Bone-remodeling markers have been proposed to monitor antiosteoporotic therapy, as substantial changes in these markers usually occur in a relatively short time interval. In this study we have evaluated the short term effects of two bisphosphonates on bone-remodeling markers with the aim of 1) defining the shortest reliable time interval after which markers should be measured, and 2) comparing the effects of different bisphophonates. To do so, 74 postmenopausal women with a lumbar spine t score of at least -1 were randomly allocated to 4 different treatments: calcium carbonate (500 mg/day; n = 18), 5 mg/day alendronate (A5; n = 18), 10 mg/day alendronate (A10; n = 20), and cyclical etidronate (CE; n = 18). Serum and 24-h urine samples were collected at baseline and 14, 28, 56, and 84 days after the beginning of therapy. Type I collagen N-terminal (NTx) and C-terminal (CTx) telopeptides and total deoxypyridinoline (tDPD) were measured in urine and normalized for urinary creatinine excretion. Osteocalcin and bone alkaline phosphatase in serum were measured. Alendronate (at both doses) and CE significantly decreased bone-remodeling markers, whereas calcium carbonate did not. Bone resorption markers reduction reached a plateau 14 (A10) or 28 (A5 and CE) days after the beginning of treatment, whereas osteocalcin and bone alkaline phosphatase were significantly reduced at 56 (A10) and 84 (CE) days. The global effects of alendronate and CE on NTx and CTx (calculated as the area under the curve) were significantly different from those of calcium (P < 0.05), but were not significantly different from each other. The percent change from baseline obtained with tDPD, NTx, or CTx during bisphosphonate treatment were significantly different (P < 0.05), but this difference disappeared when the variability in the calcium carbonate group was taken into account. In conclusion, this study shows that 1) etidronate and alendronate induce a significant and rapid reduction in bone-remodeling markers; 2) the changes in NTx, CTx, and tDPD urinary excretions reach a plateau after 2-4 wk of treatment; and 3) short term treatments with CE or alendronate induce similar changes in the urinary excretion of NTx and CTx.

Summary:We evaluated the clinical performances of the immunoenzymometric assays for type I collagen Nterminal and C-terminal telopeptides and the HPLC assay for total deoxypyridinoline, in distinguishing between subjects with a moderately increased bone resorption rate (women in postmenopause) and subjects with normal bone resorption rate (women in premenopause). The postmenopausal group consisted of 61 women who had been in menopause for no more than 10 years, while the premenopausal group consisted of 52 healthy women with normal menstrual cycles. The biochemical markers were measured in a 24 hour urine sample and the results expressed as the molar ratio with urinary creatinine. The clinical performances were estimated by calculating the accuracy (as the area under a Receiver Operated Characteristic (ROC) curve: mean ± SEM) and the discriminating power (as score) of each assay in distinguishing postmenopausal subjects from premenopausal subjects. Type I collagen C-terminal telopeptide, type I collagen N-terminal telopeptide and total deoxypyridinoline were significantly higher in the postmenopausal than in the premenopausal group (p < 0.001). Accuracies of these three markers ranged from 66.8 ± 5.1% to 76.8 ± 4.3%, while Z scores ranged from 3.54 to 5.67. Type I collagen C-terminal telopeptide, type I collagen N-terminal telopeptide and total deoxypyridinoline were not significantly different in their accuracy or discriminating power. All markers were highly correlated with coefficients of correlation ranging from 0.61 to 0.77.In summary, this study shows that 1) the immunoenzymometric assays for type I collagen N-terminal telopeptide and type I collagen C-terminal telopeptide show a high accuracy and disciminating power in distinguishing subjects with different bone resorption rate;2) the results obtained with these immunoenzymometric assays are comparable to those obtained with the HPLC assay for total deoxypyridinoline.In conclusion our data support the use of the immunoenzymometric assays for type I collagen N-terminal telopeptide and type I collagen C-terminal telopeptide for estimating bone resorption. Introductiondinium cross-links were shown to be relatively efficient