The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

Panagiotis Anagnostis; Timoleon-Achilleas Vyzantiadis; Maria Charizopoulou; Fotini Adamidou; Spyridon Karras; Dimitrios G. Goulis; Asterios Karagiannis; Vasilia Garipidou; Sofia Vakalopoulou

doi:10.1160/TH13-01-0030

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(02): 257-263
DOI: 10.1160/TH13-01-0030

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

Panagiotis Anagnostis

¹Haemophilia Centre of Northern Greece, 2^nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

⁴Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece

,

Timoleon-Achilleas Vyzantiadis

²1^st Department of Microbiology, Medical School, Aristotle University, Thessaloniki, Greece

,

Maria Charizopoulou

³Department of Psychology, School of Philosophy, Aristotle University, Thessaloniki, Greece

,

Fotini Adamidou

⁴Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece

,

Spyridon Karras

⁵Department of Endocrinology and Metabolism, Agios Pavlos General Hospital, Thessaloniki, Greece

,

Dimitrios G. Goulis

⁶Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, ‘‘Papageorgiou’’ General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

,

Asterios Karagiannis

¹Haemophilia Centre of Northern Greece, 2^nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

,

Vasilia Garipidou

¹Haemophilia Centre of Northern Greece, 2^nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

,

Sofia Vakalopoulou

¹Haemophilia Centre of Northern Greece, 2^nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

› Author Affiliations

Abstract

Summary

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, no study has so far evaluated the effects of anti-osteoporotic therapy on BMD in haemophilia. The primary endpoint of this prospective study was to estimate the effect of 12-month therapy of oral ibandronate 150 mg/ month on BMD in patients with haemophilia A and B. Secondary endpoint was its effect on turnover markers (BTM) of bone resorption [serum C-terminal telopeptide of type 1 collagen (sCTX), tartrate-resistant acid phosphatase band 5b] and bone formation (osteocalcin and bone-specific alkaline phosphatase. Ten adult patients with T-score < −2.5 SD or Z-score < −2 and/or increased risk of fracture according to FRAX model were included. All received 1,000 mg/day calcium carbonate with 800 IU/d cholecalciferol. Males with haemophilia A (n=7) or B (n=3) (mean age 43.5 ± 13.5 years) were studied. Ibandronate resulted in an increase in lumbar BMD (from 0.886 ± 0.169 to 0.927 ± 0.176 g/cm2, 4.7%, p=0.004). No change in BMD of total hip (from 0.717 ± 0.128 to 0.729 ± 0.153 g/cm2, p=0.963) or femoral neck (0.741 ± 0.135 to 0.761 ± 0.146 g/cm2, p=0.952) was noticed. Ibandronate led to a decrease in sCTX (from 0.520 ± 0.243 to 0.347 ± 0.230 ng/ml, −29.9%, p=0.042). No change was observed in other BTM. Ibandronate was generally well-tolerated. In conclusion, ibandronate significantly improved BMD in lumbar spine and reduced bone resorption in adults with haemophilia at increased risk of fracture. Its effect on hip BMD and bone formation markers was not significant.

Keywords

Haemophilia - osteoporosis - osteopenia - bone mineral density - ibandronate

Full Text

References

References
1 Anagnostis P, Vakalopoulou S, Slavakis A. et al. Reduced bone mineral density in patients with haemophilia A and B in Northern Greece. Thromb Haemost 2012; 107: 545-551.
2 Barnes C, Wong P, Egan B. et al. Reduced bone density among children with severe hemophilia. Pediatrics 2004; 114: 177-181.
3 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.
4 Iorio A, Fabbriciani G, Marcucci M. et al. Bone mineral density in haemophilia patients. A meta-analysis. Thromb Haemost 2010; 103: 596-603.
5 Forsyth AL, Quon DV, Konkle BA. Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis. Haemophilia 2011; 17: 870-876.
6 Watts NB, Bilezikian JP, Camacho PM. et al. AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 2010; 16 (Suppl. 03) 1-37.
7 Adami S, Idolazzi L, Rossini M. Evidence of sustained vertebral and nonvertebral antifracture efficacy with ibandronate therapy: a systematic review. Ther Adv Musculoskelet Dis 2011; 03: 67-79.
8 Watts NB, Adler RA, Bilezikian JP. et al. Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 1802-1822.
9 Orwoll ES, Binkley NC, Lewiecki EM. et al. Efficacy and safety of monthly ibandronate in men with low bone density. Bone 2010; 46: 970-976.
10 Genant HK, Lewiecki EM, Fuerst T. et al. Effect of monthly ibandronate on hip structural geometry in men with low bone density. Osteoporos Int 2012; 23: 257-265.
11 Baim S, Binkley N, Bilezikian JP. et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 2008; 11: 75-91.
12 Kanis JA, Johnell O, Oden A. et al. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008; 19: 385-397.
13 Anagnostis P, Vakalopoulou S, Charizopoulou M. et al. Is there any association between leptin levels and bone mineral density in haemophiliac men?. Arch Med Sci. 2013 in press.
14 Ng WH, Chu WC, Shing MK. et al. Role of imaging in management of hemophilic patients. AJR Am J Roentgenol 2005; 184: 1619-1623.
15 Diez-Perez A, Adachi JD, Agnusdei D. et al. for the IOF CSA Inadequate Responders Working Group. Treatment failure in osteoporosis. Osteoporos Int 2012; 23: 2769-2774.
16 Lips P, Bouillon R, van Schoor NM. et al. Reducing fracture risk with calcium and vitamin D. Clin Endocrinol 2010; 73: 277-285.
17 Murad MH, Elamin KB, Abu NOElnour. et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96: 2997-3006.
18 Khosla S, Bilezikian JP, Dempster DW. et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab 2012; 97: 2272-2282.
19 Lamy O, Sandini L, Pache I. et al. Intravenous ibandronate in men with osteoporosis: an open pilot study over 2 years. J Endocrinol Invest 2003; 26: 728-732.
20 Stepan JJ, Burckhardt P, Hána V. The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter’s syndrome: the influence of vitamin D deficiency and hormonal status. Bone 2003; 33: 589-596.
21 Ringe JD, Dorst A, Faber H. et al. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study. Osteoporos Int 2003; 14: 801-807.
22 Watts NB, Cooper C, Lindsay R. et al. Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 2004; 07: 255-261.
23 Watts NB, Geusens P, Barton IP. et al. Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD. J Bone Miner Res 2005; 20: 2097-2104.
24 Sarkar S, Reginster JY, Crans GG, Diez-Perez A, Pinette KV, Delmas PD. 2004 Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture. J Bone Miner Res 2004; 19: 394-401.
25 Bauer DC, Black DM, Garnero P. et al. Change in bone turnover and hip, nonspine, and vertebral fracture in alendronate treated women: the fracture intervention trial. J Bone Miner Res 2004; 19: 1250-1258.
26 Singer FR, Eyre DR. Using biochemical markers of bone turnover in clinical practice. Cleve Clin J Med 2008; 75: 739-750.
27 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.
28 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 2010; 89: 67-74.