Aseptic Osteonecrosis of the Femoral Head in Children Living with Sickle Cell Disease at the National Reference Center for Sickle Cell Disease of Brazzaville, Congo

At the osteoarticular level, the complications are multiple and can manifest themselves either acutely (vaso-occlusive crisis, bone infarction, infections) or chronically (chronic osteomyelitis, aseptic epiphyseal osteonecrosis). Aseptic epiphyseal osteonecrosis is the death of bone tissue occurring outside of infection and relating to an abnormality in blood circulation


Introduction
Sickle cell disease is a genetic disease inducing the polymerization of hemoglobin molecules in red blood cells, causing their embrittlement, hyperhemolysis, and loss of plasticity [1] which is observed in almost all vertebrates, including aquatic animals and birds [2].The most common hereditary disease in the world, with approximately 310,000 births affected each year [3], it constitutes a public health problem, particularly in sub-saharan Africa where 85% of children affected by the disease are born [4].In Congo, the homozygous and heterozygous forms represent respectively 1.25% and 25% of the population [5].The symptomatic forms are characterized by three main categories of clinical manifestations which can vary greatly depending on the case: chronic haemolytic anemia with episodes of acute worsening, predisposition to bacterial infections, and vasoocclusive manifestations [1]. of the pelvis.The prevalence of AOFH in our study and in general in Africa is probably much under estimated.Indeed, the systematic nonpractice of MRI or bone scintigraphy constitutes a limit to the early diagnosis of osteonecrosis in patients (symptomatic or not) presenting a normal standard X-ray.This fact was objectified by Kouamé-Koutouan in Côte-d'Ivoire where the prevalence of AOFH in adults with sickle cell disease presenting coxalgia with or without lameness doubled thanks to the use of bone scintigraphy, half patients with a normal plain radiograph [17].In addition, the annual systematic screening recommended by expert groups [18] cannot be applied due to the absence of social security systems limiting access to care.Thus much higher frequencies of AOFH are reported in so-called rich determining its prevalence and describing its epidemiological, clinical, and radiological characteristics in children suffering from sickle cell disease in Brazzaville, Congo.

Methodology
This was a descriptive cross-sectional study.It was conducted over a 4 years-period from October 1 st , 2017 to September 31 st , 2021.It took place at the National Reference Center for Sickle Cell Disease "Antoinette Sassou N'guesso" in Brazzaville, which since 2017 has been the largest center in the country dedicated to the care of people suffering from sickle cell disease, research, and health workers' training on the disease.Patients of all ages come from all districts of the country.Apart from any emergency and depending on their age, children are seen there four to six times a year, i.e. at least once a quarter for systematic check-up.An X-ray of the pelvis is prescribed as part of a systematic check-up from the age of 10 and/or if there are signs suggesting AOFH.The target population was constituted of children, i.e. patients under 18, who had radiologically documented AOFH.Sampling was exhaustive consecutively.Data were collected retrospectively from medical records.They were epidemiological (age at diagnosis and gender), clinical (manifestations and functional repercussions of AOFH) and paraclinical (radiological aspects of AOFH).The measurement of the length of the pelvic limbs used as landmarks the umbilicus and the medial malleolus.The Postel Merle d' Aubigner functional score [15] was used to assess the impact of AOFH on hip function.AOFH was classified according to the radiological staging of Arlet and Ficat [16].
The results of the qualitative variables are presented in absolute values and in percentage; those of the quantitative variables in the form of mean (± standard deviation), minimum and maximum.

Results
2982 patients suffering from homozygous sickle cell disease were followed at the National Reference Center for Sickle Cell Disease "Antoinette Sassou N'guesso", including 1623 children.AOFH was documented in 35 of them, which corresponds to hospital prevalence of 2.15%.Thirty-one files were used to describe their characteristics.The average age of the children was 11.51 ± 2.17 years with extremes of 8 and 17 years.They were 18 boys and 13 girls.The sex ratio was 1.38.Hip pain was the discovery circumstance of AOFH in all patients.It was mechanical and associated with lameness in some children.The lameness was analgesic type in 9 children (29.03%) and Trendelenburg type in 17 children (54.84%).
The clinical characteristics of children suffering from sickle cell disease presenting with ONFH are presented in table 1.
Due to the bilaterality of lesions in 10 children (32.26%), there were a total of 41 pathological hips for 31 children.Considering the highest stage in children with bilateral lesions, the radiological staging of AOFH is reported in table 2.
Figure 1 illustrates a right AOFH at stage III of Arlet and Ficat with bone sequestration in a 14-year-old boy living with sickle cell disease.

