Spondylolysis in patients who have osteopetrosis has, to our knowledge, been reported in only six patients in the English-language orthopaedic literature12,13. Four of these six patients were adults. These patients had a limited duration of follow-up, and the details of treatment were not always included. Brief case reports documenting an association between osteopetrosis and spondylolysis have appeared in the radiological literature, but details of treatment and follow-up were not included1,5,9.
We report on a series of five children who had osteopetrosis and were managed by us for spondylolysis. The average duration of follow-up was forty-one months. Three of the patients had spondylolysis in the lumbar spine only, one had spondylolysis in the cervical spine only, and one had spondylolysis in both the cervical and the lumbar spine. To our knowledge, spondylolysis of the cervical spine has never been reported before in association with osteopetrosis.
Materials and Methods
Seven patients were managed at our institution for skeletal and systemic manifestations of osteopetrosis between 1975 and 1995. Six of these patients had typical radiographic findings of type-II autosomal dominant osteopetrosis3,10, and one had clinical features and radiographic findings consistent with the severe form of autosomal recessive osteopetrosis10. The latter patient had recurrent respiratory infections, anemia, blindness, deafness, and macrocephaly. Of the seven patients, five were diagnosed as having spondylolysis of the spine (Table I). Radiographs of the remaining two did not reveal spondylolysis.
All five patients were diagnosed as having spondylolysis before they were ten years old. The osteopetrosis was diagnosed before the spondylolysis developed in two patients (Cases 4 and 5). In three patients (Cases 1, 2, and 3), low-back pain related to the spondylolysis led to the diagnosis of the osteopetrosis.
The spondylolysis involved the fourth lumbar vertebra in two patients (Cases 3 and 5), the fifth lumbar vertebra in two patients (Cases 1 and 2), and the axis in one patient (Case 4). One of the patients who had involvement of the fifth lumbar vertebra (Case 1) also had spondylolysis at the second and third cervical vertebrae in association with a congenital vertebral anomaly involving fusion of the second and third cervical vertebral bodies.
Of the three patients who had lumbar spondylolysis only, two (Cases 2 and 3) had low-back pain. The patient (Case 4) who had cervical spondylolysis only died when he was eight years old, without having had symptoms. The patient (Case 1) who had spondylolysis in both areas had symptoms at both levels.
All three patients (Cases 1, 2, and 3) who had persistent symptoms resulting from lumbar spondylolysis were managed non-operatively with a lumbosacral corset; the symptoms did not resolve in one of these patients (Case 2), who was then managed with a thoracolumbosacral orthosis.
Of the two patients who had cervical spondylolysis, one (Case 1) was managed with a posterior cervical arthrodesis with a modified Gallie technique and autogenous bone graft from the iliac crest. Biopsy of specimens obtained from the iliac crest confirmed the diagnosis of osteopetrosis and showed retention of cartilage cores within the bone trabeculae. There was a paucity of osteoclasts with normal-appearing marrow elements. The other patient (Case 4), who had spondylolysis at the second cervical vertebra, had the severe form of autosomal recessive osteopetrosis and died of systemic illness secondary to the osteopetrosis. No specific treatment was given for the spondylolysis.
The five patients returned to us for follow-up, which included the recording of a detailed history, physical examination, and radiographic evaluation at an average of forty-one months after the diagnosis of the spondylolysis was made.
All five patients were asymptomatic at the time of the latest follow-up examination; no patient had a new neurological deficit. One patient (Case 1), who had a grade-I spondylolisthesis6 in the lumbar spine as seen on radiographs that had been made after he had complained of back pain, did not have progression of the spondylolisthesis. None of the other patients had spondylolisthesis.
