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Role of calcium in preserving the skeletal health of aging women.

During the years from adolescence through senescence, the skeleton passes through identifiable phases: consolidation, maturity, menopause, and senescence. Skeletal dynamics and calcium requirements are different during each phase. A adult woman can avoid the skeletal deterioration caused by calcium deficiency if she maintains a minimum daily calcium intake of 800 mg. Increased calcium intake will not increase skeletal mass in mature, premenopausal women and will not prevent bone loss in postmenopausal women. Because intestinal absorption decreases with age, daily calcium intake of 1000 to 1200 mg is recommended for the elderly. Women can increase their dietary calcium intake in various ways, including increasing intake of dairy products, eating calcium-rich nondairy foods, purchasing foods fortified with calcium, and, if all other methods prove inadequate, using calcium supplements. Physicians must prescribe calcium only after learning what is needed for a particular woman's skeletal health by determining that woman's stage of skeletal development and approximate calcium intake; if intake is insufficient, it should be adjusted to the level appropriate at that stage.

Aging

Calcium requirements for optimal skeletal health in women.

There is a great deal of uncertainty concerning the requirements of calcium for skeletal health. Some argue that all mixed diets contain sufficient calcium whereas others suggest that most of the world's population is calcium deficient. This paper reviews the sources of these conflicting views and the assumptions on which both are based.

Adolescent

Osteoporosis screening and prevention in the chiropractic clinic.

Osteoporosis is a significant health problem among women. Fractures appear to occur once bone mass falls below a certain threshold. Maximization of bone mass may therefore constitute a measure for promoting skeletal health. Dietary calcium consumption of 1-1.5 g/day and adequate weight-bearing exercise maximize bone mass in all age groups. A small survey of women attending the chiropractic clinics of Phillip Institute suggests that routine screening for osteoporosis risk factors may be justified. A self-care program for improving skeletal health in women who fail to meet the dietary calcium and exercise risk minimization criteria is provided.

Adult

Multi‑omics approaches to decipher the molecular mechanisms of exercise‑mediated bone protection: From mechanistic insights to personalized exercise prescription (Review).

The global burden of bone metabolic disorders necessitates a shift from generic exercise recommendations toward personalized prescription strategies. Exercise confers skeletal protection through mechanotransduction, yet the underlying molecular networks remain incompletely understood. Multi‑omics technologies, including transcriptomics, proteomics, metabolomics and single‑cell spatial approaches, have revolutionized the capacity to decode exercise‑mediated bone adaptation at the systems level. The present review synthesizes current single‑omics landscapes and integrative multi‑omics analyses that elucidate the core regulatory networks, mechanobiological coupling mechanisms and multiorgan crosstalk that are implicated in the bone response to mechanical loading. Translational applications across clinical scenarios such as osteoporosis, osteoarthritis and disuse bone loss are evaluated, and the technical, analytical and translational challenges limiting clinical implementation are addressed. Finally, the present review provides a framework for translating multi‑omics molecular signatures into personalized exercise prescriptions for optimized skeletal health.

Humans

Hormonal replacement therapy and the skeletal system.

The two most important risk factors for maintaining skeletal health are the bone mass obtained at skeletal maturity (peak bone mass) and the subsequent bone loss. Those women with a low peak bone mass and a rapid bone loss are thus at increased risk of developing osteoporosis in the future, and should be identified. This may be accomplished by determination of the bone mass combined with an estimate of the rate of the postmenopausal bone loss. The bone mass can be accurately assessed in the forearm by single photon absorptiometry. The postmenopausal bone loss can be estimated by three or four biochemical markers of bone turnover. The women at highest risk of developing osteoporosis should be offered preventive therapy, e.g., hormonal replacement therapy (HRT). HRT arrests the bone loss not only in early, but also in elderly postmenopausal women. The effect lasts as long as the therapy is continued. Several epidemiological studies have demonstrated that HRT decreases the number of osteoporotic fractures.

Bone and Bones

Role of nutrition and exercise in osteoporosis.

