scholarly journals Genetics of osteoporosis

2007 ◽  
Vol 66 (2) ◽  
pp. 158-165 ◽  
Author(s):  
Stuart H. Ralston

Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Twin and family studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density (BMD), and other phenotypes that are associated with fracture risk, although the heritability of fracture itself is modest. Linkage studies have identified several quantitative trait loci that regulate BMD but most causal genes remain to be identified. In contrast, linkage studies in monogenic bone diseases have been successful in gene identification, and polymorphisms in many of these genes have been found to contribute to the regulation of bone mass in the normal population. Population-based studies have identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, although individually these polymorphisms only account for a small amount of the genetic contribution to BMD regulation. Environmental factors such as diet and physical activity are also important determinants of BMD, and in some cases specific nutrients have been found to interact with genetic polymorphisms to regulate BMD. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are likely to be important in increasing the understanding of the pathophysiology of the disease; providing new genetic markers with which to assess fracture risk and in identifying genes and pathways that form molecular targets for the design of the next generation of drug treatments.

2000 ◽  
Vol 166 (2) ◽  
pp. 235-245 ◽  
Author(s):  
TL Stewart ◽  
SH Ralston

Osteoporosis is a common disease with a strong genetic component characterised by low bone mass, microarchitectural deterioration of bone tissue and an increased risk of fracture. Twin and family studies have shown that genetic factors play an important role in regulating bone mineral density and other determinants of osteoporotic fracture risk, such as ultrasound properties of bone, skeletal geometry and bone turnover. Osteoporosis is a polygenic disorder, determined by the effects of several genes, each with relatively modest effects on bone mass and other determinants of fracture risk. It is only on rare occasions that osteoporosis occurs as the result of mutations in a single gene. Linkage studies in man and experimental animals have defined multiple loci which regulate bone mass but the genes responsible for these effects remain to be defined. Population-based studies and case-control studies have similarly identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, including the vitamin D receptor, oestrogen receptor and collagen type IalphaI gene. The individual contribution of these genes to the pathogenesis of osteoporosis is small however, reflected by the fact that the relationship between individual candidate genes and osteoporosis has been inconsistent in different studies. An important aim of future work will be to define how the genes which regulate bone mass, bone turnover and other aspects of bone metabolism interact with each other and with environmental variables to cause osteoporosis in individual patients. If that aim can be achieved then there is every prospect that preventative therapy could be targeted to those at greatest risk of the osteoporosis, before fractures have occurred.


2006 ◽  
Vol 50 (4) ◽  
pp. 694-704 ◽  
Author(s):  
E. Michael Lewiecki ◽  
Stuart L. Silverman

Osteoporosis is a common disease that is associated with increased risk of fractures and serious clinical consequences. Bone mineral density (BMD) testing is used to diagnose osteoporosis, estimate the risk of fracture, and monitor changes in BMD over time. Combining clinical risk factors for fracture with BMD is a better predictor of fracture risk than BMD or clinical risk factors alone. Methodologies are being developed to use BMD and validated risk factors to estimate the 10-year probability of fracture, and then combine fracture probability with country-specific economic assumptions to determine cost-effective intervention thresholds. The decision to treat is based on factors that also include availability of therapy, patient preferences, and co-morbidities. All patients benefit from nonpharmacological lifestyle treatments such a weight-bearing exercise, adequate intake of calcium and vitamin D, fall prevention, avoidance of cigarette smoking and bone-toxic drugs, and moderation of alcohol intake. Patients at high risk for fracture should be considered for pharmacological therapy, which can reduce fracture risk by about 50%.


Author(s):  
Fabio Vescini ◽  
Iacopo Chiodini ◽  
Andrea Palermo ◽  
Roberto Cesareo ◽  
Vincenzo De Geronimo ◽  
...  

: Inadequate serum selenium levels may delay the growth and the physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an anti-oxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and seleniumproteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric site. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism.


Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 149
Author(s):  
Dragos Apostu ◽  
Ondine Lucaciu ◽  
Daniel Oltean-Dan ◽  
Alexandru-Dorin Mureșan ◽  
Cristina Moisescu-Pop ◽  
...  