The patient (Case 1) who had a posterior arthrodesis of the cervical spine never had a fusion, but the neck pain resolved completely within six months. The low-back pain also resolved completely, but the spondylolysis at the fifth lumbar vertebra was still evident on radiographs. Radiographs made at the latest follow-up examination showed a new spondylolytic defect at the fourth lumbar vertebra as well. Two other patients (Cases 2 and 3) who had initially had symptomatic lumbar spondylolysis had had healing of the defects at the time of the latest radiographic examination and had also become asymptomatic. However, one patient (Case 2) had a new spondylolytic defect at the fourth lumbar vertebra. Two patients (Cases 4 and 5) remained asymptomatic throughout the entire course of follow-up. However, both of these patients continued to have radiographic evidence of spondylolysis: one (Case 5), in the lumbar spine, and the other (Case 4), in the cervical spine. The patient who had cervical spondylolysis only had no symptoms of neck pain before his death.
During the course of follow-up, no patient who had autosomal dominant osteopetrosis had other orthopaedic manifestations of osteopetrosis. The patient (Case 4) who had the severe form of autosomal recessive osteopetrosis, and later died, had undisplaced metaphyseal fractures of the long bones (the distal aspect of both femora and the distal aspect of the right tibia).
Illustrative Case Reports
CASE 1. A seven-year-old boy was seen in the emergency department because of neck pain. He had a history of cerebral palsy and mild mental retardation and had had a ventriculoperitoneal shunt for the treatment of hydrocephalus. He was unable to walk.
Five days before he was seen at our institution, the boy had fallen and struck his head after being moved out of a wheelchair. He had a momentary loss of consciousness followed by mild neck pain. When this symptom did not resolve, his mother brought him to the emergency department.
Physical examination revealed tenderness to palpation posteriorly over the entire cervical spine but no new neurological deficit. Radiographs showed spondylolysis at the second and third cervical vertebrae as well as congenital fusion between these vertebrae (Fig. 1-A). A skeletal survey showed typical features of autosomal dominant osteopetrosis. A bone scan demonstrated only minimally increased uptake in the area of the spondylolysis.
A posterior cervical arthrodesis from the first to the fourth cervical vertebra was subsequently performed with use of a modified Gallie technique and autogenous bone-grafting. This was done because the cervical spine was unstable, as determined on radiographs made with the spine in flexion and extension.
A Philadelphia collar was used for twelve months postoperatively, as it was believed that this was the only form of immobilization that would be tolerated by the patient. Interim radiographs showed a progressive increase in the fusion mass but also a pseudarthrosis.
Two years after the operation, the pseudarthrosis was still visible on radiographs (Fig. 1-B). Forty-five months postoperatively, the patient was asymptomatic but the pseudarthrosis remained.
Several months after the cervical arthrodesis, the patient began to complain of low-back pain. Radiographs revealed spondylolysis at the fifth lumbar vertebra with grade-I spondylolisthesis (Fig. 1-C). He was managed with a lumbosacral corset. The symptoms persisted intermittently for two years.
When the patient was last seen, thirty-seven months after the onset of the low-back pain, he was asymptomatic. A radiograph revealed persistent spondylolysis at the fifth lumbar vertebra with grade-I spondylolisthesis, as well as a new spondylolytic defect at the fourth lumbar vertebra (Fig. 1-D).
CASE 2. A nine-year-old boy was seen by us because he had had persistent low-back pain for several weeks. He was otherwise well, and the medical history was unremarkable.
Physical examination revealed only tight hamstrings. Radiographs, including a skeletal survey, revealed spondylolysis at the fifth lumbar vertebra as well as the typical appearance of autosomal dominant osteopetrosis (Fig. 2-A).
The patient initially was managed with a lumbosacral corset, but the symptoms persisted and the back pain became severe. After the patient's parents refused operative intervention, he was managed with a thoracolumbosacral orthosis.
After four years of treatment, the back pain resolved. At the most recent follow-up evaluation, six years after presentation, the patient was still asymptomatic. Radiographs showed a healed spondylolytic defect at the fifth lumbar vertebra, but there was a new spondylolytic defect at the fourth lumbar vertebra (Fig. 2-B).
