Risk of low bone mineral density in patients with haemophilia: a systematic review and meta-analysis
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Published on: January 29, 2018
Haojing Zhou1, Lei Chen1, Hai Su1
1Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
Introduction:
Patients with haemophilia (PWH) may have lower bone mineral density (BMD). The risk of low BMD in PWH has not been comprehensively analysed. This study aimed to examine the risk of low BMD and changes in BMD in PWH.
Methods:
A comprehensive systematic search was performed in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library. The last search was carried out on 11 December 2022. Review Manager 5.4 and Stata 16 were used for meta-analysis. Odds ratios were calculated by the incidence of low BMD between the haemophilia and control groups in each study. A meta-analysis of the odds ratios for each study was performed to estimate pooled odds ratios. Fixed effects models or random effects models were used to assess outcomes. Heterogeneity was evaluated using Higgins' I2. Subgroup analysis and sensitivity analysis were performed to interpret the potential source of heterogeneity. A funnel plot, Egger's regression test, and the trim-and-fill method were used to assess publication bias.
Results:
19 of 793 studies, published between 2004 and 2022, that were identified by search strategy were included in this meta-analysis. The risk for low BMD was approximately four times higher compared to controls. PWH have significantly lower lumbar spine, femoral neck, and total hip BMD. Subgroup analysis showed that the risk of low BMD did not increase significantly in developed countries. Very low heterogeneity was observed in the meta-analysis of the risk of low BMD. The result from Egger's regression test suggested that there may be publication bias. However, the meta-analysis results did not alter after the trim-and-fill correction and the findings were robust.
Conclusion:
Haemophilia was associated with an increased risk of low BMD. However, the risk of low BMD did not increase significantly in developed countries. And BMD was reduced in PWH, regardless of age, region, or economic ability. For PWH, our concerns should extend beyond bleeding and osteoarthritis to encompass BMD starting at a young age.
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