BackgroundPatients with rheumatoid arthritis (RA) receiving glucocorticoids develop particularly severe bone fragility accompanied with high risk factors for fragility fractures1,2. Although bisphosphonate is recommended for treatment of osteoporosis related RA and glucocorticoid-induced-osteoporosis3, there are more frequently fractures than expected from bone mineral density based prediction even after used bisphosphonate.ObjectivesTo clarify the pathological mechanisms of bone fragility of these RA patients, we investigated bone biopsy samples obtained from RA and normal postmenopausal patients.MethodsWe examined 10 female postmenopausal RA patients receiving glucocorticoid and bisphosphonate therapy (RA group) and 10 age-matched female patients with postmenopausal osteoporosis (Ctl group) selected from patients who required autologous iliac bone grafts. Analyses of clinical data, bone mineral density, serum metabolic markers, bone quality and material mechanical property of biopsy sample were performed.ResultsAlthough bone mineral density didn't show significant differences, RA group had significantly higher score of fracture risk assessment tool (FRAX), number and severity of existing vertebral fractures.ControlRAp
FRAX score (%) Major osteoporosis fx.10.7±4.833.4±8.0<0.001 Femoral neck fx.2.8±2.49.9±6.10.002Clinical fragility fx. Number416 Severity (# x grade)429 Mechanical strength (N/mm)218.8±24.6164.9±36.50.001RA group exhibited significant bone quality abnormalities including deterioration of the bone microstructure, decreased calcification of the bone matrix, increased osteocyte atrophy and empty lacunae (Figure), and an impairment bone material strength properties.ConclusionsOur findings showed that RA patients receiving glucocorticoid treatment have severe bone fragility regardless of increased bone quantity by using bisphosphonate. The functional deteriorations of the osteocyte system and the abnormalities of bone quality might induce bone fragility fracture. Therefore, management of osteoporosis associated with RA should be targeted about bone quality as well as bone quantity.References
Kanis JA et al. J Bone Miner Res 2004.Takaha M et al. Arthritis Rheum 2012.Grossman, J.M. et al. Arthritis Care Res 2010.
AcknowledgementsThis project was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan 25462357 (M. Takahata).Disclosure of InterestNone declared