THU411 Fracture And Osteoporosis In Hereditary Connective Tissue Disorders: A Systematic Review And Meta-analysis

Abstract

Abstract Disclosure: N. Charoenngam: None. T. Rittiphairoj: None. A. Jaroenlapnopparat: None. B. Ponvilawan: None. P. Waitayangkoon: None. P. Supakitjanusant: None. V. Prasitsumrit: None. C. Pongchaiyakul: None. M.F. Holick: None. Introduction: Hereditary connective tissue disorders (HCTDs) refer to a constellation of conditions caused by defects in the structure and synthesis of extracellular matrix. It is well-known that bone fragility is the hallmark feature of osteogenesis imperfecta. Interestingly, other HCTDs, including Ehlers-Danlos syndrome (EDS), Marfan’s syndrome (MFS) and Loeys-Dietz syndrome (LDS) are shown to be associated with bone fragility. However, most of the existing studies were small in sample sizes, thereby limiting validity and generalizability. Therefore, we aimed to identify all available data, using systematic review and meta-analysis, to determine the risks of fracture and osteoporosis in patients with HCTDs, including EDS, MFS and LDS. Methods: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for “HCTD”, “Fracture” and “Osteoporosis”. Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. Results: Among the 4,206 articles that were identified, 19 studies fulfilled the eligibility criteria. The pooled prevalence of fracture in patients with EDS, MFS and LDS were 44% (95%CI, 25 - 65%, I2 88%), 17% (95%CI, 11 - 26%, I2 68%), 69% (95%CI, 47 - 85%, I2 83%), respectively. The pooled prevalence of osteoporosis among patients with EDS was 17% (95%CI, 8 - 34%, I2 96%). EDS was associated with fracture [pooled odds ratio 4.90 (95%CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled odds ratio 1.34 (95%CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95%CI, 3 - 8%) prevalence of osteoporosis in MFS, and MFS was associated with fracture [incidence rate ratio 1.35 (95%CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95%CI, 2.53 - 6.25)]. Conclusion: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite the lack of data from cohort studies, there was a significantly higher rate of fracture in LDS. Presentation: Thursday, June 15, 2023