scholarly journals Role of genetic factors in the pathogenesis of osteoporosis

2000 ◽  
Vol 166 (2) ◽  
pp. 235-245 ◽  
Author(s):  
TL Stewart ◽  
SH Ralston
Keyword(s):  
Bone Mass ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Candidate Genes ◽  
Osteoporotic Fracture ◽  
Genetic Factors ◽  
Single Gene ◽  
Common Disease ◽  
Mineral Density ◽  
Increased Risk

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.

scholarly journals Genetics of osteoporosis

2007 ◽  
Vol 66 (2) ◽  
pp. 158-165 ◽  
Author(s):  
Stuart H. Ralston
Keyword(s):  
Bone Mass ◽  
Fracture Risk ◽  
Normal Population ◽  
Fragility Fractures ◽  
Population Based ◽  
Bone Diseases ◽  
Common Disease ◽  
Linkage Studies ◽  
Mineral Density ◽  
Increased Risk

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.

scholarly journals Antiresorptive Therapy and the Bone Turnover Markers—Assessed Fracture Risk in Postmenopausal Women

2020 ◽  
Author(s):  
Ljiljana Smilic ◽  
Tanja Smilic ◽  
Aleksandar N. Jovanovic ◽  
Snezana R. Markovic - Jovanovic ◽  
Zlatica Mirkovic ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Fracture Risk ◽  
Postmenopausal Women ◽  
Bone Turnover Markers ◽  
Bone Markers ◽  
Antiresorptive Therapy ◽  
Mineral Density ◽  
Metabolic Markers ◽  
Increased Risk ◽  
Turnover Markers

Abstract Purpose/Introduction: The aim of this study was to determine relationship of the bone markers levels with the fracture risk and treatment monitoring in patients with osteoporosis. Bone markers may point out to on specific aspects of bone quality, detecting changes of bone mineral density, thus providing prognostic perspective and accounting for a substantial proportion of fracture risk reduction.Methods: The case-control study comprised data from 55 patients undergoing evaluation for osteoporosis at Medicus Universalis Polyclinic in Krusevac. Densitometric findings, P1NP, CTX and osteocalcin levels were determined in all patients twice – at the first assessment and 6 months after. While 30 patients took no medical therapy, 25 of them were treated with ibandronate. Results: No convincing difference in densitometric measurements between patients with and without prevalent fractures were noted, while mean osteocalcin and P1NP levels were significantly lower (p<0.05) in osteoporotic patients who suffered fractures. A significant correlation between those bone turnover markers and T-score was established, especially in the second measurement and in patients treated with ibandronate.Conclusion: In postmenopausal women and individuals with low BMD, the presence of increased bone turnover markers suggests an increased risk of fractures. Furthermore, these metabolic markers are useful in the monitoring of patients receiving antiresorptive therapy, wherein fast decline of their levels indicate favorable course. Their determination after 6 months offers the remarkable advantage in assessing the effectiveness of medical treatment comparing to 12–24 months required to document changes by BMD.

scholarly journals Redefining osteoporosis treatment: who to treat and how long to treat

2006 ◽  
Vol 50 (4) ◽  
pp. 694-704 ◽  
Author(s):  
E. Michael Lewiecki ◽  
Stuart L. Silverman
Keyword(s):  
Risk Factors ◽  
Fracture Risk ◽  
Weight Bearing ◽  
Pharmacological Therapy ◽  
Clinical Risk Factors ◽  
Common Disease ◽  
Mineral Density ◽  
Clinical Risk ◽  
Increased Risk ◽  
Bmd Testing

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%.

Biochemical Markers of Bone Turnover and Fracture Prediction

2003 ◽  
Vol 9 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Rosemary A Hannon ◽  
Richard Eastell
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Markers Of Bone Turnover

Low bone mineral density is a strong risk factor for fractures in the older woman. Biochemical markers of bone turnover may predict fracture risk independently of bone mineral density. High levels of bone resorption markers are associated with increased risk of fracture in both retrospective and prospective studies, although the evidence for bone formation markers and fracture risk is equivocal. For example, the risk of fracture is increased up to two-fold in women with elevated levels of several markers of bone resorption. Prediction models have been developed to predict the 10–year risk of fracture using bone mineral density and biochemical markers of bone turnover and these could prove very useful in clinical practice.

scholarly journals Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics

2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias
Keyword(s):  
Bone Mass ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
High Bone Mass ◽  
Increased Risk ◽  
High Bone ◽  
Genetic Mechanisms ◽  
Additional Support

