Data from the 1-year, phase II trial of oral ibandronate for treatment of postmenopausal osteoporosis are presented (n = 180). Participants were at least 10 years past menopause and had osteopenia defined as a forearm bone mineral density at least 1.5 SD below the premenopausal mean value. Doses were 0.25, 0.50, 1.0, 2.5, or 5.0 mg daily oral ibandronate or placebo. A total of 116 women treated with ibandronate completed the study. Blood samples for pharmacokinetic analyses were drawn 20 min, 40 min, 60 min, 2 h, 4 h, and 6 h after the first and last administration of the study drug. An enzyme-linked immunosorbent assay was used to determine the concentration of ibandronic acid (BM 21.0955) in serum (Enzymun-Test System ES 600). The assay is based on streptavidine technology to fix the capture antibody to the wall of the tube. Standards were prepared for each participant using individual drug-free serum. The serum concentration-time curves of ibandronate, expressed as the area under the curve over the sampling period (AUC(0-6h)), revealed a highly significant dose-response relationship, p < 0.0001, and linear pharmacokinetic behavior. An initial half-life (T(1/2lambda1)) in serum representing distribution and early elimination was 1.3 hours. Steady-state AUC (AUC(0-6h ss)) increased by a factor of 2.5, which is consistent with an apparent elimination half-life of 32.6 h and a dosing interval of 24 h. There was an exponential association between AUC(0-6h) (ss) and the change from baseline at month 12 in the bone markers (n = 116): r = -0.37 (serum total osteocalcin), r = -0.65 (urine C-telopeptides of type I collagen), and r = -0.65 (serum C-telopeptides of type I collagen), all p < 0.0001. All bone markers were maximally depressed at values of AUC(0-6h ss) of about 3 ng h/mL. AUC(0-6h ss) furthermore revealed a logarithmic association with change from baseline at month 12 in spine BMD, r = 0.39, p < 0.0001. In conclusion, the serum concentration of ibandronate was determined validly by the enzyme-linked immunosorbent assay. The data are the first to show highly significant associations between pharmacokinetic parameters of a bisphosphonate and the clinical response in bone mass and bone turnover.