Osteopetrosis is a skeletal disorder characterized by defective bone resorption related to dysfunctioning osteoclasts3,8,11. This disorder, which was described by Albers-Schönberg1,5 in 1904, also is associated with increased bone density on radiographs. The clinical types of osteopetrosis include a severe autosomal recessive form, an intermediate autosomal recessive type, and two relatively benign autosomal dominant types3,8,10,11.
The severe form of autosomal recessive osteopetrosis is usually fatal within the first few years of life. Affected patients may have pathological fractures; recurrent infections; failure to thrive; and a hematological picture of anemia, thrombocytopenia, and leukopenia. Medical treatments have included high doses of calcitriol, to stimulate differentiation of osteoclasts, and bone-marrow transplantation7,10. These treatments appear promising, but there is not yet a well documented consensus on the long-term results of systemic treatment10.
Patients who have the intermediate mild autosomal recessive form of osteopetrosis tend to be diagnosed toward the end of the first decade of life and to survive into adulthood. They have increased bone density that is apparent on radiographs. This condition is associated with mild disproportionate short stature, macrocephaly, recurrent fractures, mandibular osteomyelitis, dental abnormalities, and mild-to-moderate anemia10.
The benign form of autosomal dominant osteopetrosis usually is associated with a normal life expectancy, but patients may have pathological fractures and low-back pain10. Two types of benign autosomal dominant osteopetrosis have been described3,10. Type I is characterized radiographically by pronounced sclerosis of the cranial vault, whereas type II is characterized by a so-called rugger jersey spine, pelvic endobones (a so-called bone within a bone), and marked osteosclerosis at the base of the skull2,3. Type-II autosomal dominant osteopetrosis has been associated with an increased risk of fracture and delayed fracture-healing2. Both types of autosomal dominant osteopetrosis are marked by increased bone density on radiographs, but the patterns vary.
The prevalence of osteopetrosis is 5.5 per 100,000 people3. The prevalence of spondylolysis in association with osteopetrosis is unknown. In the current series, five of the seven patients who had osteopetrosis had spondylolysis, suggesting that this association may be more common than has been realized. In contrast, the prevalence of spondylolysis was reported to be 4 per cent (twenty-two of 500) in children6 and 6 per cent (ten of 170) in adults who had normal bone4.
One of our patients had spondylolysis at four levels in the spine (two levels in both the lumbar and the cervical spine). This is rare in patients who have normal bone4. Two of our patients had healed spondylolytic defects at the latest follow-up examination. This is uncommon in patients who have normal bone unless treatment has been initiated within thirty days after the onset of symptoms following a clearly documented injury6. Although osteopetrosis may be associated with an increased risk of spondylolysis, healing can occur.
The presence of spondylolysis in a patient who has osteopetrosis does not imply that the patient will have back pain. Our findings suggest, however, that back pain associated with spondylolysis may be the presenting symptom that leads to the diagnosis of autosomal dominant osteopetrosis.
Non-operative treatment yielded an excellent clinical result in our patients, although prolonged use of a brace was needed. Radiographically, healing occurred in two (Cases 2 and 3) of the three patients who had a symptomatic lumbar spondylolysis, although one (Case 2) had a new (but asymptomatic) spondylolysis cephalad to the original spondylolysis. To our knowledge, there has been no previous report, in the English-language orthopaedic literature, of spinal arthrodesis performed in a patient who had osteopetrosis.
Osteopetrosis should be recognized as a cause of pathological spondylolysis that may affect the lumbar or the cervical spine, or both, particularly in children. Spondylolysis associated with osteopetrosis may be painful, and the symptoms may be protracted but will generally respond to non-operative measures such as use of a lumbosacral corset or a thoracolumbosacral orthosis.
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
Investigation performed at Janeway Child Health Center, St. John's
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