Nontraumatic Osteonecrosis Of Femoral Head Research Articles

Comparison of sartorius muscle-pedicle and circumflex iliac deep bone flap grafts in the treatment of early non-traumatic osteonecrosis of femoral head in young adults

ObjectiveThe aim of this study was to retrospectively compare and evaluate the midterm curative effect of two different bone flap grafts in the treatment of early non-traumatic osteonecrosis of the femoral head (ONFH). MethodsA total of 180 patients (199 hips) with early non-traumatic ONFH received surgical treatment by sartorius muscle-pedicle bone flap graft (SMBF) (104 patients, 64 males and 40 females; mean age 34.67 ± 3.24 years) or circumflex iliac deep bone flap graft (CIDBF) (76 patients, 44 males and 32 females; mean age: 35.54 ± 3.37 years) from July 2004 to July 2009. The comparison between the groups was made with Harris score before and after surgery, length of incision, operative time, amount of bleeding, postoperative X-ray. Association Research Circulation Osseous (ARCO) staging was performed. ResultsThe preoperative Harris hip score of two groups were 68.26 ± 1.26 and 69.35 ± 1.31, respectively. Patients' ARCO staging indicated 36 hips of stage IIa, 115 hips of stage IIb and 48 hips of stage IIc. The etiology of ONFH mainly including hormones (93 patients), alcohol (64 patients) and other (23 patients). The mean follow-up time of SMBF and CIDBF groups were (51.78 ± 2.35) and (52.73 ± 3.71) months, respectively. The time of removing sutures, operation time, amount of bleeding and length of incision in SMBF group were superior to those in the CIDBF group, and those differences between the SMBF and CIDBF groups were not significant (all p values > 0.28). The Harris score between the two groups was similar after operation and postoperative 12 month, and the difference was not statistically significant (p > 0.05), whereas the difference of the postoperative 24 and 48 months was statistically significant (p ˂ 0.05). X-ray analysis showed improvement of osteonecrosis in both two groups after surgery, and as time went on, the total hip amount decreased, the replacement amount increased. ConclusionBoth bone flap grafts appear to be effective methods for treatment of early osteonecrosis of femoral head (ARCOⅡ), and the SMBF is a relatively simple technique and easy for mastering, and it is a reliable method for clinical application. Level of evidenceLevel III, Therapeutic Study.

Elevated plasma cartilage oligomeric matrix protein (COMP) level are associated with the progression of non-traumatic osteonecrosis of femoral head

Elevated plasma cartilage oligomeric matrix protein (COMP) level are associated with the progression of non-traumatic osteonecrosis of femoral head

Nationwide study on the risk of unprovoked venous thromboembolism in non-traumatic osteonecrosis of femoral head.

Endothelial dysfunction is a risk factor for osteonecrosis of femoral head (ONFH) and venous thromboembolism (VTE) [defined as deep venous thrombosis (DVT) or pulmonary embolism (PE)]. However, the risk of unprovoked VTE in non-traumatic ONFH patients remains unclear. We investigated the relationship between ONFH and VTE using Taiwan National Health Insurance Research Database (NHIRD). Between 1997 and 2010, a total of 1514 non-traumatic ONFH patients were identified from 1,000,000 general populations after excluding initially concomitant diagnoses of DVT and PE, and subjects undergoing lower limb surgery within one year since enrollment. The comparison group (n = 15,140) without ONFH was set up by matching study cohort with age, gender, income and urbanization in a 1:10 ratio. Subjects diagnosed with VTE within one year after surgery were also excluded. The patients with non-traumatic ONFH had significantly higher frequency of unprovoked VTE, including DVT, than general population (1.19 vs. 0.5%, p < 0.0007), whereas the frequency of PE was similar between these two groups (p = 0.4922). The cumulative incidence of VTE and DVT was also remarkably higher in the ONFH than non-ONFH group (all p < 0.001). After adjusting for age, gender, medications and comorbidities with multivariate analysis, the ONFH patients had a 2.3-fold increase in risk of DVT compared with non-ONFH counterparts (95% CI 1.28 to 4.13, p = 0.0053). Apart from ONFH, age > 65years and hypertension were also identified as risk factors for DVT occurrence. The incidence and risk of unprovoked VTE were significantly increased in the non-traumatic ONFH population.

