PEDIATRICS Vol. 108 No. 3
September 2001,
p. e54
ELECTRONIC ARTICLE:
Severe Osteopenia in a Young Boy With Kostmann's Congenital
Neutropenia Treated With Granulocyte Colony-Stimulating Factor:
Suggested Therapeutic Approach
Received Mar 5, 2001; accepted May 7, 2001.
Rajagopal V. Sekhar*,
Steven Culbert
,
W. Keith Hoots,
Mary J. Klein*,
Hallie Zietz, and
Rena Vassilopoulou-Sellin*
From the Departments of * Endocrine Neoplasia and Hormonal
Disorders and Pediatrics, University of Texas M. D. Anderson
Cancer Center, Houston, Texas.
Kostmann's syndrome is a congenital disorder that
causes an impairment of myeloid differentiation in the bone marrow
characterized by severe neutropenia, which can be treated
with recombinant human granulocyte colony-stimulating factor (G-CSF).
We present the case of a 13-year-old boy with Kostmann's syndrome who
was treated with recombinant human G-CSF from age 3.5 years. His growth
and development was normal, although complicated by intermittent
infections. Bone mineral density (BMD) measurement revealed severe
osteopenia at the spine and hips (lumbar spine BMD 0.486 g/cm2; Z score 
3.6), and he was referred
to the Endocrine Service. Relevant laboratory evaluation showed a
pretreatment ionized calcium level at the upper limit of normal (1.28 mmol/L; range: 1.13-1.32 mmol/L), suppressed intact parathyroid
hormone (iPTH) level (12 pg/mL; range: 10-65 pg/mL), and a low
1,25-dihydroxy vitamin D level (21 pg/mL; range: 24-65 pg/mL). He had
evidence of increased bone turnover evidenced by elevated urinary
deoxypyridinoline (DPD) cross-links (46.9 nmol/mmol creatinine; range:
2-34 nmol/mmol creatinine) and a simultaneous increase in markers of
bone formation with elevated osteocalcin level (200 ng/mL; normal:
20-80 ng/mL) and alkaline phosphatase level (236 IU/mL; normal:
38-126 IU/mL). Because of clinical concern for his skeletal health,
bisphosphonate therapy with intravenous pamidronate was initiated. One
month after treatment, the iPTH and DPD cross-links were in the normal range (54 pg/mL and 17.7 nmol/mmol creatinine, respectively) and the
1,25-dihydroxy vitamin D level was elevated (111 pg/mL). Four months
after treatment, there was a striking increase in BMD at the lumbar
spine (+30.86%), femoral necks (left, +20.02%; right, +17.98%), and
total hips (left, +18.40%; right, +15.94%). Seven months after
bisphosphonate therapy, his biochemical parameters showed a return
toward pretreatment levels with increasing urinary DPD cross-links
(28.7 nmol/mmol creatinine) and decreasing iPTH (26 pg/mL). However,
the BMD continued to increase (8 months posttreatment), but the
magnitude of the increment was attenuated (lumbar-spine, +4.8%; left
total hip, +1.2% and right total hip +2.4%), relative to BMD at 4 months. Eight months after the initial treatment, his iPTH was
suppressed at 14 pg/mL and he again received pamidronate (at a lower
dose); 3 months later, he had an additional increase in BMD (lumbar
spine +7.4%, left total hip +3.9%, right total hip +2.7%), relative
to the previous study. We hypothesize that prolonged administration of
G-CSF as treatment for Kostmann's syndrome is associated with
increased bone resorption, mediated by osteoclast activation and
leading to bone loss. In children, the resulting osteopenia
can be successfully managed with antisreorptive bisphosphonate therapy
with significant improvement in bone density. Measurements of
biochemical parameters of bone turnover can be used to
monitor the magnitude and duration of the therapeutic response
and the need for BMD reassessment and, perhaps,
retreatment.
Key words:
osteopenia,
growth factors,
congenital
neutropenia,
bisphosphonates,
pediatrics.
