Low Bone Density In Sickle Cell Disease Is a Risk Factor in The Development Of Avascular Necrosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4688-4688
Author(s):  
Hassan A. Al-Jafar ◽  
Leena M Aytoglu ◽  
Jehan Al-Shemmari ◽  
Uzma Afzal ◽  
Iman Al-Shemmari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Factor ◽  
Bone Density ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Bone Mineral ◽  
Cell Disease ◽  
Bone Marrow Scintigraphy ◽  
Low Bone Density

Introduction Sickle cell disease (SCD) is a highly prevalent disorder in the world, specifically in the region of Kuwait. A wide population suffers from sickle cell anaemia. It has been known that bone involvement is one of the most common clinical manifestations of sickle cell disease, both in the acute setting such as painful vaso-occlusive crises, and as a chronic, progressive process such as osteoporosis ,osteopenia and avascular necrosis (AVN), which can develop due to the low bone mass and the deterioration of the micro architecture of bone tissue. In this ongoing project, we used the radionuclide imaging technique for bone and bone marrow scintigraphy and dual-energy x-ray absorptiometry (DEXA). We attempted a correlation between low bone density and the bone infarct for SCD, and identified if low bone density is a risk factor for the severity and development of osteonecrosis in an at-risk population of sickle cell patients. Patients and Methods A total of 13 sickle cell patients participated in this correlation study; 5 males and 8 females, ages ranged from 16 to 55 years with a mean age of 35.5 years. To meet the participant selection criteria, patients were selected if they were never prescribed bisphosphonates or any type of medicine used to help strengthen bones weakened by osteoporosis, nor exposed to any other AVN risk factors other than SCD. Subjects were subjected to a scintigraphy (3-phase bone SPECT-CT, bone marrow) and bone mineral density scan (BMD). All subjects consented to the study approved by the ethics committee. Bone scintigraphy was performed by Tc-99m MDP, HDP 20mCi / 70kg intravenous injection. Bone Marrow Scintigraphy was performed by Tc-99m sulfur or tin colloid, 10-15 mCi / 70 kg I.V, Bone with Bone marrow scintigraphy imaging is required to assess bone marrow infarction and infection. BMD dual-energy x-ray absorptiometry (DEXA) was also performed to indicate the reliably changes in bone mineral content of the lumbar spine and proximal femur. Statistical analysis involved descriptive statistics and chi-square test. Results According to the WHO criteria used; low bone density was found in 9/13 (69%) while normal bone density was found in 4/13 patients (31 %). Based upon the application of a chi-square test, all those subjects 9/9 having a low bone density were showing AVN in several severity and multiple sites of the skeleton; it was found that there is an association between low bone density and incidents of AVN. However, it is of importance to note that 2/4 (50%) of the normal bone density patients were found to have AVN. Conclusion The preliminary conclusion discern from this ongoing project suggest that low bone mineral density in SCD could be considered a risk factor contributing to the development of AVN. We hypothesise that the severity of AVN develops due to the low bone mass and the deterioration of the micro architecture of bone tissue. The results have shown that low bone density is highly associated with osteonecrosis. Further case studies are needed to confirm or disprove these findings. The findings of this project could inspire new protocols required for effective management of this disease. Our findings could also potentially point out and diagnose new clinical cases, which would normally not be clinically suspected. We also speculate that increasing bone density of this patient population may decrease the severity and incidents of AVN. References 1-Sch2-nog JB, Duits AJ, Muskiet FA, ten Cate H, Rojer RA, Brandjes DP. Sickle cell disease; a general overview. Neth J Med. 2004 Nov;62(10):364-74. Review. PubMed citation 2-Digiovanni, Cw; Patel, A; Calfee, R; Nickisch, F (Apr 2007). “Osteonecrosis in the foot”. The Journal of the American Academy of Orthopaedic Surgeons 15 (4): 208–17. ISSN 1067-151X. PMID 17426292. 3-eMedicine Specialties > Avascular NecrosisAuthor: Jeanne K Tofferi, MD, MPH, FACP; Coauthor: William Gilliland, MD, MPHE, FACP, FACR. Updated: Dec 17, 2009 4-Baksi, Dp (May 1983). “Treatment of post-traumatic avascular necrosis of the femoral head by multiple drilling and muscle-pedicle bone grafting. Preliminary report”. The Journal of bone and joint surgery. British volume 65 (3): 268–73. ISSN 0301-620X. PMID 6341373. Disclosures: No relevant conflicts of interest to declare.

