Bone disease induced by anticonvulsant therapy and treatment with calcitriol (1,25-dihydroxyvitamin D3)
P. A. Hunt, M. L. Wu-Chen, N. J. Handal, C. T. Chang, M. Gomez, T. R. Howell, M. A. Hartenberg and J. C. Chan
To evaluate the effects of calcitriol (1,25-dihydroxyvitamin D3) therapy
for the bone disease induced by long-term treatment with anticonvulsants,
we reviewed the medical records of 330 institutionalized oligophrenic
children and young adults under 26 years of age to identify the 144
children who required anticonvulsant therapy. Of this latter group, 52
children were found to have serum alkaline phosphatase levels elevated more
than 2 SDs above normal and were enrolled into this prospective three-year
study. To achieve rapid resolution of the bone disease, we elected to use
calcitriol at 0.25 to 0.75 micrograms/d. After 1195 patient-months of
treatment, our data suggest that the dystrophic process was reversed in
42.3% of the cases, as judged by decreases in serum alkaline phosphatase
levels at six months, 65.4% of cases at 12 months, and 83.3% of cases at 13
to 18 months. By 30 months of follow-up, all patients showed significant
lowering of serum alkaline phosphatase levels. The improvements were slow
and gradual. Twenty-six patients in the treatment series of 52 patients
initially showed signs of rickets or osteomalacia on roentgenograms of the
wrists. Of these 26 patients, 12 (46%) showed improvement on roentgenograms
within 24 months of the beginning of treatment. With reference to
complications, hypercalcemia (calcium level, greater than 11 mg/dL [2.74
mmol/L]) was encountered at the rate of one episode per 44 patient-months
of treatment. Our results strongly suggest that calcitriol is effective in
healing anticonvulsant-related osteomalacia among children and youths, with
a low incidence of complications.
