Van
Dyck et al report on bone
mineralisation as determined by Dual Energy
X-ray Absorptiometry (DEXA), of the whole body and lumbar spine prior,
to and one-year after, the initiation of rhGH
therapy in 10 pre-pubertal children with stable CRF. Inclusion
criteria for the study included: (1) a height SDS of < -2 SD or a height
velocity of < 25th percentile for age, (2) absence of growth
hormone deficiency, (3) normal thyroid function, and (4) normal PTH
levels. DEXA was used to measure total body mineral content (TBMC),
lumbar spine bone mineral content (LBMC), total body mineral density (TBMD),
and lumbar spine bone mineral density (LBMD), in patients and in a
control group of 20 healthy children of similar age. DEXA was
performed twice in the CRF patients and in the healthy controls.
Body height was measured with a stadiometer and bone age was determined
by TW2 method at the start and after one-year of treatment. Data
were analyzed using Wilcox matched pairs.
Growth hormone
treatment (1 unit or 0.3 mg/kg/week given in daily divided doses) was
associated with an increase in median height velocity from 5.1cm/year
(3.0-8.8 cm/year) to 10.6 cm/year (8.2-12.7 cm/year). Median
creatinine clearance remained unchanged as did calcium, phosphorous, and
intact PTH levels. There was, however, a marked change in serum
alkaline phosphatase. This is a well-known phenomenon in different
groups of patients treated with hGH and
reflects osteoblastic activity. At the beginning of the study, the
median bone age was delayed 1.9 years and increased 0.8 years over the
duration of treatment. The patients’ TBMC, TBMD, LBMC, and LBMD
increased significantly after one-year of rhGH
treatment (p<0.05 for each – see Table). When compared with
height/age match controls, these values were not different at the start
of treatment, nor at the end of treatment. Yet BMD, TBMD, and LBMD,
significantly improved in patients over one year (P <0.05). When
compared with age- matched controls, patients had lower TBMC and LBMC at
the start of treatment and experienced a catch-up of LBMC to values
similar to controls over the course of the year.
The authors note
that there has been discrepancy in results from previous studies of
various parameters of BMD in children with CRF treated with
rhGH. They speculate that this might
be explained by 2 factors - small sample size and selection bias.
In the current study, findings demonstrate significantly improved BMD in
children with CRF who are growth retarded. All subjects in the
current study were on calcium supplements and their bone
mineralisation was adequate for their height
at baseline. The authors state that homogeneity of their
results is most likely due to the homogeneity of the patients
studied, that is pre-pubertal with severe
renal disease from early years of life without signs of osteodystrophy.
They conclude that rhGH treatment has a
beneficial effect on BMC and BMD in pre-pubertal children with CRF.
This was the finding of Lanes et al (Horm
Res 46:263-268:1996).
Editor’s Comment:
At first glance, the results of this short paper might not be
appreciated as adding significantly to the information with regard to
the effects of rhGH on children with renal
disease. It is well known that BMC and BMD prior to puberty are
important factors of similar measures in adults. Thus, any
improvement which might be gained in the pre-pubertal
years, could potentially be realized later in
adult life. Indeed, the subjects in the Van
Dyck study had indices of bone density comparable to those of
height matched children at entry into the study and at the one-year
follow up. What is significant is the increased BMC and BMD
observed. These studies underline the importance of initiating
rhGH therapy in children with CRF even when
their absolute height deficiency is modest.