MMP9 polymorphism is associated with susceptibility to non-traumatic osteonecrosis of femoral head in a Chinese Han population.

Non-traumatic osteonecrosis of femoral head (ONFH) is an orthopedic refractory disease with escalating morbidity in Chinese Han population. In our case-control study, we examined eight previously identified MMP9 single-nucleotide polymorphisms (SNPs) in 585 non-traumatic ONFH patients and 507 healthy individuals from northern China to determine whether these SNPs associated with the risk of developing non-traumatic ONFH. Genetic model and haplotype analyses were used to evaluate the association between SNPs and non-traumatic ONFH. MMP9 rs2274755 (OR, 0.740; 95% CI, 0.578-0.949; p = 0.017) was associated with a reduced risk of non-traumatic ONFH. After adjusting for age and gender, the logistic regression results showed that rs2274755 associated with a lower risk of non-traumatic ONFH in the dominant (OR=0.71, 95% CI: 0.54-0.94, p=0.016), overdominant (OR=0.73, 95% CI: 0.55-0.96, p=0.026) and log-additive (OR=0.74740; 95% CI, 0.578-0.949; p=0.017) models. In addition, the “TGC” haplotype of rs2274755 was associated with a 0.79-fold decrease in risk while the “CTC” haplotype associated with a 0.65-fold decrease risk of the non-traumatic ONFH. These results provide evidence that the MMP9 SNP at the rs2274755 locus is associated with a decreased risk of non-traumatic ONFH in a Chinese Han population.

Comparative Evaluation of Osteonecrosis of the Femoral Head Classification: CJFH Classification versus JIC Classification

To compare China-Japan Friendship Hospital (CJFH) classification with Japanese Investigation Committee (JIC) classification by observing the regular progressive pattern of nontraumatic osteonecrosis of femoral head (ONFH) to establish the reliable and convenient new classification of ONFH. The coronal section of the femoral head was divided into three pillars (medial, central, and lateral). The midcoronal section of the femoral head on MRI was selected. The CJFH classification of ONFH was established according to the site of necrotic focus in three pillars. Total 153 hips with ONFH were classified according to CJFH and JIC classifications, respectively. The collapse rate was observed and compared between both classifications of ONFH. The CJFH classification for ONFH consists of three types: type M, the medial pillar was involved; type C, the medial and central pillars were involved; and type L, the lateral pillar was involved. According to site of necrosis focus in the lateral pillar, the type L was divided into three types: L1, there pillars were involved, but there still was some normal tissue in lateral pillar; L2, partial central pillar and all lateral pillar were involved; L3, the whole femoral head was involved. The natural history of the ONFH showed the collapse rate of types L2 and L3 in CJFH classification (95.3%) was higher than that (72.3%) of type C2 in JIC classification. The CJFH classification of ONFH based on three pillars is more applicable than JIC classification in predicting collapse of the femoral head.

Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head.

Background and aimThe biological functions of non-coding RNAs (ncRNAs) have been widely identified in many human diseases. In the present study, the relationship between long non-coding RNA HOTAIR and microRNA-17-5p (miR-17-5p) and their roles in osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head (ONFH) were investigated.MethodsThe expression levels of HOTAIR and miR-17-5p in the mesenchymal stem cells (MSCs) derived from patients with non-traumatic ONFH and osteoarthritis (OA) were examined by real-time PCR. BMP-2 induced human MSCs from bone marrow (hMSC-BM) were used for osteogenic differentiation.ResultsIt was observed that the expression level of miR-17-5p was lower and the level of HOTAIR was higher in samples of non-traumatic ONFH compared with OA. HOTAIR downregulation induced by si-HOTAIR led to the increase of miR-17-5p expression and the decrease of miR-17-5p target gene SMAD7 expression. The values of osteogenic differentiation markers, including RUNX2 and COL1A1 mRNA expression and ALP activity, were also elevated by si-HOTAIR. However, the increase of these values was canceled by miR-17-5p inhibitor or SMAD7 upregulation.ConclusionHOTAIR played a role in regulating osteogenic differentiation and proliferation through modulating miR-17-5p and its target gene SMAD7 in non-traumatic ONFH.

