Bone mineral density in haemophilia patients

Alfonso Iorio; Gianluigi Fabbriciani; Maura Marcucci; Matteo Brozzetti; Paolo Filipponi

doi:10.1160/TH09-09-0629

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 103(03): 596-603
DOI: 10.1160/TH09-09-0629

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Bone mineral density in haemophilia patients

A meta-analysis

Alfonso Iorio

¹Hemophilia Centre – Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy

,

Gianluigi Fabbriciani

²U.O. Medicina Generale, Azienda A.S.L. n. 1 dell’Umbria – Città di Castello and Umbertide, Italy

³Institute of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy

,

Maura Marcucci

¹Hemophilia Centre – Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy

,

Matteo Brozzetti

⁴Ospedale di Norcia, Azienda A.S.L. n. 2 dell’Umbria, Perugia, Italy

,

Paolo Filipponi

²U.O. Medicina Generale, Azienda A.S.L. n. 1 dell’Umbria – Città di Castello and Umbertide, Italy

› Institutsangaben

Abstract

Summary

Osteoporosis is caused by bone mineral density (BMD) reduction. Haemophilia patients are at increased risk of osteoporosis because of decreased physical activity and blood-borne virus infections. This systematic review of the literature aims at evaluating BMD reduction in severe haemophilia patients and its correlation with patients’ characteristics. Seven case-control studies evaluating lumbar BMD values [g/cm²] (all studies), BMI (5/7 studies), and hepatitis C virus (HCV) seropositivity (6/7 studies) in severe haemophilia patients and controls were meta-analysed. Standardised mean difference (SMD) of BMD was used to compare cases and controls. The effect of body mass index (BMI) and HCV infection was investigated by meta-regression. One hundred one adult cases (age 33 ± 8.9) with 101 controls and 111 paediatric cases (age 8 ± 3.6) with 307 controls were available for analysis. Lumbar BMD was significantly lower in severe haemophilia patients than in controls, both in adult (pooled SMD –1.379, 95% confidence interval [CI] –2.355 to –0.403, p=0.006) and children (pooled SMD –0.438, 95% CI –0.686 to –0.189, p=0.001). The reduction in BMD in patients versus controls was not significantly correlated with the reduction in BMI or with the percentage of HCV-infected patients. This meta-analysis confirms the association between severe haemophilia and low BMD. Future studies should investigate fracture rates and interventions to prevent bone loss in persons with haemophilia

