Endocrine Abstracts

Some hematologic malignancies might increase the risk of fractures due to intrinsic factors of the disease but also because of the treatment with steroids or chemotherapy. The direct impact of novel targeted agents on the development of osteoporosis in these patients has not been recognized yet. A 64-years old female patient with B-cell chronic lymphocytic leukemia (B-CLL) has been followed for four years with no other comorbidities. In order to measure the burden of the disease consecutive CT scans were performed. Two years ago, she underwent endocrinological evaluation because of incidental adrenal adenoma. Hypercortisolism and other endocrine disorders were excluded. She has never experienced a bone fracture before and no radiographic vertebral fractures were present. According to Fracture Risk Assessment Tool her 10 years probability of fractures with bone mineral density and adjusted for trabecular bone score was 5.2% for major osteoporotic fracture and 0.7% for hip fracture. Her B-CLL progressed with lymph nodes enlargement and first line therapy with ibrutinib – bruton tyrosine kinase (Btk) inhibitor was started. Three months later the patient presented with severe lumbar pain that occurred suddenly without clear precipitating factor. Radiologic examinations were performed and multiple osteoporotic lumbar vertebral fractures were found (Genant′s grade 2 in L2 vertebra and grade 1 in L1, L3 and L4 vertebrae). We repeated endocrinological investigation. Vitamin D was reduced (44 nmol/l) but no evident secondary causes of osteoporosis were revealed. Her bone mineral density was significantly deteriorated. We deferred vertebroplasty and the treatment with teriparatide and cholecalciferol was introduced. Increased risk of axial fractures was already observed in B-CLL patients and infiltration of bone marrow with leukemic cells has been recently shown to impair osteoblastogenesis and promote osteoclastogenesis. Ibrutinib up to now has not been labeled as a drug that could significantly impair bone health. Early experimental studies suggested that it could even inhibit osteoclast differentiation and function. However, recent observations recorded signals of potential increase of fractures with ibrutinib therapy. Although no cause and effect could be claimed, the occurrence of multiple osteoporotic vertebral fractures shortly after the ibrutinib therapy was introduced, suggests that this might play a role in bone damage and warrants further studies.