Ethyl acetate fraction of Huogu formula inhibits adipogenic differentiation of bone marrow stromal cells via the BMP and Wnt signaling pathways.

Elevated adipogenesis of bone marrow stromal cells (BMSCs) is closely associated with non-traumatic osteonecrosis of femoral head (ONFH). Our previous studies have shown that Huogu (HG) formula was effective both in clinic experience and experimental ONFH. How HG impacts the differentiation of BMSCs and what is the underlying molecular mechanism remain largely unknown. Our results showed that ethyl acetate extract of HG (HGE) significantly decreased the adipocyte differentiation as determined by oil red staining, while slightly increased the ALP activity. Investigation of the molecular mechanism revealed that HGE could inhibit the mRNA and protein expression of peroxisome proliferators-activated receptor (PPAR)γ, lipoprotein lipase (LPL) and adipocyteprotein2 (AP2). Interestingly, the inhibition of adipogenic differentiation in BMSCs by HGE could be restored by DKK-1, an inhibitor of Wnts. However, Noggin (an inhibitor of BMPs) displayed an additive role with HGE in suppressing the expression of PPARγ, LPL, and AP2. Furthermore, the bone marrow fat formation, as well as the expression of Wnt3a and PPARγ, was effectively regulated by HGE in the steroid-induced ONFH rats. Our results demonstrated that HGE treatment significantly inhibited adipogenesis and slightly promoted osteogenesis of BMSCs through regulating the BMP and Wnt pathways. The findings shed lights on the molecular mechanism of HGE in the inhibition of adipogenesis and provide scientific rationale for its clinical application of HGE in the treatment of ONFH.

Osteoprotegerin polymorphisms are associated with alcohol-induced osteonecrosis of femoral head in Chinese Han population from Henan province.

Alcohol-induced osteonecrosis of femoral head (ONFH) is one of the most important pathogenesis of nontraumatic ONFH. However, its pathogenesis mechanism is still unknown. Osteoprotegerin (OPG) has been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, promoting tumour growth and metastasis. This study is focussed on OPG gene polymorphisms associated with alcohol-induced ONFH. A total of 509 participants (209 patients and 300 normal individuals) were recruited, and we selected 13 single-nucleotide polymorphisms (SNPs) to evaluate the association between genetic susceptibility variants and alcohol-induced ONFH by using the χ2 test and genetic model analysis. Overall, OPG SNPs (rs1485286, rs1032128 and rs11573828) were confirmed the strongest increasing risks on alcohol-induced osteoporosis of femoral head in recessive model (rs1485286: OR, 1.71; 95% CI, 1.07-2.73; P = 0.025 for T/T); (rs1032128: OR, 1.73; 95% CI, 1.08- 2.77; P = 0.022 for G/G); (rs11573828: OR, 3.89; 95% CI, 1.02- 14.85; P = 0.033 for T/T). SNP rs11573856 was considered as a protective effect to the occurrence of alcohol-induced ONFH, while adjusted for age and gender in dominant and log-additive models (rs11573856: adjusted OR, 0.60; 95% CI, 0.37- 0.96; P = 0.033 for G/A- A/A); (rs11573856: adjusted OR, 0.63; 95% CI, 0.41- 0.96; P = 0.042). We conclude that OPG gene polymorphisms were associated with the occurrence of alcohol-induced ONFH.

Plasma ghrelin and von Willebrand Factor levels in non-traumatic osteonecrosis of femoral head.

Plasma ghrelin and von Willebrand Factor levels in non-traumatic osteonecrosis of femoral head.

Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis

Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA.

Effects of Modified Qing'e Pill () on expression of adiponectin, bone morphogenetic protein 2 and coagulation-related factors in patients with nontraumatic osteonecrosis of femoral head.

To observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH). A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment. After 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05). MQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway.

α-Melanocyte stimulating hormone attenuates dexamethasone-induced osteoblast damages through activating melanocortin receptor 4-SphK1 signaling

Long-term glucocorticoid (GC) usage may cause non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) is shown to exert potent cytotoxic effect to osteoblasts. Here, we investigated the potential activity of α-melanocyte stimulating hormone (α-MSH) against the process. Our data revealed that pretreatment of α-MSH significantly inhibited Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Melanocortin receptor 4 (MC4R) acts as the receptor of α-MSH in mediating its actions in osteoblasts. The MC4R antagonist SHU9119, or shRNA-mediated knockdown of MC4R, almost abolished α-MSH-induced activation of downstream signalings (Akt and Erk1/2) and its pro-survival effect in osteoblasts. Further studies showed that α-MSH activated MC4R downstream sphingosine kinase 1 (SphK1) and increased cellular sphingosine-1-phosphate (S1P) content in MC3T3-E1 cells and primary murine osteoblasts, which were blocked by SHU9119 or MC4R shRNAs. SphK1 inhibition by the its inhibitor N,N-dimethylsphingosine (DMS), or SphK1 knockdown by targeted-shRNAs, largely attenuated α-MSH-mediated osteoblast protection against Dex. Together, these results suggest that α-MSH alleviates Dex-induced damages to cultured osteoblasts through activating MC4R-SphK1 signaling.

Identification of differentially expressed microRNAs involved in non-traumatic osteonecrosis through microRNA expression profiling

Accumulating evidence has recently indicated a vital role of microRNAs (miRNAs) in the development of various bone diseases. However, the biological role of miRNAs in the pathogenesis of non-traumatic osteonecrosis of femoral head (ONFH) has not yet been investigated. The present study aimed to profile the differential miRNA expression between non-traumatic ONFH and femoral neck fracture and to develop further understanding of the molecular mechanisms involved in the pathogenesis of non-traumatic ONFH. Femoral heads from 4 patients with non-traumatic ONFH and 4 with femoral neck fracture were used to analyze the miRNA expression profiles in bone tissue using the Exiqon miRCURY™ LNA Array (v.18.0). The results of miRNA microarray analysis were further confirmed by real-time quantitative polymerase chain reaction (qPCR). The differentially expressed miRNA target genes and signaling pathways involved were predicted by bioinformatics analysis. MiRNA microarray chip analysis revealed that 22 miRNAs were significantly up-regulated and 17 were significantly down-regulated in the non-traumatic ONFH samples compared with the femoral neck fracture samples. The real-time qPCR also confirmed the microarray data. Bioinformatics analysis demonstrated that toll-like receptor (TLR), neurotrophin and NOD-like receptor signaling pathway were most likely to be regulated by these differential miRNAs. This miRNA microarray study reveals significant differences in miRNA expression between patients with non-traumatic ONFH and those with femoral neck fracture. Our data also manifests that the signaling pathways regulated by these differentially expressed miRNAs might be important in the pathogenesis of non-traumatic ONFH.

K6PC-5, a novel sphingosine kinase 1 (SphK1) activator, alleviates dexamethasone-induced damages to osteoblasts through activating SphK1-Akt signaling

Long-term glucocorticoid usage is a common cause of non-traumatic femoral head osteonecrosis. Glucocorticoids (i.e. dexamethasone (Dex)) could directly induce damages to osteoblasts. In the current study, we investigated the potential activity of K6PC-5 [N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide], a novel sphingosine kinase 1 (SphK1) activator, against this process. Our data revealed that both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts were responsible to K6PC-5. K6PC-5 activated SphK1, increased sphingosine-1-phosphate (S1P) production and induced Akt phosphorylation in cultured osteoblasts. Functionally, K6PC-5 protected osteoblasts from Dex-induced apoptosis and necrosis. Such signaling and functional effects by K6PC-5 were prevented by the SphK1 inhibitor N,N-dimethylsphingosine (DMS), and by SphK1-siRNAs. On the other hand, exogenously-added S1P activated Akt and reduced Dex-induced osteoblast damages. LY294002 and MK-2206, two established Akt inhibitors, alleviated K6PC-5- or S1P-mediated osteoblast protection against Dex. Together, our results suggest that K6PC-5 alleviates Dex-induced osteoblast injuries through activating SphK1-Akt signaling. K6PC-5 might be further investigated in animal or clinical studies for its anti-glucocorticoids-associated osteonecrosis potential.

