Osteonecrosis Of The Femoral Head In Patients Research Articles

A prediction model for osteonecrosis of femoral head after internal fixation with multiple cannulated compression screws for adult femoral neck fractures.

This study aims to investigate the high-risk factors for osteonecrosis of the femoral head (ONFH) after internal fixation with multiple cannulated compression screws for adult femoral neck fractures and to construct a prediction model. Between from January 2012 and December 2020, a total of 268 patients (138 males, 130 females; mean age: 53±10 years; range, 23 to 70 years) with ONFH who had complete follow-up data were included. Closed reduction in combination with open reduction were performed. All patients received internal fixation with multiple cannulated compression screws and were assigned to ONFH and non-ONFH groups. Logistic regression model was utilized to identify independent risk factors for postoperative ONFH, followed by constructing a nomogram prediction model. The predictive ability of the model was evaluated by receiver operating characteristic curve, Hosmer-Lemeshow test, and calibration curve. Multivariate analysis revealed that older age (odds ratio [OR]: 2.307, 95% confidence interval [CI]: 1.295-4.108], Charlson Comorbidity Index (CCI) ≥2 (OR: 2.214, 95% CI: 1.035-4.739), fracture displacement (OR: 2.426, 95% CI: 1.122-5.247), unsatisfactory reduction (OR: 2.629, 95% CI: 1.275-5.423), postoperative removal of internal fixation implant (OR: 2.200, 95% CI: 1.051-4.604) were independent risk factors for postoperative ONFH (p<0.05). The nomogram prediction model constructed based on these clinical characteristics showed high predictive value (AUC=0.807) and consistency (p>0.05). Age, comorbidity index, fracture type, reduction quality and postoperative removal of internal fixation implant are of utmost importance for postoperative ONFH in patients with femoral neck fractures. The established nomogram prediction model can accurately predict the occurrence of postoperative ONFH.

Incidence and risk factors for osteonecrosis of the femoral head in five hundred and ten sickle cell disease paediatric patients.

Osteonecrosis of the femoral head (ONFH) is a degenerative and progressive disorder that mainly affects people with sickle cell disease (SCD). Herein, we aimed to search for a better understanding of markers that can act as risk factors for ONFH in patients with SCD. We conducted a retrospective study including 510 SCD patients followed over 23years. Patients were divided into the ONFH group and the no-ONHF control group. Univariate and multivariate logistic regression analyses were performed to identify risk factors. Among 510 SCD patients, 41(8%) were diagnosed with ONFH at a mean age of 167months ± 64 (72-288). The cumulative incidence of ONHF increased from 2.3% at tenyears to 18.3% at 20years of age. The radiological grade 3 ONHF was predominant. No significant differences in sex, age at diagnosis of SCD, and Hb genotype were found between groups. The patient age and the time since diagnosis of SCD were statistically higher in patients with ONHF in univariate and multivariate analysis. ONHF was also associated with higher creatinine level (p = 0.001) lower LDH level (p = 0.006), and higher number of vaso-occlusive crisis (VOC)/patient/year (p < 0.001). The cumulative incidence of ONHF in patients having more than 3 VOC/year was significantly higher (43% versus 18.9% at 20years, p < 0.001). In addition, infections, gallstones, growth delay, delayed initiation of hydroxyurea, and a higher transfusion rate were significantly associated with ONFH. These findings confirm that ONFH is closely related to the age, severity, and duration of SCD. Better management of this disease prevents acute and chronic complications, and early screening of the ONFH as soon as the first signs of the severity of the disease are detected provides a better functional prognosis.

Outcomes Following Total Hip Arthroplasty for Osteonecrosis of the Femoral Head in Patients on Hemodialysis.

