Mechanical effects on the skeleton: Are there clinical implications?

The basic morphology of the skeleton is determined genetically, but its final mass and architecture are modulated by adaptive mechanisms sensitive to mechanical factors. When subjected to loading, the ability of bones to resist fracture depends on their mass, material properties, geometry and tissue quality. The contribution of altered bone geometry to fracture risk is unappreciated by clinical assessment using absorptiometry because it fails to distinguish geometry and density. For example, for the same bone area and density, small increases in the diaphyseal radius effect a disproportionate influence on torsional strength of bone. Mechanical factors are clinically relevant because of their ability to influence growth, modeling and remodeling activities that can maximize, or maintain, the determinants of fracture resistance. Mechanical loads, greater than those habitually encountered by the skeleton, effect adaptations in cortical and cancellous bone, reduce the rate of bone turnover, and activate new bone formation on cortical and trabecular surfaces. In doing so, they increase bone strength by beneficial adaptations in the geometric dimensions and material properties of the tissue. There is no direct evidence to demonstrate anti-fracture efficacy for mechanical loading, but the geometric alterations engendered undoubtedly increase the structural properties of bone as an organ, increasing the resistance to fracture. Like all interventions, issues of safety also arise. Physical activities involving high strain rates, heavy lifting or impact loading may be detrimental to the joints, leading to osteoarthritis; may stimulate fatigue damage leading with some to stress fractures; or may interact pharmaceutical interventions to increase the rate of microdamage within cortical or trabecular bone.

The ratio of messenger RNA levels of receptor activator of nuclear factor kappa B ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis

skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor KB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA, (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders?

Hypovitaminosis D is a candidate risk-modifying factor for a diverse range of disorders apart from rickets and osteoporosis. Based on epidemiology, and on in vitro and animal experiment, vitamin D has been linked to multiple sclerosis, certain cancers (prostate, breast and colorectal), insulin-dependent diabetes mellitus and schizophrenia. I hypothesise that low pre- and perinatal vitamin D levels imprint on the functional characteristics of various tissues throughout the body, leaving the affected individual at increased risk of developing a range of adult-onset disorders. The hypothesis draws from recent advances in our understanding of the early origin of adult disease and proposes a 'critical window' during which vitamin D levels may have a persisting impact on adult health outcomes. Methods to test the hypothesis are outlined. If correct, the hypothesis has important implications for public health. Careful attention to maternal vitamin D status could translate into diverse improvements in health outcomes for the following generation. (C) 2001 Harcourt Publishers Ltd.

Skeletal effects of low-intensity pulsed ultrasound on the ovariectomized rodent

Growing evidence supports low-intensity pulsed ultrasound (US) as an osteogenic mechanical stimulus. Its effects on isolated bone cells and on fractured bone are established. However, its effects on osteoporosis are not clear. This study examined US effects on ovariectomy (OVX) induced bone changes within the rodent hindlimb (distal femur and proximal tibia), and on normal bone in animals following sham-OVX. Animals were exposed to daily unilateral active-US and contralateral inactive-US for 12 weeks. Bone status was assessed using dual energy X-ray absorptiometry and histomorphometry. Ovariectomy resulted in significant bone changes. Low-intensity pulsed US did not influence these changes. These results suggest that the US dose introduced may not be a beneficial treatment for osteoporosis, and that intact bone may be less sensitive to US than fractured bone and isolated bone cells. This may relate to the biophysical mechanisms of action of US, US-bone interactions and tissue level processes taking place.

Estrogen receptors in human preadipocytes

Estrogen influences regional adipose tissue distribution and the accompanying cardiovascular disease risk. To elucidate the mechanisms of this link further, we assessed whether human preadipocytes (PAs) expressed estrogen receptors (ERs) and whether there were any regional or gender differences in ER complement. Human PAs expressed the ER alpha gene but not ERP by reverse transcriptase-polymerase chain reaction, possessed ER alpha protein on Western blotting, and displayed specific 17 beta -estradiol (E-2) binding with calculated dissociation constants of 0.78 nM, 0.96 nM, and 1.19 nM and maximal binding capacities of 9.3 fmol/mg, 14.6 fmol/ mg, and 18.2 fmol/mg from three whole cell binding assays. There were no regional differences in ER alpha complement for males or females. There were no gender differences in ER alpha complement for subcutaneous or visceral samples. We conclude that ER alpha but not ERP is present in human PAs. This suggests that the effect of estrogen on adipose tissue deposition has a contribution from the direct effect of estrogen on human PAs via ER alpha.

