This site is intended for US Healthcare Professionals only.
This site is intended for US Healthcare Professionals only.
smads activation

Activation of Smads ultimately resulting in BMP signaling

Activation of Smads 

Intracellular protein messengers, called Smads are activated by the addition of a phosphate group, and form complexes that deliver BMP signaling to the cell nucleus.

Bone formation 

The activated Smads regulate gene expression so the recruitment of stem cells are misdirected to differentiate into cartilage which is replaced by heterotopic bone.

bone formation

Cartilage is replaced by heterotypic bone

bone formation

Here’s what happens in FOP to case heterotopic ossification (HO)

Bone Formation Where It Doesn’t Belong

A genetic mutation causes excessive BMP signaling

The mutation allows the receptor to become more active, especially when bounded by ligands such as BMPs or Activins.

FOP Disease Progression and Pathology

There is a typical pattern of bone formation in FOP, in which heterotopic ossification (HO) is usually seen first in the dorsal, axial, cranial and proximal regions of the body and later in the ventral, appendicular, caudal, and distal regions.1 The episodic timing of HO formation and when ankylosis may occur varies among patients.2

Disease progression

FOP can have severe, disabling and life-shortening consequences,3 with the main causes of death being cardio-respiratory failure, pneumonia, and falls.3 Those consequences include:

  • Loss of mobility resulting from heterotopic ossification which often occurs after a flare-up
  • Progressive worsening of cardio-pulmonary function due to thoracic insufficiency syndrome and severe restrictive lung disease4
  • Malnutrition due to ankylosis of the jaw (which can be triggered especially after dental work is performed, due to overstretching of the jaw)5
  • Shortened lifespan (median age of death 40 years, range 3-77 years)3

Heterotopic bone formation in FOP is usually preceded by a flare-up, is episodic and unpredictable, with disability cumulative and permanent.

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Please always consult a healthcare professional if you require healthcare advice or if you have any specific concerns regarding Fibrodysplasia Ossificans Progressiva. The information provided here is not intended to replace professional advice. This website has been developed by Ipsen in collaboration with those living with Fibrodysplasia Ossificans Progressiva and the healthcare professionals who care for them. Ipsen would like to thank everyone for their valuable insights and stories. All names used on this website are not necessarily real names. Visit our website for more information about us, or to contact us directly. Website design and development by Kanga Health Ltd. Website reference NON-US-002031 December 2020