Osteonecrosis of the femoral head (ONFH) is a potentially debilitating condition, often requiring total hip arthroplasty (THA). Patients on hemodialysis (HD) are at increased risk for complications after THA for osteoarthritis, however there is limited information on outcomes of THA for ONFH in patients on HD. With increasing prevalence of chronic kidney disease (CKD) requiring HD, studies are needed to characterize the risk of complications in these patients. Therefore, the purpose of this study was to evaluate HD as a potential risk factor for complication after THA in patients with ONFH on HD. Patients on HD with ONFH who underwent THA with at least 2 years of follow-up were identified using a combination of ICD-9 and CPT codes in a national insurance database. A 10:1 matched control cohort of patients with ONFH not on HD was created for comparison. A logistic regression analysis was used to evaluate rates of death, hospital readmission, emergency room (ER) visit, infection, revision, and dislocation between cohorts. Differences in hospital charges, reimbursement, and length of stay between the two groups were also assessed. One thousand one hundred thirty-seven patients on HD who underwent THA for ONFH were compared to a matched control cohort of 11,182 non-HD patients who underwent THA for ONFH. Patients on HD experienced higher rates of death (HD 4.1%, non-HD 0.9%; odds ratio [OR] 3.35, p < 0.01), hospital readmission (HD 16.1%, non-HD 5.9%; OR 2.69, p < 0.01) and ER visit (HD 10.4%, non-HD 7.4% OR 1.5, p < 0.01). Hemodialysis was not associated with higher risk of infection, revision, or dislocation, but was associated with significantly higher charges (p < 0.01), reimbursement (p < 0.01), and hospital length of stay (p < 0.01). While patients on HD do not have increased risk of implant-related complications, they are at increased risk of developing medical complications following THA for ONFH and subsequently may require more resources. Orthopedic surgeons and nephrologists should be cognizant of the increased risk in this population to provide appropriate preoperative counseling and enhanced perioperative medical management. Therapeutic Level III.

Associations between glucocorticoids, antiphospholipid antibodies and femur head necrosis in patients with SLE: a directed acyclic graph-based multicentre study.

Background:Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE.Methods:We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis.Results:Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0–1.1; GC therapy duration (3–5 years: aOR 3.3, 95% CI 1.4–7.8; >5 years: aOR 8.0, 95% CI 3.3–19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9–10.1); positive aPLs (aOR 2.8, 95% CI 1.4–5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4–19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82–0.94).Conclusion:Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.

Risk factors for osteonecrosis of the femoral head in brain tumor patients receiving corticosteroid after surgery.

PurposeNon-traumatic osteonecrosis of the femoral head (ONFH) is a plausible complication in brain tumor patients. Frequent use of corticosteroid therapy, chemotherapy, and oxidative stress for managing brain tumors may be associated with the development of ONFH. However, there is little knowledge on the prevalence and risk factors of ONFH from brain tumor. This study aimed to investigate the prevalence and risk factors of ONFH in patients with primary brain tumors.MethodsThis retrospective cohort study included data from consecutive patients between December 2005 and August 2016 from a tertiary university hospital in South Korea. A total of 73 cases of ONFH were identified among 10,674 primary brain tumor patients. After excluding subjects (25 out of 73) with missing data, history of alcohol consumption or smoking, history of femoral bone trauma or surgery, comorbidities such as systemic lupus erythematosus (SLE), sickle cell disease, cancer patients other than brain tumor, and previous diagnosis of contralateral ONFH, we performed a 1:2 propensity score-matched, case–control study (ONFH group, 48; control group, 96). Risk factors of ONFH in primary brain tumor were evaluated by univariate and multivariate logistic regression analyses.ResultsThe prevalence of ONFH in patients with surgical resection of primary brain tumor was 683.9 per 100,000 persons (73 of 10,674). In this cohort, 55 of 74 patients (74.3%) underwent THA for ONFH treatment. We found that diabetes was an independent factor associated with an increased risk of ONFH in primary brain tumor patients (OR = 7.201, 95% CI, 1.349–38.453, p = 0.021). There was a significant difference in univariate analysis, including panhypopituitarism (OR = 4.394, 95% CI, 1.794–11.008, p = 0.002), supratentorial location of brain tumor (OR = 2.616, 95% CI, 1.245–5.499, p = 0.011), and chemotherapy (OR = 2.867, 95% CI, 1.018–8.069, p = 0.046).ConclusionsThis study demonstrated that the prevalence of ONFH after surgical resection of primary brain tumor was 0.68%. Diabetes was an independent risk factor for developing ONFH, whereas corticosteroid dose was not. Routine screening for brain tumor-associated ONFH is not recommended; however, a high index of clinical suspicion in these patients at risk may allow for early intervention and preservation of the joints.

Osteonecrosis of the Femoral Head in Korean Patients with Human Immunodeficiency Virus Infection.

