Histopathologic changes in the uterus, cervix and vagina of immature CD-1 mice exposed to low doses of perfluorooctanoic acid (PFOA) in a uterotrophic assay.

The estrogenic and antiestrogenic potential of perfluorooctanoic acid (PFOA) was assessed using an immature mouse uterotrophic assay and by histologic evaluation of the uterus, cervix and vagina following treatment. Female offspring of CD-1 dams were weaned at 18days old and assigned to groups of equal weight, and received 0, 0.01, 0.1, or 1mg PFOA/kg BW/d by gavage with or without 17-ß estradiol (E(2), 500µg/kg/d) from PND 18-20 (n=8/treatment/block). At 24h after the third dose (PND 21), uteri were removed and weighed. Absolute and relative uterine weights were significantly increased in the 0.01mg/kg PFOA only group. Characteristic estrogenic changes were present in all E(2)-treated mice; however, they were minimally visible in the 0.01 PFOA only mice. These data suggest that at a low dose PFOA produces minimal histopathologic changes in the reproductive tract of immature female mice, and does not antagonize the histopathologic effects of E(2).

Forearm bone density in primary hyperparathyroidism: long-term follow-up with and without parathyroidectomy.

OBJECTIVE: The long-term effects of primary hyperparathyroidism (PHPT), whether treated or untreated, on cortical bone are unclear, but the balance of evidence suggests that fracture risk is modestly increased in this patient group. We therefore compared changes in forearm cortical bone mineral density (BMD), at the site most relevant for PTH-mediated bone loss, in two groups of patients with PHPT; one with and one without surgery. DESIGN AND PATIENTS: We followed the course of forearm bone mineral/bone width (BM/BW, g/cm2) measured by single-energy photon absorptiometry at the standard proximal site, and Z-scores (deviations from the mean value expected for age, sex and race, calculated from a large local reference population) in 108 patients who underwent successful surgery (mean duration 47 months, range 12-120 months) and 108 who remained unoperated (mean duration 52 months, range 12-132 months). Criteria for recommending surgery had been formulated in 1975 and were generally similar to those of the NIH consensus conference published in 1991. At the time of diagnosis the Z-score was significantly reduced in both groups, indicating an earlier period of accelerated cortical bone loss. RESULTS: In the entire operated population there was no difference between the initial and final BM/BW. As the age-expected mean value declined, the Z-score became significantly less negative, and if the rate of change remained constant the values would have reached zero, indicating recovery of all bone lost as a result of the disease, after about 20 years. In the unoperated patients BM/BW fell significantly but there was no change in Z-score, indicating that the rate of bone loss was the same as expected for normal ageing. CONCLUSIONS: It is reasonable to assume that cessation of further bone loss consequent on successful parathyroid surgery would eventually lead to abatement of the excess fracture risk, but the benefit to individual patients will depend mainly on their remaining life expectancy.