Estrogen has been shown to modify calcium and skeletal homeostasis. In this study, we tested the ability of estrogen to influence the effects of short-term 1,25(OH)2D administration on biochemical indices of bone formation and resorption in a cross-sectional analysis of untreated (n = 10) and estrogen-treated (n = 14) osteoporotic women. Patients were given oral 1,25(OH)2D (Rocaltrol) 0.5 microgram twice a day for 5 days. Serum and urine were sampled at baseline and then 1 h after the first daily Rocaltrol dose for the 5 days of the study. 1,25(OH)2D levels rose similarly in both groups with plateaus reached by the third day of the investigation. Serum PTH levels decreased by the first sampling period (1 h after first Rocaltrol dose; p < 0.008 both groups) and continued to fall gradually in both groups. There were no changes in serum calcium but serum phosphorus rose by the second day (p < 0.05 both groups) and remained elevated throughout the remainder of the protocol. Serum bone Gla protein increased approximately 40% (p < 0.05) with no group differences. In contrast, total alkaline phosphatase and carboxy-terminal propeptide of type I collagen did not increase in either group. Furthermore, there were no significant increments in any bone resorption indicators, including serum tartrate-resistant acid phosphatase and cross-linked carboxy-terminal telopeptide of type I collagen, as well as urine hydroxyproline and pyridinoline. Serum IGF-1 levels also remained unchanged in both groups. We conclude that oral 1,25(OH)2D administration decreased 1-84PTH levels, probably due to a suppression of parathyroid production, and did not stimulate bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)