Osteonecrosis In Sickle Cell Disease Research Articles

Quantification and Comprehensive Analysis of Mesenchymal Stromal Cells in Bone Marrow Samples from Sickle Cell Disease Patients with Osteonecrosis.

The potential use of bone marrow mesenchymal stromal cells (BM-MSCs) for the treatment of osteonecrosis in sickle cell disease (SCD) patients is increasing. However, convenient BM-MSC quantification and functional property assays are critical factors for cell-based therapies yet to be optimized. This study was designed to quantify the MSC population in bone marrow (BM) samples from SCD patients with osteonecrosis (SCD group) and patients with osteoarticular complications not related to SCD (NS group), using flow cytometry for CD271+CD45-/low cell phenotype and CFU-F assay. We also compared expanded BM-MSC osteogenic differentiation, migration, and cytokine secretion potential between these groups. The mean total cell number, CFU-F count, and CD271+CD45-/low cells in BM mononuclear concentrate were significantly higher in SCD than in NS patients. A significant correlation between CD271+CD45-/low cell number and CFU-F counts was found in SCD (r = 0.7483; p = 0.0070) and NS (r = 0.7167; p = 0.0370) BM concentrates. An age-related quantitative reduction of CFU-F counts and CD271+CD45-/low cell number was noted. Furthermore, no significant differences in the morphology, replicative capacity, expression of surface markers, multidifferentiation potential, and secretion of cytokines were found in expanded BM-MSCs from SCD and NS groups after in vitro culturing. Collectively, this work provides important data for the suitable measurement and expansion of BM-MSC in support to advanced cell-based therapies for SCD patients with osteonecrosis.

CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis.

Recent evidence suggests that abnormalities involving CD4+T lymphocytes are associated with the pathophysiology of osteonecrosis (ON); however, few studies have addressed the CD4+T cells in ON related to sickle cell disease (SCD/ON). In addition, T cells producing multiple cytokines simultaneously are often present in the inflammatory milieu and may be implicated in the immune response observed in SCD/ON. In the present study, we aimed to characterize the functional status of CD4+T cells in SCD by simultaneously determining the frequency of IFN-γ+, IL-4+, and IL-17+ CD4+T in cell cultures under exogenous stimuli. Peripheral blood mononuclear cells (PB-MNCs) from 9 steady-state SCD patients, 15 SCD/ON patients, and 19 healthy controls had functional status of CD4+T cells analyzed. Bone marrow mononuclear cells (BM-MNCs) from 24 SCD/ON patients (SCD BM) and 18 patients with ON not related to SCD (non-SCD BM) were also analyzed. We found that PB-MNC of SCD patients with or without ON presented significantly reduced TCD4+, TCD8+, and TCD4+ naïve cell frequencies and increased frequency of circulating CD4+T cells able to simultaneously produce IFN-γ+/IL4+ and IL-17+/IL4+ compared to healthy controls. Conversely, the polyclonal stimulation of BM-MNC induced an increased frequency of CD4+IFN-γ+ and CD4+IL-17+ in SCD BM compared to non-SCD BM. The increased proportion of CD4+ T cells able to produce a broad spectrum of proinflammatory cytokines after a strong stimulus indicates that the immune system in SCD/ON patients presents an expressive pool of partially differentiated cells ready to take on effector function. It is possible that this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and the pathophysiology of osteonecrosis in sickle cell disease.

Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management

Osteonecrosis, a form of ischemic bone injury that leads to degenerative joint disease, affects ∼30% of people with sickle cell disease. Although osteonecrosis most commonly affects the femoral head (often bilaterally, with asymmetric clinical and radiographic progression), many people with sickle cell disease also present with multifocal joint involvement. We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes. In this review, partly based on recommendations on osteonecrosis management from the 2014 evidence-based report on sickle cell disease from the National Heart, Lung and Blood Institutes, we also discuss early signs or symptoms of osteonecrosis of the femoral head, radiographic diagnosis and staging criteria, hydroxyurea effect on progression to femoral head collapse, and surgical outcomes of total hip arthroplasty in the modern era. In summary, we failed to find an association between hydroxyurea use and femoral head osteonecrosis; we also showed that evidence-based perioperative sickle cell disease management resulted in superior postoperative outcomes after cementless total hip arthroplasty in sickle cell-related osteonecrosis of the femoral head.

