In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P < 0.005) and the osteoporotic (r = -0.61; P < 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P < 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P < 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/ progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.Postmenopausal osteoporosis is an extremely common disabling condition characterized by a reduced bone mass and a heightened risk of fracture (1). It stems in part from a dramatic acceleration of bone loss that begins in the perimenopausal period and lasts for 5-10 years thereafter (2-4). The bone loss is attributable to a defect in bone remodeling in which bone resorption is excessive (5).Although estrogen deficiency underlies (2-4) and estrogen therapy mitigates this defect (6-8), the nature ofthe estrogenresponsive resorption stimulus is unknown. There are no consistent changes in the levels of endocrine resorption stimulators, parathyroid hormone and 1,25-dihydroxyvitamin D3 (9, 10), and plasma calcitonin, an inhibitor of resorption, while lower in women than in men (11), is not remarkably diminished in postmenopause (12). These findings have suggested that estrogen may act by modifying the production of one or more of the local factors now known to influence remodeling events. Among the most potent of these is interleukin 1 (IL-1), one of seve...

The purpose of this study was to identify associations between the use of commonly taken medications and groups of medications and the risk of falls in elderly people living in the community. A stratified random sample of 1358 persons aged 65 years and over was selected from the 15,000 members of an educational organization for functionally independent, community-dwelling elderly people in St Louis, Missouri. Twenty-seven per cent of subjects reported at least one fall in the past year and 8% reported two or more falls. After adjusting for potential confounders (including age, sex, relevant medical conditions, health status, cognitive impairment, use of alcohol, depression and use of other medications), the following medications were found to be important risk factors for multiple falls: diazepam [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.5-9.3], diltiazem (OR: 1.8, 95% CI: 0.8-4.1), diuretics (OR: 1.8, 95% CI: 1.2-2.8) and laxatives (OR: 2.1, 95% CI: 1.0-4.5). We conclude that caution is needed before prescribing diuretics and psychotropics, especially diazepam, for elderly people. The safety of diltiazem in this age group should be assessed further.

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)-a marker of bone formation-were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.Primary osteoporosis is an extremely common condition in which inadequate accumulation of bone tissue during maturation or excessive loss thereafter (or both) culminates in a clearly subnormal level of bone mass (1). Among its clinical forms are senile osteoporosis attributable to the undefined impact ofaging on bone remodeling, postmenopausal osteoporosis reflecting excessive bone loss due to estrogen (and perhaps progestin) withdrawal, and idiopathic osteoporosis, a poorly understood acceleration of bone loss occurring in young men and premenopausal women (2). In each case, the insufficiency of bone mass is visualized as stemming from a remodeling disturbance in which bone resorption exceeds formation.The various clinical forms of primary osteoporosis also exhibit histological heterogeneity, as disclosed by quantitative histomorphometric studies with bone biopsies (3). Subsets of these osteoporotic populations exhibit "high-turnover" disease, characterized by accelerated rates of remodeling. At the other end of the spectrum are patients with "low-turnover" osteoporosis characterized by low rates of remodeling (4). High-turnover osteoporosis is of special interest because it could stem from an abnormality of one or more of the factors known to activate bone remodeling. However, studies have failed to incriminate significant differences in systemically elaborated remodeling stimulators, including parathyroid hormone, calcitonin, calcitriol (1a,25-dihydroxyvitamin D3), and insulin-like growth factor 1 (5-7).Evidence has accumulated that suggests that cells of the monocyte-macrophage series may serve as local ...

Short-term incubation of rat calvaria in buffered crude collagenase permitted the isolation of morphologically intact cells that absorb vital dyes, contain alkaline phosphatase, and multiply in tissue culture. Freshly harvested cells were similar to whole bone segments in aerobic glucose metabolism.

To determine risk factors for falls, previous studies have classified falls according to the contribution of factors both intrinsic and extrinsic to the host. Due partly to the lack of operational definitions and the absence of information on reliability, no consensus on classification has been reached. Consequently, in a 3-year prospective study of falls occurring in a probability sample of community-dwelling elderly (n = 1,358), a fall classification system was developed and tested for interrater reliability. The 366 falls in the first year of the study were independently classified by two reviewers on the basis of a narrative description and structured interview. The falls in the four major categories of the classification system included: falls related to extrinsic factors (55%), falls related to intrinsic factors (39%), falls from a non-bipedal stance (8%) and unclassified falls (7%). The interrater reliability for the four major categories was 89.9% with a kappa of 0.828. The system provides operational definitions for types of falls and a reliable and flexible method for classifying falls in the elderly.