To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.
A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.
With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.
AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.
[Show abstract][Hide abstract] ABSTRACT: Despite the large number of the outstanding researches, pathogenesis of osteonecrosis remains unknown. During the last decades the hypothesis that increased intravascular coagulation may be the pathogenetic mechanism which leads to osteonecrosis is gaining constantly support. Both primary factors of hyper-coagulability, such as resistance to activated protein C, protein C and protein S deficiency, low levels of tissue plasminogen activator, high levels of plasminogen activator inhibitor, von Willebrand factor, lipoprotein (a), and secondary factors of hypercoagulability with factors potentially activating intravascular coagulation, such as pregnancy, antiphospholipid antibodies, systemic lupus erythematosus, hemoglobinopathies and sickle cell disease, and hemato-oncologic diseases are discussed in this article. Although coagulation abnormalities in patients with hip osteonecrosis might represent increased risk factors for the development of bone necrosis by predisposing the patient to thromboembolic phenomena, further investigation is needed to indicate the definite correlation between factors leading to increased intravascular coagulation and pathogenesis of osteonecrosis.
"As observed in other studies, a history of connective tissue disease or cancer were significant risk factors for ON. This may be confounded by the frequent use of corticosteroids in these populations [4–6, 20]. In addition, overall disease severity/morbidity may also contribute to a higher rate of ON in these populations [1, 4]. "
[Show abstract][Hide abstract] ABSTRACT: We conducted a case-control study to examine osteonecrosis (ON) incidence, patient characteristics, and selected potential risk factors using two health record databases in the UK. Statistically significant risk factors for ON included systemic corticosteroid use, hospitalization, referral or specialist visit, bone fracture, any cancer, osteoporosis, connective tissue disease, and osteoarthritis.
The purpose of this case-control study was to examine the incidence of osteonecrosis (ON), patient characteristics, and selected potential risk factors for ON using two health record databases in the UK: the General Practice Research Database and The Health Improvement Network.
ON cases (n = 792) were identified from 1989 to 2003 and individually matched (age, sex, and medical practice) up to six controls (n = 4,660) with no record of ON. Possible risk factors were considered for inclusion based on a review of published literature. Annual incidence rates were computed, and a multivariable logistic regression model was derived to evaluate selected risk factors.
ON of the hip represented the majority of cases (75.9%). Statistically significant risk factors for ON were systemic corticosteroid use in the previous 2 years, hospitalization, referral or specialist visit, bone fracture, any cancer, osteoporosis, connective tissue disease, and osteoarthritis within the past 5 years. Only 4.4% of ON cases were exposed to bisphosphonates within the previous 2 years.
This study provides further perspective on the descriptive epidemiology of ON. Studies utilizing more recent data may further elucidate the understanding of ON key predictors.
Osteoporosis International 07/2009; 21(4):569-77. DOI:10.1007/s00198-009-1003-1 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SUMMARY Dexamethasone is a synthetic glucocorticosteroid which has minimal mineralocorticoid activity. It is a potent anti-inflammatory drug with 25-50 times the potency of hydrocortisone and is up to sixteen times as potent as prednisolone. Dexamethasone is utilised frequently in the perioperative setting, including prophylaxis against postoperative nausea and vomiting, reduction of airway and cerebral oedema, and it may be useful in the management of acute and chronic pain. This review is intended to outline some of the perioperative uses of dexamethasone and elucidate areas where further research is needed. PHARMACOLOGY Like all glucocorticoids, dexamethasone acts on the glucocorticoid receptor which is a member of the nuclear receptor superfamily, subfamily 3C. Multiple signalling pathways are involved following binding of the steroid to the receptor, including direct DNA binding which results in changes to gene transcription. This results in changes to carbohydrate, protein and fat metabolism as well as changes to gluconeogenesis. Of interest in the perioperative setting is the decreased release of bradykinin, tumour necrosis factor, interleukin-1, interleukin-2 and interleukin-6 and decreased production of prostaglandins
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