Endocrine Abstracts

Case History: A 37 year-old gentlemen was referred to metabolic bone clinic due to recurrent recent fragility fractures. He had several fractures throughout childhood, and these had continued to occur into his adult life. He was blind in his left eye since birth. He felt that this had contributed to his fractures, due to falls. There had been no other previous major health problems. His brother had a similar eye condition. There were no other risk factors for osteoporosis. There was nothing of significance to find on examination.

Investigations & Results: DXA scan- Spine L1-L4 T-score −3.6, Left hip T-score −2.4. CTX 0.24 mcg/L (normal), P1NP 34 mcg/L (normal). Spine X-rays: T11 grade 1 fracture & T4 grade 2 fracture. No other secondary cause of low bone mass identified (normal levels of testosterone, parathyroid hormone, vitamin D, calcium, phosphate and coeliac antibodies)

Discussion: This is a case of a young man with seemingly unexplained fragility fractures and low bone mass. The clue to the aetiology for low bone mass was the gentleman’s hereditary eye condition. The eye problems are caused by a condition known as Familial Exudative Vitreoretinopathy (FEVR); a rare genetic disorder affecting retinal angiogenesis that can cause progressive visual loss. FEVR may be mediated by mutation in LRP5 coding for the LRP5 transmembrane receptor. LRP5 plays a key role, alongside Frizzled protein, in the Wnt signalling pathway, which has effects on cellular proliferation, adhesion and migration. Importantly, Wnt signalling is also known to regulate bone mass. Therefore, it is the defect in this pathway that is the common denominator for this gentleman’s blindness and bone problems. We speculate that upcoming new drugs that target Wnt signalling in osteoporosis, such as Romosuzumab (a Sclerostin inhibitor), may be particularly beneficial in patients with low bone mass associated with FEVR.