Occult Axillary Lymph Node Metastases in Breast Cancer Do Matter: Results of 10-Year Survival Analysis

Axillary lymph node status is one of the most powerful prognostic factors for patients with breast cancer and is often critical in stratifying patients into adjuvant treatment regimens. In 203 apparently node-negative cases of breast cancer, a combination of immunohistochemical staining and step-sectioning identified occult metastases in 25% of cases. Ten-year follow-up information is available for these patients. Histologic features of the primary tumor and immunohistochemical staining for estrogen receptor, progesterone receptor, Her-2, and p53 were also evaluated. With multivariate analysis, both occult metastases and higher histologic grade of the primary tumor were independent predictors of disease-free survival. Histologic grade was the only significant independent predictor of overall survival. Estrogen receptor, progesterone receptor, Her-2, and p53 status did not predict the presence of metastases or survival when all tumor types were considered together. Metastases >0.5 mm significantly predicted a poorer disease-free survival when invasive ductal carcinomas were considered alone. Histologic grade was significantly associated with disease-free survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients. The presence of occult metastases approached significance for overall survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients.

Changes in physical symptoms during the menopause transition

This article analyzes physical symptoms experienced by mid-age Australian women in different stages of the menopause transition. A total of 8,623 women, aged 45 to 50 years in 1996, who participated the mid-age cohort of the Australian Longitudinal Study on Women's Health, completed Survey I in 1996 and Survey 2 in 1998. Women were assigned to I of 6 menopause groups according to their menopausal status at Surveys 1 and 2, and compared on symptoms experienced at Surveys I and 2, adjusted for lifestyle, behavioral and demographic factors. At Survey 1, the most commonly reported symptoms were headaches, back pain, stiff joints, tiredness, and difficulty sleeping. Perimenopausal women were more likely than premenopausal or postmenopausal women to report these symptoms. Hot flushes and night sweats were more common among postmenopausal women. Compared with those who remained premenopausal, women who were in the early stages of menopause or perimenopausal were more likely to report tiredness, stiff joints, difficulty sleeping, and hot flushes at Survey 2. Women who remained perimenopausal were also more likely to report back pain and leaking urine. Compared with premenopausal women, odds ratios for night sweats increased for women in consecutive stages of the menopause transition and remained high in the postmenopausal women.

Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications

Osteoarthritis is a major cause of disability in both the developed and developing world. With the population aging, the prevalence of osteoarthritis is increasing and its consequences are impacting significantly on society. This is one of the reasons why osteoarthritis has been adopted as a major focus (along with osteoporosis, rheumatoid arthritis, back pain, and musculoskeletal trauma) by the global initiative-the Decade of Bone and Joint Disease. Adequate studies on the costs of osteoarthritis are urgently required so that cogent arguments can be made to governments to appropriately fund prevention and treatment programs for this condition. Its recognition as a major cause of disability, particularly in the aging population, should increase community focus on this important condition. (C) 2002 Lippincott Williams Wilkins, Inc.

Perceived stress as a predictor of the self-reported new diagnosis of symptomatic CHD in older women

This article describes one aspect of a prospective cohort study of 10,432 women aged between 70 and 75 years. After a 3-year period, 503 women self-reported a new diagnosis by a doctor of angina or myocardial infarction (symptomatic coronary heart disease [CHD]). Time one psychosocial variables (Duke Social Support Index, time pressure, Perceived Stress Scale, Mental Health Index, having a partner, educational attainment, and location of residence) were analyzed using univariate binary logistic regression for their ability to predict subsequent symptomatic CHD. Of these variables, the Duke Social Support Index, Perceived Stress Scale and the Mental Health Index were found to be significant predictors of symptomatic CHID diagnosis. Only the Perceived Stress Scale, however, proved to be a significant independent predictor. After controlling for time one nonpsychosocial variables, as well as the frequency of family doctor visits, perceived stress remained a significant predictor of the new diagnosis of symptomatic CHD in this cohort of older women over a 3-year period.