Bone Marrow and Bone Mineral Scintigraphic Studies in Sickle Cell Disease

1973 ◽  
Vol 25 (5) ◽  
pp. 593-598 ◽  
Author(s):  
C. F. Hammel ◽  
S. J. DeNardo ◽  
G. L. Nardo ◽  
J. P. Lewis
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Bone Mineral ◽  
Cell Disease

scholarly journals Hemopexin deficiency promotes acute kidney injury in sickle cell disease

Blood ◽  
2020 ◽  
Author(s):  
Solomon Ofori-Acquah ◽  
Rimi Hazra ◽  
Oluwaseun O Orikogbo ◽  
Danielle Crosby ◽  
Bethany Flage ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Inflammatory Process ◽  
Clinical Evidence ◽  
Kidney Injury ◽  
Red Cell ◽  
Cell Disease

Acute kidney injury (AKI) is a major clinical concern in sickle cell disease (SCD). Clinical evidence suggests that red cell alarmins may cause AKI in SCD however the sterile inflammatory process involved has hitherto not been defined. We discovered that hemopexin deficiency in SCD is associated with a compensatory increase in alpha-1-microglobulin (A1M) resulting in up to 10-fold higher A1M/hemopexin ratio in SCD compared to health controls. The A1M/hemopexin ratio is associated with markers of hemolysis and AKI in both humans and mice with SCD. Studies in mice showed that excess heme is directed to the kidneys in SCD in a process involving A1M causing AKI while excess heme in controls is transported to the liver as expected. Using genetic and bone marrow chimeric tools, we confirmed that hemopexin deficiency promotes AKI in sickle mice under hemolytic stress. However, AKI was blocked when hemopexin deficiency in sickle mice was corrected with infusions of purified hemopexin prior to the induction of hemolytic stress. This study identifies acquired hemopexin deficiency as a risk factor of AKI in SCD and hemopexin replacement as a potential therapy.

Hydroxyurea Use Is Associated with Avascular Necrosis of the Femoral Head among Children with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2477-2477 ◽  
Author(s):  
Kris Michael Mahadeo ◽  
Suzette Oyeku ◽  
Karen Moody ◽  
Swapmil N. Rajpathak ◽  
Abraham Groner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Femoral Head ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Odds Ratio ◽  
Demographic Characteristics ◽  
Cell Disease ◽  
Health Maintenance ◽  
Laboratory Values

