Abstract
Background: Fabry disease (FD) is an inherited X-linked lysosomal storage disease with widespread clinical manifestations. Small prospective studies have shown increased osteopenia and osteoporosis in male FD patients. Limited information however exists about bone metabolism and osteoporosis risk factors within this group. We reviewed osteoporosis risk factors within our cohort.
Methods: A retrospective analysis of bone mineral density (BMD) results and fracture incidence in 44 patients (22 males and 22 females) was undertaken. Dual X-ray absorptiometry scans were performed at the lumbar spine, hip and femoral neck. The impact of risk factors including renal function, antiepileptic drug (AED), analgesia and vitamin D levels were assessed.
Results: Male FD patients had low T scores at all sites (spine −1.2 ± 1.06, hip −1.6 ± 0.9, femoral neck −2.23 ± 1.01). Female T scores showed more typical distribution (spine −0.07 ± 1.47, hip 0.02 ± 1.14, femoral neck −0.49 ± 1.31). A higher incidence of osteopenia and/or osteoporosis occurred in males versus females (spine 46.9% versus 31.8%, hip 75.5% versus 18.2% and femoral neck 86.4% versus 45.5%). Multiple regression analysis showed a 50.8% (p < 0.001) reduction in femoral neck BMD with AED usage, after adjustment for age, gender and renal function. Non-traumatic fractures occurred in 27.3% males over 205 patient-years versus 4.6% in females over 149 patient-years, p = 0.095.
Conclusions: Low bone density was highly prevalent in male patients with increased incidence of non-traumatic fractures. AED usage significantly reduces BMD. Treatment to prevent BMD deterioration will depend on determining the bone turnover status.
Competing interests: None declared
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Blake GM, Fogelman I (2009) The clinical role of dual energy X-ray absorptiometry. Eur J Radiol 71:406–414
Desnick RJ, Brady R, Barranger J et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138:338–346
Drake MT, Murad MH, Mauck KF et al (2012) Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis. J Clin Endocr Metab 97:1861–1870
Ebeling P (2008) Osteoporosis in men. New Engl J Med 358:1474–1482
Ferrari S, Bianchi ML, Eisman JA et al (2012) Osteoporosis in young adults: pathophysiology, diagnosis, and management. Osteoporosis Int 23:2735–2748
Germain DP (2010) Bone and muscle involvement in fabry disease. In: Elstein D, Altarecu G, Beck M (eds) Fabry disease. Chap 16, pp 293–298
Germain DP (2010) Fabry disease. Orphanet J Rare Dis 5:30
Germain DP, Benistan K, Boutouyrie P, Mutschler C (2005) Osteopenia and osteoporosis: previously unrecognized manifestations of Fabry disease. Clin Genet 68:93–95
Hauser AC, Gessl A, Harm F et al (2005) Hormonal profile and fertility in patients with Anderson–Fabry disease. Int J Clin Pract 59:1025–1028
Hofbauer LC, Hamann C, Ebeling PR (2010) Approach to the patient with secondary osteoporosis. Eur J Endocrinol 162:1009–1020
International Society of Clinical Densitometry (ISCD) (2013) Official positions of the International Society of Clinical Densitometry: updated 2013. www.iscd.org/official-positions/2013-iscd-official-positions-adult/
Isenor JE, Ensom MH (2010) Is there a role for therapeutic drug monitoring of vitamin D level as a surrogate marker for fracture risk? Pharmacotherapy 30:254–264
Johnell O, Kanis JA, Oden A et al (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20:1185–1194
Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporosis Int 4:368–381
Kanis JA, Bianchi G, Bilezikian P et al (2011) Towards a diagnostic consensus in male osteoporosis. Osteoporosis Int 22:2789–2798
Lips P, Bouillon R, van Schoor NM et al (2010) Reducing fracture risk with calcium and vitamin D. Clin Endocrinol 73:277–285
Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone density predict occurrence of osteoporotic fracture. Brit Med J 312:1254–1259
Mehta A, Clarke JTR, Giugliani R, on behalf of the FOS Investigators et al (2009) Natural course of Fabry disease: changing pattern of causes of death in FOS – Fabry Outcome Survey. J Med Genet 46:548–552
Mersebach H, Johansson J-O, Rasmussen A et al (2007) Osteopenia: a common aspect of Fabry disease. Predictors of bone mineral density. Genet Med 9:812–818
Montalcini T, Romeo S, Ferro Y, Migliaccio V, Gazzaruso C, Pujia A (2013) Osteoporosis in chronic inflammatory disease; the role of malnutrition. Endocrine 43:59–64
Nakken KO, Taubøll E (2010) Bone loss associated with use of antiepileptic drugs. Expert Opin Drug Saf 9:561–571
Nishizawa Y, Ohta H, Miura M et al (2013) Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition). J Bone Miner Metab 31:1–15
Pack AM, Reddy DS, Duncan S, Herzog A (2011) Neuroendocrinological aspects of epilepsy: Important issues and trends in future research. Epilepsy Behav 22:94–102
Petty SJ, O’Brien TJ, Wark JD (2007) Anti-epileptic medication and bone health. Osteoporosis Int 18:129–142
Ross G, Kuwamura GA (1993) Association of Fabry’s disease with femoral head avascular necrosis. Orthopedics 16:471–473
Stone KL, Seeley DG, Lui L-Y et al (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of osteoporotic fractures. J Bone Miner Res 18:1947–1954
Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F (2010) Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosur 112:1–10
von Scheidt W, Eng CM, Fitzmaurice TF et al (1991) An atypical variant of Fabry’s disease with manifestations confined to the myocardium. N Engl J Med 324:395–399
Zarate YA, Hopkin RJ (2008) Lysosomal storage disease 3: Fabry’s disease. Lancet 372:1427–1435
Acknowledgements
The authors would like to thank the following for their expert advice: Professor John Wark, Dr Paul Wraight and the late Dr Sue Kantor. Additional thanks are given to Ms Alexandra Gorelik for assistance with statistical analysis.
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Communicated by: Francois Feillet, MD, PhD
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Take-Home Message
Osteoporosis is highly prevalent in male Fabry patients, and antiepileptic medications, used for neuropathic analgesia, increase the risk of osteoporotic fractures.
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Andrew Talbot was primarily responsible for planning the study and conducting the analysis of all bone mineral data. He also performed the primary data interpretation, including statistical analysis and original manuscript preparation.
Joanna R Ghali contributed to data collection and interpretation including manuscript editing.
Kathy Nicholls consented all patients and was the primary clinician responsible for bone mineral examination and pathology requests and follow-up. She also contributed to data interpretation and original manuscript preparation.
Conflict of Interest
Andrew Talbot has received research support, speaker honoraria and travel assistance from Shire Corporation and Sanofi Corporation, speaker honoraria and travel assistance from Dainippon Sumitomo Pharma Co. and research support from Amicus Therapeutics and Protalix Biotherapeutics.
Joanna R Ghali has received research support, speaker honoraria and travel assistance from Shire Corporation and Sanofi Corporation and research support from Amicus Therapeutics and Protalix Biotherapeutics.
Kathy Nicholls has received research support, speaker honoraria and travel assistance from Shire Corporation and Sanofi Corporation and research support from Amicus Therapeutics and Protalix Biotherapeutics.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). Informed consent was obtained from all patients for data analysis of results included in the study.
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Talbot, A., Ghali, J.R., Nicholls, K. (2014). Antiepileptic Medications Increase Osteoporosis Risk in Male Fabry Patients: Bone Mineral Density in an Australian Cohort. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 17. JIMD Reports, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_328
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DOI: https://doi.org/10.1007/8904_2014_328
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