High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann's syndrome).

OBJECTIVE

Clinical observation of bone pain, unusual fractures in two patients, and diffuse osteopenia/osteoporosis led us to assess bone mineral content and density in 30 patients with severe congenital neutropenia who were treated with recombinant-methionyl-human granulocyte colony-stimulating factor (r-metHuG-CSF).

METHODS

We reviewed roentgenograms in 29 of these 30 patients to evaluate bone loss before and during treatment. In addition, in 17 of the 30 patients, bone mineral status could be assessed by both quantitative computed tomography (Q-CT; n = 16) and dual energy x-ray absorptiometry (DXA; n = 1). In one patient, Q-CT was not possible because of severe vertebral fractures.

RESULTS

Of the 30 patients investigated, 15 had evidence of osteopenia/osteoporosis observed on spine radiographs (n = 5), on Q-CT/DXA (n = 1/n = 1), or on radiographs and Q-CT (n = 8). In 13 of the 30 patients, only a lateral radiograph of the lumbar spine was available, 5 of 13 showing either increased kyphosis and wedging of the vertebrae or compression fractures of the vertebral bodies, indicating severe established osteoporosis. In eight patients, the findings of the spinal radiographs were normal. In nine patients, spinal radiographs were taken before r-metHuG-CSF treatment. Osteoporotic vertebral deformation (n = 3) or reduced bone mass (n = 3) was seen in six of these nine patients. The levels of serum biochemical markers of bone metabolism were all within normal ranges except for mild elevation of the serum alkaline phosphatase level. The degree of spinal bone mineral loss did not correlate with dose and duration of r-metHuG-CSF treatment or with the age or sex of the patients.

CONCLUSIONS

These data indicate a high incidence of bone mineral loss in children with severe congenital neutropenia. The underlying pathogenesis of bone demineralization is not clear. It is more likely that the bone loss was caused by the pathophysiologic features of the underlying disease, but it is possible that r-metHuG-CSF accelerates bone mineral loss.