Seeking SOCS and sex steroids

In seeking to explain why oral estrogen inhibits the GH-IGF-I axis, a recent study has unearthed a new way that steroid hormones can influence growth hormone action. This involves suppressors of cytokine signalling (SOCS), which offer a new level of understanding in signal control and crosstalk.

Physical Activity and Bone Mineral Accrual During Childhood and Adolescence

The epidemic that is osteoporosis has led to an increasing interest in bone mineral, and the factors that influence the levels of bone mineral, in recent years. While it is unrealistic to try and turn back the clock, a return to an increased level of physical activity may be an important consideration in terms of skeletal health. Peak bone mass is largely determined by heredity, but lifestyle and dietary patterns also influence the level of bone mineral accrued during the growing years. In this review, we summarize the evidence that vigorous weight-bearing physical activity and adequate calcium intake represent the best possibility for enhancing the attainment of an optimal level of bone mineral, within genetic limits.

Sex- and race-related differences in cross-sectional geometry and bone density of the femoral mid-shaft in older adults

Background : Femoral shaft fracture incidence increases in older adults and is associated with low-energy trauma. Apart from bone density, the distribution and size of bone contributes to its strength. Aim : To examine if bone geometry and density of the femoral mid-shaft in older adults differs by sex and race, we studied 197 White women, 225 Black women, 242 White men, and 148 Black men aged 70-79 years participating in the Health, Aging, and Body Composition study; a prospective cohort study in the USA. A secondary purpose of the study was to examine the association of site-specific muscle and fat to bone geometry and density. Subjects and methods : Subjects were community-dwelling and reported no difficulty walking one-quarter of a mile or climbing stairs. Mid-femoral volumetric bone mineral density (vBMD, mg cm -3 ), total area (TA), cortical area (CA), medullary area (MA), cross-sectional moments of inertia (CSMI: I x , I y , J ), and muscle and fat areas (cm 2 ) were determined by computed tomography (CT; GE CT-9800, 10 mm slice thickness). Results : vBMD was greater in men than women with no difference by race ( p < 0.001). Bone areas and area moments of inertia were also greater in men than women ( p < 0.001), with Black women having higher values than White women for TA and CA. Standardizing geometric parameters for body size differences by dividing by powers of femur length did not negate the sex difference for TA and MA. Significant differences ( p < 0.05) among the four groups also remained for I x and J . Mid-thigh muscle area was an independent contributor to TA in all groups (Std beta = 0.181-0.351, p < 0.05) as well as CA in women (Std beta = 0.246-0.254, p < 0.01) and CSMI in White women (Std beta = 0.175-0.185, p < 0.05). Further, muscle area was a significant contributor to vBMD in Black women. Conclusion : These results indicate that bone geometry and density of the femoral diaphysis differs primarily by sex, rather than race, in older well-functioning adults. In addition, site-specific muscle area appears to have a potential contributory role to bone geometry parameters, especially in women.

Desenvolvimento de uma linha de metropolitano ligeiro entre as linhas ferroviárias de Cascais e Sintra: "Metro de Oeiras"

