A series of studies, first reported by Ratliff and his colleagues in the 1960s, have portrayed TFHN as a severe complication secondary to paediatric FNF[1, 2]. Since then, the unsatisfactory outcomes of this condition have been repeatedly reported by numerous studies; however, the specific natural history of and relevant risk factors for TFHN in children and adolescent remain unknown. This study is the first, to our knowledge, to address these deficiencies through a retrospective study that included 64 conservatively treated cases, which is thought to be the largest currently utilized sample size. The natural history of TFHN in children and adolescent was characterized in detail by femoral head collapse, hip deformity and hip degeneration, which can aid in the treatment planning process. The most important finding in our study is that TFHN in children and adolescent is a rapidly progressing disease with a natural history characterized by a high risk of femoral head collapse and deformity; some cases showed hip degeneration in the short term when lateral subluxation of the hip appeared.
Several limitations still exist. First and foremost, although more than thirty patients treated surgically in our institute, they were inappropriately enrolled as the control group for a variety of indications. Only the cases at severe collapsed stage, and combined with hip subluxation were suggested hip preserved operations; Those with severe hip degeneration already were suggested to hip arthroplasty. Such outcome will be reported in other study. Numeral included cases in current study who had met our surgical indication were suggested surgical treatment, but they refused for personal reasons, which gave us a chance to observe their rapid progression of disease and poor outcome in a short term. Second, although this investigation is the first, to our knowledge, to describe the natural history of TFHN via a case series of children and adolescent treated with conservative or observational treatment, the disease progression and related factors reported in our results were not absolutely equivalent to the “genuine natural history” that was described through the observation that ideally untreated patients rarely exist. Third, we set up a minimum follow-up of 2 years, and finally presented a middle-term result of 4 years on average. To be sure, it was not a long enough period to describe the complete course for most hip problems in paediatric population. However, under the limited follow-up, our results provided a cautionary and useful note of TFHN in children and adolescent, “rapid deterioration and relevant factors”, that would be beneficial for clinical decision. Further prospective multi-centre control trials with more cases or control groups are suggested to confirm the results.
Femur head necrosis in the paediatric population can be induced by both non-traumatic and traumatic aetiologies. The non-traumatic aetiologies include corticosteroid-associated osteonecrosis, Legg-Calve-Perthes disease, sickle cell disease-induced osteonecrosis and Gaucher’s disease[18]. Unlike non-traumatic cases, TFHN are far less common due to the rare incidence of FNF in children and adolescents. Thus, therapists might remain foreign to TFHN because of the lack of guidelines and consensus documents. According to our study, a distinct difference exists in the natural history of cases of TFHN and other non-traumatic cases of osteonecrosis.
The most intuitive characteristic during our observation of TFHN in children and adolescent was the high incidence of femoral head collapse progression, which is generally considered a turning point indicating poor prognosis in the short term [15]. Eight of 33 hips collapsed at the early stage, and 17 of 31 hips that collapsed at the collapsed stage demonstrated collapse progression during the follow-up. The presence of collapse primarily depended on the lesion size and the location of the necrotic area, as the large involvement of necrotic lesions results in a high risk of femoral head collapse[14, 15]. We believe that patients with TFHN were susceptible to extensive necrosis due to and large damage of blood supply induced by high-energy primary trauma. Ratliff et al demonstrated the highest incidence of TFHN occupying the total head (type I), followed by partial necrosis of the epiphysis (type II) and necrosis between the epiphyseal plate and the fracture line (type III) [1]. A high risk of total head necrosis, ranging from 35.7–80.7%[1, 5, 19–22], has been confirmed repeatedly by studies on the same subject.
The high risk of large lesions and disease progression does not seem to be common in corticosteroid-associated children and adolescents. Kaste et al used MRI to detect 462 cases of corticosteroid-associated osteonecrosis in children and adolescents, and the overall rate of osteonecrosis and the rate of extensive cases involving > 30% were 21.7% and 6.5%, respectively, with a four-year follow-up. Similarly, Karimova et al reported that the proportion of extensive cases involving > 30% and the rate of lateral involvement (Type C) of osteonecrosis in paediatric and young adult patients with leukaemia or lymphoma were 26.3% (30/114 hips) and 31.6% (36/114 hips), respectively. In contrast, 79.7% (51/64) of hips in this study were defined to have lateral involvement (type C). The actual ratio must be higher in our institute because the remaining patients treated surgically all had hips with largely lateral involvement.
