Age-associated Bone Research Articles

Effects of exercise at different ages on bone density and mechanical properties of femoral bone of aged mice.

We determined the bone density and mechanical properties of bone specimens from 5 groups of aged mice, which had been subjected to voluntary exercise at different ages. ICR 10-week-old female mice were divided into control (C), and exercise-trained during age periods of 10-70 weeks (EE), 10-30 weeks (GPE), 30-50 weeks (MPE) and 50-70 weeks (APE). It was found that in the exercise-trained groups body weight gain was suppressed during the exercise-training period, and that de-training accelerated weight gain. Bone density was significantly higher in all the exercise-trained groups than in the C group and cortical thickness index (CTI) was higher in the exercise-trained groups, except for the APE group. Maximum breaking force, ultimate stress and elasticity in the exercise-trained groups were higher than in the C group except for the APE group, whereas deformation in the APE group had a tendency to be higher than in the other groups. Blood C-terminal parathyroid hormone, calcitonin and calcium concentrations were similar among every group, but phosphorus concentrations tended to be higher in the exercise-trained groups than in the C group. These observations suggest that exercise-training at every age suppresses age-associated bone loss, and that the effect of exercise during youth is greater than that during old age. The results of this study suggest that the effect of exercise on bone at an older age is different from that at other ages.

Osteoporosis: diagnosis and management today and tomorrow.

Osteoporosis is a disease in which low bone mass and microarchitectural deterioration of bone tissue lead to increased bone fragility and a consequent increase in fracture risk. The risk of developing osteoporosis can be assessed by determining the maximum density and strength achieved at maturity (peak bone mass) and the rate and duration of age-associated bone loss. The major cause of osteoporosis is estrogen withdrawal in women, most commonly associated with the menopause, but also with other causes of ovarian failure. Androgen insufficiency in men, although much less common, can also lead to osteoporosis. Measurements of bone mineral density (BMD) have been used to predict fractures, and current evidence suggests that fractures at any site can be predicted by taking measurements of BMD at any other site in the skeleton, using noninvasive techniques such as single or dual energy absorptiometry, quantitative computed tomography and ultrasound, a promising but experimental approach. Rapid bone loss at the start of the menopause is also an important contributing factor to the development of osteoporosis. Levels of biochemical markers of bone turnover in plasma and urine have been found to correlate with rapid and prolonged bone loss. Powerful new assays for estimating bone turnover have emerged and more are being developed. Various combinations of these biochemical tests may be used in conjunction with bone densitometry to predict future risk of osteoporosis and osteoporosis-related fractures. Furthermore, biochemical tests can also be useful in assessing response to therapy. Although many factors, including sex, race, heredity and lifestyle (e.g., calcium intake, minerals, nutrition and exercise), influence the risk of osteoporosis, i.e., they affect peak bone mass and subsequent bone loss, and are of little use in predicting future occurrence.

Bone progenitor cell deficits and the age-associated decline in bone repair capacity

Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, irregardless of donor age or the age of the recipient into which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.

Age-related bone loss in mice is associated with an increased osteoclast progenitor pool

Age-associated osteopenia has been documented to occur in mice and, therefore, provides a model system whereby mechanisms of bone loss can be assessed in vivo and in vitro. One such mechanism, that could explain the increased resorptive activity seen in some forms of osteopenia, is an age-associated increase in the osteoclast precursor pool and osteoclastogenic formation. To test this hypothesis, we studied the bone marrow composition of aged (24 months) mice to determine if increased numbers of monocyte/macrophage/osteoclast precursor cells (MMOPC) were present when compared to young (4–6 months) animals. Our data show a moderate increase of 20–30% more hematopoietic cells obtained from the long bones of the aged animals. However, both liquid and semi-solid culture techniques demonstrate an approximately 2–3.5-fold increase in the numbers of plastic adherent macrophages or mononuclear colonies in bone marrow derived from the aged mice when stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GMCSF) or macrophage colony stimulating factor (M-CSF), indicating a preferential increase in MMOPCs. In addition, cells derived from the aged mice show higher levels of cytokine stimulated incorporation of [ 3H]-thymidine and [ 3H]-leucine, with increased protein synthesis seen up to 7 days after cytokine stimulation, suggesting that these cells also have an enhanced sensitivity to cytokines. Finally, coculture of bone marrow cells from aged mice with the ST-2 stromal cell line also gave rise to approximately twofold more tartrate-resistant acid phosphatase (TRAP) staining osteoclast-like multinucleated cells than did marrow from young animals which had the ability to degrade devitalized [ 3H]-proline-labelled bone and produced cAMP following calcitonin stimulation. Collectively, these data suggest that hi aged mice there is an increase in the numbers of MMOPCs that, under the proper conditions, give rise to increased numbers of osteoclasts. This may suggest a mechanism that could account for, in part, age-associated bone loss.