Both adequate nutrition and exercise are essential for development of peak adult bone mass and maintenance of bone during aging. The optimal dietary level of a nutrient may vary from individual to individual and may change with age, intake of other nutrients, disease, drug therapy, or sex hormone status. Effects on spinal trabecular bone may not parallel effects on axial cortical bone. Calcium nutrition is important in the prevention of osteoporosis, as calcium is a major constituent of bone. The intake of calcium among most American adults is below the levels recommended by public health agencies. There have been no adequate prospective studies to determine the optimal intake of calcium for preservation of bone mass in young or middle-aged adults, although calcium balance studies indicate that premenopausal women require approximately 1,000 mg of calcium per day. The negative calcium balance of early menopause may be ameliorated by 1,000 mg of calcium per day; however, there is no proof that greater intakes fully reverse the effects of estrogen deficiency. Calcium requirements of both elderly men and women are likely to be greater (between 1,000 and 1,500 mg per day) due to an age-related decrease in the efficiency of intestinal calcium absorption. The optimal level of weight-bearing exercise for maintenance of bone mass in old age is probably similar to that of an active young adult. Maintenance of this activity level in middle and old age improves bone mass. An exercise prescription for elderly individuals must include an appraisal of cardiovascular and muscular-skeletal health and be designed to minimize the risk of trauma during exercise.

Adult

Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia.

The effects of aging on calcium and bone metabolism have not been systematically examined in men. To identify age-related alterations in vitamin D and PTH physiology and to assess their impact on skeletal health, we studied 62 normal men, aged 30-92 yr. The men were in excellent health, and none had any evidence of metabolic bone disease and/or known risk factors for osteopenia. Serum 25-hydroxyvitamin D (25OHD) concentrations declined steadily with advancing age (r = -0.47; P less than 0.001), and there was a corresponding decline in serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] levels (r = -0.41; P less than 0.001). Serum 1,25-(OH)2D concentrations, however, did not vary over this age range (r = -0.07; P = NS). Plasma PTH levels increased with aging (r = -0.24; P less than 0.001), and there was a concomitant increase in urinary cAMP excretion (r = 0.38; P less than 0.001). Renal function (creatinine clearance) clearly declined with increasing age (r = -0.71; P less than 0.001). In conjunction with these changes in calcium metabolism, radial and vertebral bone mineral content declined. Whereas the fall in radial bone mineral content (single photon absorptiometry) at both proximal and distal sites was slight, there was a marked decrease in vertebral bone mineral content, as measured by quantitative computed tomography (r = -0.72; P less than 0.0001). The fall in vertebral bone mineral content correlated well with the declines in serum 25OHD and 24,25-(OH)2D concentrations (r = 0.47; P less than 0.001 and r = 0.51; P less than 0.001, respectively) and with the decline in renal function (r = 0.46; P less than 0.001). Multiple regression analysis revealed that the effects of aging on bone mineral content could be accounted for in large part by concomitant changes in mineral metabolism. Both the decline in renal function and the fall in serum 24,25-(OH)2D levels were closely associated with the fall in bone mineral content. These results indicate that a decline in renal function and alterations in vitamin D metabolism occur with aging in normal men. These changes contribute to, if not cause, the associated decline in skeletal mineral content in aging men.

Adult

Intraskeletal Variation in Cortical Bone Quantity in a Medieval Italian Sample: A Multivariate Exploratory Approach.

Bioarcheologists interpret skeletal health by examining variability within and between individuals. Studies of bone loss have generated contradictory and conflicting results regarding the onset and severity of age-related bone loss on a global and temporal scale, perhaps due to mismatched methodologies. Intraskeletal comparisons of bone tissue prove challenging precisely because of heterogeneous baselines in quantity and remodeling of cortical bone throughout the skeleton, as well as evolutionary histories and environmental impacts on growth and development. Here we analyze cortical bone indicators from the rib, metacarpal, and femoral cortical bone in a subset of individuals (n = 72) regions from the medieval Italian archaeological site of Pieve di Pava. To facilitate intraskeletal comparisons across elements with different biological baselines, we standardize cortical bone parameters using z-scores. Variation in relative intraskeletal cortical bone was assessed using accessible multivariate methods (principal component analysis and hierarchical cluster analysis). Results suggest an association between femoral and metacarpal cortical bone values, with stochastic trends in metacarpal and femoral relative bone quantity in relation to the rib bone quantity at the sample level. Our study demonstrates that while intraskeletal analyses are challenging, they are made more robust by synthesizing multivariate methods alongside exploratory data analysis (EDA) methods to tack between sample-level and individual-level scales and variability. Ultimately, we advocate for leveraging multivariate techniques not as a final step, but rather as a means of generating new hypotheses and challenging tendencies to a priori establish typological groups in the research process.

Skeleton

Spinal bone density and calcium intake in healthy postmenopausal women.

