S293: risk of fractures in adult patients with primary and secondary immune thrombocytopenia: a danish nationwide cohort study

Background: The mainstay of first line treatment in immune thrombocytopenia (ITP) has remained high-dose corticosteroids for decades. Although steroid treatment is recommended to be tapered quickly in ITP, previous data shows that during the first six weeks of primary ITP treatment the mean accumulated steroid dose was 2-3 g of prednisolone. In addition, patients may be exposed to repeated courses of corticosteroids during relapses due to its rapid effect on platelet count. Corticosteroids is a well-known risk factor for bone demineralization and osteoporosis that may lead to fractures, but it is unknown if patients with ITP suffer an increased risk of fractures. Aims: In this study we investigated incidences of fractures in primary (pITP) and secondary ITP (sITP) compared to the general population. Methods: Incident patients with ITP ≥18 years were identified in the nationwide Danish health registries during 1980-2016 by using the first registration of the designated codes 287.10 (ICD-8) or D.69.3 (ICD-10). Prevalent ITP and other thrombocytopenic conditions were excluded. Secondary ITP was classified when one or more associated diagnoses were registered any time before or up to 30 days after ITP diagnosis. Each patient with ITP was age-sex matched with up to 40 comparators from the general population. Date of the first ITP registration marked start date of follow-up, and comparators were assigned the same start date. Incident fractures were identified using designated fracture registrations, and divided into five groups: hip and femoral, humeral, antebrachial, axial, and any of the before mentioned. All individuals were followed from start date until the first of the following: fracture, death, emigration, or end of study. Using these data, we calculated rates, incidence-rate-ratios (IRR) and cumulative incidences for fractures in patients vs. comparators after 1, 5 and 10 years, and end of study period. Results: We identified 4,789 patients with pITP, 654 patients with sITP, and 217,370 comparators. Median age was 59.6 years for primary ITP and 57.3 for secondary ITP. Women constituted 54% of primary ITPs, and 64% of secondary ITP patients. IRR in pITP was 1.15 [95% CI 1.04; 1.27] for any fracture, and 1.34 [1.09; 1.62] for axial fractures. For sITP, overall IRR was 1.37 [1.06; 1.74] for any fracture, and 1.65 [1.16; 2.29] for hip – and femoral fractures. IRR was significantly elevated for any fracture during the first 5 years after diagnosis of pITP, but equalized hereafter. The IRR of hip – and femoral fractures in the first year after diagnosis was 2.04 [1.41; 2.86] in pITP, and 2.30 [1.32; 3.74] for axial fractures, however these differences also equalized over time. For sITP, the risk of any fracture was particularly elevated during the first year with an IRR of 2.65 [1.39; 4.63], as well as the risk of distal antebrachial fracture with an IRR of 3.16 [1.33; 6.46]. During year 2-5, IRR for hip – and femoral fracture was 1.92 [1.04; 3.26]. All remaining IRR-estimates were not statistically significant. Cumulative incidence proportions showed similar trends (Figure) with largest differences during first years after diagnosis, but equalizing over time. Image:Summary/Conclusion: The incidence of some fractures in ITP is increased during the first years after diagnosis compared to the general population. Clinical attention and action should be directed upon this matter. Data on comorbidity, sub grouped cumulative incidences, and additional risk estimates will be presented with the abstract.