Discussion
Our pediatric series is one of the highest among those reported in Africa: Mouba in Gabon reported 22 cases over 10 years [13].Akakpo-Numado in Togo reported 14 (including 8 HbSS and 6 HbSC) over a period of 20 years, but these were data from a pediatric surgery department and not from a treatment center for sickle cell disease [14].The diagnosis was based solely on the realization of a standard X-ray countries where routine radiographic screening for AOFH is carried out in the majority of patients, symptomatic or not: from 9% in the USA(Philadelphia) in the study by Worrall between 0 and 21 years old [19], to 14.13% in Brazil between 0 and 20 years old [20,21].Still in the USA (New York), Mahadeo reports a prevalence of all genotypes of 12.4% which increases to 14.2% for the HbSS and HbSβ0 thalassemia forms in patients aged 10 to 21 years [22].Several risk factors are implicated in the occurrence of osteonecrosis in sickle cell disease.Among clinical and laboratorial factors, the most promising risk factors were the severity of sickle cell disease and acute chest syndrome.As a result, from studies of a moderate level of quality, blood pressure, body weight, previous trauma, haemoglobin to haematocrit ratio, and number of hospitalizations can be highlighted.Others, such as genetic markers and male gender, have also been positively associated [23,24].
It important to research them in the African context.
In our study, the mean age at the time of diagnosis of AOFH of 11.51 ± 2.17 years is slightly lower than that found in the literature, which often varies from 12 to 14 years [12,[24][25][26][27].However, these studies report a slightly younger age of onset: 7 years [13,28], 6 years [26] and even 5 years for osteonecrosis of the shoulder [27].The particularity of our serie is that nearly half of the children were under 11 years old (45.16%), whereas Mouba [13] and Man and Koren [27] reported a prevalence of AOFH clearly greater after the age of 11.The average age is 14 in Brazil and the USA [19,20].All these results testify to the early onset of this bone complication diagnosed in sometimes young children.
The pain of AOFH is either acute during the infarction, or chronic during the progressive constitution of osteoarthritic lesions, then accompanied by a reduction in joint mobility [3].In our study, the diagnosis was made in all patients at a symptomatic stage in which hip pain was the constant sign.None of the diagnosis was systematic.In addition, our data showed a high proportion of children in whom bone damage was bilateral (one-third of cases), classified at the two most advanced stages of Arlet and Ficat (stage II or III in almost two-thirds of cases) and presenting functional impotence (two-thirds of cases).This profile is common in Africa and most likely linked to diagnostic delay, itself related to various social and/or economic reasons, as pointed out by other authors [13,27].Bilaterality of osteonecrosis lesions over time is usual [29].Its frequency can reach 91% of adults for hip joints [30].Our series is characterized by a high rate of bilaterality compared to that of other pediatric series: 20% in Gabon [13] and 18% in Benin [27].In Mahadeo's study in the USA [22], the diagnosis was made at an earlier stage: 68.75% of patients were asymptomatic, 64% of AOFH corresponded to Steinberg's early stages 1 or 2 [31] and the bilateral damage only concerned 12% of patients whose average age was 18 years, compared to 32% of bilaterality in ours whose average age, it should be remembered, was 11 years.

Conclusion
Our findings reflect the early onset of AOFH in african children suffering from sickle cell disease in Africa and its late diagnosis, most often at the stage of joint destruction.To overcome this, special emphasis should therefore be placed on its prevention, at least on the means of delaying its onset.It is important to identify its predictive factors through further investigation in a larger population and to put in place a strategy for early diagnosis such as screening radiographs of the hips from the age of 7.

Table 1 :
Epidemiological and clinical characteristics of children suffering from sickle cell disease presenting with AOFH on National Reference Center for Sickle Cell Disease of Brazzaville, Congo.

Table 2 :
Distribution of children suffering from sickle cell disease presenting AOFH according to Arlet and Ficat radiological stage, at National Reference Center for Sickle Cell Disease of Brazzaville, Congo.