Pathogenesis and natural history of osteonecrosis

Assouline-Dayan, Yehudith; Chang, Christopher; Greenspan, Adam; Shoenfeld, Yehuda; Gershwin, M. Eric

doi:10.1053/sarh.2002.33724b

Cited by 636 publications

(118 citation statements)

References 137 publications

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“…We conclude that our findings, in part, are a result of the concurrent use of antiangiogenic agents and bisphosphonates. In a significant proportion of these patients, impaired blood supply has been implicated in the development of ONJ [1]. Bisphosphonates have been reported to possess antiangiogenic activity [6, 7].…”

Section: Discussionmentioning

confidence: 99%

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Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone

et al. 2009

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Background: The use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). Antiangiogenic agents are used with increasing frequency and may induce the risk of ONJ, especially when administered concurrently with bisphosphonates. Patients and Methods: We retrospectively reviewed data of 116 patients receiving bisphosphonates, 78 zoledronic acid and 38 ibandronic acid, with or without antiangiogenic agents for osseous metastases from various tumors in our department from June 2007 to June 2008. Results: ONJ developed in: 2 patients with breast cancer and 1 with colon cancer receiving concurrently bisphosphonates and bevacizumab, 1 patient with renal cell carcinoma receiving sunitinib and zoledronic acid concurrently, and 1 patient with prostate cancer receiving zoledronic acid without antiangiogenic agents. The incidences of ONJ among patients receiving bisphosphonates with or without antiangiogenic agents were 16 and 1.1%, respectively. The difference was statistically significant (p = 0.008). The treatment duration of bisphosphonates did not differ significantly between the 2 groups. Conclusions: The combination of bisphosphonates and antiangiogenic factors induces ONJ more frequently than bisphosphonates alone. These preliminary observations should be evaluated in large cohorts of patients and in prospective studies.

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Section: Discussionmentioning

confidence: 99%

“…Cancer and its treatment have been described as risk factors for the development of osteonecrosis [1]. Particularly, the use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ) [2,3,4,5].…”

Section: Introductionmentioning

confidence: 99%

Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone

et al. 2009

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“…Hence, new diagnoses of ON, initially made by the radiologist and confirmed by the orthopedic or dental surgeon or clinician [55], rarely undergo a rigorous workup for thrombophilia or hypofibrinolysis [5]. This represents a clinically important missed-opportunity as many patients may be inadequately treated for their joint pain [56] while thrombophilia-hypofibrinolysis, a treatable [7, 26] causative etiology of primary ON (Ficat Stages I-II), goes unaddressed [5]. …”

Section: Discussionmentioning

confidence: 99%

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

et al. 2017

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BackgroundFamilial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentationCase 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months.ConclusionsIdiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

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“…The relationship between systemic steroids and osteonecrosis has been established, particularly in regard to adults and systemic steroids [3]. The information on the role of inhaled corticosteroids is markedly less publicized, but their use has been shown to have a negative effect on bone health, especially in regard to impeding bone remodeling [4]. Fluticasone propionate, one of the most prescribed medications for chronic asthma, has in particularly been shown to exhibit greater dose related systemic bioactivity compared to other available inhaled corticosteroids, especially at doses >0.8 mg/d [5].…”

Section: Discussionmentioning

confidence: 99%

Osteonecrosis of the Femoral Head in an Adolescent on Long-Term Inhalational Corticosteroids

Egger

Ballock

2017

Case Reports in Pediatrics

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A relationship between the development of osteonecrosis of the femoral head and systemic corticosteroids has been well established in the literature, particularly in adults. However, the link between osteonecrosis and inhaled corticosteroids is less researched and understood. We report an usual case report of a 10-year-old male who developed ipsilateral femoral head osteonecrosis after long-term inhalational corticosteroid and intermittent short courses of oral steroid usage with a unique presentation and delayed diagnosis.

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Pathogenesis and natural history of osteonecrosis

Cited by 636 publications

References 137 publications

Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone

Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

Osteonecrosis of the Femoral Head in an Adolescent on Long-Term Inhalational Corticosteroids

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