Keywords

Bone mineral density - osteoporosis - haemophilia - HCV infection

Volltext

Referenzen

References
1 Iorio A, Oliovecchio E, Morfini M. et al. Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis. Haemophilia 2008; 14: 444-453.
2 O’Connor GI, Temperley IJ. A database for a National Haemophilia Centre. Clin Lab Haematol 1996; 18: 195-200.
3 Hoots WK, Nugent DJ. Evidence for the benefits of prophylaxis in the management of hemophilia A. Thromb Haemost 2006; 96: 433-440.
4 Schobess R, Kurnik K, Friedrichs F. et al. Effects of primary and secondary prophylaxis on the clinical expression of joint damage in children with severe haemophilia A. Results of a multicenter non-concurrent cohort study. Thromb Haemost 2008; 99: 71-76.
5 Madhok R, Bennett D, Sturrock RD. et al. Mechanisms of joint damage in an experimental model of hemophilic arthritis. Arthritis Rheum 1988; 31: 1148-1155.
6 Hoots WK, Rodriguez N, Boggio L. et al. Pathogenesis of haemophilic synovitis: clinical aspects. Haemophilia 2007; 13 (Suppl. 03) 4-9.
7 Musso R, Santagostino E, Faradji A. et al. Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting. Thromb Haemost 2008; 99: 52-58.
8 den Uijl IE, Fischer K. Including the life-time cumulative number of joint bleeds in the definition of primary prophylaxis. Thromb Haemost 2008; 99: 965-968.
9 Coppola A, Franchini M, Tagliaferri A. Prophylaxis in people with haemophilia. Thromb Haemost 2009; 101: 674-681.
10 NIH consensus Development Panel on Osteoporosis Prevention.. Osteoporosis prevention, diagnosis, and therapy. J Am Med Assoc 2001; 285: 785-795.
11 Nelson DA, Norris SA, Gilsanz V. Childhood and adolescence. In: Favus MJ. ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 2006, ed. Washington, DC: ASBMR Press; 2006: 55-63.
12 Adomaityte J, Farooq M, Qayyum R. Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis. Thromb Haemost 2008; 99: 338-342.
13 Vik A, Brodin E, Sveinbjornsson B. et al. Heparin induces mobilization of osteoprotegerin into the circulation. Thromb Haemost 2007; 98: 148-154.
14 Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost 2007; 98: 120-125.
15 Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost 2008; 100: 530-547.
16 Nair AP, Jijina F, Ghosh K. et al. Osteoporosis in young haemophiliacs from western India. Am J Hematol 2007; 82: 453-457.
17 Tlacuilo-Parra A, Morales-Zambrano R, Tostado-Rabago N. et al. Inactivity is a risk factor for low bone mineral density among haemophilic children. Br J Haematol 2008; 140: 562-567.
18 Wells G, Shea B, O’Connel D. et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analysis. 2009. Internet Communication. Available at: http://www.ohri.ca/programs/clinical_epidemiology/nosgen.doc. Accessed online on September 5, 2009.
19 Jackson D, White IR, Thompson SG. Extending DerSimonian and Laird’s methodology to perform multivariate random effects meta-analyses. Stat Med. 2009 Published online in Wiley InterScience www.interscience.wiley.com doi: 10.1002/sim.3602.
20 Wallny TA, Scholz DT, Oldenburg J. et al. Osteoporosis in haemophilia – an underestimated comorbidity?. Haemophilia 2007; 13: 79-84.
21 Gerstner G, Damiano ML, Tom A. et al. Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia. Haemophilia 2009; 15: 559-565.
22 Ghosh K, Madkaikar M, Jijina F. et al. Fractures of long bones in severe haemophilia. Haemophilia 2007; 13: 337-339.
23 Katsarou O, Terpos E, Chatzismalis P. et al. Increased bone resorption is implicated in the pathogenesis of bone loss in hemophiliacs: correlations with hemophilic arthropathy and HIV infection. Ann Hematol 2009; 89: 67-74.
24 Mansouritorghabeh H, Rezaieyazdi Z, and Rezai J. Reduced bone density in individuals with combined factor V and VIII deficiency. Haemophilia 2007; 13: 340-343.
25 Gallacher SJ, Deighan C, Wallace AM. et al. Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study. Q J Med 1994; 87: 181-186.
26 Abdelrazik N, Reda M, El-Ziny M. et al. Evaluation of bone mineral density in children with hemophilia: Mansoura University children hospital (MUCH) experience, Mansoura, Egypt. Hematology 2007; 12: 431-437.
27 Mansouritorghabeh H, Rezaieyazdi Z, Badiei Z. Are individuals with severe haemophilia A prone to reduced bone density?. Rheumatol Int 2008; 28: 1079-1083.
28 Barnes C, Wong P, Egan B. et al. Reduced bone density among children with severe hemophilia. Pediatrics 2004; 114: e177-e181.
29 Zhao B, Takami M, Yamada A. et al. Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis. Nat Med 2009; 15: 1066-1071.
30 Schiefke I, Fach A, Wiedmann M. et al. Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol 2005; 11: 1843-1847.
31 Collier J. Bone disorders in chronic liver disease. Hepatology 2007; 46: 1271-1278.
32 Heaney RP. Pathophysiology of osteoporosis. Endocrinol Metab Clin North Am 1998; 27: 255-265.
33 Katzman DK, Bachrach LK, Carter DR. et al. Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 1991; 73: 1332-1339.
34 Douma-van Riet DC, Engelbert RH, van Genderen FR. et al. Physical fitness in children with haemophilia and the effect of overweight. Haemophilia 2009; 15: 519-527.
35 World Health Organization.. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva, Switzerland: WHO; 1994
36 Ward KA, Ashby RL, Roberts SA. et al. UK reference data for the Hologic QDR Discovery dual-energy x ray absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch Dis Child 2007; 92: 53-59.
37 Karlsson MK, Nordqvist A, Karlsson C. Physical activity increases bone mass during growth. Food Nutr Res. 2008 52 : doi: 10.3402/fnr.v52i0.1871.
38 Cazanave C, Dupon M, Lavignolle-Aurillac V. et al. Reduced bone mineral density in HIV-infected patients: prevalence and associated factors. AIDS 2008; 22: 395-402.
39 Rodriguez M, Daniels B, Gunawardene S. et al. High frequency of vitamin D deficiency in ambulatory HIV-Positive patients. AIDS Res Hum Retroviruses 2009; 25: 9-14.
40 Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20: 2165-2174.