Phosphopenic osteomalacia of tumor genesis under mask of ankylosing spondylitis

Aim. To present a clinical case of osteomalacia associated with fibroblast growth factor-23-secreting tumor under the mask of ankylosing spondylitis (AS).

Materials and methods. Clinical observation of a 31-year-old patient with long-time diagnosis of AS is presented. Underestimation of back pain cause at the initial stage of diseaseled to an erroneous diagnosis of AS. A thorough assessment of the anamnesis, additional examination using modern imaging methods in combination with laboratory analysis (low blood phosphorus level, hyperphosphaturia, normal value of C-reactive protein, erythrocyte sedimentation rate, negative HLA-B27), made it possible to establish the correct diagnosis of “mesenchymal phosphaturic tumor of the left foot (surgical intervention dated 11.26.2020), secondary hypophosphatemic tumor-induced osteomalacia complicated by multiple bone fractures”, to carry out timely treatment with full recovery.

Results. The literature data on epidemiology, pathogenetic mechanisms, clinical manifestations and management approaches of tumor induced phosphopenic osteomalacia are presented. An algorithm for examining patients with suspected of this disease is described, taking into account the expression of somatostatin transmembrane receptors on the surface of a mesenchymal phosphaturic tumor.

Conclusion. One of the rarest causes of specific back pain is osteomalacia, which can be caused by various diseases, for example, a tumor secreting FGF23 The complexity of the diagnosis lies in the non-specificity of clinical manifestations – generalized myalgia and myopathy, ossalgia, pathological fractures, etc. Timely diagnosis and radical treatment makes it possible to achieve stable remission with complete leveling of symptoms, therefore surgical excision of the tumor is the “gold” standard of therapy.

1. Klimov L.V., Akarachkova E.S., Klimenko A.A. et al. Back pain in adults. Clinical guidelines. Moscow: Izd-e Mezhdunarodnogo obshchestva po izucheniyu i effektivnomu kontrolyu stressa i svyazannyh s nim rasstroystv,, 2024. (In Russ.).

2. Pravdyuk N.G., Shostak N.A., Novikova A.V. Back pain in young people: clinical and instrumental features considering long-term observations. Lechebnoe delo = Medical Business 2021;3:81–93. (In Russ.). DOI: 10.24412/2071-5315-2021-12363

3. Hurwitz E.L., Randhawa K., Yu H. et al. The Global Spine Care Initiative: a summary of the global burden of low back and neck pain studies. Eur Spine J 2018;27(6):796–801. DOI: 10.1016/S0140-6736(16)30970-9

4. Maher C., Underwood M., Buchbinder R. Non-specific low back pain. The Lancet 2017;389(10070):736–47. DOI: 10.1016/S0140-6736(16)30970-9

5. Bhatt A.A., Mathews S.S., Kumari A. et al. Tumour-induced osteomalacia. Hong Kong Med J 2014;20(4):350.e1–2. DOI: 10.12809/hkmj133981

6. Takashi Y., Kosako H., Sawatsubashi S. et al. Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation. Proc Natl Acad Sci USA 2019;116(23):11418–27. DOI: 10.1073/pnas.1815166116

7. Rhee Y., Bivi N., Farrow E. et al. Parathyroid hormone receptor signaling in osteocytes increases the expression of fibroblast growth factor-23 in vitro and in vivo. Bone 2011;49(4):636–43. DOI: 10.1016/j.bone.2011.06.025

8. Álvarez-Rivas N., Lugo-Rodríguez G., Maneiro J.R. et al. Tumorinduced osteomalacia: A systematic literature review. Bone Reports 2024;21:101772. DOI: 10.1016/j.bonr.2024.101772

9. Folpe A.L., Fanburg-Smith J.C., Billings S.D. et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004;28(1):1–30. DOI: 10.1097/00000478-200401000-00001.

10. Gronskaya S.A., Belaya Zh.E., Rozhinskaya L.Ya. et al. Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases. Problemy endokrinologii = Problems of Endocrinology 2023;69(5):25–38. (In Russ.). DOI: https://doi.org/10.14341/probl13221

11. Sieper J., Van Der Heijde D., Landewe R. et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Annals of the Rheumatic Diseases 2009;68(6):784–8. DOI: 10.1136/ard.2008.101501

12. Chong W.H., Molinolo A.A., Chen C.C. et al. Tumor-induced osteomalacia. Endocr Relat Cancer 2011;18(3):R53–77. DOI: 10.1530/ERC-11-0006

13. Hana T., Tanaka S., Nakatomi H. et al. Definitive surgical treatment of osteomalacia induced by skull base tumor and determination of the half-life of serum fibroblast growth factor 23. Endocr J 2017;64(10):1033–9. DOI: 10.1507/endocrj.EJ17-0177

14. Brandi M.L., Clunie G.P.R., Houillier P. et al. Challenges in the management of tumor-induced osteomalacia (TIO). Bone 2021;152:116064. DOI: 10.1016/j.bone.2021.116064

15. Jiang Y., Hou G., Cheng W. Performance of 68Ga-DOTA-SST PET/CT, octreoscan SPECT/CT and 18F-FDG PET/CT in the detection of culprit tumors causing osteomalacia: a meta-analysis. Nucl Med Commun 2020;41(4):370–6. DOI: 10.1097/MNM.0000000000001163

16. Gronskaia S.A., Belaya Zh.E., Melnichenko G.A. FGF23 tumor induced osteomalacia. Problemy endokrinologii = Problems of Endocrinology 2022;68(5):56–66. (In Russ.). DOI: 10.14341/probl13130

17. Minisola S., Fukumoto S., Xia W. et al. Tumorinduced osteomalacia: a comprehensive review. Endocr Rev 2023;44(2):323–53. DOI:10.1210/endrev/bnac026

18. Jiang Y., Li X., Huo L. et al. Consensus on clinical management of tumor-induced osteomalacia. Chin Med J (Engl) 2021;134(11): 1264–6. DOI: 10.1097/CM9.0000000000001448

19. Huang Q.L., Feig D.S., Blackstein M.E. Development of tertiary hyperparathyroidism after phosphate supplementation in oncogenic osteomalacia. J Endocrinol Investр 2000;23(4):263–7. DOI: 10.1007/BF03343720