Evaluation of a New Commercial IRMA for Bone - Specific Alkaline Phosphatase

Postmenopausal osteoporosis can be prevented by use of antiresorptive agents, but how the individual response to therapy should be monitored has not yet been settled [1]. Because the concentrations of markers of both bone resorption and formation are 50-100% greater in postmenopausal women than in premenopausal women, and decrease by the same magnitude after a few months of antiresorptive therapy [2, 3], biochemical markers of bone turnover have been suggested as an alternative tool for monitoring the therapeutic response [1, 4, 5]. Recently, a direct IRMA for human bone alkaline phosphatase (B-AP; EC 3.1.3.1) has been developed (Tandem-R Ostase; Hybritech, San Diego, CA). The intraassay variation of this assay is 4-7%, the interassay variation 7-8%, and the detection limit 2.0 g/L [6]. We used this new IRMA to assay human B-AP in premenopausal (n = 71), early (n = 122), and late (n = 172) postmenopausal women. Furthermore, we investigated the response in early postmenopausal women who completed two 2-year placebo-controlled trials of the effect of different hormone replacement treatment (HRT) regimens. Half of the women participated in study A, in which 20 received estradiol valerate (E2V) and cyproterone acetate (CPA) daily, 21 received sequential E2V and levonorgestrel (LNG; Schering, Berlin, Germany), and 24 received placebo. The other half of the women participated in study B, in which 18 received sequential E2V and medroxyprogesterone acetate (MPA; Organon, Oss, The Netherlands), 20 received sequential estrogen (E2) and desogestrel (DG; Organon), and 19 received placebo. Dosage details of studies A and B are given in the legend to Fig. 1. Finally, we investigated women of ages 68-72 years, who were randomized to daily treatment with salmon calcitonin (SCT; Sandoz, Basel, Switzerland)-50 IU (n = 39), 100 IU (n = 42), 200 IU (n = 40)-or placebo (n = 40). Informed consent was obtained from all participants according to Helsinki Declaration H, and the trials were approved by the Ethical Committee of Copenhagen County. Bone mineral content of the individuals in studies A and B was measured in the distal forearm by single-photon absorptiometry every 3 months during the 2-year period of the studies. Bone mineral content of the lumbar spine was measured by dualenergy absorptiometry every year and its bone density every 3 months. Treatment groups were well matched with placebo groups in the study populations (data not shown). In the 50and 70-yearold women, the mean values of B-AP were 146% and 143% of the mean in premenopausal women, respectively. Z-scores (the difference from the values in premenopausal women, expressed in standard deviations) were respectively 1.3 and 1.2 for the 50and 70-year-old women. Fig. 1 shows the serial mean values (± SE) of B-AP in study groups A and B during treatment with HRT. Gradual decreases of 40% were seen in all four HRT groups, reaching a minimum within 12 months (P <0.001) and remaining there during the rest of the study. There were no statistically significant differences in the decline in B-AP (calculated as the slopes) of the four HRT groups. The placebo groups showed virtually no changes. Correlating the 12-month 1201Bone -A? (%)