Legg-Calve-Perthes disease is also a common aetiology of childhood osteonecrosis, usually with extensive and severe involvement of the epiphysis. Canavese et al described the prognosis of Legg-Calve-Perthes disease in patients under six years old[23]. According to the Catterall classification, 50 hips had mild involvement (grade I/II), and 116 hips had severe involvement (grade III/IV). Similarly, 358 patients with Legg-Calve-Perthes disease (mean age, 5.8 years) were followed for more than five years with radiographic data by Wiig et al, 87.7% (314/358) of whom exhibited severe involvement (grade III/IV)[24].
However, these severely involved patients with Legg-Calve-Perthes disease had a better prognosis than children and adolescent with TFHN. First, TFHN tended to be associated with severe deformity. The percentages of Stulberg class III and IV/V hips in our study were 28.1% (18/64) and 31.3% (20/64) in patients with TFHN after PFNF. The matched data for patients with Legg-Calve-Perthes disease were 22.4% (26/116) and 10.3% (12/116) in the study of Canavese et al and 36.6% (115/314) and 19.2% (60/314) in the study of Wiig et al. Second, during our follow-up of children and adolescent with TFHN, hip degeneration progressed rapidly, with an incidence of 30% in the first years and 50% in total, which was obvious different from patients with Legg-Calve-Perthes disease, who experienced hardly any osteoarthritic changes in the short term until their 40 s and 50s[12].
In general, TFHN seemed to be more susceptible to hip deformity and degeneration compared with Legg-Calve-Perthes disease in paediatric population, finally resulting worse prognosis. As we speculated, the weakened abilities of bone repair and remodelling with older age were other potential causes of poor prognosis in patients with TFHN. The average age of the included patients in our study was nearly 13 years old. In this age group, patients with bone necrosis lack satisfactory repair and remodelling abilities and show completely different natural histories and pathological processes than younger patients[25, 26]. Spontaneous femoral head repair and remodelling into a spherical shape were never observed in our patients at the collapsed stage. Even with the largest sample size of such condition, the sample still did not report the results for all ages of children and adolescents. For instance, we only included small proportion of children younger than 11 years of age (six cases), who would presumably have a better prognosis.
Hip incongruency and instability secondary to irreversible deformity were the major causes of rapid cartilage damage. According to our multivariate analysis, as lateral subluxation of the hip occurred during the follow-up, the risk increased sharply by 26-fold for severe hip deformity and 13-fold for severe hip degeneration (Table 2). In addition, it was difficult to rule out the adverse effect on cartilage of the femoral head, even chondrolysis, due to the presence of primary dramatic injury. Osteoarthritic changes represented the primary cause of arthroplasty in our patients. Our work determined that the natural history of TFHN in children and adolescent was specific and different from corticosteroid-associated osteonecrosis or Perthes disease. However, such a comparison was theoretical and indirect.
As a sign of a “head at risk”, lateral subluxation of the hip was defined as the strongest independent risk factor for primary outcomes in our results. For immature patients, lateral subluxation signifies poor containment and instability of the hip joint. The former is a widely recognized adverse effect of femoral head remodelling, and the latter increasingly exacerbates hip degeneration. Other recognized prognostic factors of progression of femoral head collapse for most types of osteonecrosis of femoral head, such as the initial degree of femoral head collapse[27], JIC classification[15] and symptoms[28], show no apparent relation to severe hip deformity and degeneration. Therefore, these factors did have value for predicting femoral head collapse, but after collapse, not all hip showed further progression to severe hip deformity and degeneration. If the lateral subluxation emerged, cases at collapsed stage showed increasingly tendency towards severe hip deformity and degeneration in the short term (Fig. 3), otherwise they might keep satisfactory hip condition (Fig. 4).