Hip Fracture
A hip fracture is a serious break in the upper part of the femur (thigh bone), near the hip joint. These fractures are often caused by falls, particularly in older adults, and can lead to significant pain, loss of mobility, and a decreased quality of life.
Biological Basis
Section titled “Biological Basis”The risk of hip fracture is strongly influenced by bone mineral density (BMD), a complex and highly heritable trait eavor, and current research, primarily relying on genome-wide association studies (GWAS) and related methodologies, faces several inherent limitations. These constraints affect the comprehensiveness and generalizability of findings, influencing how genetic insights are translated into clinical understanding and patient care.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Many genetic association studies are inherently constrained by statistical power, which impacts the ability to robustly identify all genetic variants contributing to hip fracture risk or related traits. Studies may be powered only to detect common variants with small effect sizes, explaining a minimal percentage of trait variance (e.g., approximately 0.2%), meaning that other real effects, particularly those specific to certain age or sex groups, may not be adequately identified[1]. Furthermore, these power limitations often prevent the comprehensive assessment of gene-gene and gene-environment interactions, or the detection of rare alleles that are not effectively captured by the common haplotype tagging approaches typically employed in GWAS. The presence of heterogeneity in genetic effects across different populations, where some markers may not maintain genome-wide significance under random effects models, further underscores the need for larger and more diverse cohorts for thorough evaluation [1].
The process of identifying reliable genetic associations also requires rigorous replication across independent populations. While various studies employ both in silico and de novo replication strategies, challenges arise when markers show significant heterogeneity, failing to reach genome-wide significance in all analyses [2]. This highlights the importance of consistent replication to confirm initial findings and ensure their robustness. Without sufficient power and consistent replication across varied cohorts, the full genetic landscape influencing hip fracture risk, including the contributions of rare alleles and complex interactions, remains incompletely mapped.
Generalizability and Phenotype Definition
Section titled “Generalizability and Phenotype Definition”A significant limitation in current genetic research for hip fracture and related traits is the imbalance in population representation. Many large-scale genetic studies have historically focused predominantly on populations of European ancestry[2], while other ancestries, such as African [3] and Hispanic [4]populations, have been less extensively studied, especially concerning hip fracture. This ancestral bias limits the generalizability of findings, as genetic risk factors identified in one population may not be equally relevant or effective in others due to differing genetic backgrounds, linkage disequilibrium patterns, and environmental exposures. Consequently, the development of universally applicable genetic risk prediction models for hip fracture is hindered.
Furthermore, direct genetic studies of hip fracture incidence are often limited, with many insights derived from surrogate phenotypes like bone mineral density (BMD) or hip bone size[5]. While these traits are highly heritable and fundamental to bone strength, a substantial portion of their genetic variance remains unexplained, and critically, many identified BMD-associated variants appear to contribute minimally to actual fracture risk[6]. This disconnect indicates a significant knowledge gap, as genetic determinants of bone density may not fully capture the complex biological pathways and biomechanical factors that culminate in hip fracture susceptibility. Understanding the specific genetic variants that directly influence fracture risk, beyond their effects on BMD, is crucial.
Complex Genetic Architecture and Environmental Factors
Section titled “Complex Genetic Architecture and Environmental Factors”Despite the identification of numerous genetic loci, a considerable portion of the genetic variance for traits relevant to hip fracture, such as BMD, remains unexplained, a phenomenon often referred to as “missing heritability”[6]. This suggests that current genetic models may not fully account for the complex interplay of genetic factors, including contributions from rare variants, structural variations, and intricate gene-gene interactions. The limited power of many studies to comprehensively investigate such complex interactions means that a complete picture of the genetic architecture of hip fracture risk, including how multiple genes might jointly influence susceptibility, is still emerging[1].
Beyond genetic factors, environmental and lifestyle influences play a critical role in hip fracture risk. While studies often adjust for basic covariates like age, sex, height, and weight[7], the full spectrum of environmental confounders and their complex interactions with genetic predispositions is challenging to capture and model comprehensively. Factors such as nutrition, physical activity, medication use, and exposure to specific environmental stressors can significantly modify genetic effects, but their detailed integration into genetic analyses is often limited. Unaccounted environmental factors or unmodeled gene-environment interactions can lead to an incomplete understanding of hip fracture etiology and limit the precision of genetic risk prediction.
