Fibrodysplasia ossificans progressiva – A rare genetic disorder and the role of Technetium-99m methylene diphosphonate bone scan

Objectives: Reports in the rhinology literature suggest that osteitis of the ethmoid bone may be responsible for refractory and/or recurrent sinusitis. If so, bone scanning technologies capable of detecting osteitis may be useful in diagnosing this condition and its response to treatment. The objective of this prospective cohort study was to determine the correlation of single photon emission computed tomography (SPECT) bone scintigraphy with the histopathology of the ethmoid bulla. Methods: Thirty-six patients with a diagnosis of chronic sinusitis who were scheduled to undergo sinus surgery underwent a presurgical SPECT bone scan using technetium 99m-methylene diphosphonate. All bone scans were done within 5 days of surgery. During the procedure, bone samples from the face of the ethmoid bulla were obtained and examined by a pathologist blinded to the bone scan result. In this study, histopathology consistent with osteitis was defined as a change from lamellar to woven bone. A positive bone scan was defined by the presence of increased radiotracer uptake in the ethmoid sinuses. Results: Thirty-two of the 36 patients had a positive bone scan on SPECT imaging, and 31 specimens demonstrated histopathologic bone changes consistent with osteitis, for a sensitivity of 93.9%. An additional 4 patients had a negative bone scan on SPECT imaging, and osteitis was identified in 2 of the 4. The specificity was 66.7%, and the positive predictive value was 96.9%. Conclusions: We found that SPECT bone scanning with technetium 99m-methylene diphosphonate is a highly sensitive test for identifying osteitis in patients with chronic rhinosinusitis. It may be a useful tool in the armamentarium of the otolaryngologist to better define this disease process.

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The role of Activin A in fibrodysplasia ossificans progressiva: a prominent mediator

Bioscience Reports ◽

10.1042/bsr20190377 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 3

Author(s):

Hui Lin ◽

Fuli Shi ◽

Jiayu Gao ◽

Ping Hua

Keyword(s):

Signaling Pathway ◽

Genetic Disorder ◽

Activin A ◽

Bmp Signaling ◽

The Body ◽

Fibrodysplasia Ossificans Progressiva ◽

Type I ◽

Heterotopic Bone ◽

Heterotopic Bone Formation

Abstract Heterotopic ossification (HO) is the aberrant formation of mature, lamellar bone in nonosseous tissue. Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder that causes progressive HO in the ligaments, tendons, and muscles throughout the body. FOP is attributed to an autosomal mutation in activin receptor-like kinase 2 (ALK2), a bone morphogenetic protein (BMP) type I receptor. Initial studies show that mutant ALK2 drives HO by constitutively activating the BMP signaling pathway. Recently, mutant ALK2 has been shown to transduce Smad1/5 signaling and enhance chondrogenesis, calcification in response to Activin A, which normally signals through Smad2/3 and inhibits BMP signaling pathway. Furthermore, Activin A induces heterotopic bone formation via mutant ALK2, while inhibition of Activin A blocks spontaneous and trauma-induced HO. In this manuscript, we describe the molecular mechanism of the causative gene ALK2 in FOP, mainly focusing on the prominent role of Activin A in HO. It reveals a potential strategy for prevention and treatment of FOP by inhibition of Activin A. Further studies are needed to explore the cellular and molecular mechanisms of Activin A in FOP in more detail.

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