Osteoporosis in hemophilia: what is its importance in clinical practice?

References

• Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535–544.
   PubMed Web of Science ®Google Scholar
• Nilsson IM, Berntorp E, Lofqvist T, et al. Twenty-five years´experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992;232:25–32.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Merchan EC, Valentino LA. Emicizumab: review of the literature and critical appraisal. Haemophilia. 2019;25:11–20.
   PubMed Web of Science ®Google Scholar
• Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137:2231–2242.
   PubMed Web of Science ®Google Scholar
• Cafuir L, Kruse-Jarres R, Mancuso ME, et al. Emicizumab for hemophilia A without inhibitors. Expert Rev Hematol. 2019;12:515–524.
   PubMed Web of Science ®Google Scholar
• Shapiro AD. Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood Adv. 2021;5(1):279.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Merchan EC, Valentino LA. Bone resoption in hemophilia. Blood Rev. 2019;33:6–10.
   PubMed Web of Science ®Google Scholar
• Chen X, Wang Z, Duan N, et al. Osteoblast-osteoclast interactions. Connect Tissue Res. 2018;59:99–107.
   PubMed Web of Science ®Google Scholar
• Khosla S, Riggs BL. Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin North Am. 2005;34:1015–1030.
   PubMed Web of Science ®Google Scholar
• Eriksen EF, Hodgson SF, Eastell R, et al. Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res. 1990;5:311–319.
   PubMed Web of Science ®Google Scholar
• Parfitt AM, Villanueva AR, Foldes J, et al. Relations between histologic indices of bone formation; implications for the pathogenesis of spinal osteoporosis. J Bone Miner Res. 1995;10:466–473.
   PubMed Web of Science ®Google Scholar
• Kempton CL, Antoniucci DM, Rodriguez-Merchan EC. Bone health in persons with haemophilia. Haemophilia. 2015;21:568–577.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Merchan EC. Osteoporosis in hemophilia. Int Blood Res Rev. 2014;2:48–55.
   Google Scholar
• Song S, Guo Y, Yang Y, et al. Advances in pathogenesis and therapeutic strategies for osteoporosis. Pharmacol Ther. 2022 Mar 10;237:108168. Online ahead of print.PMID: 35283172.
   PubMed Web of Science ®Google Scholar
• Hart DP, Matino D, Astermark J, et al. International consensus recommendations on the management of people with haemophilia B. Ther Adv Hematol. 2022;13:20406207221085202.
   Web of Science ®Google Scholar
• Mazess R, Chesnut CH 3 rd, McClung M, et al. Enhanced precision with dual-energy X-ray absorptiometry. Calcif Tissue Int. 1992;51:14–17.
   PubMed Web of Science ®Google Scholar
• Njeh CF, Fuerst T, Hans D, et al. Radiation exposure in bone mineral density assessment. Appl Radiat Isot. 1999;50:215–236.
   PubMed Web of Science ®Google Scholar
• Kanis JA, Melton LJ 3 rd, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–1141.
   PubMed Web of Science ®Google Scholar
• Kanis JA, Kanis JA. Assessment of fracture risk and its implication to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO study group. Osteoporos Int. 1994;4:368–381.
   PubMed Web of Science ®Google Scholar
• Looker AC, Borrud LG, Hughes JP, et al. Total body bone area, bone mineral content, and bone mineral density for individuals aged 8 years and over: United States, 1999–2006. National Center for Health Statistics. Vital Health Stat 11. 2013;253:1–78.
   Google Scholar
• Palacios S. Medical treatment of osteoporosis. Climacteric. 2022;25:43–49.
   PubMed Web of Science ®Google Scholar
• Chakhtoura M, Bacha DS, Gharios C, et al. Vitamin D supplementation and fractures in adults: a systematic umbrella review of meta-analyses of controlled trials. J Clin Endocrinol Metab. 2022;107:882–898.
   PubMed Web of Science ®Google Scholar
• Lee SE, Park JH, Kim KA, et al. Discordance in bone mineral density between the lumbar spine and femoral neck is associated with renal dysfunction. Yonsei Med J. 2022;63:133–140.
   PubMedGoogle Scholar
• Citla-Sridhar D, Sidonio RF Jr, Ahuja SP. Bone health in haemophilia carriers and persons with von Willebrand disease: a large database analysis. Haemophilia. 2022 Apr 13;28:671–678. Online ahead of print. PMID: 35416396.
   PubMed Web of Science ®Google Scholar
• Zhao D, Riquelme MA, Guda T, et al. Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading. Elife. 2022 Feb 8;11:e74365.
