Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy

The Serum CrossLaps (CTx) enzyme-linked immunosorbent assay (ELISA) is spec ific for a cross-linked, beta-aspartate-isomerized form of the epitope EKAH DGGR derived from the carboxyterminal telopeptide region of type I collagen alpha(1) chain. Collagen type I fragments reactive in the CTx assay are re leased during osteoclastic bone resorption and can be used as a measure of bone resorption activity. Our objectives mere to assess the intraindividual variation of serum CTx concentration as well as the clinical value of the serum CTx assay for monitoring antiresorptive therapy in individual patient s. The influence of the sampling time and fasting on the serum CTx: measure ments was studied with the aim of determining an optimal sampling protocol. Studies of circadian variation in serum CTx concentration in 15 postmenopa usal women showed that fasting significantly reduced the average circadian variation of the marker from 36% to 8.7%. This was further supported by ass essing short-term (2 weeks) intraindividual variation in ten postmenopausal women who were sampled in the morning, either fasting or nonfasting, The a verage short-term intraindividual coefficient of variation (CV) was 7.9% in the samples obtained from fasting women, and 14.3% in the samples obtained from nonfasting women. The long-term intraindividual biological variation was 13.4% in 44 postmenopausal women sampled every 6 months (fasting mornin g samples) over al year period, The ability of the serum CTx assay to monit or individual responses to antiresorptive therapy was assessed in studies o f the effects of hormone replacement therapy (HRT) and bisphosphonate (alen dronate). Serum samples (morning fasting) were obtained from postmenopausal women treated with either bisphosphonate or WRT at baseline and then after various timepoints of therapy. Spine bone mineral density (BMI) measuremen ts were carried out and the annual percentage change in spine BRID (alpha B MD) was calculated. Sixteen of 17 (94%) of the HRT-treated and 12 of 13 (92 %) of the bisphosphonate-treated women showed a decrease in serum CTx after 6 months that was greater than the calculated least significant change (LS C) of the marker (LSCCTx). In contrast, only 59% of the HRT-treated and 64% of the bisphosphonate-treated women showed a response in spine BMD greater than the LSCBMD after 1 year follow-up. When the two study populations wer e combined, the decrease in serum CTx after 6 months showed an analytical s ensitivity of 83.8% and specificity of 100% to differentiate women with a g ain in spine BMD (alpha BMD > 0%) from women with a loss in spine BMD (alph a BMD < 0%), In conclusion, the serum CTx showed high specificity and sensi tivity for monitoring individual responses to antiresorptive therapy. More than 92% of the treated women showed significant responses in serum CTx mea surements after 6 months. (C) 2000 by Elsevier Science Inc, All rights rese rved.