Tumorinduzierte Osteomalazie, verursacht durch ein FGF23-sezernierendes Myoperizytom

Literaturübersicht und Fallbericht

Tumor-induced osteomalacia caused by an FGF23-secreting myopericytoma

Case report and literature review

Zusammenfassung

Hintergrund

Die Symptome Muskelschwäche, Knochenschmerzen und Insuffizienzfrakturen können ein Hinweis auf eine Osteomalazie sein. Phosphat wird als osteologischer Parameter häufig nicht berücksichtigt und erniedrigte Werte daher übersehen. Die zusätzliche Untersuchung von FGF23 („fibroblast growth factor“ 23) als Nachweis eines osteomalazieinduzierenden Tumors ist noch überwiegend unbekannt.

Ziele der Arbeit

Die Schlüsselrolle von Phosphat und darüber hinaus von FGF23 im Knochenstoffwechsel soll durch den langjährigen Verlauf unseres klinischen Falls veranschaulicht und einem breiteren Publikum vorgestellt werden.

Methoden

Wir führten eine Literaturrecherche via PubMed und Google Scholar mit den relevanten Schlüsselwörtern durch und fassten die diagnostischen und therapeutischen Informationen zusammen. Die untersuchten Studien waren überwiegend Einzelfallberichte. Wir erstellten einen Fallbericht einer 70-jährigen Patientin mit tumorinduzierter Osteomalazie (TIO) durch ein Myoperizytom und untersuchten retrospektiv den klinischen Fall. Das Follow-up betrug 6 Monate.

Ergebnis

Die Literaturrecherche ergab unter 124 Fällen von Myoperizytomen einen mit TIO und Nachweis von FGF23. Es sind über 300 Fälle von TIO dokumentiert. Bei unserem klinischen Fall fanden wir retrospektiv ein FGF23-sezernierendes Myoperizytom aus der Gruppe der phosphaturischen mesenchymalen Tumoren (PMT) als Ursache einer Humerusschaftpseudarthose rechts und zunehmender Bewegungseinschränkung bei einer Patientin mit unerkannter TIO. Nach chirurgischer Resektion des Tumors wurde die Patientin wieder mobil, die osteologischen Parameter, insbesondere des Phosphats, normalisierten sich von 0,21 auf 1,52 mmol/l.

Schlussfolgerung

Erniedrigte Phosphatwerte sind in unserem Fall der entscheidende Hinweis auf eine TIO. Im Umkehrschluss sollte bei einer Osteomalazie immer an eine Phosphatkontrolle gedacht werden. Eine Hypophosphatämie und Hyperphosphaturie sollten frühzeitig erkannt und diagnostisch abgeklärt werden. Die Untersuchung von FGF23 (C-terminales Fragment und intaktes FGF23) ist zu erwägen.

Abstract

Background

The symptoms of muscle weakness, bone pain and fragility fractures can be an indication of osteomalacia. Phosphate is often not considered within osteologic parameters, decreased levels are therefore easily overseen. The additional test for fibroblast growth factor 23 (FGF23) as indicator for tumor-induced osteomalacia (TIO) is still largely unfamiliar.

Objective

By emphasizing the role of phosphate and furthermore FGF23 in bone metabolism illustrated by the long-term disease process of our clinical case we would like to introduce these parameters to a broader public.

Methods

We performed a literature search via PubMed and Google Scholar with the relevant key words and summarized the diagnostic and therapeutic information. The studies evaluated were mainly case reports. We present a case report of a 70-year-old patient with TIO and a myopericytoma and retrospectively analyzed the clinical case. The follow-up was 6 months.

Results

Our literature search found one case of TIO and evidence of FGF23 among 124 cases of myopericytomas in total. Over 300 cases of TIO are reported. In our case, we retrospectively found an FGF23-secreting myopericytoma in the phosphaturic mesenchymal tumors (PMT) group to be the cause of pseudarthrosis on the right humerus shaft and increasing disablement in a patient with osteomalacia. After surgical resection the patient was mobile again, and the osteologic parameters, especially phosphate, normalized from 0.21 to 1.52 mmol/l.

Conclusion

Low phosphate levels are the decisive indication of TIO in our case. Therefore, we should always think of phosphate level control when dealing with osteomalacia. A hypophosphatemia and hyperphosphaturia should be recognized in time and be diagnostically verified. The additional FGF23 test (c-terminal and intact FGF23) should be considered.

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Abbreviations

ADHR:

Autosomal-dominante hypophosphatämische Rachitis

cFGF23:

c-terminales Fragment

CT:

Computertomographie

DOTATATE:

Dota-[Tyr3]-Octreotat

DVO:

Dachverband Osteologie

DXA:

Dual-Röntgen-Absorptiometrie

ELISA:

„Enzyme-linked immunosorbent assay“

ERG:

„Ets related gene“

FDG:

Fluordesoxyglukose

FGF23:

„Fibroblast growth factor 23“

FGFR1:

„Fibroblast growth factor receptor 1“

iFGF23:

Intaktes FGF23

ISH:

In-situ-Hybridisierung

Ki67-Färbung:

Immunhistologischer Marker

MRT:

Magnetresonanztomographie

PET:

Positronenemissionstomographie

PMT:

Phosphaturischer mesenchymaler Tumor

PTH:

Parathormon

RNA:

Ribonukleinsäure

RT-PCR:

Reverse-Transkriptase-Polymerase-Kettenreaktion

SATB2:

„Special AT-rich sequence-binding protein 2“

SPECT:

„Single photon emission computed tomography“

TIO:

Tumorinduzierte Osteomalazie

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Fälle onkogener Osteomalazie ab 1990 und Fälle von Myoperizytomen: NA not available, DOD deceased of disease [17,18,19, 22, 25, 30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111].

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Muro Bushart, N., Tharun, L., Oheim, R. et al. Tumorinduzierte Osteomalazie, verursacht durch ein FGF23-sezernierendes Myoperizytom. Orthopäde 49, 1–9 (2020). https://doi.org/10.1007/s00132-019-03719-4

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Schlüsselwörter

  • Knochenerweichung
  • Fibroblast growth factor 23, human
  • Hypophosphatämie
  • Neoplasie
  • Phosphat

Keywords

  • Adult rickets
  • Fibroblast growth factor 23, human
  • Hypophosphatemia
  • Neoplasia
  • Phosphate