Risk factors for multi-joint disease in patients with glucocorticoid-induced osteonecrosis

Krez, Alexandra; Lane, Joseph M.; Heilbronner, Alison K; Park‐Min, Kyung‐Hyun; Kaneko, Kaichi; Pannellini, Tania; Mintz, Douglas N.; Hansen, David V.; McMahon, Donald J.; Kirou, Kyriakos A.; Roboz, G.J.; Bockman, Richard S.; Stein, Emily

doi:10.1007/s00198-021-05947-x

Cited by 10 publications

(13 citation statements)

References 44 publications

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“…The administration of these drugs may increase the risk of ON by up to 20 times [ 5 ]. It was also found that steroid use in some conditions is associated with multifocal disease, mainly rheumatic diseases—including SLE, malignancies (such as acute lymphoblastic leukemia and non-Hodgkin lymphoma), and pulmonary disease [ 51 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

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Osteonecrosis Related to Steroid and Alcohol Use—An Update on Pathogenesis

Konarski,

Poboży,

Konarska

et al. 2023

Healthcare

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Osteonecrosis (ON) is usually a progressive disease that negatively affects the quality of life and leads to significant disability. Most patients are aged 30–50 years and require multiple surgical interventions throughout their lifetime. In non-traumatic ON, alcohol abuse and corticosteroids are involved in up to 80% of cases. This narrative review aims to summarize data on their impact on healthy bone and the development of pathophysiological processes leading to ON development. We conducted EMBASE and MEDLINE database reviews to identify relevant research. We found that for both agents, the risk was time and dose-dependent. ON in alcohol and steroid use shared many pathogenetic mechanisms leading to the development of necrosis, including increased adipogenesis, the induction of chronic inflammation, vascular alterations, and impaired bone-cell differentiation. Because both alcohol and steroid use are modifiable factors, both general physicians and orthopedic surgeons should encourage patients to limit ethanol intake and avoid corticosteroid overuse. In the presence of ON, because both alcohol- and steroid-induced disease tend to be multifocal, addiction treatment and limiting steroid use are justified.

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Section: Resultsmentioning

confidence: 99%

“…Physiological levels of endogenous steroids are necessary for bone mass maintenance [ 50 , 59 ]. It is clear, however, that excess endogenous (as in the Cushing syndrome) and therapeutic steroids, as well as their deficiency (as seen in Addison’s syndrome), may seriously impact bone homeostasis [ 50 , 51 , 53 , 55 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

Osteonecrosis Related to Steroid and Alcohol Use—An Update on Pathogenesis

Konarski,

Poboży,

Konarska

et al. 2023

Healthcare

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“…Furthermore our study showed for the first time on an homogeneous population that children who received treatment against leukemia, presented with multifocal joint involvement (mainly weight-bearing joints) at ON diagnosis while in other systemic pathologies, such as sickle cell anemia, also known for the frequent occurrence of osteonecrosis, involvement is predominantly unifocal (80% of cases) 29 . This is probably due to corticosteroid therapy, since Kuhlen et al has shown it in adult population 30 and Krez et al also showed that a high cumulative dose of glucocorticoids was associated with a risk of multifocal disease in patients with different underlying conditions like systemic lupus erythematosus 31 .…”

Section: Discussionmentioning

confidence: 99%

Symptomatic osteonecrosis in French survivors of Childhood and Adolescent Leukemia: a clinical and radiological study from the L.E.A. program

HUAULT

Gautier

Charon

et al. 2022

Preprint

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Background. Osteonecrosis (ON) is a long-known complication of acute leukemia (AL) management affecting 1 to 10% of young patients, leading to long-term morbidity. Widespread access to Magnetic Resonance Imagery (MRI) over the past ten years has allowed earlier detection and more accurate assessment. This study investigated clinical and radiological features of ON, among the large French cohort L.E.A (Leucémie Enfant Adolescent) Procedure. Patients with ON were retrospectively enrolled and risk factors for the onset, the multifocal involvement and severe damage were analyzed. Quality of life (QoL) was also evaluated. A sub-study described radiological features. Results. 129/4973 patients developed ON (2.5%) and were preferentially aged over 10 years at time of AL diagnosis (OR 22.46, p <10-6). Females were preferentially affected (OR 1.8, p=0.002) like patients treated for relapse (OR 1.81, p=0.041). Patients presenting ON suffered more frequently from other sequelae (p<10-6). Most of the necrosis were involving weight-bearing joints and multiple joints in 69% of cases. MRI of 39 patients with ON were double blinded reviewed. Overall, 14/39 suffered from severe impairment, preferentially on hips. QoL of adolescents and adults was poor and permanently affected once ON occurred. Conclusions. Age of over 10 years at diagnosis of AL, relapse and female sex were at risk of developing ON involving preferentially multiple joints. One third was severe and lasting poor QoL impacting several domains was found. Future studies should include prospective data on management and biological genetic features to build a targeted screening program to detect and manage ON earlier.

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“…As a progressive and degenerative disease, osteonecrosis of the femoral head (ONFH) can cause subchondral micro-fracture and subsequent femoral head collapse, eventually leading to hip joint dysfunction ( 1 2 ). ONFH usually affects young to middle-aged individuals and poses a huge socioeconomic burden.…”

Section: Introductionmentioning

confidence: 99%

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

et al. 2022

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IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

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Risk factors for multi-joint disease in patients with glucocorticoid-induced osteonecrosis

Cited by 10 publications

References 44 publications

Osteonecrosis Related to Steroid and Alcohol Use—An Update on Pathogenesis

Osteonecrosis Related to Steroid and Alcohol Use—An Update on Pathogenesis

Symptomatic osteonecrosis in French survivors of Childhood and Adolescent Leukemia: a clinical and radiological study from the L.E.A. program

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

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