Osteonecrosis in sickle cell disease patients from Bahia, Brazil: a cross-sectional study.

The aim of this study was to describe the clinical features of osteonecrosis (ON) in sickle cell disease (SCD) patients in Bahia, a Northeast state with the highest prevalence of the disease in Brazil. Between 2006 and 2017, 283 cases of osteonecrosis in SCD patients were enrolled to analyse the age at diagnosis, genotype, gender, pain, distribution of the lesions and disease staging. MRI and radiograph were obtained at the participation. Of the 283 SCD cases, 120 (42.4%) were haemoglobin SS genotype while 163 (57.6%) were SC genotype. Two hundred and forty-six cases were bilateral and 37 were unilateral, with an average age at diagnosis of 33.7 (range 10-67) years. The most frequent identified ON site not only was the hip (74.6%), but also affected shoulder, knee and ankle. Most cases presented at early stage I (172, 60.8%) disease. No significant differences on the features of osteonecrosis were identified between haemoglobin SS and haemoglobin SC cases. Given the relatively high prevalence of bilateral osteonecrosis at early stages, painful symptoms and rather late age at diagnosis, SCD patients should have radiological examination of their joints more often in order to prevent severe functional disability and increase patient's life quality.

Osteonecrosis in Sickle Cell Disease.

Osteonecrosis is one of the most devastating musculoskeletal manifestations of sickle cell disease and most commonly affects the femoral head. Although the exact pathophysiology of this condition in patients with sickle cell disease is unknown, it is suggested that red cell sickling and repetitive vaso-occlusion may be associated with tissue hypoxia, inflammation, and subsequent bone necrosis and collapse. If left untreated, osteonecrosis can be extremely debilitating and may lead to severe pain, loss of function, and degenerative joint changes. Although several conservative management approaches exist, total joint arthroplasty remains the most effective treatment intervention. A multidisciplinary approach among the primary care physician, hematologist, and orthopedic surgeon is essential in optimizing patient management.

Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease.

Femoral head osteonecrosis (ON) secondary to sickle cell disease (SCD) often progresses to femoral head collapse, requiring total hip arthroplasty. However, this treatment has a limited durability and patients with SCD have higher rates of complications, requiring multiple revision operations. Identifying risk factors linked to ON in SCD can facilitate earlier precollapse diagnosis and surgical treatment aimed at preservation of the native hip joint. Fifty-nine children treated at our institution between January 2001 and April 2012 with SCD and ON, as diagnosed by magnetic resonance imaging or radiographic imaging, were compared with age-matched and sickle cell phenotype-matched (SS, SC, Sβ, Sβ) controls with no evidence of ON. Two sided t-tests assuming unequal variances determined statistically risk factors and threshold values were assigned to calculate odds ratios. Systolic blood pressure (P=1.2×10, OR=3.68), diastolic blood pressure (P=0.0084, OR=1.41), weight in the SCD-SS population (P=0.04, OR=1.85), and hemoglobin (Hb) in the SCD-SS population (P=0.036, OR=2.56) were elevated in cases. Curiously, dividing the Hb by the hematocrit to serve as a clinical proxy for the mean corpuscular Hb concentration (MCHC) produced an excellent predictor of ON (P=2.06×10, OR=5.17), which was especially pronounced in the SCD-SS subpopulation (P=2.28×10, OR=8.65). Among children with SCD, the overall prevalence of ON was 9% (59/658) and the phenotype with the highest prevalence of ON was Sβ thalassemia with an ON prevalence of 11.1%. There was no observed correlation between ON and height, body mass index, cholesterol, mean corpuscular volume, hematocrit, or glucocorticoid use. These data support a novel clinical marker, the MCHC proxy, as the strongest predictor of ON in children with SCD. High-risk children should receive hip magnetic resonance imaging to diagnose early ON and facilitate interventions focused on hip preservation, forestalling, or possibly preventing, the need for total hip arthroplasty.

