Familial expansile osteolysis (FEO)

(OMIM phenotype number #174810)

Familial expansile osteolysis (FEO) is an extremely rare, autosomal dominant, bone dysplasia. Clinical manifestations include: early-onset deafness, tooth loss and progressive lytic expansion within several limb bones causing bone pain, deformity, and fracture, associated with high serum alkaline phosphatase (ALP) and urinary hydroxyproline (Ur OHP) concentrations. Initially, the focal skeletal defects have an active osteolytic phase, similar to Paget disease of bone, but evolve to expanded, shell-like bones that are fat filled. In osteoclasts from affected bone by FEO have been identified nuclear inclusion bodies identical to those found in PDB. Bone lesions have been observed mostly in the lower leg, forearm, hand and foot bones but rarely in the axial skeleton.

The management for FEO is unclear, but inhibitors of osteoclastic bone resorption (bisphosphonates and calcitonin), are effective at reducing biochemical markers of disease activity and improving bone pain. It has not yet been described whether bisphosphonate therapy alters natural history of the disease or prevents complications.


TNFRSF11A gene, 18q21.33 (OMIM gene/locus number #603499), encoding receptor activator of NFkB (RANK), which binds RANK ligand. RANK and RANKL (RANK ligand) have a fundamental physiological role in the regulation of osteoclast differentiation.


Deafness and loss of dentition, focal skeletal changes, with predominantly peripheral distribution, progressive osteoclastic resorption accompanied by medullary expansion led to severe, painful, disabling deformity and a tendency to pathologic fracture.

Main biochemical alterations

High ALP, high Ur OHP, possible high Ca.


  1. Ralston SH. Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):101-11.
  2. Whyte MP, Reinus WR, Podgornik MN, et al. Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred. Medicine (Baltimore). 2002 Mar;81(2):101-21.
  3. Hughes AE, Ralston SH, Marken J, et al. Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.Nat Genet. 2000 Jan;24(1):45-8.
  4. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  5. http://www.omim.org