Epigenetics of Osteoporosis

Fragile bone is the root cause of osteoporosis. For inherited or acquired reasons, the fragile bone does not provide sufficient fracture resistance to withstand the physical strains of a normal lifestyle. Accordingly, clinical characteristics consist of fragility fractures that occur during daily life activities or low energy trauma. Hip fractures and vertebral fractures are so called "major osteoporotic fractures”, that also cause the highest burden of disease. Although the clinical osteoporosis manifestations are relatively uniform, there is a vast spectrum of underlying molecular causes. Impaired bone formation, accelerated bone loss, and impaired lifetime adaptive regeneration according to physical impact characterize the cruder facets of osteoporosis. The signaling cascades that govern bone formation and metabolism may be altered by genetically or epigenetically inherited defects or acquired epigenetic changes due to tissue aging and/or underlying diseases. While molecular genetics and mechanisms and specific osteoporosis treatments have made impressive progress over the last three decades, there is still an urgent need to better understand the role of epigenetics in this disease.Epigenetic mechanisms such as covalent modifications of DNA, histones, or essential core factors like the osteogenic transcription factors (e. g., RUNX2) and inhibitory modulators of osteogenic WNT-signaling (e. g., Dickkopf-1 (DKK-1), sclerostin (SOST)) are all intricately implicated in developmental bone formation and adaptive regeneration and remodeling processes throughout adult life. These mechanisms are accompanied by chromatin architecture and gene expression changes of small (e. g., microRNAs (miRs)) and long, noncoding RNAs (lncRNAs). The timely execution of these mechanisms either facilitates or inhibits bone formation and remodeling. Together, epigenetic mechanisms controlling bone homeostasis widen the spectrum of potential dysregulations that can cause osteoporosis and open new avenues for therapeutic interventions.Apart from the core mechanisms of bone formation and regeneration, recent research revealed that tissue-resident cells of the immune system such as tissue-specific macrophages, myeloid precursors, and lymphocytes have surprisingly fundamental influence on tissue regeneration, including bone. Those tissue resident cells are also subject to epigenetic changes and may substantially contribute to the development of disease. Epigenetic constellations can be inherited, but the dynamic epigenetic mechanisms involved in physiological processes of tissue regeneration may also be affected by pathologies such as cellular aging and senescence. Recently, several studies aimed at identifying DNA methylation signatures in peripheral blood leukocytes from osteoporosis patients that reveal novel disease mechanisms and potential targets for diagnosis and treatment. Overall, these studies rendered, however, yet inconclusive results.By contrast, studies using bone marrow-derived skeletal progenitors identified transcriptome changes in osteoporosis patients, which could have epigenetic reasons in the absence of genetic causes. Respective changes may be related to the local milieu in bone and bone marrow as a kind of segmental attitude of a specific tissue acquired through tissue aging and/or supported by underlying aging-associated diseases such as arteriosclerosis or aging of cells of the immune system.In summary, there is cumulating evidence linking epigenetic factors to the pathogenesis of aging-associated osteoporosis. However, we are currently still limited in our knowledge with respect to the causal traits that are common, inherited, or acquired in a lifetime in the respective tissues and cells involved in bone formation and regeneration. During the following years, the field will most certainly learn more about molecular processes and factors that can be targeted therapeutically and/or used as biomarkers for risk assessment.

Health Beneficial Effects of Cucumber

Cucumber is a healthy fruit which having lots of benefits. Cucumber regulates hydration and maintain adequate blood pressure and sugar, soothes skin, helped in digestion and reduces fat and help to weight loss. Cucumber contains a plenty of potassium, fiber, magnesium, manganese and vitamin A, C, K. Cucumber has several health beneficial activities such as antimicrobial properties, hydrating and detoxification, help in digestion and weight loss, preventing cancer and other fragile bone disease. In this book chapter we have discussed about the health beneficial activities of cucumber along with its different contents.

Biomechanical Computed Tomography Captures Older Men at High Risk of Hip Fracture Despite Low Fracture Risk Calculation by FRAX

