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Byline: C. Christiansen (1), L. B. Tanko (1), L. Warming (1), A. Moelgaard (1), S. Christgau (2), P. Qvist (2), M. Baumann (3), L. Wieczorek (3), N. Hoyle (4) Keywords: Bisphosphonates; Bone markers; Intermittent intravenous therapy; Postmenopausal women; Serial measurements Abstract: The aim of the present paper was to delineate in detail the dose-dependent effects of intermittent intravenous (IV) ibandronate treatment on the dynamics of markers of bone resorption and formation. The study included 73 healthy postmenopausal women between 50 and 70 years of age. Two groups received an IV injection of either 1 mg or 2 mg ibandronate on day 0 and 84 and one group, which received no treatment, served as control. Study duration was 168 days. Bone turnover was estimated by measuring the serum concentration of the C-terminal collagen I telopeptide (s-CTx, bone resorption) and osteocalcin (s-OC, bone formation) at 19 consecutive time-points. Serum CTx decreased rapidly reaching a nadir 7 days after drug administration. Maximal changes from baseline in the 1 and 2 mg ibandronate groups were -81% and -90%, respectively (P&lt 0.001). However, already 2 weeks after drug administration, s-CTx started to rise again in both treatment groups, reaching -16% and -20% by day 84, i.e. immediately before the second drug administration. In contrast, s-OC showed a slower but progressive decrease over time reaching a nadir at -35% inhibition after 5 months. On a group level, the suppression of bone resorption was greater or equal to the suppression of bone formation at all time points. However, the least significant change (LSC) analysis performed at the individual level highlighted individuals who at certain time points showed apparently greater suppression of formation than resorption, which could also contribute to the inefficacy of this dosing regime. Although the physiological relevance of this latter finding would require further analysis, the results draw attention to the need to optimize the intermittent IV dosing of ibandronate in order to approximate more closely the sustained and balanced anti-resorptive effect provided by daily oral treatment. Author Affiliation: (1) Center for Clinical and Basic Research A/S, Ballerup Byvej 222, 2750, Ballerup, Denmark (2) Nordic Bioscience A/S, Herlev, Denmark (3) Integrated Health Care Solutions, Hoffmann-La Roche Ltd, Basel, Switzerland (4) Department of Bone Metabolism and Anaemia, Centralised Diagnostics, Roche Diagnostics GmbH, Penzberg, Germany Article History: Received Date: 02/12/2002 Accepted Date: 03/03/2003 Online Date: 26/06/2003

There are many different potential applications for a biosensing technique in which the conductance of a population of molecular ion channels is switched by the recognition event. These could include cell typing and the detection of DNA, electrolytes and viruses. The biosensor can operate in plasma, human serum and whole blood, and can be used on electrodes with a wide range of dimensions. Its sensitivity can be boosted by operating it under conditions of low channel density.