Age-associated bone loss in men and women and its relationship to weight.

The relationship of bone mineral density (BMD) to age and weight was investigated in a cross-sectional study of 942 community-dwelling men and women aged 65-74 years. BMD continues to decline after the age of 65 at a similar rate in men and women. BMD was positively associated with weight in both men and women with similar regression slopes; approximately one third of the decline in BMD with age could be explained by the associated age-related decline in weight. Maintaining weight in later life may prevent some of the age-related loss of bone. Whatever factors are responsible for the age-related decline in bone mass apply similarly in men and women at these older ages: there is no evidence for accelerated decline in women in this age group.

Bone loss in rheumatoid arthritis and primary generalized osteoarthrosis: effects of corticosteroids, suppressive antirheumatic drugs and calcium supplements.

The annual rate of bone loss in rheumatoid arthritis (RA) and primary generalized osteoarthrosis (PGOA) was determined by measurement of total body calcium (TBCa). The mean annual rate of bone loss in 24 patients with RA treated with nonsteroidal anti-inflammatory drugs (NSAIDs) alone was 3.4%. This rate of bone loss was not reduced in ten RA patients responding to suppressive antirheumatic drugs (4.3%) or seven patients receiving oral calcium supplements (4.5%). The mean annual rate of loss of TBCa in 19 patients with PGOA was 1.6%, a figure which probably represents age-associated bone loss. The rate of bone loss in PGOA was significantly less than that in RA patients not receiving corticosteroids. The mean annual rate of change of TBCa in 30 RA patients receiving corticosteroids (+0.7%) was significantly less than that in any of the other RA groups despite an initial normalized bone mass which was significantly less than in those RA patients receiving NSAIDs alone. The data supported the hypothesis that bone loss occurred early in the course of corticosteroid therapy and thereafter the drugs might have a protective effect on the loss of bone in RA.

Effects on blood pressure of calcium supplementation of women

The relationship between dietary and supplemental (1.5 g/d) calcium intake and blood pressure was examined in 81 normotensive and 34 medicated hypertensive women between the ages of 35 and 65 years who completed a 4-yr clinical trial to assess age-associated bone loss in women. Calcium intakes were monitored during the entire study. Resting blood pressures and systolic blood pressure response (SBPR) to a stress test were recorded three times during the study. At the end of the study there was no relationship between systolic or diastolic blood pressure or SBPR and total calcium intake in normotensive women (n = 81). In the medicated hypertensive group (n = 34) there was a 13 mm Hg decrease in systolic pressure of supplemented women (n = 18) and a 7 mm Hg increase in unsupplemented women (n = 16) over the 4 yr (p less than .02).

The effect of endurance exercise on bone dimensions, collagen, and calcium in the aged male rat

Sixteen weeks of a relatively mild running program, started at 22 months of age, lowered the body weights of 26-month-old male rats to the level of 9-month-old rats and increased the weights and the collagen densities of hind limb bones to levels greater than those of 9-, 22-, and 26-month-old sedentary rats. The densities (g/cm 3) and the calcium densities (mg/cm 3) of the hind limb bones decreased with age and were restored to the 9-month level by training the elderly rats to run. These data suggest that exercise is capable of inducing a compensation for, or a reversal of, age-associated bone loss (osteoporosis) and restoring the bone mineral content in aged rats to the level of those of mature young adult animals.

The antiquity of age-associated bone demineralization in man.

ABSTRACT:Adult males and females in contemporary populations undergo age‐associated demineralization of the skeleton (osteoporosis). Males lose less bone mineral than females, partly because of the slower rate and later age at onset of the loss in males. This study demonstrates that age‐associated demineralization also characterizes prehistoric populations. Demineralization in a prehistoric, hunting‐and‐gathering skeletal population was studied cross‐sectionally. The bone mineral content of radii from skeletons (5‐year age groups from 20 years to 60+) was measured by means of a photon absorptiometry technique. Males not only lost less cortical and trabecular bone than did females but began demineralization at a later age. These sexual differences also apply to modern populations.The apparent universality of osteoporotic demineralization in both time and space attests to a basic genetic unity within our species. Medical science has met with only limited success in combatting the osteoporosis which so often results in collapsed vertebrae and fractured femora in the geriatric population. Bone loss with age has a strong genetic basis and therefore will not easily be arrested or even slowed by the nutritional and hormonal therapy that is employed today.