Outcome after tantalum rod implantation for treatment of femoral head osteonecrosis

Background and purpose Tantalum rod implantation has recently been proposed for treatment of early stages of femoral head osteonecrosis. The purpose of our study was to report the early results of its use in pre- and post-collapse stages of the disease.Methods We studied prospectively 27 patients who underwent tantalum rod implantation for treatment of nontraumatic femoral head osteonecrosis between December 2000 and September 2005. Patients were evaluated radiologically and clinically using the Steinberg classification and the Harris hip score (HHS). Disease stage varied between stages II and IV. Mean follow-up time was 38 (15–71) months.Results 1 patient (1 hip) died 15 months after surgery for reasons unrelated to it. 13 of 26 hips remained at the same radiographic stage, and 13 deteriorated. Mean HHS improved from 49 to 85. 6 patients required conversion to total hip arthroplasty. When the procedure was used for stages III and IV, both radiological outcome and revision rates were worse than for the stage II hips. There was, however, no difference in postoperative HHS between patients at pre- and post-collapse stages at the time of initial evaluation. Survivorship, with revision to THA as the endpoint, was 70% at 6 years.Interpretation The disease process does not appear to be interrupted, but there was a significant improvement in hip function initially in most hips. Tantalum rod implantation is a safe “buy-time” technique, especially when other joint salvage procedures are not an option. Appropriate patient selection and careful rod insertion are needed for favorable results.

Importance of sagittal MR imaging in nontraumatic femoral head osteonecrosis in children

In nontraumatic femoral head osteonecrosis, characterization of femoral head collapse is important in staging disease progression and planning treatment. Few prior studies have quantitatively compared the ability of sagittal and coronal MR images to detect femoral head collapse. We hypothesized that sagittal MR images show a greater degree and angular span of femoral head collapse than coronal images. We reviewed 38 hip MRI scans of nontraumatic femoral head osteonecrosis from 34 pediatric patients. In both sagittal and coronal images, the maximal extent and angular location along with the angular span of the femoral head collapse were measured. Differences were evaluated using a paired t-test. The extent of bone and cartilage loss from the femoral head was evaluated. Sagittal MR images showed 29% maximal femoral head radius collapse, whereas coronal images showed 16% collapse (P<0.001). Sagittal images showed a larger angular span of collapse (115 degrees ) than coronal images (55 degrees , P<0.001). Sagittal images showed greater epiphyseal bone loss in the anterior than in the posterior portion (P<0.001), whereas coronal images did not show a significant difference in bone loss between the medial and lateral portion (P=0.32). Sagittal images show greater femoral head collapse than coronal images in nontraumatic femoral head osteonecrosis.