   PubMed Web of Science ®Google Scholar
• McKiernan FE, Berg RL, Linneman JG. The utility of BMD Z-score diagnostic thresholds for secondary causes of osteoporosis. Osteoporos Int. 2011;22:1069–1077.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Iorio A, Fabbriciani G, Marcucci M, et al. Bone mineral density in haemophilia patients. A meta-analysis. Thromb Haemost. 2010;103:596–603.
   PubMed Web of Science ®Google Scholar
• Baud´huin M, Duplomb L, Teletchea S, et al. Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival. J Biol Chem. 2009;284:31704–31713.
   PubMed Web of Science ®Google Scholar
• Liel MS, Grenberg DL, Recht M, et al. Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency. Br J Haematol. 2012;158:140–142.
   PubMed Web of Science ®Google Scholar
• Recht M, Liel MS, Turner RT, et al. The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption. Haemophilia. 2013;19:908–912.
   PubMed Web of Science ®Google Scholar
• Paschou SA, 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. 2014;25:2399–2407.
   PubMed Web of Science ®Google Scholar
• Forsyth AL, Quon DV, Konkle BA. Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis. Haemophilia. 2011;17(5):e870–e876.
   PubMed Web of Science ®Google Scholar
• De la Corte-Rodriguez H, Rodriguez-Merchan EC. The role of physical medicine and rehabilitation in haemophiliac patients. Blood Coagul Fibrinolysis. 2013;24:1–9.
   PubMed Web of Science ®Google Scholar
• Anagnostis P, Vyzantiadis T-A, Charizopoulou M, et al. 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. Thromb Haemost. 2013;110:257–263.
   PubMed Web of Science ®Google Scholar
• Eldash HH, Atwa ZT, Saad MA. Vitamin D deficiency and osteoporosis in hemophilic children: an intermingled comorbidity. Blood Coagul Fibrinolysis. 2017;28:14–18. .
   PubMed Web of Science ®Google Scholar
• Kiper Unal HD, Comert Ozkan M, Atilla FD, et al. Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study. Am J Blood Res. 2017;7:59–66.
   PubMed Web of Science ®Google Scholar
• Ulivieri FM, Rebagliati GAA, Piodi LP, et al. Usefulness of bone microarchitectural and geometric DXA-derived parameters in haemophilic patients. Haemophilia. 2018;24:980–987.
   PubMed Web of Science ®Google Scholar
• Dagli M, Kutlucan A, Abusoglu S, et al. Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia. Bosn J Basic Med Sci. 2018;18:206–210.
   PubMed Web of Science ®Google Scholar
• Sossa Melo CL, Wandurraga EA, Peña AM, et al. Low bone mineral density and associated factors in patients with haemophilia in Colombia. Haemophilia. 2018;24:e222–e229.
   PubMed Web of Science ®Google Scholar
• Anagnostis P, Vakalopoulou S, Christoulas D, et al. The role of sclerostin/dickkopf-1 and receptor activator of nuclear factor kB ligand/osteoprotegerin signalling pathways in the development of osteoporosis in patients with haemophilia A and B: a cross-sectional study. Haemophilia. 2018;24:316–322.
   PubMed Web of Science ®Google Scholar
• Sahin S, Sadri S, Baslar Z, et al. Osteoporosis in patients with hemophilia: single-center results from a middle-income country. Clin Appl Thromb Hemost. 2019;25:1076029619861689.
   Web of Science ®Google Scholar
• El-Mikkawy DME, Elbadawy MA, Abd El-Ghany SM, et al. Serum sclerostin level and bone mineral density in pediatric hemophilic arthropathy. Indian J Pediatr. 2019;86:515–519.
   PubMed Web of Science ®Google Scholar
• Ekinci O, Demircioglu S, Dogan A, et al. Decreased bone mineral density and associated factors in severe haemophilia A patients: a case-control study. Haemophilia. 2019;25:e315–e321.
   PubMed Web of Science ®Google Scholar
• Klintman J, Akesson KE, Holme PA, et al. Bone mineral density in haemophilia - a multicentre study evaluating the impact of different replacement regimens. Haemophilia. 2022;28:239–246.
   PubMed Web of Science ®Google Scholar
• Fischer K, Steen Carlsson K, Petrini P, et al. Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s. Blood. 2013;122:1129–1136.
   PubMed Web of Science ®Google Scholar
• Pergantou H, Papakonstantinou O, Xafaki P, et al. Uncoupling of bone turnover may compromise skeletal health of young patients with haemophilia A. J Clin Densitom. 2022;25:89–96.
   PubMed Web of Science ®Google Scholar
• Tang GH, Norris E, Petrucci J, et al. Bone health in symptomatic carriers of haemophilia A: a protocol for a multicentre prospective matched-cohort study. BMJ Open. 2019;9:e032891.