Bone Scintigraphy Scanning Safety and Necessity for Silent and Multifocal Osteonecrosis in Sickle Cell Disease

Bone Scintigraphy Scanning Safety and Necessity for Silent and Multifocal Osteonecrosis in Sickle Cell Disease

Management of Osteonecrosis By Adult and Pediatric Sickle Cell Providers

Introduction:Osteonecrosis (ON) is a debilitating complication in 40% of adult sickle cell disease (SCD) patients. Almost all SCD ON will collapse, develop intractable pain or require surgery in 8 to 15 years from diagnosis. Majority of treatments have not been examined in a controlled setting, leading to variations in care, impeding research to verify the efficacy of existing therapies, and development of new treatments. The study's objective is to describe the screening, diagnostic and management patterns of ON in pediatric and adult SCD patients by US and Canadian providers.Materials and Methods:A cross-sectional survey of SCD providers from the Sickle Cell Adult Provider Network, the American Society of Pediatric Hematology/Oncology, and the Canadian Hemoglobinopathy Association was conducted from March to July 2015. The survey had 24 questions about provider demographics, characteristics of SCD population, ON diagnosis, staging and treatment. The survey was distributed electronically over 9 weeks with 2 reminders 3 weeks apart. Descriptive statistics were calculated and logistic regression was used to identify factors (specialty, location, years of practice, number of patients, adult vs. pediatric centers) that were associated with screening, diagnostic, staging and treatment approaches.Results:Of the 2,475 health care providers surveyed, 78 participants responded from 63 centers with 17,232 patients (17-23% of the estimated SCD population in US and Canada). Majority of respondents were located in urban teaching centers (93%). All (100%) respondents self-identified as SCD providers: 44 adult hematology/oncology (heme/onc) specialist; 3 internists; 24 pediatric heme/onc specialist; 5 nurse clinicians; 1 pharmacist; and 1 social worker. The median time in practice was 16 years (min 1, max 40). The estimated number of unique patients under the care of the respondents was 10,697, of which 1,946 (18%) had ON. More than half of the ON patients had joint collapse (n=1,050, 54%), and 72% had joint replacement. Only (13%) of the respondents screened for ON in asymptomatic patients, and screening measures include 50% by x-ray; 38% by physical, 12% by other modalities. All (100%) respondents screened for ON in symptomatic patients: 51% using x-ray and MRI, 41% x-ray, 7% MRI. The majority of respondents (72%) did not know the ON staging methods used. Frequencies of respondents using non-surgical and surgical treatments in pre-collapse and collapsed ON are shown in Table 1. Respondents' years in practice was the only factor significantly associated with the use of screening in asymptomatic SCD patients (OR 2.9/decade in practice, p=0.030). Respondents' years in practice was also associated with a reduced likelihood of hydorxyurea (HU) use in pre-collapse ON (OR 0.44/decade more in practice, p=0.011). Patients with collapsed ON under the care of pediatric heme/onc specialists were more likely to be treated with core decompression than adult heme/onc specialist or internist (OR 10.7, p=0.016).Discussion:Our survey suggests that the diagnosis, classification and management of ON is highly heterogeneous, despite the 2014 NIH expert panel report on the management of SCD prior to the distribution of the survey. The lower prevalence of ON in our study compared to that in cohort-wide screening may be due to the lack of screening by surveyed providers in asymptomatic SCD patients, suggesting ON may be underdiagnosed. Despite lack of evidence for their efficacy, HU and core decompression were used by majority of respondents in pre-collapse ON. A limitation of the study is difficulty in estimating the true response rate since the number of SCD providers in US and Canada is not known, potentially impacting the results' generalizability. The variations in practice and the high prevalence of collapsed joints requiring replacement in the surveyed population confirms the need to develop a uniformed approach in screening, diagnosis, and evidence-based therapies in SCD ON.Table 1Non-surgical and surgical treatments used by respondents in pre-collapse and collapsed ON. Some respondents selected multiple responsesTreatmentsNumber of Respondents (%)Non-surgicalPre-collapse (n=54)Collapsed (n=53)Analgesia53 (98%)52 (98%)Physiotherapy49 (91%)37 (70%)Hydroxyurea32 (59%)28 (53%)SurgicalPre-collapse (n=38)Collapsed (n=45)Core decompression33 (87%)10 (22%)Hip replacement9 (24%)43 (95%) DisclosuresOff Label Use: Hydroxyurea for treatment of osteonecrosis in sickle cell disease. Kuo:Novartis Canada: Honoraria, Other: Advisory Board; Alexion Pharmaceuticals: Honoraria, Other: Advisory Board.

