Osteoporosis: An Age-Related and Gender-Specific Disease – A Mini-Review

Osteoporosis, a classical age-related disease and known to be more common in women than in men, has been reported increasingly often in men during the past few years. Although men at all ages after puberty have larger bones than women, resulting in greater bending strength, mortality after a hip fracture, one of the major complications of osteoporosis, is more common in men than in women. Sex hormone deficiency is associated with unrestrained osteoclast activity and bone loss. Even though estrogen deficiency is more pronounced in women, it appears to be a major factor in the pathogenesis of osteoporosis in both genders. In contrast to osteoporosis in postmenopausal women, the treatment of osteoporosis in men has been scarcely reported. Nevertheless, some drugs commonly used for the treatment of osteoporosis in women also appear to be effective in men. The aim of this study is to review primary osteoporosis in the elderly with particular emphasis on gender-related aspects.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Is weight loss harmful for skeletal health in obese older adults?

Purpose of Review: In view of the existing uncertainty about the implications of intentional weight loss in older obese adults, the present review (a) summarizes the available evidence from epidemiological and interventional studies concerning the effects of weight loss through lifestyle modifications on skeletal health parameters in older overweight/obese individuals, (b) proposes mechanisms that link weight loss to bone loss in this age group, and (c) identifies appropriate animal models. Main Findings and Future Directions: Based on prospective epidemiological studies, weight loss is associated with bone loss, impaired bone macro- and microstructure, and increased fracture risk in the elderly. Data from interventional studies confirm the negative effects of intentional weight loss achieved by lifestyle modifications on skeletal health outcomes in obese older individuals. These effects appear to be modest following a single weight loss attempt, but may persist in the longer term, and presumably, during subsequent weight loss efforts. Current evidence suggests that resistance exercise coupled with caloric restriction mitigates bone and muscle loss. However, alternative strategies do not exist for older individuals, especially those who are unable or unwilling to exercise. Clinical weight loss studies in obese older individuals and preclinical research in relevant animal models with obesity and osteoporosis are required. These will advance our understanding of the pathophysiology of weight-loss-associated skeletal alterations and provide evidence on how bone loss can be counteracted or prevented

Osteoporosis

Osteoporosis is a metabolic bone disease that, on a cellular level, results from osteoclastic bone resorption not compensated by osteoblastic bone formation. This causes bones to become weak and fragile, thus increasing the risk of fractures. Traditional pathophysiological concepts of osteoporosis focused on endocrine mechanisms such as estrogen or vitamin D deficiency as well as secondary hyperparathyroidism. However, research over the last decades provided exiting new insights into mechanisms contributing to the onset of osteoporosis, which go far beyond this. Selected mechanisms such as interactions between bone and the immune system, the gut microbiome, and cellular senescence are reviewed in this article. Furthermore, an overview on currently available osteoporosis medications including antiresorptive and bone forming drugs is provided and an outlook on potential future treatment options is given

The Power Spectrum of Mass Fluctuations Measured from the Lyman-alpha Forest at Redshift z=2.5

We measure the linear power spectrum of mass density fluctuations at redshift z=2.5 from the \lya forest absorption in a sample of 19 QSO spectra, using the method introduced by Croft et al. (1998). The P(k) measurement covers the range 2\pi/k ~ 450-2350 km/s (2-12 comoving \hmpc for \Omega=1). We examine a number of possible sources of systematic error and find none that are significant on these scales. In particular, we show that spatial variations in the UV background caused by the discreteness of the source population should have negligible effect on our P(k) measurement. We obtain consistent results from the high and low redshift halves of the data set and from an entirely independent sample of nine QSO spectra with mean redshift z=2.1. A power law fit to our measured P(k) yields a logarithmic slope n=-2.25 +/- 0.18 and an amplitude \Delta^2(k_p) = 0.57^{+0.26}_{-0.18}, where $\Delta^2$ is the contribution to the density variance from a unit interval of lnk and k_p=0.008 (km/s)^{-1}. Direct comparison of our mass P(k) to the measured clustering of Lyman Break Galaxies shows that they are a highly biased population, with a bias factor b~2-5. The slope of the linear P(k), never previously measured on these scales, is close to that predicted by models based on inflation and Cold Dark Matter (CDM). The P(k) amplitude is consistent with some scale-invariant, COBE-normalized CDM models (e.g., an open model with \Omega_0=0.4) and inconsistent with others (e.g., \Omega=1). Even with limited dynamic range and substantial statistical uncertainty, a measurement of P(k) that has no unknown ``bias factors'' offers many opportunities for testing theories of structure formation and constraining cosmological parameters. (Shortened)Comment: Submitted to ApJ, 27 emulateapj pages w/ 19 postscript fig