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.

scholarly journals 64 Association between Risk of Osteoporotic Fractures with Spinal Morphology, Muscle Strength and Physical Performance

2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv13-iv17
Author(s):  
Siew Kuan Chua ◽  
Devinder ◽  
KA Singh ◽  
Bala S Rajaratnam ◽  
Sabarul Afian Mokhtar ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Fracture Risk ◽  
Physical Performance ◽  
Tracking System ◽  
Osteoporotic Fractures ◽  
Limited Information ◽  
Functional Impairments ◽  
Mineral Density ◽  
Increased Risk ◽  
Study Results

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&lt;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.

scholarly journals Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

2016 ◽  
Vol 28 (3) ◽  
Author(s):  
Claudia Harper ◽  
Andrea L. Pattinson ◽  
Hamish A. Fernando ◽  
Jessica Zibellini ◽  
Radhika V. Seimon ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Dietary Restriction ◽  
Mineral Density ◽  
Pre Treatment ◽  
Obesity Treatments

AbstractBackground:New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this.Materials and methods:This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction.Results and conclusions:All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%–11% of pre-surgical values) and weakest for dietary restriction (1%–1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) – but not BMD – and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in obesity, suggesting that future research in this field could focus on hip rather than spine BMD. Various mechanisms have been proposed for BMD loss with obesity treatments, notably reduced nutritional intake/absorption and insufficient exercise, and these are potential avenues for protection against bone loss. However, a pressing outstanding question is whether this BMD reduction contributes to increased fracture risk, as has been observed after RYGB, and whether any such increase in fracture risk outweighs the risks of staying obese (unlikely).

Low Bone Mass in Thalassemia: The Thalassemia Clinical Research Network (TCRN) Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3613-3613
Author(s):  
Maria G. Vogiatzi ◽  
Joseph Lane ◽  
Martin Fleisher ◽  
Eric A. Macklin ◽  
Ellen B. Fung ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Turnover ◽  
Bone Disease ◽  
Bone Turnover Markers ◽  
Research Network ◽  
Dietary Calcium Intake ◽  
Low Bone Mass ◽  
Mineral Density ◽  
T Score ◽  
Turnover Markers

Abstract Low bone mass is emerging as a frequent and debilitating morbidity in Thalassemia (thal). The TCRN conducted a cross-sectional observational study to determine the prevalence and factors contributing to bone disease among North American thal patients (pts). Spinal (L1-L4) Bone Mineral Density (BMD) Z- and T-score measurements by DXA (Hologic 4500 and Delphi models) were read centrally. Each subject’s weight, height, hematologic, endocrine and genetic parameters, iron chelation and transfusion regimens, dietary calcium intake, history of fractures and bone pain, self-reported physical activity and bone turnover markers were assessed. BMD was measured in 302 pts: 207 Thal Major (TM), 37 Thal Intermedia (TI), 35 Beta E, 7 Hemoglobin H disease (HbH), 2 homozygous alpha (α) and 14 HbH/Constant Spring (HbH/CS). Among all diagnostic groups, the prevalence of low bone mass (LBM; Z/T <-2), reduced bone mass (RBM; Z/T -2 to -1) and normal bone mass (NBM; Z/T >-1) was 52%, 27% and 21%, respectively. LBM prevalence was 55% in TM, 53% in TI, 51% in Beta E, 0% in HbH, 50% in α and 43% in HbH/CS. RBM prevalence was 26% in TM, 22% in TI, 31% in Beta E, 71% in HbH, 50% in α and 29% in HbH/CS. Pt groups aged: 6–11 yrs, 11–20 yrs, 20+ yrs had Z/T-scores mean±SD[n] were: −1.32±0.82[51], −1.73±1.08[77] and −2.43±1.14[174], respectively. Z/T-scores were significantly lower among older pts (p<.001) and significantly higher among heavier pts after controlling for Tanner stage. Mean age-adjusted Z/T-scores of thal diagnostic groups and their slopes vs. age did not differ significantly although the samples of some groups were small. Among TM and TI pts, those with genotype β°/β° tended to have lower age- and weight-adjusted Z/T-scores (mean [95% CI]: −2.25 [−2.65 to −1.86], n=39). Less than 1% had hypoparathyroidism, 4% vit D deficiency, 8.5% diabetes mellitus, 8.5% hypothyroidism and 11.5% growth hormone deficiency (GHD). Only GHD was significantly correlated with decreased Z/T-scores after controlling for age and diagnosis. Urinary N-telopeptide (NTx) is elevated across all three age groups (median[IQR] mM BCE/mM creatinine: 664[456–930], 302[90–624], 69[34–124]), respectively. Preliminary analysis of bone turnover markers in a subset of subjects (n=114) suggests that NTx, urinary or serum was a significant independent predictor of spine Z/T-scores controlled for age and age-adjusted weight. There was no relationship between Z/T-score and serum osteocalcin. This large and comprehensive study of thal bone disease has demonstrated that decreased bone mass occurs with high frequency, worsens with age, is affected by weight and GHD and is associated with elevated NTx, i.e. increased bone resorption. Future studies are needed to identify efficacious long-term therapies to improve thal bone disease.