A Systematic Review of the Classification, Diagnosis, Treatment and Outcome of Osteonecrosis of the Hips in Sickle Cell Disease

Background: Osteonecrosis (ON) is a prevalent (30-50% by age 30) yet underdiagnosed complication in patients with sickle cell disease (SCD), commonly affecting the femoral and humeral head. SCD ON is progressive resulting in chronic intractable pain and disability. Various imaging modalities are available for the diagnosis of ON and a number of staging methods have been proposed to classify its severity. Numerous surgical and non-surgical treatments exist for different stages of ON. There is a lack of consensus on how to best investigate, classify and treat patients with SCD ON. A previous systematic review included only 1 randomized controlled trial (RCT) but the majority of the literature are non-randomized studies.Objectives: To systematically review and summarize the available evidence from randomized and non-randomized studies with regard to the classification, diagnosis, treatment options and outcome of ON of the hips in SCD adults.Methods: Searches were conducted using the following search concepts: (sickle cell disease OR sickle cell anemia OR hemoglobin SC disease) AND (osteonecrosis OR avascular necrosis OR bone and joint complications) NOT Bisphosphonate-Associated Osteonecrosis of the Jaw. Related terms were also searched in order to maximize sensitivity. MEDLINE, Embase, CINAHL, Current Controlled Trials, and Cochrane Central Register of Controlled Trials were queried. Two independent reviewers (DM-A and AP) excluded abstracts based on pre-defined criteria. A third reviewer (KK) resolved all conflicts. Full-text of included abstracts were translated to English as needed, extracted by DM-A, AP, KK and YP and screened based on the inclusion/exclusion criteria. Two assessors (DM-A and KK) independently assessed trial quality of extracted data. Study limitations (risk of bias) and confidence in effect estimates (quality of evidence) were assessed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies.Results and Discussion: 25 studies (1 RCT, 1 case-control, 10 prospective and 13 retrospective studies) were included from 544 unique citations (kappa=0.82). A total of 2,640 participants (median number of patients/study 34, range 10-1,031) with mean age of participants in each study between 19 and 40 years. Majority were HbSS (n=1,888), followed by 302 HbSC, 98 HbS/thalassemia, 27 sickle cell trait, 22 unspecified SCD genotype and 1 HbS/hereditary persistence of fetal hemoglobin. The male to female distribution was equal. Mean duration of follow-up was between 3 and 19 years. Majority (n=12) of the studies included symptomatic patients only. Nine studies used x-rays only to identify ON and 9 used x-ray with CT and/or MRI. Classification of ON between studies was heterogeneous (Ficat and Arlet: 3, Steinberg: 4, Ficat: 4, Mitchell 1987: 1, Arlet: 1, no classification scheme: 12). Treatment modalities used were extremely diverse. Of the 22 studies that described an intervention: 11 used hip arthroplasty only, 1 with cement injection only, 1 with core decompression only, and 9 used a combination of surgical and non-surgical interventions. There was also tremendous heterogeneity with the outcomes reported which precluded the conduct of any meta-analysis. The revision rate after hip arthroplasty, cement injection, and core decompression were 21% (range 3-40%), 13%, and 12% respectively. Median difference in Harris Hip Score post-hip arthroplasty was 52 (range 44-58), and 25 post-cement injection. The median rate of prosthesis infection post-hip arthroplasty was 5.5% (range 2-34%). Summary statistics were not possible on other outcome measurements since they were used in single study. Risk of bias in all the studies was moderate to high.Conclusion: The heterogeneity in diagnosing, classifying and treating ON makes the development of a consensus guideline difficult. Ficat and Arlet, Steinberg, and Ficat were the most common method in ON staging. Hip arthroplasty alone or in combination with non-surgical interventions were the most commonly used treatment options. Although hip arthroplasty offers post-surgical pain relief, it is associated with high rates of revision. The paucity of RCT and the high risk of bias with the existing non-randomized studies highlight the importance of developing prospective controlled studies examining existing and novel therapies using a unified approach in determining the severity of ON and outcome measures. DisclosuresKuo:Novartis Canada: Honoraria, Other: Advisory Board; Alexion Pharmaceuticals: Honoraria, Other: Advisory Board.