BackgroundOsteonecrosis of the femoral head (ONFH) is a disabling condition that often necessitates total hip arthroplasty (THA). Although ONFH occurs more frequently among patients with human immunodeficiency virus (HIV) than among the general population, there is little epidemiological information regarding ONFH in Korean patients with HIV. In the present study, we aimed to investigate the incidence and clinical features of ONFH among Korean patients with HIV.Materials and MethodsIn this retrospective study, we reviewed the medical records of 1,250 Korean patients with HIV treated from January 1990 to December 2019. A standardised data collection sheet was used to obtain clinical information. Imaging data were analysed by a radiologist in accordance with the 2019 revised version of the Association Research Circulation Osseous (ARCO) staging system for ONFH.ResultsAmong the 1,250 included patients, 13 patients (1.04%; 3 women, 10 men) were diagnosed with ONFH. The overall incidence of ONFH was 1.29 per 1,000 person-years (PYs) (95% confidence interval [CI]: 0.7 – 2.4 per 1,000 PYs). Median age among the 13 patients with ONFH was 47 years (interquartile range [IQR]: 41 – 57 years). The median duration since HIV diagnosis was 4.8 years (IQR: 2.3 – 10.1 years). The median CD4 cell count at the time of ONFH diagnosis was 381 cells/ mm3 (IQR: 161 – 551 cells/mm3). At the initial diagnosis of ONFH, 83.3% of patients exhibited bilateral involvement. ARCO stage 3 or 4 osteonecrosis was observed in 83% of patients. Among 22 hips, stage 1 ONFH was noted in 2 (9.1%), stage 2 ONFH was noted in 7 (31.8%), stage 3 ONFH was noted in 9 (40.9%), and stage 4 ONFH was noted in 4 (18.2%). THA was eventually performed in 84.6% of patients. Five (38.5%) patients had a history of steroid use, 4 (30.8%) patients had a history of alcohol abuse and 10 (76.9%) were smokers. Eight (61.5%) patients had a history of acquired immune deficiency syndrome-defining illness, including 7 with tuberculosis and 1 with pneumocystis pneumonia. Nine patients (69.2%) had a nadir CD4 cell count <200/µL, and 3 (23.1%) had a history of bone fracture. Overall, 84% of patients were exposed to antiretroviral therapy, while 54% had taken protease inhibitors for more than 1 year.ConclusionConsidering that relatively high incidence of ONFH in patients with HIV, a high index of suspicion for those with risk factors and those with groin or hip pain for is required in HIV-infected patients.

Increased COUP-TFII Expression Mediates the Differentiation Imbalance of Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Osteonecrosis.

Objective Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation potential, which allows them to progress to osteogenesis, adipogenesis, and chondrogenesis. An imbalance of differentiation between osteogenesis and adipogenesis will result in pathologic conditions inside the bone. This type of imbalance is also one of the pathological findings in osteonecrosis of the femoral head (ONFH). Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was previously reported to mediate the differentiation of mesenchymal stem cells. This study investigated the expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, and COUP-TFII in the femoral head tissue harvested from ONFH patients, and characterized the effect of COUP-TFII on the differentiation of primary BMSCs. MethodsThirty patients with ONFH were recruited and separated into 3 groups: the trauma-, steroid- and alcohol-induced ONFH groups (10 patients each). Bone specimens were harvested from patients who underwent hip arthroplasty, and another 10 specimens were harvested from femoral neck fracture patients as the control group. Expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, C/EBP-α, and COUP-TFII was analyzed by Western blotting. Primary bone marrow mesenchymal cells were harvested from ONFH cells treated with COUP-TFII RNA interference to evaluate the effect of COUP-TFII on MSCs. ResultsONFH patients had significantly increased expression of the adipogenesis regulator PPARγ and C/EBP-α and decreased expression of the osteogenesis regulator osteocalcin. ONFH bone tissue also revealed higher COUP-TFII expression. Immunohistochemical staining displayed strong COUP-TFII immunoreactivity adjacent to osteonecrotic trabecular bone. Increased COUP-TFII expression in the bone tissue correlated with increased PPARγ and decreased osteocalcin expression. Knockdown of COUP-TFII with siRNA in BMSCs reduced adipogenesis and increased osteogenesis in mesenchymal cells. ConclusionIncreased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. This study might reveal a new target in the treatment of ONFH.

