Background -Recent reports have suggested short term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. Methods -Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 tg inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/ creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 jg beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2 5 years of treatment. Results -In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. Conclusions -No detrimental long term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short term studies with single serum parameters of bone metabolism, but well designed long term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism. (Thorax 1994;49:652-656) Inhaled corticosteroids are currently administered to more patients with asthma and chronic obstructive pulmonary disease (COPD), at an earlier stage, and in higher dosages than previously.'13 Long term use of inhaled steroids has been shown to reduce exacerbations and hospital stay and to delay further deterioration of lung function.3 As far as current knowledge goes, however, this requires patients to take inhaled corticosteroids 2-4 times daily for many years. Although the short term direct adverse effects of inhaled corticosteroids seem to be acceptable, there is increasing discussion of possible adverse effects after years of usage.One of the important adverse effects of oral corticosteroids is osteoporosis, eventually leading to fractures.4 A few studies on the effects of inhaled corticosteroids on bone tu...

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1 alpha-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p = 0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/ 1, p< 0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1 alpha-calcidol and calcium treatment did not prevent bone loss.

1. The effect of terbutaline infusion over 4 h on serum levels of potassium, ionized calcium, phosphate and magnesium and urinary excretion of potassium, calcium, magnesium and adenosine 3':5'-cyclic monophosphate was studied in six healthy volunteers. 2. Serum levels of potassium, calcium, phosphate and magnesium decreased. Urinary excretion of potassium decreased, whereas those of calcium, magnesium and adenosine 3':5'-cyclic monophosphate increased. 3. These results indicate that the hypocalcaemic and hypomagnesaemic effects of terbutaline can, at least partly, be explained by enhanced urinary excretion of calcium and magnesium. This may have important implications for the short-term terbutaline treatment of patients with, for example, cardiac disease.

Background With the introduction of Computerised Physician Order Entry (CPOE) in routine hospital care, a great deal of effort has been put into refining Clinical Decision Support Systems (CDSS) to identify patients at risk of preventable medication-related harm. Objectives This study compared a CPOE with basic CDSS and 16 clinical rules with a manual pharmacist medication review to detect overdose and drugedrug interactions that actually required a change in medication. Methods The study involved the review of 313 patients admitted over 5 months at an internal medicine ward where a change in medication as a result of dosing of therapeutic errors was detected by a manual medication review by a trained pharmacist. Subsequently, all these patients' medication orders (MOs) were entered into the authors' CPOE with basic CDSS. Medication orders with a safety alert indicating overdose and drugedrug interactions generated by the authors' CPOE with basic CDSS were compared with the same type of medication errors identified through manual review. The positive predictive value (PPV), sensitivity and specificity compared with manual review were determined. Second, a set of 16 clinical rules was applied to the patient and prescribing data. The overlap between the clinical rules and manual review was determined by comparing patients triggered by the clinical rule with patients with a corresponding error in the manual medication review. Results Manual medication review identified 57 medication errors involving overdose and 143 therapeutic errors of which 46 were drugedrug interactions. The CPOE with basic CDDS generated 297 safety alerts involving overdose (PPV 0.06, sensitivity 0.32, specificity 0.92) and 365 safety alerts involving drugedrug interactions (PPV 0.12, sensitivity 0.96, specificity 0.91). The clinical rules generated 313 safety alerts identifying 39% of all the overdoses and therapeutic errors found in the manual review at which they were targeted. In 23% of the alerts generated by a clinical rule, the patients actually required a change of medication as indicated by the manual review. When CPOE with basic CDSS and the rules were combined, 66% of the overdoses and therapeutic errors were identified. Conclusions The authors' CPOE with basic CDSS and the clinical rules are useful early strategies for preventing medication-related harm. They could be a first step towards more advanced decision support. These computerised systems will be even more useful in daily practice, once they are further fine-tuned to decrease the number of alerts that need no clinical action.