Background: Biomechanical computed tomography (BCT) can be applied to hip-containing CT scans to estimate femoral bone strength using finite-element analysis and to measure DXA-equivalent femoral neck (FN) BMD. Current guidelines recommend osteoporosis pharmacotherapy initiation in men with BMD T-score ≤ -2.5 or T-score between -1.0 and -2.5 with 10-year hip fracture risk ≥ 3% by FRAX.1 Estimated femoral strength by BCT is associated with incident hip fractures in men, independent of BMD,2 and can be used in conjunction with clinical risk factors for consideration of therapy initiation per the International Society of Clinical Dosimetry.3 Aim: To determine how many men are at increased risk of fractures with fragile bone strength (≤ 3500N) despite normal-to-low BMD (T-score > -2.5) and low 10-year hip fracture risk (< 3%). Methods: 625 men age ≥ 65 with hip-containing CT scans were randomly selected for BCT analysis out of 4209 scans performed from 2017 to 2019 at a single academic hospital. Scans were excluded if an intact femur was not imaged. BCT was performed for 557 men after accounting for un-processable scans. Electronic health records were retrospectively reviewed by investigators blinded to BCT results. 10-year hip fracture risks were calculated by FRAX based on available clinical data and FN BMD T-score from BCT. Chi-squared and t-test were used to investigate differences in clinical parameters between men with and without fragile bone strength. Results: The mean age was 77 (± 7.6 years), and 69% of men were white. Out of 102 men (18.3%) who met criteria for fragile bone strength by BCT, 42 (7.5%) had low FN BMD (T-score between -1.0 and -2.5) and 2 (0.4%) had normal FN BMD (T-score ≥ -1.0). The percentage of men with fragile bone strength and discrepant BMD increased with age (5.4% in age 65–74; 8.2% in age 75–84; 13.0% in age ≥ 85). The average 10-year hip fracture risk by FRAX of men with fragile bone strength was 6.5% (± 4.0%). However, 13 out of 44 men with normal-to-low BMD had 10-year hip fracture risks < 3% despite fragile bone strength presence and did not meet recommendation for osteoporosis pharmacotherapy. Examining men with normal-to-low BMD (n=493), those with fragile bone strength tended to be older, have lower BMI, and of Hispanic ethnicity compared to those with normal-to-low bone strength (p<0.05). Conclusions: Our study showed that fragile bone strength is present in older men with normal-to-low BMD, and that inclusion of 10-year hip fracture risk by FRAX may capture some, but not all, men at increased risk of hip fractures. Skeletal fragility measured by BCT may serve as additional data to assist with clinical decision making for men with osteoporosis, though further prospective research is needed. Reference: 1. Watts et al, J Clin Endocrinol Metab. 2012 Jun;97(6):1802–22. 2. Adams et al, J Bone Miner Res 2018 Jul;33(7):1291–1301. 3. Shuhart et al, J Clin Densitom. 2019 Oct-Dec;22(4):453–471.

Opportunistic diagnosis of osteoporosis, fragile bone strength and vertebral fractures from routine CT scans; a review of approved technology systems and pathways to implementation

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient’s spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.

Adult Morquio syndrome requiring occipito-thoracic fusion

Morquio syndrome is a relatively rare entity that is often associated with atlantoaxial instability from early childhood due to odontoid dysplasia based on a mucopolysaccharoidal disorder. Here, we present the case of a 55-year-old male patient with Morquio syndrome who developed cervical myelopathy, which is an extremely rare condition in the older population. Myelopathy developed gradually with upper-limb paresthesia and clumsiness of both hands. The patient had a characteristic “gargoyle-like” coarse face with a trunk shortening-type short stature. Imaging of the cervical spine demonstrated several problems, including diminutive structures called platyspondyly with small pedicles and fragile bone quality, hypoplasia of the C1 posterior arch that migrated into the spinal canal, and os odontoideum with atlantoaxial instability. With intraoperative navigation guidance, posterior decompression of C1 followed by occipito-cervico-thoracic spinal fusion was successfully performed in this complicated case. Clinical and radiographic outcomes were both excellent and have been maintained for 2 years postoperatively.

Note on the paleobiogeography of Compsognathidae (Dinosauria: Theropoda) and its paleoecological implications

The paleobiogeography of the theropod clade Compsognathidae is here reaccessed in order to test the hypothesis of this taxon being adapted specifically to inhabit semi-arid environments. Data about localities where these fossils were collected and their paleoenvironments were gathered from the literature. Compsognathids seem to be found especially in sedimentary deposits known as Fossil Lagerstätten, which were formed under a set of specific conditions that allowed the preservation of the fragile bone remains of these animals. This bias limits an accurate analysis of the historical and/or ecological paleobiogeography of this taxon. Actually, it is possible that compsognathids had an almost worldwide distribution during the Mesozoic Era. Their occurrence in Lower Cretaceous rocks of China suggests that they also inhabited environments with moist conditions instead of being restricted to semi-arid to arid environments.

Bilateral Insufficiency Fracture of the Pelvis Following THA: A Case Report

Insufficiency fracture is of the stress fractures and is caused by repetitive stress on fragile bone. Insufficiency fractures of pubic rami are rare occurrences in association with total hip arthroplasty (THA). Postoperative stress fractures occur due to increase of patients activity following years of disability. The physician should consider the possibility of a pelvic insufficiency fracture in patients with RA after THA, if the patients present with groin pain. We demonstrate here the first case of bilateral insufficiency fracture of pubic rami and iliac bone following THA.