Dietary calcium intake and bone mineral density (BMD) of the lumbar spine (L2-L4) were determined in 131 healthy free-living postmenopausal women (aged 64.7 +/- 7.6 y, means +/- SD). The calcium consumption for the total population was 606 +/- 302 mg/d. Subjects consuming less than the population mean of dietary calcium had significantly lower BMDs than did subjects with intakes above the mean (P less than 0.009); these two groups did not differ in basic demographic characteristics. Additional analyses using a stepwise univariate regression model demonstrated that BMD was significantly associated with body weight (P less than 0.001) and dietary calcium intake (P less than 0.02). These data support the hypothesis that dietary calcium intake is a determinant of skeletal health in postmenopausal women.

Aged

Genetic Evidence Links Sex Hormone-binding Globulin to Total Body Bone Mineral Density at Age 45-60 Years: A Two-sample Mendelian Randomization Study.

The menopausal transition and early postmenopause represent important periods for women's skeletal health, but the genetic relevance of metabolic, behavioral, and hormone-related factors to bone mineral density during midlife remains incompletely understood. This study used publicly available genome-wide association study summary statistics to examine associations between body mass index, 25-hydroxyvitamin D, sex hormone-binding globulin, high-density lipoprotein cholesterol, smoking initiation, and alcohol intake frequency and total body bone mineral density at ages 45-60 years. Exposure genome-wide association study summary statistics were derived from large European-ancestry populations and were not restricted to midlife women, whereas the outcome genome-wide association study captured an age-stratified total body bone mineral density phenotype at age 45-60 years. This age range overlaps with the menopausal transition and early postmenopause in women. Univariable, reverse, and multivariable Mendelian randomization analyses were performed, with inverse-variance weighting as the primary method and complementary sensitivity analyses used to assess heterogeneity, pleiotropy, and result stability. Genetically predicted higher sex hormone-binding globulin was associated with lower total body bone mineral density (β = -0.111, 95% CI: -0.170 to -0.051; P = 0.0003). Reverse Mendelian randomization did not support reverse causation from bone mineral density to sex hormone-binding globulin. Multivariable analyses suggested that this association persisted after adjustment for selected metabolic biomarkers. The other examined exposures did not show consistent evidence of association. These findings provide genetic evidence linking sex hormone-binding globulin to total-body bone mineral density at ages 45-60 years. Further prospective and predictive studies are needed to evaluate its clinical relevance beyond established bone health assessment tools.

Humans

Hormone replacement therapy and coronary heart disease.

Proper use of postmenopausal hormone replacement has been the subject of debate for decades. Prevailing medical opinion has swung between enthusiastic endorsement and extreme caution. The wave of optimism over estrogen's beneficial effects on menopausal symptoms and skeletal health was temporarily set back by the evidence that linked estrogen to endometrial cancer. Once studies showed that progestogen cotherapy could protect against this adverse effect, physicians were again encouraged to prescribe hormone replacement. Since 1980, increasing epidemiologic and experimental evidence has suggested a hitherto unappreciated and immense CHD health benefit from use of postmenopausal estrogen therapy. Although addition of progestogen may offset the cardiovascular benefits of estrogen slightly, its use is reasonable and practical. No woman need be subjected to unopposed estrogen's carcinogenic effects on her endometrium. Based on available evidence, hormone replacement therapy, appropriately administered, is both safe and beneficial. Unfortunately, there is no single way to prescribe it. The treating physician must make a series of best judgments. Practically speaking, this entails, in each case, finding the form of therapy that is acceptable to the patient and that provides the greatest health benefits with the least likelihood of adverse affects. Our prescribing habits have evolved in the last 15 to 20 years. We have better discrimination of the woman most likely to benefit; improved therapy through use of newer formulations, dosages, routes, and schedules; and more appropriate implementation of monitoring procedures. Although questions remain, we should not let our imperfect knowledge dissuade us from more widespread prescribing of hormone replacement therapy.

Aged

A practical guide to preventing osteoporosis.

Physicians should advise women reaching menopause about the risk of osteoporosis and what practical steps can be taken to reduce this risk. The average woman at menopause can expect to live to be 80 years old; during these years she will face a 15% risk of hip fracture and a 10% risk of vertebral fracture. These risks are increased in Asians and whites, in women who are short and thin, and in those with poorly developed musculature. General advice regarding the correction of certain unhealthy habits and changes in life-style may enhance skeletal health, but prompt restoration and long-term maintenance of physiologic levels of estrogen remain the only proved effective way of reducing bone loss and the risk of fracture.

Adult

The surgical management of osteomyelitis: with special reference to a surgical classification.