Thyroid hormones are important factors that regulate metabolism and cell differentiation throughout the human body. A complication of thyroid pathology is represented by an alteration of the bone metabolism which can lead to osteoporosis and fragility fractures, known to have a high mortality rate. Although there is a consensus on the negative impact of hyperthyroidism on bone metabolism, when referring to hypothyroidism, subclinical hypothyroidism, or subclinical hyperthyroidism, there is no general agreement. The aim of our review was to update clinicians and researchers about the current data regarding the bone health in hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism patients. Thyroid disorders have an important impact on bone metabolism and fracture risk, such that hyperthyroidism, hypothyroidism, and subclinical hyperthyroidism are associated with a decreased bone mineral density (BMD) and increased risk of fracture. Subclinical hypothyroidism, on the other hand, is not associated with osteoporosis or fragility fractures, and subclinical hyperthyroidism treatment with radioiodine could improve bone health.


2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias

Abstract Purpose of Review This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. Recent Findings We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Summary Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.


Endocrine ◽  
2021 ◽  
Author(s):  
Enisa Shevroja ◽  
Francesco Pio Cafarelli ◽  
Giuseppe Guglielmi ◽  
Didier Hans

AbstractOsteoporosis, a disease characterized by low bone mass and alterations of bone microarchitecture, leading to an increased risk for fragility fractures and, eventually, to fracture; is associated with an excess of mortality, a decrease in quality of life, and co-morbidities. Bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA), has been the gold standard for the diagnosis of osteoporosis. Trabecular bone score (TBS), a textural analysis of the lumbar spine DXA images, is an index of bone microarchitecture. TBS has been robustly shown to predict fractures independently of BMD. In this review, while reporting also results on BMD, we mainly focus on the TBS role in the assessment of bone health in endocrine disorders known to be reflected in bone.


2016 ◽  
Vol 67 (1) ◽  
pp. 28-40 ◽  
Author(s):  
Thomas M. Link

The radiologist has a number of roles not only in diagnosing but also in treating osteoporosis. Radiologists diagnose fragility fractures with all imaging modalities, which includes magnetic resonance imaging (MRI) demonstrating radiologically occult insufficiency fractures, but also lateral chest radiographs showing asymptomatic vertebral fractures. In particular MRI fragility fractures may have a nonspecific appearance and the radiologists needs to be familiar with the typical locations and findings, to differentiate these fractures from neoplastic lesions. It should be noted that radiologists do not simply need to diagnose fractures related to osteoporosis but also to diagnose those fractures which are complications of osteoporosis related pharmacotherapy. In addition to using standard radiological techniques radiologists also use dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to quantitatively assess bone mineral density for diagnosing osteoporosis or osteopenia as well as to monitor therapy. DXA measurements of the femoral neck are also used to calculate osteoporotic fracture risk based on the Fracture Risk Assessment Tool (FRAX) score, which is universally available. Some of the new technologies such as high-resolution peripheral computed tomography (HR-pQCT) and MR spectroscopy allow assessment of bone architecture and bone marrow composition to characterize fracture risk. Finally radiologists are also involved in the therapy of osteoporotic fractures by using vertebroplasty, kyphoplasty, and sacroplasty. This review article will focus on standard techniques and new concepts in diagnosing and managing osteoporosis.


2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv13-iv17
Author(s):  
Siew Kuan Chua ◽  
Devinder ◽  
KA Singh ◽  
Bala S Rajaratnam ◽  
Sabarul Afian Mokhtar ◽  
...  

Abstract Osteoporotic related fractures (OF) are associated with functional impairments and declined quality of life. Low bone mineral density is one of the main risk factor for OF. However, there is limited information regarding the association of spinal morphology, muscle strength and physical performance with OF. The aim of the study was to examine association between risk of osteoporotic fractures with spinal morphology (thoracolumbar curvature and back extensors muscle strength), muscle strength and physical performance. 105 adults aged 50 years and above (69.3+ 8.5 years) were recruited for this cross-sectional study from a spine orthopaedic clinic. Thoracolumbar curvature, back extensors (BEMS) and handgrip (HGS) muscle strength were measured using an electromagnetic tracking system, a load-cell system and hand-held dynamometer respectively. Physical performance was assessed using Short Physical Performance Battery (SPPB). Participants were categorised for major osteoporotic fracture risk (major OF) with cut-point 10% using fracture risk calculator (FRAX®) with BMD. Student t-test analysis demonstrated that there is a significant (p<0.05) difference between participants with low risk and moderate to high risk of major OF for BEMS, HGS, and SPPB. Adjusted logistic models (forward and backward), showed that lower HGS and physical performance were associated with increased risk of major OF (HGS: OR = 0.18 [95% CI, 0.07–0.48]; SPPB: OR = 0.32[95% CI, 0.13–0.80]). Our study results suggest that declined muscle strength and physical performance is associated with higher risk of OF. It is important to promote optimum muscle strength and physical performance among older adults in the prevention of OF.


