Bone remodeling, comprising resorption of existing bone and de novo bone formation, is required for the maintenance of a constant bone mass. Prostaglandin (PG)E 2 promotes both bone resorption and bone formation. By infusing PGE 2 to mice lacking each of four PGE receptor (EP) subtypes, we have identified EP4 as the receptor that mediates bone formation in response to this agent. Consistently, bone formation was induced in wild-type mice by infusion of an EP4-selective agonist and not agonists specific for other EP subtypes. In culture of bone marrow cells from wild-type mice, PGE2 induced expression of core-binding factor ␣1 (Runx2͞Cbfa1) and enhanced formation of mineralized nodules, both of which were absent in the culture of cells from EP4-deficient mice. Furthermore, administration of the EP4 agonist restored bone mass and strength normally lost in rats subjected to ovariectomy or immobilization. Histomorphometric analysis revealed that the EP4 agonist induced significant increases in the volume of cancellous bone, osteoid formation, and the number of osteoblasts in the affected bone of immobilized rats, indicating that activation of EP4 induces de novo bone formation. In addition, osteoclasts were found on the increased bone surface at a density comparable to that found in the bone of control animals. These results suggest that activation of EP4 induces bone remodeling in vivo and that EP4-selective drugs may be beneficial in humans with osteoporosis.B ones undergo continuous remodeling through repeated cycles of destruction and rebuilding (1). This remodeling is mediated by the well balanced actions of osteoclasts, which resorb old bones, and osteoblasts, which form new bones. However, in the elderly, especially in postmenopausal women, the extent of bone resorption far exceeds that of bone rebuilding, resulting in osteoporosis and the associated increases in bone fragility and susceptibility to fractures (2). About 100 million people are estimated to suffer from this debilitating disease worldwide. Several drugs have been developed to treat osteoporosis, with most inhibiting bone resorption and only a few promoting bone formation (3). Such modulation of only one of the two processes in bone remodeling renders these drugs of limited efficacy in restoring the normal balance and bone mass.Recently, significant advances have been made in our understanding of molecular mechanisms of osteoclast and osteoblast differentiation (4), but such knowledge has not been exploited fully to develop a drug that corrects the imbalance and restores normal bone remodeling. Prostaglandins (PGs) are a group of lipid mediators that are produced from arachidonic acid in a variety of tissues under various physiological and pathophysiological conditions and serve to maintain local homeostasis (5). Among them, PGs of the E type work bimodally in bone metabolism (6). PGE 2 potently induces bone resorption in bone organ cultures, whereas repeated injection of this compound in vivo induces bone formation in a variety of animals includ...

A 12-week physical and cognitive exercise program can improve the efficiency of brain activation during cognitive tasks in older adults, which is associated with improvements in memory and executive function.

The purpose of this study was to clarify the difference in muscle coactivation during postural control between older and young adults and to identify the characteristics of postural control strategies in older adults by investigating the relationship between muscle coactivation and postural control ability. Forty-six healthy older adults (82.0±7.5 years) and 34 healthy young adults (22.1±2.3 years) participated. The postural tasks selected consisted of static standing, functional reach, functional stability boundary and gait. Coactivation of the ankle joint was recorded during each task via electromyography (EMG). The older adults showed significantly higher coactivation than the young adults during the tasks of standing, functional reach, functional stability boundary (forward), and gait (p<0.01). Postural sway area (ρ=0.42, p<0.05) and functional reach distance (ρ=-0.52, p<0.05) significantly correlated with coactivation during the corresponding task in older adults, i.e., muscle coactivation was significantly higher in the elderly with low postural control ability than in the elderly with high balance ability. Increased muscle coactivation could be a necessary change to compensate for a deterioration in postural control accompanying healthy aging. Further research is needed to clarify in greater detail positive and negative effects of muscle coactivation on postural control.

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting and disabling side effect of taxane anticancer agents. We prospectively evaluated the efficacy of cryotherapy for CIPN prevention.MethodsBreast cancer patients treated weekly with paclitaxel (80 mg/m2 for one hour) wore frozen gloves and socks on the dominant side for 90 minutes, including the entire duration of drug infusion. Symptoms on the treated sides were compared with those on the untreated (nondominant) sides. The primary end point was CIPN incidence assessed by changes in tactile sensitivity from pretreatment baseline in a monofilament test at a cumulative dose of 960 mg/m2. We also assessed thermosensory deficits, subjective symptoms (Patient Neuropathy Questionnaire [PNQ]), manipulative dexterity, and the time to events and hazard ratio by PNQ. All statistical tests were two-sided.ResultsAmong the 40 patients, four did not reach the cumulative dose (due to the occurrence of pneumonia, severe fatigue, severe liver dysfunction, and macular edema), leaving 36 patients for analysis. None dropped out due to cold intolerance. The incidence of objective and subjective CIPN signs was clinically and statistically significantly lower on the intervention side than on the control (hand: tactile sensitivity = 27.8% vs 80.6%, odds ratio [OR] = 20.00, 95% confidence interval [CI] = 3.20 to 828.96, P < .001; foot: tacile sensitivity = 25.0% vs 63.9%, OR = infinite, 95% CI = 3.32 to infinite, P < .001; hand: warm sense = 8.8% vs 32.4%, OR = 9.00, 95% CI = 1.25 to 394.48, P = .02; foot: warm sense: 33.4% vs 57.6%, OR = 5.00, 95% CI = 1.07 to 46.93, P = .04; hand: PNQ = 2.8% vs 41.7%, OR = infinite, 95% CI = 3.32 to infinite, P < .001; foot: PNQ = 2.8% vs 36.1%, OR = infinite, 95% CI = 2.78 to infinite, P < .001; hand: hazard ratio [HR] = 0.13, 95% CI = 0.05 to 0.34; foot: HR = 0.13, 95% CI = 0.04 to 0.38, dexterity mean delay = −2.5 seconds, SD = 12.0 seconds, vs + 8.6 seconds, SD = 25.8 seconds, P = .005).ConclusionsCryotherapy is useful for preventing both the objective and subjective symptoms of CIPN and resultant dysfunction.