Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach

Alito, Angelo; Bellone, Federica; Portaro, Simona; Leonardi, Giulia; Cannavò, Vittorio; Coppini, Francesca; Leonetti, Danilo; Catalano, Antonino; Squadrito, Giovanni; Fenga, Domenico

doi:10.3390/ijms24119395

Cited by 5 publications

(2 citation statements)

References 72 publications

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“…Secondary OP is caused by rheumatoid arthritis, diabetes mellitus, chronic kidney disease, liver disease, and alcoholism, as well as endocrine, nutritional, drug-related (such as glucocorticoid-induced OP, etc. ), immobility, and congenital causes, and is still under active investigation [76][77][78][79][80][81][82].…”

Section: Epidemiologymentioning

confidence: 99%

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights

Yokota,

Ishizu,

Miyazaki

et al. 2024

Biomedicines

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The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential.

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Section: Epidemiologymentioning

confidence: 99%

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights

Yokota,

Ishizu,

Miyazaki

et al. 2024

Biomedicines

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“…32,33 Increased levels of DHCR7 have been found to contribute to the degradation of 7-DHC, a factor linked to the development of osteoporosis. 32,33 Although the activity and quantity of 1,25(OH)2D are not affected in patients with cirrhosis caused by cholestatic liver disease, 34,35 bone loss persists, 36 with the elevated content of DHCR7 potentially playing a contributing role. In addition, CYP2R1 and CYP27A1 exhibit decreased expression in the cirrhotic liver, leading to the levels of 1,25(OH)2D products, namely, 24,25-dihydroxyvitamin D (24,25(OH)2D) and 1,24,25-trihydroxyvitamin D (1,24,25(OH)3D3), are increased in cirrhosis patients, indicating diminished activity of VitD3 in individuals with chronic liver disease.…”

Section: Vitamind 3 (Vitd 3 )mentioning

confidence: 99%

The Regulation of Bone Metabolism by the Liver

Luo,

Zhang,

et al. 2024

Nature Cell and Science

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Chronic liver diseases and osteoporosis, seemingly unrelated diseases that occur with advanced age, are involved in different mechanisms contributing to liver and bone metabolic disorders. Secondary osteoporosis and increased bone fragility are common complications in patients with chronic liver disease, including common liver diseases such as nonalcoholic fatty liver disease, alcoholic fatty liver disease, and cholestatic hepatitis. Despite these associations, the intricate link between the liver and bones remains ambiguous. Here, we review the current molecules involved in liver-bone communication in three aspects: metabolic factors in the liver, hepatic modifying enzymes, and pro-inflammatory factors affected by liver and bone metabolism. The emphasis is on delineating the regulation of bone metabolism by the liver, with the aim of elucidating the intricate interplay between hepatic and bone metabolic processes. This exploration not only contributes to a better understanding of the dynamic relationship between the liver and bone but also lays the groundwork for more comprehensive therapeutic strategies targeting osteoporosis in patients with advanced chronic liver disease.

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Effects of coagulation factors on bone cells and consequences of their absence in haemophilia a patients

Battafarano,

Lancellotti,

Sacco

et al. 2024

Sci Rep

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Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients’ osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-75747-w.

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Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach

Cited by 5 publications

References 72 publications

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights

The Regulation of Bone Metabolism by the Liver

Effects of coagulation factors on bone cells and consequences of their absence in haemophilia a patients

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