Abstract Hydroxyurea therapy is associated with reduced morbidity among patients with sickle cell disease (SCD). Avascular necrosis of the femoral head (AVN) is one potentially debilitating complication of SCD. In this study, we examined the relationship between hydroxyurea use and the prevalence of AVN among children with SCD. We performed a retrospective chart review of 202 children with SCD, aged 10–21 years, followed in the pediatric hematology program at the Children’s Hospital at Montefiore (Bronx, NY) between July 2007 and 2008. Abstracted data included age, ethnicity, SCD genotype, frequency of hospitalization, hip radiograph results, laboratory data and hydroxyurea use. Hip radiographs were performed prospectively as part of SCD health maintenance from 2005–2008. Forty-four patients were excluded because they did not have a screening hip radiograph. Descriptive statistics were calculated for independent variables. T-tests and chi-square tests were used to compare clinical and demographic characteristics of children with and without AVN. Multivariate logistic regressions were used to estimate the odds ratio of having AVN among SCD patients. Our final sample consisted of 158 patients whose demographic characteristics are listed in Table 1. The prevalence of AVN was 16.5% (n=26). Of the clinical variables analyzed, we identified significant associations between the presence of AVN and hydroxyurea use (p=.005), as well as older age (p=.013) (Table 1.) Children with AVN had significantly lower mean lactic dehydrogenase levels (LDH) (p=.04) and higher mean corpuscular volumes (MCV) (p=.012). (Table 2.) After controlling for gender, ethnicity, sickle cell genotype, and frequency of hospitalizations, age was also found to be associated with AVN (OR 1.15, 95% confidence interval (CI): 1.01,1.31, p=0.033). SCD patients on hydroxyurea had higher odds of having AVN compared to non-users (OR 3.51, 95% CI: 1.31, 9.38, p= 0.013). Laboratory values (MCV, Hemoglobin, LDH and Hematocrit) had a high degree of collinearity and were removed from the final model. In summary, the prevalence of AVN in our sample was 16.5%. This is substantially higher than the prevalence of approximately 6% reported by the Cooperative Study of Sickle Cell Disease for comparative age groups in a prospective study1. SCD patients exposed to hydroxyurea were three times more likely to have AVN than those not exposed to this drug. Vaso-occlusive pain crisis is a recognized risk factor for AVN, thus we could expect a higher rate of AVN among patients on hydroxyurea. However, the odds ratio of 3.5 is unexpectedly high and warrants further investigation into the role of hydroxyurea as a risk factor for AVN. Nonetheless, these preliminary results suggest that more stringent screening regimens for AVN may be indicated among this subset of patients. Table 1. Clinical characteristics of patients with and without avn *p<0.05 **p<0.01 No AVN (N =132) AVN (N = 26) Age * 15.7 years 17.4 years Sex Male 64 (49%) 17 (65%) Ethnicity Black 110 (83%) 23 (88%) Hispanic 22 (17%) 3 (12%) HgbSS 84 (64%) 20 (77%) HgbSC 38 (29%) 4 (15%) HgbSBthal0 5(3.8%) 2 (8%) Hgb SC HgbSBthal+ 5 (3.8%) 0 On Hydroxyurea** 38 (29%) 15 (58%) # Hospitalizations 0 60 (45%) 10 (38%) 1–5 64 (49%) 14 (54%) >5 8 (6%) 2 (8%) Table 2. Mean Laboratory Values for Patients With And Without AVN No AVN AVN *p<0.05 (N =132) (N = 26) WBC 10.7 k/uL 10.5 k/uL Hgb 9.4 gm/dL 9.6 gm/dL MCV* 83 fL 89 fL Platelets 381 k/uL 376 k/uL Reticulocyte 7.70% 8.10% Ferritin 369.8 ng/mL 438.7 ng/mL LDH* 471.6 U/L 389 U/L Creatinine 0.6 mg/dL 0.6 mg/dL Hgb F 9.80% 11.30%

Evaluation of panoramic radiomorphometric indices related to low bone density in sickle cell disease

2011 ◽  
Vol 23 (7) ◽  
pp. 2037-2042 ◽  
Author(s):  
F. S. Neves ◽  
L. S. A. F. Oliveira ◽  
M. G. G. Torres ◽  
M. B. P. Toralles ◽  
M. C. B. O. da Silva ◽  
...  
Keyword(s):  
Bone Density ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Low Bone Density

Usual Clinical Parameters Underestimate the Incidence and Significance of Erythropoietin Deficiency as a Risk Factor for Death in Sickle Cell Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3791-3791
Author(s):  
Santosh Saraf ◽  
Seema Sidhwani ◽  
Mohammed Farooqui ◽  
Stephen Vara ◽  
Joseph DeSimone ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Early Death ◽  
Organ Damage ◽  
Endocrine Function ◽  
Clinical Parameters ◽  
Cell Disease ◽  
Epo Deficiency

Abstract A robust reticulocytosis is necessary to maintain hemoglobin levels compatible with life in patients with sickle cell disease. Relative reticulocytopenia, defined as a absolute reticulocyte count less than 250 x 109/L despite hemoglobin <9g/dl, has been identified as a risk factor for early death. RR could result from chronic bone marrow vaso-occlusive insult or a renal endocrine defect leading to erythropoietin (EPO) deficiency. In non-SCD patients, EPO levels and creatinine clearance are clinical parameters that are used to define patients with anemia from EPO deficiency. The normal ranges for these parameters may not apply to SCD, and therefore the incidence and significance of EPO deficiency in SCD may have been underestimated, compromising rational EPO replacement therapy. In a retrospective analysis of 417 patients with HbSS or S-β-thalassemia, confirming previous findings, RR was a risk factor for early death. There was a significant association between RR and proteinuria. Usually, there is an inverse correlation between hemoglobin and EPO levels (negative feed-back), this was seen in patients without RR. However, in patients with proteinuria, the correlation between hemoglobin and EPO levels was a positive one, suggesting hemoglobin dependence on EPO levels. Proteinuria or increased creatinine levels were a risk factor for early death but not if RR was included in the model, suggesting the increased risk of death associated with proteinuria and creatinine was mediated by RR. RR was also associated with decreased platelet and WBC counts, suggesting a contribution by cumulative vaso-occlusive bone marrow damage to RR. However, platelet and WBC counts were not risk factors for early death within the cohort. Damage to renal endocrine function/EPO deficiency should be added to the list of clinically significant chronic organ damage in SCD. EPO deficiency may precede and be causative of other end-organ damage, such as cardiac diastolic dysfunction and renal exocrine failure. Proteinuria should be recognized as a clinical parameter that should prompt consideration of EPO deficiency. Since EPO replacement is clinically feasible, renal endocrine dysfunctiton is a cause of symptoms, clinical deterioration and death that could be rationally addressed.

