Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach
Abstract
:1. Introduction
2. Search Strategy
3. Evidence of Fractures in Haemophilia
Publication | Study Design | Patient Features | Fracture Incidence | Results | Correlations between Haemophilia and Fractures |
---|---|---|---|---|---|
Pai et al., 2022 [35] | Retrospective study (compared the incidence of all-site fractures, repeated fractures and osteoporotic fractures occurring in all PWH) | 9152 (832 vs. 8320) Age: <20 years 4576 (50.00%) 20–39 years 3135 (34.25%) 40–64 years 1210 (13.22%) ≥65 years 231 (2.52%) Sex: NA | The incidence of fractures in PWH is inconclusive, and no research has yet explored repeated fractures among PWH. | Screening, prevention and treatment of osteoporosis and further osteoporotic fractures among PWH remain essential in order to improve quality of life and achieve healthy aging in this particular population. | PWH had a higher risk of osteoporotic fracture, but the haemophilia only had a neutral effect in all sites of fracture and repeated fractures. |
Tuan et al., 2019 [32] | Nationwide population-based cohort study based on the data in the Taiwan National Health Insurance Research Database (PWH vs. control patients without haemophilia) | 375 (75 vs. 300) Age: 35.7 (11.2–48.3) vs. 35.7(11.2–48.3) Sex: M:45 F: 30 vs. M:120 F:180 | The cumulative incidence was significantly higher for PWH diagnosed more than 5 years | Strong association between haemophilia and the development of osteoporotic fractures after haemophilia diagnosis. The relative risk of osteoporotic fracture after haemophilia in PWH increased with age in those aged <65 years compared with non-PWH. Clinicians should pay particular attention to osteoporotic fractures after haemophilia in PWH as they age. | PWH have significantly lower bone mineral density. Lower bone mineral density may lead to fragile in-bone structure and even osteoporotic fractures. |
Angelini et al., 2016 [54] | Review (focused on common complications affecting the older haemophilia population, including joint disease, cardiovascular disease, malignancy, renal insufficiency and liver disease) | Comparison of age distribution of PWH between 2011 and 2015 (Age <45 vs. Age 45–64 vs. Age >65) Sex: NA | Markedly increased risk of fracture in PWH, which corresponding with both disease severity and increasing age | The elderly PWH must cope with chronic joint arthropathy, which provokes falls and fractures, and complications related to HIV and HCV infections, which greatly impact the incidence of cancer and liver disease. | Aside from functional impairment, PWH are also at higher risk of fractures secondary to decreased bone mineral density. |
Strauss et al., 2016 [57] | Retrospective study (PWH with surgical fracture fixation compared to a matched non-haemophilic control group) | 46 fractures after low-energy trauma in 44 PWH vs. 46 non-haemophilic patients Age: 42.4 ± 20.5 years (range, 7–85 years) vs. 43.8 ± 20.7 years (range, 14–84 years) Sex: M: 38 F: 6 vs. M:23 F: 23 | Higher incidence of fractures in PWH compared to a population without haemophilia | There was no significant difference regarding the duration of the preoperative hospital stay between PWH and controls. | End-stage haemophilic arthropathy, muscle atrophy and joint contracture on the one hand increase the risk of falling and on the other hand lead to osteoporosis, making the bone more susceptible to fracture after trivial trauma. |
Anagnostis et al., 2015 [28] | Review (on the current understanding of the association between haemophilia A or B and low bone mass, as well as the optimal approach and management of bone disease in these patients) | Age: NA Sex: NA | Data for increased fracture risk in PWH are currently not robust because of the rarity of the disease and the patients’ relatively young age; it can be speculated that it should be higher than in the general population | Regular exercise, prophylactic factor replacement therapy for severe haemophilia, fall prevention strategies and optimising calcium and vitamin D intake are recommended. | Except for low bone mineral density, PWH seem to be at increased fracture risk. Individualized multidisciplinary approach and careful assessment and management of risk factors associated with increased fracture risk are recommended. |
