This study evaluates serum creatine kinase isoenzyme
activity in children with osteogenesis imperfecta to determine
its usefulness as a biochemical marker during treatment
with bisphosphonate. The changes of creatine kinase
(CK) isoenzyme activity during and after discontinuation therapy
were observed. These results could be useful in addressing
over-treatment risk prevention.
Introduction The brain isoenzyme of creatine kinase (CKbb)
is highly expressed in mature osteoclasts during osteoclastogenesis,
thus plays an important role in bone resorption. We
previously identified high serum CKbb levels in 18 children
with osteogenesis imperfect (OI) type 1 treated for 1 year with
bisphosphonate (neridronate). In the present study, serum CK
isoenzymes were evaluated in the same children with continuous
versus discontinued neridronate treatment over a further
2-year follow-up period.
Methods This study included 18 children with OI type 1, 12
with continued (group A) and 6 with ceased (group B)
neridronate treatment. Auxological data, serum biochemical
markers of bone metabolism, bone mineral density z-score,
and serum total CK and isoenzyme activities were determined
in both groups.
Results Serum CKbb was progressively and significantly increased
in group A (p < 0.004) but rapidly decreased to undetectable
levels in group B. In both groups, the cardiac muscle
creatine kinase isoenzyme (CKmb) showed a marked decrease,
while serum C-terminal telopeptide (CTx) levels were
almost unchanged.
Conclusions This study provides evidence of the cumulative
effect of neridronate administration in increasing serum CKbb
levels and the reversible effect after its discontinuation. This
approach could be employed for verifying the usefulness of
serum CKbb as a biochemical marker in patients receiving
prolonged bisphosphonate treatment. Moreover, the decreased
serum CKmb levels suggest a systemic effect of these drugs