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system’s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures

Age- and strain-related differences in bone microstructure and body composition during development in inbred male mouse strains

We explored age- and strain-related differences in bone microstructure and body composition in male C57BL/6J, DBA/2JRj and C3H/J mice. Bone microstructure of the femur, tibia and L4 was assessed by μCT at the age of 8, 16 and 24 weeks. The weight of several muscles and fat depots were measured at the same time points. At all timepoints, C3H/J mice had the thickest cortices followed by DBA/2JRj and C57BL/6J mice. Nevertheless, C57BL/6J mice had higher Tb.BV/TV and Tb.N, and lower Tb.Sp than DBA/2JRj and C3H/J mice at least at 24 weeks of age. Skeletal development patterns differed among strains. C57BL/6J and DBA/2JRj mice, but not C3H/J mice, experienced significant increases in the sum of the masses of 6 individual muscles by 24 weeks of age. In C57BL/6J and DBA/2JRj mice, the mass of selected fat depots reached highest values at 24 weeks, whist, in C3H/J mice, the highest values of fat depots masses were achieved at 16 weeks. Early strain differences in muscle and fat masses were largely diminished by 24 weeks of age. C3H/J and C57BL/6J mice displayed the most favorable cortical and trabecular bone parameters, respectively. Strain differences in body composition were less overt than strain specificity in bone microstructure, however, they possibly influenced aspects of skeletal development

Differential Expression of Dickkopf 1 and Periostin in Mouse Strains with High and Low Bone Mass

By expressing different genes and proteins that regulate osteoclast as well as osteoblast formation, osteocytes orchestrate bone metabolism. The aim of this project was the evaluation of the differences in the osteocytes’ secretory activity in the low bone mass mouse strain C57BL/6J and the high bone mass strain C3H/J. The femura of eight- and sixteen-week-old male C57BL/6J and C3H/J mice—six animals per group—were analyzed. Using immunohistochemistry, osteocytes expressing dickkopf 1, sclerostin, periostin, fibroblast growth factor 23 (FGF23), and osteoprotegerin were detected. By means of the OsteoMeasure-System, 92.173 osteocytes were counted. At the age of eight weeks, approximately twice as many cortical and trabecular osteocytes from the C57BL/6J mice compared to the C3H/J mice expressed dickkopf 1 (p < 0.005). The number of cortical osteocytes expressing sclerostin was also higher in the C57BL/6J mice (p < 0.05). In contrast, the cortical and trabecular osteocytes expressing periostin were twice as high in the C3H/J mice (p < 0.005). The dickkopf 1 expressing osteocytes of the C57BL/6J mice decreased with age and showed a strain-specific difference only in cortical bone by 16 weeks of age (p < 0.05). In the C3H/J mice, the amount of osteocytes expressing periostin tended to increase with age. Thus, strain-related differences were maintained in 16-week-old rodents (p < 0.005). No strain-specific differences in the expression of FGF23 or osteoprotegerin in the cortical compartment could be detected. This experimental study showed that the osteocytes’ protein expression reflects differences in bone characteristics and strain-related differences during skeletal maturation. Besides the osteocytes’ expression of sclerostin, their expression of dickkopf 1 and periostin seems to be important for bone properties as well

Assessment of Bone Microstructure by Micro CT in C57BL/6J Mice for Sex-Specific Differentiation

It remains uncertain which skeletal sites and parameters should be analyzed in rodent studies evaluating bone health and disease. In this cross-sectional mouse study using micro-computed tomography (µCT), we explored: (1) which microstructural parameters can be used to discriminate female from male bones and (2) whether it is meaningful to evaluate more than one bone site. Microstructural parameters of the trabecular and/or cortical compartments of the femur, tibia, thoracic and lumbar vertebral bodies, and skull were evaluated by µCT in 10 female and 10 male six-month-old C57BL/6J mice. The trabecular number (TbN) was significantly higher, while the trabecular separation (TbSp) was significantly lower in male compared to female mice at all skeletal sites assessed. Overall, bone volume/tissue volume (BV/TV) was also significantly higher in male vs. female mice (except for the thoracic spine, which did not differ by sex). Most parameters of the cortical bone microstructure did not differ between male and female mice. BV/TV, TbN, and TbSp at the femur, and TbN and TbSp at the tibia and lumbar spine could fully (100%) discriminate female from male bones. Cortical thickness (CtTh) at the femur was the best parameter to detect sex differences in the cortical compartment (AUC = 0.914). In 6-month-old C57BL/6J mice, BV/TV, TbN, and TbSp can be used to distinguish male from female bones. Whenever it is not possible to assess multiple bone sites, we propose to evaluate the bone microstructure of the femur for detecting potential sex differences