Abstracts

Various antiepileptic drugs (AEDs), particularly cytochrome P450 enzyme inducers, have been linked to increases in bone turnover and decreases in bone mineral density. Collagen degradation that accompanies bone resorption produces amino-terminal pyridinole cross-linked telopeptides (NTX) that are excreted into the urine. NTX levels can therefore be used as a biomarker of bone turnover. A double-blind, placebo-controlled study of topiramate (TPM) in obese adults with dyslipidemia included measurements of urinary NTX/creatinine (Cr) ratios to evaluate the effect of TPM on bone metabolism in adults., Obese subjects 18-75 yrs of age with a BMI [underline][gt][/underline]27 kg/m² and [lt]50 kg/m² and mild-to-moderate hypertriglyceridemia were randomized to placebo, 96 mg/day TPM, or 192 mg/day TPM. TPM was titrated in 16 mg/day increments at 2-wk intervals to the assigned dose or maximum tolerated dose. Urine specimens were obtained at baseline, every 2 wks during the 8-wk titration phase, and every 4 wks during maintenance. NTX/Cr ratios, expressed as nmol bone collagen equivalent/mmol creatinine, were determined as a part of the study[apos]s safety evaluations., Baseline and last-visit urine samples were available for 29 subjects receiving placebo, 29 assigned to TPM 96, and 34 assigned to TPM 192. 72% of subjects were female, in whom mean age was 46-48 yrs. Median treatment durations were 167 (placebo), 151 (TPM 96), and 161 (TPM 192) days. Mean % changes from baseline NTX/Cr ratios were 18.3%, 26.5%, and 3.3%, respectively. In the placebo group, NTX/Cr ratios increased in 45% of patients; in 52% of the TPM 96 group, and in 44% of the TPM 192 group., In obese adults, bone turnover as measured with the urinary biomarker NTX was similar in TPM and placebo groups during long-term ([sim]6 months) exposure., (Supported by Johnson [amp] Johnson Pharmaceutical Research [amp] Development, LLC.)