BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (PCONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

BACKGROUND: Exposure to high levels of oxalate induces oxidant stress in renal epithelial cells and produces diverse changes in cell function, ranging from cell death to cellular adaptation, as evidenced by increased DNA synthesis, cellular proliferation, and induction of genes associated with remodeling and repair. These studies focused on cellular adaptation to this oxidant stress, examining the manner by which oxalate exposure leads to increased expression of immediate early genes (IEGs). Specifically, our studies assessed the possibility that oxalate-induced changes in IEG expression are mediated by phospholipase A2 (PLA2), a common pathway in cellular stress responses. METHODS: Madin-Darby canine kidney (MDCK) cells were exposed to oxalate in the presence or absence of PLA2 inhibitors: mepacrine and arachidonyl trifluoromethyl ketone (AACOCF3). Expression of IEG (c-jun, egr-1, and c-myc) mRNA was assessed by Northern blot analysis. PLA2 activity was determined by measuring the release of [3H]arachidonic acid (AA) from prelabeled cells. RESULTS: Oxalate exposure (1 to 1.5 mmol/L) induced time- and concentration-dependent increases in IEG mRNA. Treatment with mepacrine resulted in a 75 to 113% reduction of oxalate-induced c-jun, egr-1, and c-myc mRNA, while AACOCF3 caused a 41 to 46% reduction of oxalate-induced c-jun and egr-1 mRNA. Of the two major byproducts of PLA2, only lysophosphatidylcholine (20 micromol/L) increased c-jun and egr-1 mRNA. In contrast, AA (25 micromol/L) attenuated the oxalate-induced increase in c-jun and egr-1 mRNA, presumably by inhibiting PLA2 activity. CONCLUSIONS: These findings suggest that PLA2 plays a major role in oxalate-induced IEG expression in renal epithelial cells and that lysophospholipids might be a possible lipid mediator in this pathway.