P060 High bone mass in two unrelated patients with sitosterolaemia

Abstract Background/Aims Sitosterolaemia is an autosomal recessive condition, caused by mutations in ABCG5 or ABCG8, and resulting in impaired excretion of plant sterols (phytosterols). Patients typically present with premature complications of dyslipidaemia, as well as thrombocytopaenia, haemolytic anaemia and splenomegaly. Methods Here, we describe two cases of sitosterolaemia who presented with the novel finding of diffuse skeletal sclerosis. Results A 44-year-old South Asian male with a previous diagnosis of ankylosing spondylitis initially presented for biopsy of bilateral lower eyelid lesions. Anaesthetic evaluation revealed anaemia and thrombocytopaenia, prompting haematology referral. He underwent bone marrow trephine (inadequate sample) and aspirate, which showed no signs of malignancy but lipidic vacuolisation of the haematological progenitors. Cytogenetic microarray identified homozygous loss of 2p21, containing exons 5-11 of ABCG5, and plasma phytosterols were elevated, confirming the diagnosis of sitosterolaemia. Computed tomography (CT) identified splenomegaly, cholelithiasis, significant atheromatous disease of the abdominal aorta and symmetrical sclerosis of the axial skeleton, prompting referral to the metabolic bone disease clinic. He described back pain, but no other symptoms. Serum phosphate and vitamin D were low, and alkaline phosphatase was elevated, with normal calcium and parathyroid hormone, indicating a co-existent osteomalacia. Quantitative CT (QCT) bone density analysis revealed L1-3 average density of 197.69mg/cm3 (Z-score +1.55). Further investigations, including successful bone biopsy and bone turnover markers, are pending. A 60-year-old Caribbean female, with a background of HbC haemoglobinopathy, was under investigation over ten years ago for long-standing thrombocytopaenia, when CT identified splenomegaly, fatty liver disease and diffuse skeletal sclerosis. This prompted referrals to hepatology and the metabolic bone disease clinic. She reported headaches, skeletal pain and an inability to float in water. Bone marrow biopsy at this time found excessively thick cortices, with evidence of normally functioning osteoclasts and increased remodelling from osteoblasts, appearances consistent with a high bone mass disorder. Genetic studies carried out recently for investigation of her premature liver disease revealed a point mutation in ABCG8, and laboratory blood tests confirmed elevations in plasma phytosterols. A recent QCT bone density analysis demonstrated L1-3 spine density of 215.45mg/cm3 (Z-Score +4.20). Both patients have commenced ezetimibe for treatment of sitosterolaemia and intravenous bisphosphonate therapy for their arthralgia and skeletal sclerosis. Conclusion These two cases are the first describing an association between high bone mass and sitosterolaemia. Interestingly, sitosterol is a component of traditional Chinese medicine for bone disorders and increases in bone density following sitosterol treatment have been observed in vitro and in vivo. Taken together, these may suggest a link between elevated plasma phytosterols and increased bone mass, although the underlying mechanisms are unclear. High bone mass phenotypes have previously provided key insights into bone metabolism, and further investigation of this association may highlight new pathways for therapeutic intervention. Disclosure E.G. Palmer: None. I. Jawad: None. P. Flynn: None. M. Allison: None. K.E.S. Poole: None.