Nos últimos anos tem-se constatado um agravamento da mobilidade em Agualva- Cacém e nas áreas envolventes ao eixo definido pela EN249-3. No desenvolvimento da linha de metro ligeiro considerou-se como objectivo prioritário a definição dum espaço canal e das respectivas infra-estrururas associadas, de forma a assegurar uma boa interligação das Linhas de Sintra e de Cascais e a conexão aos pólos tecnológicos TagusPark, Lagoas Park e Quinta da Fonte, abrangendo uma zona de influência significativa. A construção de “park & ride” junto às estações de metro ligeiro vai fomentar a transferência do transporte individual para o transporte colectivo contribuindo para a melhoria de qualidade de vida em zonas muito congestionadas e com elevados índices de poluição. Na elaboração do projecto foram superadas as dificuldades de inserção nas zonas com alta densidade e com orografia caracterizada por vales profundos. A linha tem uma extensão de 16,8 km em sítio próprio, com 23 estações e será explorada com 22 composições de 310 lugares, realizando o tempo de percurso de 25 minutos entre Oeiras e o Tagus Park ou entre Cacém e o Tagus Park. Para a concretização deste projecto foi estimado um investimento de 402 milhões de euros, incluindo a aquisição de material circulante em três fases. O custo da manutenção e exploração será de 12 milhões de euros/ano. A linha de metro ligeiro servirá cerca de 201 mil pessoas na sua área envolvente (a uma distância de 450m do eixo) e transportará 32 milhões de passageiros no Ano 0 e 54 milhões no Ano 30. O custo por passageiro transportado será de 0,74€ no Ano 0 e de 0,50€ no Ano 30.

Alimentação, composição corporal e cancro da mama

Introdução – A nível mundial, o cancro da mama é o tipo de cancro mais frequente nas mulheres. Estudos têm sugerido que os fatores de estilo de vida (alimentação, consumo de álcool, atividade física) e a adiposidade corporal estão implicados na sua etiologia, sobretudo nos tumores diagnosticados após a menopausa. O objetivo deste artigo foi o de identificar quais os fatores nutricionais e de composição corporal implicados na etiologia da doença e qual a sua relação. Metodologia – Foi realizada uma revisão da literatura referente a estudos de revisão, de coorte e experimentais, de acordo com a temática em estudo. Resultados – As mulheres obesas têm maior risco de desenvolver cancro da mama após a menopausa e a adiposidade corporal, localizada na região abdominal, é também fator de risco. A obesidade, além de fator promotor, relaciona-se inversamente com o prognóstico da doença. Relativamente ao padrão alimentar, a ingestão de ácidos gordos saturados confere risco, ainda que com uma associação fraca e, com uma associação modesta, a dieta mediterrânica parece estar associada a um menor risco de cancro da mama pós-menopausa. Conclusão – A adoção de um estilo de vida saudável (alimentação e atividade física) e a obtenção/manutenção de um peso corporal saudável devem ser encorajados para prevenir o cancro da mama. Mais estudos devem ser realizados no futuro para consolidar a associação com outras variáveis dietéticas. ABSTRACT - Background – Breast cancer is worldwide the most common cancer in women. Studies have suggested that lifestyle such as nutrition, alcohol intake and physical activity are enrolled in aetiology, especially in postmenopausal tumours. This review aimed to investigate the relationship between nutritional factors and body composition with the disease. Methods – A selective review of the literature for recent studies and meta-analyses on this topic. Results – Obese women have higher risk to develop breast cancer after menopause. Abdominal adiposity is also a risk factor. Obesity, beside of promote the disease, is also a negative factor of prognoses. In respect to dietary pattern, the intake of saturated fatty acids seems to attribute risk, even if with a weak association. Although with a modest association, Mediterranean diet may be associated with lower breast cancer risk among postmenopausal women. Conclusion – Adopt a healthy lifestyle (nutrition and physical activity) and maintain a healthy body weight should be encouraged to prevent breast cancer. Future research should focus other dietary variables already investigated but still with no clear evidence.

Prevalência de Osteoporose numa amostra de mulheres Portuguesas

A osteoporose é uma doença crónica e progressiva. O diagnóstico baseia-se na avaliação de densidade mineral óssea (DMO), por absorciometria bifotónica por RX (DXA) e no conceito operacional da Organização Mundial de Saúde (OMS) indicando que a doença acontece para valores de DMO inferiores a 2,5 desvios-padrão do valor médio máximo para mulheres jovens, saudáveis de etnia caucasóide. Existe variabilidade nos valores de pico de massa óssea entre diferentes populações. Este estudo pretende avaliar a prevalência de osteoporose quando utilizada a base de referência do equipamento e quando utilizada a base de dados para score-T construída a partir da amostra.