Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion. We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes. Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobar-bituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r = 0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r = 0.77) and G6PD (130%/110%/190%, r = 0.78). Both MDA (r = 0.68) and G6PD (r = 0.71) correlated with hepatic ALT, which decreased 27%o/43%/48%, respectively. Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.

Prolonged high-dose corticosteroid therapy is known to result in an increased risk of osteoporotic fracture. Reductions in bone density have been demonstrated at the distal radius and lumbar spine in patients receiving corticosteroids; however there have been few studies of bone density in the hip (the most important site of osteoporotic fracture) in this context. To examine the effect of corticosteroids on the hip we measured bone mineral density (BMD) by dual-photon absorptiometry at three sites in the proximal femur as well as the lumbar spine in 32 patients aged 18-77 years who had been treated with corticosteroids (mean daily prednisone dose 12.7 mg) for up to 23 years. BMD was compared with the expected values using age regressions in normal subjects. BMD was significantly reduced in the femoral neck, Ward's triangle, and the trochanteric region (p less than 0.001 all sites). In the lumbar spine BMD was also significantly reduced (p less than 0.001). We also measured BMD serially in 29 patients receiving corticosteroids. BMD measurements were made in 12 patients who had already been treated with long-term corticosteroids at the time of first BMD measurement (chronic group) and from the commencement of corticosteroid therapy in 17 patients (acute group). The mean (+/- SEM) change in BMD (g/cm2 per year) in the lumbar spine and femoral neck were 0.006 +/- 0.006 and -0.021 +/- 0.007, respectively, for the chronic group and -0.02 +/- 0.005 and -0.039 +/- 0.006 for the acute group.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of osteoporotic fractures increases with advancing age. Despite advances in therapy, reversal of bone loss in established osteoporosis remains problematic and deformities and disability due to fractures often persist. Therefore the logical approach to osteoporosis treatment is preventive. Risk of fracture is determined largely by bone density, which is the end result of peak value achieved at skeletal maturity and subsequent age- and menopause-related bone loss. Thus the determinants of peak bone density and bone loss require full characterization. Environmental and lifestyle factors are important determinants of bone density, particularly physical activity and diet. For example, muscle strength and physical fitness predict bone density, so that regular moderate exercise may help maintain bone mass but probably does not reverse loss. Long-term calcium intake appears to be important for achievement and maintenance of peak bone density, especially in males. Smoking and excessive alcohol intake are deleterious to bone mass. Cultural norms in diet, lifestyle and physical activity obviously have an impact on bone density. Genetic factors have a strong role in determining the wide range in 'normal' peak bone mass. Moreover we have found strong genetic determinants of rates of change of bone mass in the lumbar spine and similar trends for sites in the femoral neck. We have shown previously that genetic factors influence bone turnover indices, particularly osteocalcin. Investigating these relationships with restriction fragment length polymorphisms, we have identified variants of the vitamin D receptor gene which predict osteocalcin levels and presumably bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)