Abstract
Chemotherapy and radiotherapy are provoking orthopaedic complications with serious therapeutic dilemmas. We want to highlight the importance of early recognition of these complications and the difficulties in their management.
Survival rates in children with oncological diseases have significantly increased and patients now frequently survive into adulthood due to the successful advances in chemotherapy and radiotherapy treatment over the last decade. We are therefore seeing an increase in the longer term complications of these treatments. For example, from our experience we have two specific cases, one of bilateral slipped capital femoral epiphyses (SCFE) and another of bilateral avascular necrosis of the femoral heads, which occurred in association with combination chemotherapy and irradiation treatment for leukaemia. Anecdotal evidence states an increase in the prevalence of SCFE and avascular necrosis, despite research previously stating the causative associated risks. These previously unrecognized radiation-related growth disturbances may be more likely to be seen in the future. 1
Avascular necrosis
The most common cause of avascular necrosis is corticosteroid medication in adults, and several hundred cases have been reported. It is reasonable to conclude that there is a substantial risk of osteonecrosis in patients treated with high dose steroids even on a short-term basis. In contrast, aseptic bone necrosis in relation to corticosteroid treatment is rare in children and adolescents. Despite the large amounts of prednisone which have been used in the standard treatment of acute lymphocytic leukaemia (ALL), avascular necrosis has rarely been reported in children with that disease. Adequate treatment protocols provide excellent results in management of lymphoma, leukaemia and other malignancies in children. Despite their serious side effects, corticosteroids are still being considered as an important part of haematological therapy and are not being omitted in the near future, so the earliest possible diagnosis of bone necrosis will remain of great importance, so as to limit disability. Avascular necrosis was identified in patients treated at a major paediatric oncology centre with a predominant underlying diagnosis of acute leukaemia. Both steroids and radiation therapy appear implicated in the pathogenesis of avascular necrosis. Thus, like adult cancer patients, children who receive high doses of steroids or local irradiation involving femoral heads are at risk for avascular necrosis. Children aged 10–20 years who receive intensive ALL therapy, including multiple courses of corticosteroid, are at significant risk for developing avascular necrosis. 2 Awareness of this possibility will lead to a more rapid diagnosis and early treatment of avascular necrosis. The average time to developing bone necroses has been 12–29 months from diagnosis of ALL to development of avascular necrosis. 3 Therapy related sequelae like avascular necrosis have become a matter of increasing concern and orthopaedists will be increasingly called on to manage avascular necrosis affecting multiple joints in children and young adults. 4 Weight-bearing joints are involved in over 90% of cases. Because the bone pain of avascular necrosis can mimic that of leukaemia relapse, this is an important entity to be aware of. 5 The need for long term follow-up of therapeutically irradiated children is stressed. There may be a risk period of 12 months for developing femoral head osteonecrosis in patients receiving long-term steroid treatment. Close observation and more aggressive screening are recommended within the first year of long-term steroid treatment to prevent advanced osteonecrosis of the femoral head. 6 Since radiological changes only develop several weeks to months after the onset of the clinical symptoms and because of the disabling consequences for patients, a 99Technetium bone scan or MRI should be done as early as possible. MRI is the most sensitive means of detecting the earlier stages of avascular necrosis. A strong indicator is to screen all those with pain; however, 40% of avascular necrosis patients are asymptomatic. 7 If the MRI appearances are typical, an early diagnosis can be made, enabling therapeutic interventions to prevent joint collapse and its associated morbidity.
Treatment aims to prevent collapse of the femoral head and hope that healing will occur. It is therefore necessary to offload the hips. Total joint replacement is often necessary to restore function. Yet endoprostheses in young patients again bear the risk of later complications and the need for several revision surgeries. In one report, the average age at the time of surgery was 18 years (range 14–26 years). The procedures included retrograde drilling (core decompression), bone grafting, implantation of collagen sponges with autologous bone marrow aspirate, osteochondral autograft transplantation and transplantation of periosteal flaps, and total joint replacement. The aim of surgery for avascular necrosis after chemotherapy should be the reduction of pain and preservation of the joint to bypass the risks of joint replacement in young patients, although total joint replacement may become indicated in end stage degeneration of the involved joint.
Slipped capital femoral epiphyses
Atypical SCFE after radiotherapy and combination chemotherapy is uncommon. Those who received radiation to the proximal femoral epiphysis and chemotherapy in childhood appear to have an increased risk of subsequently developing epiphyseolysis. 8 Children with radiation-therapy associated SCFE are usually thin (median weight 10th centile) in contrast to children with typical SCFE, who are usually obese (>95th centile). 9 Because patients may have slippage at atypical ages, the need to heighten clinicians' awareness of this condition in patients who have received radiation and chemotherapy for pelvic tumours is paramount. Every effort should be made to exclude the proximal femoral epiphysis from the radiation port whenever possible. 8
Typical SCFE during puberty has to be differentiated from the atypical form, which may be associated with an endocrinological disorder or with its therapy. The aetiology of this disease is still not fully understood but seems to be multifactorial: a physis that is weakened by some underlying condition fails when it is subjected to more than normal stress, resulting in slipping of the proximal femoral epiphyses. 10 In studies of atypical SCFE, age at presentation of the first SCFE ranged from 7–35 years. Only those with hypothyroidism or growth hormone deficiency were less than 10 years of age. All patients with other endocrinopathies (hypothyroidism, panhypopituitarism, hypogonadism), when seen first with an SCFE at an atypical age, were more than 16 years old. During growth hormone treatment, close monitoring with both clinical and radiographic examination is mandatory. All cases of SCFE were diagnosed while they were receiving growth hormone therapy, though the exact aetiology and the role of growth hormone in the pathogenesis of these conditions are still unknown. Because hypothyroidism can be easily overlooked, all patients with SCFE should be screened for hypothyroidism. Pituitary deficiency should be considered in children short for their age that have hypogonadism. 11
The ideal treatment of SCFE should prevent additional slipping of the epiphysis and stimulate early physeal closure, while avoiding the complication of avascular necrosis, chondrolysis and osteoarthritis. Because of possible alterations of blood supply to the femoral head, acute SCFE is an emergency. 10 Bilateral involvement is reported in 21–80% of cases. Where bilateral slips occur, the second slip usually occurs within 12–18 months of the original slip. Symptomatic slipping of the contralateral hip after unilateral slipping has been estimated to occur in 12.5% of patients before skeletal maturity, and asymptomatic slipping in as many of 40% of the contralateral hip. 12 Prophylactic pinning is even more controversial. Because of the frequency of complications such as chondrolysis, prophylactic pinning of the contralateral hip is not usually performed. The controversy over prophylactic pinning of the uninvolved hip in radiotherapy-associated slipped capital femoral epiphysis is unresolved. It may be justifiable to fix the non-slipped epiphysis if possible prodromal signs of abnormal radiographic findings are detected. This is more evident in young patients where slip progression appears inversely related to the number of screw threads engaging the epiphysis on the postoperative frog-leg lateral radiograph. 13 The younger the child, the more difficult it is to achieve adequate fixation in a small epiphysis and hence there is likely to be an increased incidence of progression.
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