Aging bone loss from the femur, spine, radius, and total skeleton

In order to establish a comprehensive model for involutional bone loss, the following measurements were made of healthy white women: total body calcium by neutron activation analysis, bone density of the distal radius by single-photon absorptiometry, and dual-photon absorptiometry of the lumbar spine and femur (neck, Ward's triangle, and intertrochanteric areas). Longitudinal measurements were made for each of these skeletal sites except the femur. Evidence for a curvilinear component to the pattern of bone loss with aging was found for total body calcium and bone density of the radius, but not for the other measurements on analysis of cross-sectional data. Longitudinal studies confirmed that substantial bone loss begins only after menopause for the radius, whereas there is substantial premenopausal loss of bone from the lumbar spine. Prevention of vertebral osteoporosis requires maximizing bone mass before menopause. If longitudinal data confirm the model of linear rates of bone loss for the femur, there will be important implications for prevention of hip fractures.     

Aging and bone quality

At the research level, various factors have been correlated with changes in bone quality that underlie age-associated fragility. On the other hand, biochemical markers and imaging technology that can faithfully assess bone quality and are applicable to clinical practice remain to be developed.     

Alcohol-induced bone loss and deficient bone repair

BACKGROUND: Chronic consumption of excessive alcohol eventually results in an osteopenic skeleton and increased risk for osteoporosis. Alcoholics experience not only increased incidence of fractures from falls, but also delays in fracture healing compared with non-alcoholics. In this review the term "alcohol-induced bone disease" is used to refer to these skeletal abnormalities. Alcohol-induced osteopenia is distinct from osteoporoses such as postmenopausal osteoporosis and disuse osteoporosis. Gonadal insufficiency increases the rate of bone remodeling, whereas alcohol decreases this rate. Thus, histomorphometric studies show different characteristics for the bone loss that occurs in these two disease states. In particular, alcohol-induced osteopenia results mainly from decreased bone formation rather than increased bone resorption. Human, animal and cell culture studies of the effects of alcohol on bone strongly suggest alcohol has a dose-dependent toxic effect on osteoblast activity. The capacity of bone marrow stromal cells to differentiate into osteoblasts has a critical role in the cellular processes involved in the maintenance of the adult human skeleton by bone remodeling. Chronic alcohol consumption suppresses osteoblastic differentiation of bone marrow cells and promotes adipogenesis. In fracture healing, the effect of alcohol is to suppress synthesis of an ossifiable matrix, possibly due to inhibition of cell proliferation and maldifferentiation of mesenchymal cells in the repair tissue. This results in the deficient bone repair observed in animal studies, characterized by repair tissue of lower stiffness, strength and mineral content. Current knowledge of cellular effects and molecular mechanisms involved in alcohol-induced bone disease is insufficient to develop interventional strategies for its prevention and treatment. OBJECTIVES: The objectives of this review are 1) to identify the characteristics of alcohol-induced bone loss and deficient bone repair as revealed in human and animal studies, 2) to determine the current understanding of the cellular effects underlying both skeletal abnormalities, and 3) to suggest directions for future studies to resolve current ambiguities regarding the cellular basis of alcohol-induced bone disease.     

Calcitonin and postmenopausal bone loss

In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females (p less than 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18-25 years old), older premenopausal (35-40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 +/- 4% decrease of serum alkaline phosphatase and 35 +/- 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis.     

Osteoporosis and periodontal bone loss

Osteoporosis and osteopenia are characterized by reductions in bone mass, and may lead to skeletal fragility and fracture. Until the advent and widespread use of such methodology to measure bone density, such as dual energy X-ray absorption (DXA), the definition of osteoporosis was usually made using the clinical signs of a fracture. In 1994 the World Health Organization defined osteoporosis as a bone mineral density level more than 2.5 standard deviations below the mean of young normal women (WHO, 1994). The potential inter-relationship of the two diseases will be discussed in this paper.     