Bone infection requires a multifaceted approach that may be more clearly defined by a pathophysiologic and pathoanatomic classification. Seven types of bone infection are described, which differ by pathophysiology. Anatomically, infection may involve nonmedullary bone tissues, medullary bone, or the epiphyseal growth plate. Treatment can be prescribed accordingly. The isolation and persistence of bone infection usually requires invasion of the septic space by a surgical approach. By this means, bacterial colonization is denied and vascular return can reclaim the tissue domain. Bone infection is difficult to eradicate, yet a proficient surgical approach to sepsis can restore skeletal health and form.

Anti-Bacterial Agents

Prognostic Association of Handgrip-Defined Probable or Possible Sarcopenia Status and Polygenic Risk with 10-Year Fracture Incidence among Black, Hispanic, and White Women: A Women's Health Initiative Study.

PURPOSE: The Fracture Risk Assessment Tool (FRAX) excludes objective skeletal muscle health and genetic variables. We evaluated the prognostic associations of handgrip-defined probable/possible sarcopenia and genome-wide polygenic scores (GPS) with 10-year fracture risk, and their incremental predictive value beyond FRAX across racial/ethnic groups and GPS strata. METHODS: We analyzed 2,051 postmenopausal women from the Women's Health Initiative. Race-specific analyses focused on Black, Hispanic, and White participants (n=2,009), excluding American Indian/Alaska Native and Asian/Pacific Islander individuals due to sparse fracture events. Sarcopenia status was operationalized by low handgrip strength alone via EWGSOP2 (<16.0 kg) and AWGS 2025 (<18.0-20.0 kg) criteria. Fine-Gray models estimated subdistribution hazard ratios (sHR), treating death as a competing risk. Predictive performance at 10 years was assessed using time-dependent AUC, Brier scores, and decision curve analysis (DCA). RESULTS: Handgrip-defined probable or possible sarcopenia prevalence was 4.4% (EWGSOP2) and 6.4% (AWGS 2025). Black women demonstrated lower risk for major osteoporotic fractures (MOF) (adjusted sHR=0.19, 95% CI: 0.08-0.48) and hip fractures (adjusted sHR=0.07, 95% CI: 0.01-0.52) compared to White women. Neither sarcopenia status nor high GPS showed statistically significant independent associations with fractures after FRAX adjustment. Adding sarcopenia status to baseline FRAX (AUC: 0.71 for MOF; 0.69 for hip) yielded near-identical AUCs, Brier scores, and within-sample net benefit. CONCLUSION: Handgrip-defined probable/possible sarcopenia and current GPS do not provide independent or incremental predictive value beyond the clinical FRAX framework within this genomic sub-sample of older women.

FRAX

Function of vitamin E in physical exercise: a review.

Even though vitamin E may not improve physical achievements in sports competitions, as shown in several swimming experiments, it is important for the health of skeletal muscle: in its role as the major lipid-soluble chainbreaking antioxidant in lipid cell membranes, vitamin E protects muscle tissue in aerobic exercise, in which oxygen metabolism and, consequently, free radical production are greatly accelerated. Animal studies in several laboratories have shown that endurance exercise results in the same type of oxidative muscle damage as does vitamin E deficiency: there is an increase in the peroxidation products pentane and malondialdehyde and in enzymes leaked from muscles to plasma. Oxidative tissue damage in vitamin-E deficient animals is exacerbated by endurance training and, conversely, it is reduced by high-dose vitamin E supplementation; also, preliminary studies in humans have demonstrated antioxidant protection by high-dose vitamin E supplementation. After endurance exercise leakage of enzymes into the plasma and output of pentane in the breath were significantly reduced. During a high-altitude expedition in the Himalayas, protection was shown to be significantly better in the supplemented group than in the placebo group, as determined by anaerobic threshold and pentane exhalation.

Animals

[Interindividual differences in personality and behavior and subjective health problems in shift workers].

A total of 604 experienced shift workers were administered a battery of questionnaires in order to examine the relationships between the shift workers' features and subjective health complaints taken as signs of intolerance to shift work. The individual difference measures included: hard-driving and competitiveness, speed and impatience, relaxed, efficiency, flexibility of behaviour, evening, rigidity of sleeping habits, vigorous, languidness, inveterate, flexibility of habits, neuroticism, extraversion, lie-scale, age and work experience. The subjective health complaints included: generally poor health, musculo-skeletal, respiratory and psychosomatic-digestive complaints, and digestive problems. Correlation and multiple regression analyses showed that in workers some personality features and patterns of behaviour were related to the subjective health complaints. More health complaints were placed by workers who were emotionally unstable, less relaxed, inefficient, rigid (e.g. unable to control the behavioral arousal level), hard-driving and competitive, speedy and impatient (A-types), rigid in sleeping and other life habits, languid, older and with longer shift work experience.

Adult