High triglyceride is a risk factor for silent osteonecrosis of the femoral head in systemic lupus erythematosus.

The purpose of this study was to clarify the factors related to silent osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Seventy-eight patients with SLE were selected on the basis of having been newly diagnosed and requiring high-dose prednisolone, including pulse therapy with methylprednisolone, as the initial treatment. All the patients initially underwent MRI at 3 months after the start of corticosteroid treatment to detect any early changes in the femoral head. These examinations were then performed again 3 months later. Laboratory parameters were evaluated at the start of steroid treatment and at 1 month thereafter. By 3 months after the start of corticosteroid treatment, silent ONFH was diagnosed by MRI in 21 patients (26.9 %), being bilateral in 11 patients and unilateral in 10. The occurrence of silent ONFH was not related to SLE disease activity index, serological activity, or renal function; it was also unrelated to body mass index (BMI), body surface area (BSA), and the initial dose of prednisolone per unit body weight. However, the total cholesterol level at 4 weeks after the start of steroid treatment tended to be higher in patients with silent ONFH. Patients with a higher triglyceride level showed a significantly higher frequency of silent ONFH both before (p = 0.002) and 4 weeks after (p = 0.036) steroid initiation.A high triglyceride level is an important risk factor for silent ONFH in patients with SLE, and large-scale epidemiologic surveys of such early events are needed in this patient population.

Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan

Objectives. To elucidate the epidemiology of nontraumatic osteonecrosis of the femoral head (ONFH), and to estimate the annual incidence rate in Japan.Methods. We examined, over the course of 3 years, personal records and radiographic images from the national registry of documents used for the study of nontraumatic ONFH in patients in Aichi Prefecture, Japan (population: 7.4 million). Those patients not meeting the diagnostic criteria according to the Japanese Investigation Committee for nontraumatic ONFH were excluded from this study.Results. A total of 285 out of the 327 patients who applied for the national registration of nontraumatic ONFH during the 3-year study met the diagnostic criteria for personal records, radiographic images, and magnetic resonance images. Forty-two patients (12.8%) were not considered to have nontraumatic ONFH. The mean age of patients was 50.4 years, and the male-female ratio was 2.1:1. Nontraumatic ONFH was steroid-induced in 135 cases (47.4%), alcohol-associated in 87 cases (30.5%), steroid-induced and alcohol- associated in 14 cases (4.9%), and idiopathic in 49 cases (17.2%).Conclusions. The age-adjusted annual incidence of nontraumatic ONFH in Aichi Prefecture was estimated at 138.5 patients.Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000.

Free vascularized fibular grafting for patients receiving postoperative corticosteroids.

Free vascularized fibular grafting (FVFG) is an effective method to treat corticosteroid-induced osteonecrosis of the femoral head (ONFH). Some patients continued to receive maintenance doses of corticosteroids to treat the primary disease postoperatively. This study was performed to evaluate outcomes of FVFG for corticosteroid-induced ONFH in patients who continued to receive corticosteroids postoperatively. The authors retrospectively reviewed the records of 44 patients (78 hips) who had received corticosteroid treatment for their primary disease after FVFG. They were followed up for at least 2 years (mean, 5.6 years). Demographic details, Harris Hip scores, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and radiographic data were collected and analyzed. The mean Harris Hip score for all hips was 70.9±9.9 points before surgery and increased to 84±12.1 points at the latest follow-up. There were also significant increases (P<.05) in physical component summary score and mental component summary score. According to the latest radiographic evaluation, 49 hips (62.8%) appeared improved, 10 hips (12.8%) appeared unchanged, and only 19 hips (24.4%) appeared worse. Seven hips (9%) underwent total hip arthroplasty during the follow-up period. Therefore, the results showed that FVFG was a viable method of treating corticosteroid-induced ONFH in patients who receive maintenance doses of corticosteroids postoperatively.