2020 ◽  
Author(s):  
Michael A Clynes ◽  
Nicholas C Harvey ◽  
Elizabeth M Curtis ◽  
Nicholas R Fuggle ◽  
Elaine M Dennison ◽  
...  

Abstract Introduction With a worldwide ageing population, the importance of the prevention and management of osteoporotic fragility fractures is increasing over time. In this review, we discuss in detail the epidemiology of fragility fractures, how this is shaped by pharmacological interventions and how novel screening programmes can reduce the clinical and economic burden of osteoporotic fractures. Sources of data PubMed and Google Scholar were searched using various combinations of the keywords ‘osteoporosis’, ‘epidemiology’, ‘fracture’, ‘screening’, `FRAX’ and ‘SCOOP’. Areas of agreement The economic burden of osteoporosis-related fracture is significant, costing approximately $17.9 and £4 billion per annum in the USA and UK. Areas of controversy Risk calculators such as the web-based FRAX® algorithm have enabled assessment of an individual’s fracture risk using clinical risk factors, with only partial consideration of bone mineral density (BMD). Growing points As with all new interventions, we await the results of long-term use of osteoporosis screening algorithms and how these can be refined and incorporated into clinical practice. Areas timely for developing research Despite advances in osteoporosis screening, a minority of men and women at high fracture risk worldwide receive treatment. The economic and societal burden caused by osteoporosis is a clear motivation for improving the screening and management of osteoporosis worldwide.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 945-945
Author(s):  
Cecilie Blimark ◽  
Ulf-Henrik Mellqvist ◽  
Ola Landgren ◽  
Magnus Björkholm ◽  
Malin L Hultcrantz ◽  
...  

Abstract Abstract 945 Background Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM). No large population-based evaluation has been made to assess the risk of infections in MM patients compared to the normal population. Therefore, we performed a large study, using population-based data from Sweden, to estimate the risk of bacterial and viral infections among 9,610 MM patients compared to 37,718 matched controls. Methods We gathered information on all MM patients reported to the nationwide Swedish Cancer Registry from 1988 to 2004, with follow-up to 2007. For each MM patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on occurrence and date of infections was obtained from the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient (with very high coverage) and outpatient care (since 2000). Cox proportional hazard models were used to estimate the overall, one- and five-year risk of infections. In addition, the effect of gender, age and calendar period of diagnosis was evaluated. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for the occurrence of different infections. Results Overall, MM patients had a 6-fold (HR= 5.9; 95% CI=5.7-6.1) risk of developing any infection compared to matched controls (Figure). The increased risk of developing a bacterial infection was 6-fold (HR=5.9; 95%; CI=5.6-6.1), and for viral infections 9-fold (HR=9.0; 95% CI=8.0-10.1), compared to controls. More specifically, MM patients had an increased risk (p<0.05) of the following bacterial infections: cellulitis (HR=2.6; 95% CI =2.2-3.1), osteomyelitis (HR=3.0; 95% CI 2.0–4.4), endocarditis (HR=4.4; 95% CI 2.9–6.6), meningitis (HR=14.5; 95% CI 9.1–23.0), pneumonia (HR=6.2; 95% CI 5.9–6.5), pyelonephritis (HR=2.5; 95% CI 2.1–3.0), and septicaemia (HR=13.7; 95% CI 12.5–14.9) and for the viral infections influenza (HR=5.4; 95% CI 4.4–6.7) and herpes zoster (HR=12.8; 95% CI 10.5–15.5). The risk of infections was highest during the first year after diagnosis; the risk of bacterial infections was 11-fold (95% CI 10.7–12.9) and the risk of viral infections was 18-fold (95% CI 13.5–24.4) higher compared to controls during the first year after diagnosis. MM patients diagnosed in the more recent calendar periods had significantly higher risk of infections, reflected in a 1.6-fold (95% CI=1.5-1.7) and 2-fold (95% CI=1.9-2.1) increased risk in patients diagnosed during 1994–1999 and 2000–2004, compared to patients diagnosed 1986–1993. Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 9,000 MM patients and 35,000 matched controls, we found that bacterial and viral infections represent a major threat to myeloma patients. We found the risk of specific infections like pneumonia, and septicemia to be over ten times higher in patients than in controls during the first year after MM diagnosis. Importantly, the risk of infections increased in more recent years. The effect on infectious complications due to novel drugs in the treatment of MM needs to be established and trials on prophylactic measures are required. Disclosures: Mellqvist: Janssen, Celgene: Honoraria.


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