POSTERIOR ROTATIONAL OSTEOTOMY FOR NONTRAUMATIC OSTEONECROSIS WITH EXTENSIVE COLLAPSED LESIONS IN YOUNG PATIENTS

Background: In young patients with nontraumatic femoral head osteonecrosis with extensive and collapsed lesions, joint preservation is a goal if total joint arthroplasty is to be avoided. We evaluated the effectiveness of a posterior rotational osteotomy in this patient population. Methods: We reviewed thirty-five hips in twenty-eight young patients with nontraumatic femoral head osteonecrosis treated by posterior femoral neck rotational osteotomy. All femoral heads were collapsed, and seven hips showed joint-space narrowing. Lateral radiographs of the femoral head revealed that 15% of the mean posterior portion and 17% of the mean anterior portion of the femoral head consisted of radiographically apparent living bone. The mean age of the patients (ten women and eighteen men) was twenty-eight years. The mean follow-up period was eight years. Results: Less than six months after surgery, the radiographically apparent area of living bone of the femoral head below the acetabular roof was shown to be 59% on the standard anteroposterior radiograph and 54% on the 45°-flexion radiograph. In thirty-three hips (94%), further collapse of the femoral head was prevented and an adequate amount of living bone was demonstrated on the loaded lateral portion of the femoral head on the final follow-up radiographs. Progressive joint-space narrowing was seen in four hips. Conclusions: In young patients with osteonecrosis and extensively collapsed lesions of the femoral head, posterior femoral neck rotational osteotomy appears to be effective in delaying the progression of degeneration if an adequate area of living bone can be placed under the loaded lateral portion of the acetabulum. Level of Evidence: Therapeutic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.

Posterior Rotational Osteotomy for Nontraumatic Osteonecrosis with Extensive Collapsed Lesions in Young Patients

In young patients with nontraumatic femoral head osteonecrosis with extensive and collapsed lesions, joint preservation is a goal if total joint arthroplasty is to be avoided. We evaluated the effectiveness of a posterior rotational osteotomy in this patient population. We reviewed thirty-five hips in twenty-eight young patients with nontraumatic femoral head osteonecrosis treated by posterior femoral neck rotational osteotomy. All femoral heads were collapsed, and seven hips showed joint-space narrowing. Lateral radiographs of the femoral head revealed that 15% of the mean posterior portion and 17% of the mean anterior portion of the femoral head consisted of radiographically apparent living bone. The mean age of the patients (ten women and eighteen men) was twenty-eight years. The mean follow-up period was eight years. Less than six months after surgery, the radiographically apparent area of living bone of the femoral head below the acetabular roof was shown to be 59% on the standard anteroposterior radiograph and 54% on the 45 degrees -flexion radiograph. In thirty-three hips (94%), further collapse of the femoral head was prevented and an adequate amount of living bone was demonstrated on the loaded lateral portion of the femoral head on the final follow-up radiographs. Progressive joint-space narrowing was seen in four hips. In young patients with osteonecrosis and extensively collapsed lesions of the femoral head, posterior femoral neck rotational osteotomy appears to be effective in delaying the progression of degeneration if an adequate area of living bone can be placed under the loaded lateral portion of the acetabulum. Therapeutic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.

Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis

As endothelial nitric oxide synthase (eNOS) has beneficial effects on skeletal, vascular, and thrombotic systems, the association between nontraumatic femoral head osteonecrosis (FHON) and eNOS gene polymorphisms was investigated in Korean patients with FHON. Genomic DNA from 103 patients with nontraumatic FHON (idiopathic in 50, steroid-induced in 29, and alcohol abuse in 24) and 103 control subjects matched for gender and age (3-year range) was analyzed for the 27-bp repeat polymorphism in intron 4 and Glu298Asp polymorphism in exon 7. The frequencies of alleles and genotypes were compared between patients and control subjects. The frequency of 4a allele was significantly higher in total patients than control subjects [6.8% vs. 2.4%, p = 0.0345, odds ratio (OR) 2.931]. In subgroup analysis, the 4a allele significantly increased in patients with idiopathic FHON versus control subjects (9.0% vs. 2.4%, p = 0.0297, OR 3.976). The frequency of the 4a/b genotype in total patients (13.6% vs. 4.9%, p = 0.0302, OR 3.083) as well as patients with idiopathic FHON (18.0% vs. 4.9%, p = 0.0246, OR 4.302) was higher than control subjects. The distribution of Glu298Asp polymorphisms was not significantly different between patients and control subjects. Microstellate polymorphism in intron 4 of eNOS polymorphism was significantly associated with idiopathic FHON in Korean patients. Because 4a allele is associated with lower synthesis of eNOS, these results suggest that carrier state of 4a allele in intron 4 might be a genetic risk factor of FHON and could provide insight into the protective role of nitric oxide in the pathogenesis of FHON.