Could Denosumab Support Bone Integrity in Sickle Cell Disease

Sickle cell anaemia is a congenital disease characterized by painful vaso-occlusive crises. It is associated with vitamin D deficiency, osteoporosis and recurrent attacks of micro-infarctions lead to bone osteonecrosis. The most common sites of osteonecrosis in sickle cell disease are the femoral and humeral heads which could lead to severe pain and extensive physical disability. Denosumab is a new human monoclonal antibody product; it is a receptor activator of nuclear factor kappa B ligand RANKL. That decreases osteoclastic bone restoration. It is Food and Drug Administration FDA approved for osteoporosis for women with high risk of fracture; and it is also being used for the treatment and prevention of bone loss in patients undergoing hormone ablation therapy for breast and prostate cancer. Denosumab is not restricted for sickle cell disease patients within its approved indications. It has less nephrotoxicity effect than the bisphosphonates which is a big advantage for sickle cell patients. It also used as an adjuvant agent to reduce metastatic bone pain in solid tumors. The extension of Denosumab use for sickle cell patients’ osteoporosis and osteonecrosis deserve a randomized multi central trail aiming to improve bone integrity and possible reduction of the devastating pain in sickle cell disease patients.

Flow cytometry analyses reveal association between Lu/BCAM adhesion molecule and osteonecrosis in sickle cell disease

Flow cytometry analyses reveal association between Lu/BCAM adhesion molecule and osteonecrosis in sickle cell disease

Osteonecrosis and Leg Ulceration in Indian Sickle Cell Patients

Sir, Avascular necrosis of bone and cutaneous leg ulcers are the most common manifestation of patients with sickle cell disease (SCD) [1, 2]. The bone areas most frequently affected are cortical bone of the acetabulum, head of the femur, and head of the humerus. Osteonecrosis of the femoral head is common in patients with sickle cell disease. The hip and shoulder abnormalities are also seen in patients. Multifocal osteonecrosis is defined as disease of 3 or more anatomic sites. Patients diagnosed with osteonecrosis of the knee, shoulder and ankle should be evaluated for other joints for osteonecrosis. In patients with sickle cell disease, clinical complications including osteonecrosis can vary in frequency and severity, presumably due to the effects of genes that modify the pathophysiology initiated by the sickle mutation [3]. Baldwin et al. suggested genetic influence of BMP6 and ANXA2 SNPs with osteonecrosis in SCD [3]. The incidence of leg ulcers in patients with SCD ranges from 25.7% to 75% [4, 5]. Leg ulcers are a common sub-phenotype of sickle cell disease. Their cause is unknown, their prevention is impractical and their management, once present, is often difficult. Leg ulceration and avascular necrosis (AVN) in SCD has become serious problem in a few decades in India, however the incidence of leg ulcer and AVN in sickle cell patients has not been studied extensively in India till date. We had 150 sickle cell patients (60 sickle cell anemia, 75 sickle β-thalassemia and 15 sickle hemoglobin D) recruited from out patient department hematology AIIMS, New Delhi, India. Study period was 3 y. Signed consent form taken from all the patient and study was approved by institutional ethical committee. Diagnosis of patients was done by high performance liquid chromatography (Bio-Rad-VariantTMBio Rad, CA, USA). Complete blood count and red cell indices were measured by automated cell analyzer (SYSMEXK-4500, Kobe Japan). Osteonecrosis screening was done by X-ray and confirmation was done by magnetic resonance imaging (MRI) while leg ulceration was reported on physical examination. MRI is the most sensitive means of diagnosing AVN. MRI facilitates better response to treatment because with the use of MRI, avascular necrosis is diagnosed at an earlier stage and therapeutic measures are more successful the earlier they are begun. Out of 150 cases 14 (8 boys and 6 girls with mean age; 11.5±3.4 y) presented with osteonecrosis where seven were from HbSS, 6 from sickle beta thalassemia and one fromHbSD patients. Nine patients presented with femoral head ( 5 HbSS and 4 HbSβ-thal) while 3 hip (2 HbSS and 1HbSD) and 2 (HbSβ-thal)with shoulder osteonecrosis. Seven patients (4 boys and 3 girls with mean age; 12.3±2.6 y) presented with leg ulceration out of 150 SCD patients (5HbSS and 2 HbSβ-thal). None of the patients presented both complications i.e., leg ulceration and AVN together. Observation of the study concludes the increased risk of AVN (9.34%) and leg ulceration (4.67%) in Indian sickle cell patients where alpha thalassemia and high HbF is prevalent in patients.

