dis. 2025;84(4):554-561. doi: 10.1016/j.ard.2025.01.047
22. Puvvada CS, Soomro FH, Osman HA, Haridi M, Gonzalez NA, Dayo SM, et al. Efficacy and safety of teriparatide in improving fracture healing and callus formation: A systematic review. Cureus. 2023;15(4):e37478. doi: 10.7759/cureus.37478
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For citations:
Kozyreva M.V., Sukhinina A.V., Kudinsky D.M., Feklistov A.Yu., Korotkova T.A., Toroptsova N.V. Methotrexate osteopathy in rheumatoid arthritis: A case from clinical practice. Rheumatology Science and Practice. 2026;64(2):208-213. (In Russ.) https://doi.org/10.47360/1995-4484-2026-208-213
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