The influence of age, gender and treatment with steroids on the incidence of osteonecrosis of the femoral head during the management of severe acute respiratory syndrome

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Clinico-radiological factors affecting the joint space narrowing after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head

PurposeThe purpose of this study was to investigate the factors that affect the joint space narrowing after transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH). MethodsWe reviewed 39 cases (43 hips) of ONFH in patients who underwent ARO between 2000 and 2004. Their mean age was 42years (23–61) at the time of surgery. The mean follow-up period was 7.3years (3–10). The following clinical and radiological factors were investigated: the preoperative stage, localization and extent of the necrotic lesion, and the postoperative intact ratio (transposed intact articular surface of the femoral head to the weight-bearing surface of the acetabulum). The 43 hips were divided into two groups: a joint space narrowing (JSN) group and a non-joint space narrowing (non-JSN) group. ResultsThirty-seven hips (86 %) were categorized as non-JSN and six (14 %) as having JSN. The preoperative Japanese Orthopaedic Association score was significantly higher in the non-JSN group than in the JSN group (P = 0.01). In the non-JSN group, the rate of early stage disease was significantly higher than in the JSN group (P = 0.03). The postoperative intact ratio was significantly higher in the non-JSN group than in the JSN group (P = 0.002). A multivariate analysis revealed that the postoperative intact ratio was an independent predictor of the progression of joint space narrowing after ARO, and the cutoff point was 39.2 %. ConclusionThe results of this study suggest that the postoperative intact ratio is one of factors determining the progression of joint space narrowing after ARO and that an approximately 40 % or higher postoperative intact ratio is recommended to prevent joint space narrowing.

Increased prevalence of osteonecrosis of the femoral head in children and adolescents with sickle‐cell disease

anemia. Blood 2010;115:5300–5311. 10. Thornburg CD, Calatroni A, Telen M, Kemper AR. Adherence to hydroxyurea therapy in children with sickle cell anemia. J Pediatr 2010;156:415–419. 11. Sichle Cell Disease Guidelines-Hydroxyurea Chapter. http://rover.nhlbi.nih. gov/guidelines/scd/about.htm. Accessed November 21, 2011. 12. de Montalembert M, Brousse V, Elie C, et al. Long-term hydroxyurea treatment in children with sickle cell disease: Tolerance and clinical outcomes. Haematologica 2006;91:125–128. 13. Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 2004;103:2039–2045. 14. Burgess SW SP, Morawska A, Devadason SG. Assessing adherence and factors associated with adherence in young children with asthma. Respirology 2008;13:559–563. 15. Jentzsch NS, Camargos PA, Colosimo EA, Bousquet J. Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods. Allergy 2009;64:1458–1462. 16. Thornburg CD, Calatroni A, Telen M, Kemper AR. Adherence to hydroxyurea therapy in children with sickle cell anemia. J Pediatr 2010;156:415– 419. 17. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353: 487–497. 18. Franklin VL, Waller A, Pagliari C, Greene SA. A randomized controlled trial of Sweet Talk, a text-messaging system to support young people with diabetes. Diabet Med 2006;23:1332–1338. 19. Lee SJ, Joffe S, Kim HT, et al. Physicians’ attitudes about quality-of-life issues in hematopoietic stem cell transplantation. Blood 2004;104:2194– 2200. 20. Wong EC, Perez-Albuerne E, Moscow JA, Luban NL. Transfusion management strategies: A survey of practicing pediatric hematology/oncology specialists. Pediatr Blood Cancer 2005;44:119–127. 21. Streiff MB, Smith B, Spivak JL. The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: A survey of American Society of Hematology members’ practice patterns. Blood 2002;99: 1144–1149.

Risk factor of osteonecrosis of the femoral head in patients with systemic lupus erythematosus

Objective To investigate the risk factor of osteonecrosis of the femoral head (ONFH)in patients with systemic lupus erythematosus (SLE).Methods 376 patients with SLE in our hospital were enrolled in the present study.The retrospective analysis was made to investigate the risk factor of ONFH on the pathological and follow-up data.Results The incidence of ONFH in 376 SLE patients was 7.18%.Oral ulcer,Renault's phenomenon,vasculitis,osteoporosis,TC,TG,accumulated dosage of hormone and hormone intensive therapy were the risk factors of ONFH.Conclusion The incidence of ONFH in patients with SLE is relatively high,and the risk factors include Renault' s phenomenon,vasculitis,osteoporosis,TC,TG and usage of immunosuppresive treatment,especially the hormone intensive therapy with large doses. Key words: Lupus erythematosus; Femur head necrosis; Risk factor

