Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

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A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41 Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41 Ca after 4-8 wk in each individual.

Psychiatric wills are advance directives for an eventual involuntary treatment in psychiatry. We attempted to determine psychiatric professionals' knowledge and opinion about this legal option and obtain their formulations of advance directives for themselves. A total of 101 psychiatric nurses and psychiatrists at the Department of Psychiatry of the University of Vienna responded to a questionnaire about psychiatric wills and anonymously drafted advance directives for themselves concerning psychiatric treatment in case of an acute psychosis. Fifty-four percent knew about this legal option, 55% considered it an appropriate legal possibility, and 29% considered it inappropriate. The study also found that 75% of respondents reject certain methods of therapy, e.g. 30% want to exclude the use of neuroleptic medications, and 46% reject ECT. We conclude that although there is little experience so far with advance directives for psychiatric patients, there is an interest and predominance of positive attitudes towards this legal option among mental health professionals. Concerning their preferences, professionals felt inclined to make very specific statements as to which available treatment strategies they would reject and which they would request for their treatment. This bodes well for the widespread use of advance directives in mental health settings.

The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D(3). The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin D status.