Hélder Fonseca

Bone Quality: The Determinants of Bone Strength and Fragility

Bone fragility is a major health concern, as the increased risk of bone fractures has devastating outcomes in terms of mortality, decreased autonomy, and healthcare costs. Efforts made to address this problem have considerably increased our knowledge about the mechanisms that regulate bone formation and resorption. In particular, we now have a much better understanding of the cellular events that are triggered when bones are mechanically stimulated and how these events can lead to improvements in bone mass. Despite these findings at the molecular level, most exercise intervention studies reveal either no effects or only minor benefits of exercise programs in improving bone mineral density (BMD) in osteoporotic patients. Nevertheless, and despite that BMD is the gold standard for diagnosing osteoporosis, this measure is only able to provide insights regarding the quantity of bone tissue. In this article, we review the complex structure of bone tissue and highlight the concept that its mechanical strength stems from the interaction of several different features. We revisited the available data showing that bone mineralization degree, hydroxyapatite crystal size and heterogeneity, collagen properties, osteocyte density, trabecular and cortical microarchitecture, as well as whole bone geometry, are determinants of bone strength and that each one of these properties may independently contribute to the increased or decreased risk of fracture, even without meaningful changes in aBMD. Based on these findings, we emphasize that while osteoporosis (almost) always causes bone fragility, bone fragility is not always caused just by osteoporosis, as other important variables also play a major role in this etiology. Furthermore, the results of several studies showing compelling data that physical exercise has the potential to improve bone quality and to decrease fracture risk by influencing each one of these determinants are also reviewed. These findings have meaningful clinical repercussions as they emphasize the fact that, even without leading to improvements in BMD, exercise interventions in patients with osteoporosis may be beneficial by improving other determinants of bone strength.

Physical Inactivity is a Major Contributor to Ovariectomy-Induced Sarcopenia

Since the mechanism(s) underlying menopause-related sarcopenia remain unknown we aimed to investigate the role of physical inactivity in its etiology. Ovariectomized and sham-operated rats were allocated into 2 experimental groups: (1) sedentary-standard housing; and (2) exercise-housed with running wheel. After a 9-month experimental period, soleus muscle structure and biochemical properties were analyzed. No differences existed in muscle fibre size or ultrastructure between sedentary sham and ovariectomized animals housed in standard conditions. In the exercise groups, average daily running distance was 10-fold less in ovariectomized compared to sham-animals. Further, in exercised animals, soleus fibre size was smaller in ovariectomized compared to sham-animals. Nonetheless, compared to both sedentary groups, muscle fibre size was larger in the exercised ovariectomized animals. Our results indicate that ovariectomy-induced sarcopenia is not due to the loss of ovarian hormones per se, but is largely due to physical inactivity.

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli.

Moderate exercise training provides left ventricular tolerance to acute pressure overload

The present study evaluated the impact of moderate exercise training on the cardiac tolerance to acute pressure overload. Male Wistar rats were randomly submitted to exercise training or sedentary lifestyle for 14 wk. At the end of this period, the animals were anaesthetized, mechanically ventilated, and submitted to hemodynamic evaluation with biventricular tip pressure manometers. Acute pressure overload was induced by banding the descending aorta to induce a 60% increase of peak systolic left ventricular pressure during 120 min. This resulted in the following experimental groups: 1) sedentary without banding (SED + Sham), 2) sedentary with banding (SED + Band), and 3) exercise trained with banding (EX + Band). In response to aortic banding, SED + Band animals could not sustain the 60% increase of peak systolic pressure for 120 min, even with additional narrowing of the banding. This was accompanied by a reduction of dP/dt(max) and dP/dt(min) and a prolongation of the time constant tau, indicating impaired systolic and diastolic function. This impairment was not observed in EX + Band (P < 0.05 vs. SED + Band). Additionally, compared with SED + Band, EX + Band presented less myocardial damage, exhibited attenuated protein expression of active caspase-3 and NF-κB (P < 0.016), and showed less protein carbonylation and nitration (P < 0.05). These findings support our hypothesis that exercise training has a protective role in the modulation of the early cardiac response to pressure overload.

Lifelong Sedentary Behaviour and Femur Structure

The aim of the present study was to analyze the lifelong differences of femur structure in sedentary and physically active animal models. Thirty male C57BL/6 mice, 2 months old, were either: i) housed in cages with running wheel (AA; n=10), ii) housed in cages without running wheel (AS; n=10), iii) or sacrificed without intervention (Y; n=10). AA and AS animals were sacrificed after 23 months of housing. Right femur structure was analyzed in all animals by histomorphometry. Significant differences in several microarchitectural parameters of cancellous and cortical bone were identified between Y mice and both groups of aged mice, as well as between AA and AS groups. Lifelong physically active mice had significantly higher cancellous bone surface (Cn.BS) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) at both epiphyses when compared to AS animals. No differences were observed between Y and AA groups regarding osteocyte number (N.Ot) despite its significant reduction in AS animals, suggesting that age alone was not a cause for decreases in N.Ot. Our results suggest that the reduced bone quality observed in the elderly is not only a consequence of age but also of lack of physical activity since sedentary behaviour significantly aggravated the degenerative age-related bone differences.

Skeletal deterioration following ovarian failure: can some features be a direct consequence of estrogen loss while others are more related to physical inactivity?

AbstractFindings on experimental animals show that ovarian failure is a ccompanied by a decrease in motor activity. As mechanical loading has a vital role in the maintenance of skeletal health, our aim was to determine to what extent this decrease in motor activity contributes to ovariectomy-induced bone loss. Thirty-two female Wistar rats were ovariectomized or sham-operated and housed in standard cages or with access to running wheels for 36 weeks with their running distance monitored. Markers of bone turnover were assayed in the serum, and bone geometry, trabecular and cortical bone microarchitecture, mineralization degree, and biomechanical properties were assessed in the femur. Differences between groups were determined by one-way ANOVA. Although reduced motor activity and sex steroid deficiency both resulted in decreases in trabecular bone volume, trabecular number decreases were mostly associated with sex steroid deficiency, whereas trabecular thickness decreases were mostly associated with sedentary behavior. Cortical bone appeared to be more sensitive to variations in motor activity, whereas bone turnover rate and bone tissue mineralization degree seemed to be primarily affected by sex steroid deficiency, even though they were further aggravated by sedentary behavior. Increases in femur length were mostly a consequence of sex steroid deficiency, whereas femoral neck length was also influenced by sedentary behavior. Differences in mechanical properties resulted mostly from differences in physical activity. Both the direct effect of sex steroid deficiency and the indirect effect of motor activity changes are implicated in bone loss following ovariectomy.