Vertebral Abnormalities by Spine Morphometry in Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3829-3829
Author(s):  
Maria Vogiatzi ◽  
Eric Macklin ◽  
Robert Schneider ◽  
Joseph Lane ◽  
Irina Chaikodinov ◽  
...  
Keyword(s):  
Back Pain ◽  
Bone Mass ◽  
Bone Turnover ◽  
Odds Ratio ◽  
Bone Pain ◽  
Research Network ◽  
Cell Transplant ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Negatively Associated

Abstract Background: The Thalassemia Clinical Research Network previously reported a high prevalence of low bone mass in thalassemia (thal) despite current treatment practices. Currently we report the association of vertebral compression fractures (frs) and vertebral (vert) growth disturbances with bone pain, bone mass, bone turnover and therapies in thal. Methods: Vert frs (T10-L4) were assessed by morphometry. Vert compression frs by quantitative assessment (Fr-qt) were defined as anterior or mid-vert hts at least 25% shorter than posterior hts or average vert ht at least 25% shorter than hts of adjacent vert. Frs by qualitative assessment (Fr-ql) and growth plate (GP) abnormalities were determined. Bone mineral density by DXA and bone turnover markers were measured. Results: 353 thal pts were studied 64% beta-thal major (beta-TM) 12% beta-thal Intermedia 11% E/beta-thal 11% HbH 1% alpha thal 1% stem cell transplant pts, mean age 23 (SD 12 yrs, range 6 – 75 yrs). General bone pain and back pain were self-reported for the 30 days prior to morphometry by 34% and 26% pts, respectively. Fr-qt occurred in 41 (12%) and Fr-ql in 9 (2.5%), while only 7 pts (2%) had a history of vertebral fr and prevalence did not differ by type of thal or gender. Fr-qt and Fr-ql prevalence increased with age (Fr-qt p < 0.1; Fr-ql p < 0.001). After controlling for age, lumbar DXA Z or T scores were negatively associated with frs (odds ratio for 1-SD increase: Fr-qt 0.670, 95% CI 0.488 to 0.921, p = 0.01; Fr-ql 0.303, 95% CI 0.125 to 0.730, p < 0.01). Hypertransfusion, yrs or onset of chelation, serum transferrin receptor or ferritin did not correlate with frs after controlling for age. Decreased ht Z score (p < 0.01) and growth hormone deficiency (GHD) (p = 0.01) were associated with higher risk for Fr-qt after correcting for age. Hypogonadism was also associated with Fr-qt but not after correction for age (odds ratio 1.916, 95% CI 0.927 to 3.959 p = 0.08). Presence of Fr-ql but not Fr-qt was correlated with generalized bone and back pain specifically (Fr-ql vs. back pain odds ratio 11.05, 95% CI 2.035 to 110.2, p = 0.001). GP abnormalities were present in 30 pts (9%), including 7 (2%) who also had Fr-qt. Prevalence of GP did not differ by gender but was more common in beta-TM pts (13%), E-beta thal (5%) and among all others (0%) (p=0.04). In beta-TM pts, lumbar DXA Z or T scores (p < 0.01), ht Z scores (p < 0.001) and age that chelation was started (p < 0.01) were all negatively associated with GP abnormalities after controlling for age. Hypogonadism (p = 0.001) and GHD (p = 0.04) were positively associated with GP abnormalities after controlling for age. Presence of GP was not correlated with either general bone pain or back pain specifically. Conclusions: Morphometry identified vert abnormalities in 18% of thal pts. These included moderate to severe vert wedging or GP disturbances. A subgroup of pts (2.5%) also had vert compression frs by radiologic assessment. Morphometry vert lesions were associated with low bone mass. Back pain was strongly correlated with radiologic frs but not with other lesions seen by morphometry.

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