Extracorporeal shockwave for hip necrosis in systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) frequently received corticosteroid therapy, resulting in osteonecrosis of the femoral head (ONFH). Prior studies demonstrated the effectiveness of extracorporeal shockwave treatment (ESWT) for ONFH.. This study evaluated the effectiveness of ESWT for ONFH in patients with SLE. We studied 39 patients, including 15 patients with SLE (26 hips) and 24 controls (29 hips). To each affected hip we applied ESWT (6000 impulses at 28 kV in a single session). Patients were ambulated with partial weight bearing for 4-6 weeks. The primary endpoint was the need for hip replacement. The secondary endpoints were improvement in hip pain and function and image changes on X-ray and MRI. Patients received total hip replacement in 12% of patients with SLE and in 14% of controls (P = 0.802). There was no statistically significant difference in pain scores (0.86 vs. 0.89; P = 0.467) and function scores (89% vs. 91%; P = 0.194) between patients with SLE and controls. SLE response to ESWT for ONFH is comparable with ONFH in patients without SLE.

Notable Difference between the Development of Vertebral Fracture and Osteonecrosis of the Femoral Head in Patients Treated with High-dose Glucocorticoids for Systemic Rheumatic Diseases

Vertebral fracture (VF) and osteonecrosis of the femoral head (OFH) are serious concerns in patients with rheumatic diseases treated with high-dose glucocorticoids (GCs). We comparatively examined the risk factors of VF and OFH in patients who had recently received high-dose GC therapy. Patients with rheumatic diseases receiving GCs (> or =0.5 mg/kg/day for prednisolone equivalent) within the past 2 months were enrolled in this study, and treated with 200 mg/day of etidronate cyclically. The bone mineral density (BMD) of the lumbar spine (L2-4) was examined by QDR2000. OFH was evaluated by magnetic resonance imaging (MRI). [ClinicalTrials.gov identifier: NCT00679978]. Forty-four patients completed the 2-year study including annual X-rays and the BMD analysis. MRI evaluation at entry and 2 years was performed in 41 patients. The BMD values with anteroposterior (AP) and lateral views decreased by 6.4% and 9.7%, respectively, in the first year, but were stable in the second year. Eleven patients developed VF and 9 patients developed OFH. The risk factors for VF included previous VF and a low BMD value (T score<-1.5) of AP view at baseline with an odds ratio (OR) of 14.9 (95%CI 2.9-76.4), while the risk factor for OFH was a recent maximum GC dosage (>1.2 mg/kg/day versus< or =; OR=7.7, 95%CI 1.3-45.5) and a decrease in BMD value of lateral view (>15% versus< or =; OR=6.7, 95% CI 1.2-36.1) in the first year. The development of VF relies on the predisposing factors, while that of OFH depends on the response to high-dose GC therapy.

Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis

Osteonecrosis of the femoral head (ONFH) is one of the major side effects of corticosteroid therapy. Because corticosteroids are metabolized by hepatic cytochrome P450 (CYP) 3A, a low endogenous activity of this enzyme may contribute to the pathogenesis of ONFH. The purpose of this study was to examine the possible association of hepatic CYP3A activity and the susceptibility to ONFH in patients treated with corticosteroids. In this prospective controlled study we measured the clearance of intravenous midazolam (0.25 mg/kg) to estimate hepatic CYP3A activity in patients with steroid-induced ONFH (n = 26), patients with alcohol-related ONFH (n = 29), and non-ONFH control patients (n = 75) undergoing orthopedic surgery. Midazolam clearance was compared between the groups, and the relationship between the level of hepatic CYP3A activity and the prevalence of ONFH was evaluated by multivariate analysis. Midazolam clearance in patients with steroid-induced ONFH was significantly lower than that in control patients and patients with alcohol-related ONFH (7.7 +/- 1.8 mL x kg(-1) x min(-1) versus 11.4 +/- 3.5 mL x kg(-1) x min(-1) and 10.5 +/- 2.8 mL x kg(-1) x min(-1), respectively; P < .001). Patients with low midazolam clearance (<9.5 mL x kg(-1) x min(-1)) had a 9-fold greater risk for steroid-induced ONFH (adjusted odds ratio, 9.08 [95% confidence interval, 2.79-29.6]; P < .001). Midazolam clearance did not show a significant correlation with the prevalence of alcohol-related ONFH. Low hepatic CYP3A activity may significantly contribute to the risk for steroid-induced ONFH.