scholarly journals The Clinical and Radiological Effectiveness of Autologous Bone Marrow Derived Osteoblasts in the Management of Avascular Necrosis of Femoral Head in Sickle Cell Disease.

2021 ◽  
Author(s):  
Mir Sadat-Ali ◽  
Abdallah S Al-Omran ◽  
Sadananda Acharya ◽  
Tarek M Hijazi ◽  
Abid H Gullenpet
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Joint Arthroplasty ◽  
Long Term Results ◽  
Cell Disease ◽  
Necrosis Of Femoral Head

Abstract Background and Objective: Avascular necrosis of femoral head is a common Issue faced by orthopaedic surgeons which ranges between 10-18% but in sickle cell Disease the incidence reaches 30%. There is no definite treatment except joint arthroplasty. Regenerative medicine is an option to cure or delay joint arthroplasty. We report here our experience with injection of ABMDO to manage ANFH and report our long term results,progression of the ANFH if any and delay in THA (Total Hip Arthoplasty).Patients and Methods: Sixty-Three (63) consecutive patients with SCD with ANFH were examined, thoroughly investigated and those who had ANFH < grade II were consented to receive ABMDO. Pre-operatively patients were clinically assessed using Visual analogue scale (VAS), Modified Harris Hips Score (MHHS) and Azam-Sadat Score (ASS) for Quality of Life Score for Chronic Hip Disease. Ten milliliter of bone marrow was aspirated under local anesthesia and was placed in 20 CC culture media. Osteoblasts were cultured from the bone marrow aspirated. Under anesthesia using 3 mm cannulated drill, the osteonecrosed lesion was drilled and 5 million osteoblasts were injected at the lesion site. Patients were evaluated in out patient clinic after two weeks. At four months a repeat MRI was done and patients were followed up a minimum for 2 years.Results: The average age was 25.93±5.48 years. There were 41 (65%) females and 22 (35%) males. The mean hemoglobin S was 83.2±5.1 percent. The average follow up was 49.05±12.9 ( range 24-60) months. VAS significantly improved from 7.79±1.06 at 2 weeks 4.07±1.08 p<0.0001 continued to improve for the next 24 months 2.38±0.55 (P<0.0001). MHHS improved from 41.77±5.37 to 73.19± 6.48 at 4 months (P<0.001) and at 24 months it was 88.93±3.6 (p<0.001). The ASS also significantly improved from 2.76±0.49 preoperatively to 7.92±0.09 (p<0.0001) at 24 months. A comparison of the MRI’s of before and after osteoblast implantation revealed new bone formation and amelioration of the avascular lesions. Three patients were unhappy with the outcome and one patients repeated attacks of the vaso-occlusive crisis within six months of the osteoblasts injection.Conclusions: The results give credence to our earlier short follow up results that osteoblasts transplantation has a great potential in healing of avascular lesions. Our study fits the criteria of Phase II clinical trial and We believe a larger study equivalent to Phase III numbers and include patients not only with sickle cell disease but also steroid induced and idiopathic avascular necrosis.

scholarly journals Evidence for complement-mediated bone marrow necrosis in a young adult with sickle cell disease

2021 ◽  
Vol 86 ◽  
pp. 102508
Author(s):  
Melissa Azul ◽  
Surbhi Shah ◽  
Sarah Williams ◽  
Gregory M. Vercellotti ◽  
Alexander A. Boucher
Keyword(s):  
Bone Marrow ◽  
Young Adult ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Bone Marrow Necrosis
Sign in / Sign up

Export Citation Format

Share Document