The pathophysiology of bone loss

Aging is associated with a decline in cancellous and cortical bone mass and with a deterioration of microarchitecture in both skeletal compartments. These changes are more marked in women than men and are exaggerated in patients with fracture. With the insight gained from histomorphometry, we are beginning to understand the cellular mechanisms that underlie these changes. We recognize that deterioration in microarchitecture contributes to fracture risk, independently of bone mass. Techniques to assess bone microarchitecture noninvasively in a clinical setting are currently under development; it is likely that advances in this area will improve our ability to identify and manage patients with osteoporosis in the not too distant future.     

Predictive factors for bone loss

A clear understanding of the pattern and determinants of bone loss in later life is required to the design of preventive strategies against osteoporosis. However, there have been few longitudinal studies of changes in bone mineral density (BMD) in the general population. The objective of this review was to characterise the determinants of bone loss and assess whether they could predict the bone loss in the future. Aging, female sex, perimenopausal period were significantly associated with the rate of bone loss. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline values and the change of weight, height and BMI were statistically significant predictors for bone loss. By contrast, longitudinal cohort study showed the difference of residence was no longer associated with the bone loss. Furthermore, what the rate of bone change was different from birth cohort was introduced. Thus, the comparison of the data obtained in same strata at the present and 10 years ago, there were significant generation gaps in men in their 60s and in women in their 50s. Concerning bone metabolic markers, some markers were significantly related to the change of lumbar BMD, however, the coefficient for determination for these markers in the prediction of bone loss was only less than 10%. It therefore was concluded that bone metabolic markers might not be sufficiently helpful to predict the change of BMD in individuals. Other factors including new biochemical markers and lifestyle factors should be considered in a clinical diagnosis.     

Vertebral bone loss in menopause

A direct correlation between loss of ovarian function and reduction of bone mass is well established. The incidence of fractures sharply increases with age starting from the menopause. Therefore, it is very important to know the rate of bone loss occurring after menopause, at both trabecular and cortical levels. Several factors may contribute to the reduction of bone mass in menopause. Reduced estrogen secretion results in reduced intestinal calcium absorption, increased bone resorption, and probably a deficient production of calcitonin. Furthermore, in vivo and in vitro experimental data confirm that estrogen failure is associated with histologic changes, mirroring the biochemical changes described in postmenopausal osteoporosis.     

Interleukin 7 and estrogen-induced bone loss.

During the past decade, we have increased greatly our understanding of the pathogenesis of postmenopausal osteoporosis, a major cause of morbidity and mortality. We know now that estrogen regulates the expression of cytokines that target cell types involved in modulating bone turnover. Although early work demonstrated that tumor necrosis factor alpha plays an important role in regulating bone mass, recent studies also implicate the lymphopoietic molecule interleukin 7. This protein is unique in that it suppresses the bone-forming osteoblast, whilst stimulating formation and function of the osteoclast, the exclusive resorptive cell. Furthermore, the latest findings confirm and expand the concept that T cells are key mediators of bone loss following gonadal failure.     

Age-related bone loss: old bone, new facts

The human skeleton serves several functions for the body: support, locomotion, protection of vital organs, and housing of bone marrow. Bone remodeling is the result of the interactions of multiple elements, including osteoblasts, osteoclasts, hormones, growth factors, and cytokines, the end result being the maintenance of the bone architecture and to maintain systemic calcium homeostasis. In early life, a careful balance exists between bone formation by osteoblasts and bone resorption by osteoclasts. With aging, the process of coupled bone formation is affected by the reduction of osteoblast differentiation, activity, and life span which is further potentiated in the perimenopausal years with hormone deprivation and increased osteoclast activity. Age-related bone loss is thus not only a consequence of hormone deprivation, but also the result of changes in bone formation and cell-cell interactions with a unique pathophysiology. In this review, we describe the cellular and metabolic changes associated with aging bone and present recent evidence regarding cell differentiation within the bone marrow. We also consider the mechanism of programmed cell death, apoptosis, as being an important determinant of aging in bone as well as describe possible future interventions to prolong the life span of osteoblasts.