Angelini et al., 2015 [55] | Review (focus on common complications affecting the older PWH, including cardiovascular disease, malignancy, liver disease, renal insufficiency, and joint disease) | Age: mean age 54.5 years (range 31 to 72) vs. mean age 46.7 years (range 23 to 76) Sex: M: 11 F: 18 | Higher incidence of fractures in PWH | Elderly PWHs should be treated similarly to their peers without haemophilia, with the addition of factor replacement therapy as appropriate. Primary prevention of risk factors should be emphasized, and close coordination between specialties is essential | In the older PWH, chronic joint arthropathy provokes falls and thus an increased fracture risk |
Caviglia et al., 2015 [56] | Retrospective study (on 28 years’ experience treating PWH who suffered fractures and evaluating the impact of access to treatment) | 151 fractures in 141 PWH (25 vs. 35 vs. 33 vs. 31 vs. 27) Age: NA Sex: NA | Higher incidence of LL fractures in the first period analysed (1986–1990); over time, the ratio LL/UL changed as UL fractures became more frequent. This change is due access to treatment and specifically to the prophylaxis. | Fractures in PWH became more common in the UL than in the LL, lowering the age at which they occur and being less frequent. The advent of new and accessible treatments decreased the development of orthopedic complications and favours improvement in the quality of life of PWH. | Daily activities for PWH are reduced due to the impact of multiple bleeding episodes in the musculoskeletal system, leading to arthropathy and contractures. In addition, muscle wasting, osteoporosis, joint stiffness and malalignment can increase the risk of fractures. |
Gay et al., 2015 [52] | Retrospective study (on increased fracture rates in PWH: a 10-year single institution retrospective analysis) | 382 patients (316 with haemophilia A vs. 66 with haemophilia B) Age: 20 (±18) vs. 26 (±21) Sex: NA | PWH had an increased fracture rate compared with the control population. PWH with mild to moderate haemophilia had a significantly reduced risk of fracture compared with those with severe disease. | Increased fracture risk with increasing severity of haemophilia, coupled with the evidence for bleeding-independent mechanisms of decreased skeletal health, suggest factor replacement may directly impact bone health and fracture risk in PWH. | PWH have a higher risk of reduced bone mineral density than the general population. It is currently unclear how this predilection for reduced bone mineral density translates into fracture rates. |
Lee et al., 2007 [53] | Case report (comprehensive report on the management of a cohort of patients with fracture of neck of femur in haemophilia) | 11 Age: mean age was 30 years (range: 16–55) Sex: NA | In PWH, most of the femoral neck fractures (9 out of 11) are seen almost two decades earlier than in general population (where they occur in patients over 50 years of age) | In PWH, femoral neck fractures can be treated as in the general population, with modest dose of factor replacement. Postoperatively, prolonged use of plaster immobilization should be avoided and early mobilization of the ipsilateral knee joint should be initiated. | Although physical activity is often reduced in PWH, poor musculature, osteoporosis and haemophilic bone changes may predispose to an increased risk of fractures. |
4. Discussion
5. Conclusions
6. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Alito, A.; Bellone, F.; Portaro, S.; Leonardi, G.; Cannavò, V.; Coppini, F.; Leonetti, D.; Catalano, A.; Squadrito, G.; Fenga, D. Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach. Int. J. Mol. Sci. 2023, 24, 9395. https://doi.org/10.3390/ijms24119395
Alito A, Bellone F, Portaro S, Leonardi G, Cannavò V, Coppini F, Leonetti D, Catalano A, Squadrito G, Fenga D. Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach. International Journal of Molecular Sciences. 2023; 24(11):9395. https://doi.org/10.3390/ijms24119395
Chicago/Turabian StyleAlito, Angelo, Federica Bellone, Simona Portaro, Giulia Leonardi, Vittorio Cannavò, Francesca Coppini, Danilo Leonetti, Antonino Catalano, Giovanni Squadrito, and Domenico Fenga. 2023. "Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach" International Journal of Molecular Sciences 24, no. 11: 9395. https://doi.org/10.3390/ijms24119395