Comparing Two Articles on Osteonecrosis in Sickle Cell Disease

This issue contains two articles on osteonecrosis of the femoral head in patients with sickle cell disease: “The Natural History of Asymptomatic Osteonecrosis of the Femoral Head in Adults with Sickle Cell Disease,” by Hernigou et al., and “Physical Therapy Alone Compared with Core Decompression and Physical Therapy for Femoral Head Osteonecrosis in Sickle Cell Disease: Results of a Multicenter Study at a Mean of Three Years After Treatment,” by Neumayr et al. Both are meaningful studies that add to our body of knowledge in the orthopaedic management of patients with sickle cell disease but appear to report strikingly different outcomes in similar patient populations. In the report by Hernigou et al., ninety-one (75%) of 121 patients required reconstructive surgery during the term of the study, with total hip replacement being performed in forty-two patients, valgus femoral osteotomy in twenty-three, and injection of cement into the femoral head in twenty-six. In comparison, in the study by Neumayr et al., only three (7.9%) of thirty-eight patients required reconstructive surgery in the form of total hip replacement. There are some similarities between the two studies, but several important differences may account for some of the variance in outcome. The two …

Physical Therapy Alone Compared with Core Decompression and Physical Therapy for Femoral Head Osteonecrosis in Sickle Cell Disease

Osteonecrosis of the femoral head is a common complication in patients with sickle cell disease, and collapse of the femoral head occurs in 90% of patients within five years after the diagnosis of the osteonecrosis. However, the efficacy of hip core decompression to prevent the progression of osteonecrosis in these patients is still controversial. In a prospective multicenter study, we evaluated the safety of hip core decompression and compared the results of decompression and physical therapy with those of physical therapy alone for the treatment of osteonecrosis of the femoral head in patients with sickle cell disease. Forty-six patients (forty-six hips) with sickle cell disease and Steinberg Stage-I, II, or III osteonecrosis of the femoral head were randomized to one of two treatment arms: (1) hip core decompression followed by a physical therapy program or (2) a physical therapy program alone. Eight patients withdrew from the study, leaving thirty-eight who participated. Seventeen patients (seventeen hips) underwent decompression combined with physical therapy, and no intraoperative or immediate postoperative complications occurred. Twenty-one patients (twenty-one hips) were treated with physical therapy alone. After a mean of three years, the hip survival rate was 82% in the group treated with decompression and physical therapy and 86% in the group treated with physical therapy alone. According to a modification of the Harris hip score, the mean clinical improvement was 18.1 points for the patients treated with hip core decompression and physical therapy compared with 15.7 points for those treated with physical therapy alone. With the numbers studied, the differences were not significant. In this randomized prospective study, physical therapy alone appeared to be as effective as hip core decompression followed by physical therapy in improving hip function and postponing the need for additional surgical intervention at a mean of three years after treatment.

COMPARING TWO ARTICLES ON OSTEONECROSIS IN SICKLE CELL DISEASE

COMPARING TWO ARTICLES ON OSTEONECROSIS IN SICKLE CELL DISEASE

Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis

In patients with sickle cell disease, clinical complications including osteonecrosis can vary in frequency and severity, presumably due to the effects of genes that modify the pathophysiology initiated by the sickle mutation. Here, we examined the association of single nucleotide polymorphisms (SNPs) in candidate genes (cytokines, inflammation, oxidant stress, bone metabolism) with osteonecrosis in patients with sickle cell disease. Genotype distributions were compared between cases and controls using multiple logistic regression techniques. An initial screen and follow-up studies showed that individual SNPs and haplotypes composed of several SNPs in bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis. These genes are important in bone morphology, metabolism, and vascular disease. Our results may provide insight into the pathogenesis of osteonecrosis in sickle cell disease, help identify individuals who are at high risk for osteonecrosis, and thus allow earlier and more effective therapeutic intervention.

Humeral head osteonecrosis in sickle cell disease

Humeral head osteonecrosis in sickle cell disease

9 Knee arthroplasties for sickle cell disease.

Sickle cell disease sometimes presents with knee arthropathy secondary to osteonecrosis. We report our experience with 9 total knee arthroplasties in 5 patients. The joint fluid, synovium, capsule, and excised bones were sent for culture. Tissue cultures from 5 knees grew organisms. The outcome was: 6 excellent, 1 good, 1 satisfactory, and 1 poor. Infection in 1 case led to removal of the prosthesis and subsequent arthrodesis. 1 patient had persistent peroneal nerve palsy. There were no hematological complications. We suggest that osteonecrosis in sickle cell disease should be considered septic.