   PubMedGoogle Scholar
• Tardy-Poncet B, Play B, Montmartin A, et al. PHILEOS (haemoPHILia and ostEoporOSis) study: protocol of a multicentre prospective case-control study. BMJ Open. 2021;11:e042283.
   PubMedGoogle Scholar
• Frost A, Jonsson KB, Rideflet P, et al. Thrombin, but not bradykinin, stimulates proliferation in isolated human osteoblasts via a mechanism not dependent on endogen prostaglandin formation. Acta Orthop Scand. 1999;70:487–503.
   PubMedGoogle Scholar
• Strande JL, Phillips SA. Thrombin increases inflammatory cytokine and angiogenic growth factor secretion in human adipose cells in vitro. J Inflamm (Lond). 2009 Mar 6;6:4.
   PubMed Web of Science ®Google Scholar
• Tudpor K, van der Eerden BC, Jongwattanapisan P, et al. Thrombin receptor deficiency leads to a high bone mass phenotype by decreasing the RANKL/OPG ratio. Bone. 2015;72:14–22.
   PubMed Web of Science ®Google Scholar
• Haxaire C, Hakobyan N, Pannellini T, et al. Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNF-α pathway. Blood. 2018;132:1064–1074.
   PubMed Web of Science ®Google Scholar
• Taves S, Sun J, Livingston EW, et al. Hemophilia A and B mice, but not VWF(-/-)mice, display bone defects in congenital development and remodeling after injury. Sci Rep. 2019;9:14428.
   PubMed Web of Science ®Google Scholar
• Weitzmann MN, Roser-Page S, Vikulina T, et al. Reduced bone formation in males and increased bone resorption in females drive bone loss in hemophilia A mice. Blood Adv. 2019;3:288–300.
   PubMed Web of Science ®Google Scholar
• Larson EA, Larson HJ, Taylor JA, et al. Deletion of coagulation factor IX compromises bone mass and strength: murine model of hemophilia B (Christmas disease). Calcif Tissue Int. 2021;109:577–585.
   PubMed Web of Science ®Google Scholar
• Yen CC, Liu YW, Chang GR, et al. Therapeutic effects of kefir peptides on hemophilia-induced osteoporosis in mice with deficient coagulation factor VIII. Front Cell Dev Biol. 2022;10:794198.
   PubMed Web of Science ®Google Scholar
• Gebetsberger J, Schirmer M, Wurzer WJ, et al. Low bone mineral density in hemophiliacs. Front Med (Lausanne). 2022;9:794456.
   PubMed Web of Science ®Google Scholar
• Gaudio A, Xourafa A, Rapisarda R, et al. Hematological diseases and osteoporosis. Int J Mol Sci. 2020;21:3538.
   Google Scholar
• Brunetti G, D’Amato G, Chiarito M, et al. An update on the role of RANKL-RANK/osteoprotegerin and WNTß- catenin signaling pathways in pediatric diseases. World J Pediatr. 2019;15:4–11.
   PubMed Web of Science ®Google Scholar
• Ranta S, Viljakainen H, Mäkipernaa A, et al. Hypercalciuria in children with haemophilia suggests primary skeletal pathology. Br J Haematol. 2011;153:364–371.
   PubMed Web of Science ®Google Scholar
• Lau AG, Sun J, Hannah WB, et al. Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement. Haemophilia. 2014;20:716–722.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Linari S, Melchiorre D, Pieri L, et al. Low bone mass and hypovitaminosis D in haemophilia: a single-centre study in patients with severe and moderate haemophilia A and B. Haemophilia. 2020;26:898–906.
   PubMedGoogle Scholar
• Kempton CL, Antun A, Antoniucci DM, et al. Bone density in haemophilia: a single institutional cross-sectional study. Haemophilia. 2014;20:121–128.
   PubMed Web of Science ®Google Scholar
• Italian Association Hemophilia Centre (AICE). Tagariello G, Iorio A, Santagostino E, et al. Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders. Blood. 2009;114:779–784.
   PubMed Web of Science ®Google Scholar
• Nagel K, Walker I, Decker K, et al. Comparing bleed frequency and factor concentrate use between haemophilia A and B patients. Haemophilia. 2011;17:872–874.
   PubMed Web of Science ®Google Scholar
• Tobase P, Lane H, Siddiqi -A-E-A, et al. Hemophilia treatment center network (HTCN) study investigators. Risk factors associated with invasive orthopaedic interventions in males with haemophilia enrolled in the universal data collection program from 2000 to 2010. Haemophilia. 2018;24:964–970.
   PubMed Web of Science ®Google Scholar
• Petkovic MJ, Tran HA, Ebeling PR, et al. Osteoporosis management and falls prevention in patients with haemophilia: review of haemophilia guidelines. Haemophilia. 2022;28:388–396.
   PubMed Web of Science ®Google Scholar