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Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis

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Abstract

Summary

Although haemophilia is not considered among the classic causes of secondary osteoporosis, the present meta-analysis provides strong evidence that men with haemophilia have a significant reduction in both lumbar spine and femoral bone mineral density, which appears to begin in childhood.

Introduction

Haemophilia is not considered among the classic causes of secondary osteoporosis. The aim of this study was to systematically review the literature for case–control trials that have studied bone mass in males with haemophilia and to meta-analyze the best evidence available.

Methods

Electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for case–control trials that have studied bone mass in men or boys with haemophilia. Standardized mean difference (SMD) for bone mineral density (BMD) in the lumbar spine was the main study outcome and SMD in femoral neck and total hip BMD the secondary ones. Patient and control characteristics, such as age, body mass index (BMI), level of physical activity and blood-borne infections were recorded as possible predictors of the main outcome.

Results

Thirteen studies were included in the systematic review and ten in the main outcome meta-analysis. Men with haemophilia demonstrated reduced lumbar spine [random effects SMD [95 % confidence interval (CI)] = −0.56 (−0.84, −0.28), between-study heterogeneity (I 2) = 51 %] and femoral neck BMD [random effects SMD (95 % CI) = −0.82 (−1.21, −0.44), I 2 = 63 %] compared with controls, which indicated a large and clinically significant association. Similar results were obtained for children [random effects SMD (95 % CI) = −0.92 (−1.77, −0.07), I 2 = 92 %]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity or presence of blood-borne infections predicted lumbar spine BMD.

Conclusions

This meta-analysis shows that men with haemophilia present a significant reduction in both lumbar spine and hip BMD, which appears to begin in childhood.

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Conflicts of interest

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Author information

Authors and Affiliations

  1. Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki Medical School, “Papageorgiou” General Hospital, Ring Road, 56403, Nea Efkarpia, Thessaloniki, Greece

    S. A. Paschou, S. Karras & D. G. Goulis

  2. Haemophilia Centre of Northern Greece, Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    P. Anagnostis, S. Vakalopoulou & V. Garipidou

  3. Department of Geriatric Medicine, UPRES EA 4638, University Hospital, Angers, France

    C. Annweiler

  4. Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

    C. Annweiler

Authors
  1. S. A. Paschou
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  2. P. Anagnostis
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  3. S. Karras
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  4. C. Annweiler
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  5. S. Vakalopoulou
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  6. V. Garipidou
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  7. D. G. Goulis
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Corresponding author

Correspondence to D. G. Goulis.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online resource 1

Characteristics and outcomes of the studies included in the systematic review (XLS 62 kb)

Online resource 2

Quality of the studies included in the systematic review, according to the Newcastle-Ottawa scale for case–control studies (DOC 38 kb)

Online resource 3

Forest plot of comparison between men with haemophilia and controls in study outcomes: (a) lumbar spine T-score (adult population) and (b) lumbar spine Z-score (pediatric population) (DOC 67 kb)

Online resource 4

Funnel plot of comparison between men with haemophilia and controls in study outcomes: (a) lumbar spine, (b) femoral neck and (c) total hip bone mineral density. (DOC 53 kb)

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Paschou, S.A., Anagnostis, P., Karras, S. et al. Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis. Osteoporos Int 25, 2399–2407 (2014). https://doi.org/10.1007/s00198-014-2773-7

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  • DOI: https://doi.org/10.1007/s00198-014-2773-7

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