No abstract

The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Despite often higher disability, mental disorders are under-treated compared with physical disorders in both high-income and in low- and middle-income countries.

The association of bone loss with age, sex, and several prevalent and modifiable potential risk factors for osteoporosis was studied in 1,856 men and 2,452 women aged 55 years and over from the Rotterdam Study, a population-based cohort study in the Netherlands. The rate of change in femoral neck bone mineral density was estimated longitudinally between 1990 and 1995, after 2 years of follow-up on average. These rates, adjusted for age and body mass index, were -0.0025 (95% confidence interval -0.0038 to -0.0012) in men and -0.0045 (95% confidence interval -0.0056 to -0.0034) g/cm2/year in women (p=0.03). Bone loss accelerated with age, as seen more clearly in men than in women. Lower body mass index and cigarette smoking were associated with increased bone loss in both men and women. In men, higher calcium intake was associated with lower rates, and disability was associated with borderline significantly higher rates of bone loss (p=0.07). In women, a nonsignificant relation was observed with disability, but not with dietary calcium intake. Alcohol intake was not consistently related to the rate of bone loss in either sex. It is concluded that in elderly people the rate of bone loss is higher in women, progresses with age, and is further determined by several modifiable risk factors, particularly in men.

Objective. To investigate the relationship of osteoarthritis (OA) to bone mineral density (BMD) and rate of bone loss.Methods. The study group consisted of 2,745 persons (1,624 women) from the general elderly population. Disability was assessed by the Health Assessment Questionnaire. Femoral neck BMD was measured at baseline and, in 1,723 subjects, after 2 years of followup. Knee and hip radiographic OA was assessed on anteroposterior radiographs. Resubs.With the exception of knee radiographic OA in men, radiographic OA was associated with significantly increased BMD (H%). BMD increased significantly according to the number of affected sites and the Kellgren score. Radiographic OA was also associated with significantly elevated bone loss with age (in men, only for radiographic OA of the hip). A significant increase in relation to the number of atTected sites and the Kellgren score (except with regard to knee OA in men) was found, independent of disability.Conclusion. Radiographic OA is associated with higher BMD and increased rate of bone loss.

Objective: To estimate the contribution of excessive alcohol use to socioeconomic variation in mortality among men and women in Finland. Design: Register based follow up study. Subjects: The population covered by the 1985 and 1990 censuses, aged >20 in the follow up period 1987-93. Main outcome measures: Total mortality and alcohol related mortality from all causes, from diseases, and from accidents and violence according to socioeconomic position. The excess mortality among other classes compared with upper non-manual employees and differences in life expectancy between the classes were used to measure mortality differentials. Results: Alcohol related mortality constituted 11% of all mortality among men aged >20 and 2% among women and was higher among manual workers than among other classes. It accounted for 14% of the excess all cause mortality among manual workers over upper non-manual employees among men and 4% among women and for 24% and 9% of the differences in life expectancy, respectively. Half of the excess mortality from accidents and violence among male manual workers and 38% among female manual workers was accounted for by alcohol related deaths, whereas in diseases the role of alcohol was modest. The contribution of alcohol related deaths to relative mortality differentials weakened with age. Conclusions: Class differentials in alcohol related mortality are an important factor in the socioeconomic mortality differentials in Finland, especially among men, among younger age groups, and in mortality from accidents and violence.

To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eight patients were enrolled. Dose levels were 10, 20, 30, 45, 70, 85, and 100 mg. At 100 mg dose-limiting toxicity (DLT) (common toxicity criteria grade 3 skin rash and grade 3 diarrhoea despite treatment with loperamide) occurred in two patients. In the next-lower dose of 70 mg, DLT (grade 3 fatigue and ALAT elevation) occurred in one of six patients. An intermediate dose level of 85 mg was studied. Here DLT occurred in two patients (grade 3 diarrhoea despite treatment and grade 2 diarrhoea lasting more than 7 days despite treatment). An additional 12 patients were treated at 70 mg. BIBW 2992 PK after single and multiple doses revealed moderately fast absorption, and no deviation from dose proportionality. Pharmacodynamics analysis in skin biopsies did not show significant changes in EGFR-associated biomarkers. However, a significant inhibitory effect on the proliferation index of epidermal keratinocytes was observed. No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD.

The objective of this study was to assess the prevalence and health effects of vertebral deformities in men and women. The study was carried out as part of the cross-sectional baseline phase of The Rotterdam Study, a prospective population-based cohort study of residents aged 55 years or over of a district of Rotterdam, The Netherlands. The prevalence of vertebral deformities according to a modification of the Eastell method and concomitant functional impairment were assessed in a random sample of 750 men and 750 women. The prevalence of moderate (grade I) vertebral deformities was 8 and 7% in men and women, respectively. For severe deformities (grade II), these percentages were 4 and 8%. In men, the prevalence of both moderate and severe deformities increased with age. In women, however, the prevalence of moderate vertebral deformities remained constant, opposite to a marked increase in severe deformities. Moderate vertebral deformity was significantly associated with impaired rising in men only. Severe vertebral deformity was associated with a significantly increased risk of general disability and the use of a walking aid in both men and women, impaired bending in men, and impaired rising in women. It is concluded that (1) vertebral deformities are only slightly less common in men than in women from the general population and (2) severe progression with age occurs in women only and (3) severe vertebral deformity is, particularly in men, related to functional impairment. (J Bone Miner Res 1997;12:152-157)