Variants
Section titled “Variants”Genetic variants play a crucial role in influencing bone mineral density (BMD), bone geometry, and ultimately, the risk of hip fracture. Many genes involved in diverse biological processes, from lipid metabolism to skeletal development and gene regulation, contribute to the complex genetic architecture of bone health. Understanding these variants can provide insights into the underlying mechanisms of osteoporosis and fracture susceptibility.
The APOE gene, encoding Apolipoprotein E, is central to lipid metabolism and cholesterol transport, and thers429358 variant is one of two key single nucleotide polymorphisms (SNPs) that define the APOE isoforms (E2, E3, E4). The T allele ofrs429358 is particularly associated with the APOE4 isoform, which has implications for various age-related conditions. Given bone’s dynamic metabolic activity and the significance of lipid signaling in the function of bone cells, variations in APOE can indirectly affect bone mineral density and its microarchitecture. Lower BMD, especially in the femoral neck, is a well-established risk factor for hip fractures[1]. Extensive genetic studies have identified numerous loci associated with femoral neck BMD and overall fracture risk, underscoring the intricate genetic factors that govern bone strength[6].
Other variants impact genes critical for skeletal development and cellular regulation. The rs4142680 variant is located within a region containing the HOXC8 and HOXC6 genes, which are members of the Homeobox (HOX) gene family. HOX genes are fundamental transcription factors that direct the patterning and development of the skeleton during embryonic stages. Alterations caused by variants like rs4142680 could subtly modify the precise expression of these genes, potentially affecting bone growth, morphology, and long-term strength. Similarly,rs35339719 is found near SPINK2 and REST, genes with roles in cellular processes relevant to bone. SPINK2 encodes a protease inhibitor, crucial for the remodeling of the extracellular matrix in bone, while REST is a transcriptional repressor involved in cell differentiation. Genetic variations influencing key signaling pathways, such as the Hedgehog and Wnt pathways, are known to modulate bone density and fracture risk[8]. These genetic contributions are vital for dissecting the complex heritability of osteoporosis and individual susceptibility to fractures[5].
Furthermore, variants in non-coding regions, such as rs11088458 and rs62028332 , highlight the regulatory complexity of bone health. These variants are situated in areas containing long intergenic non-coding RNAs (lincRNAs), specifically LINC01700, LINC02940, LINC02128, and LINC02127. LincRNAs do not produce proteins but instead act as crucial regulatory molecules influencing gene expression, chromatin modification, and various cellular pathways, including those involved in tissue development and maintenance. Although their exact functions in bone metabolism are still under investigation, changes in lincRNA expression or activity due to genetic variants could affect the differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts, or impact the overall structural integrity of bone. Research frequently identifies novel genetic loci, including those in non-coding regions, that contribute to variations in bone mass and susceptibility to conditions like hip osteoarthritis and related bone traits[9].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs429358 | APOE | cerebral amyloid deposition measurement Lewy body dementia, Lewy body dementia measurement high density lipoprotein cholesterol measurement platelet count neuroimaging measurement |
| rs11088458 | LINC01700 - LINC02940 | heel bone mineral density osteoporosis Drugs affecting bone structure and mineralization use measurement bone fracture hip fracture |
| rs62028332 | LINC02128 - LINC02127 | heel bone mineral density femoral neck bone mineral density bone fracture hip fracture bone tissue density |
| rs4142680 | HOXC8, HOXC6 | hip fracture |
| rs35339719 | SPINK2 - REST | hip fracture |
Definition and Anatomical Considerations of Hip Fracture
Section titled “Definition and Anatomical Considerations of Hip Fracture”A hip fracture is primarily defined as a break in the upper part of the femur, or thigh bone, specifically in the region around the hip joint[1]. The femoral neck is identified as a common site for such fractures, underscoring the anatomical focus of this injury [1]. Beyond the direct fracture, the structural integrity and geometry of the femur itself are critical determinants of hip fracture susceptibility. Specific measurements at the “narrow neck” region of the hip, such as the narrow neck section modulus (NeckZr) and narrow neck width (NeckWr), provide valuable insights into bone strength and shape[5]. Simple measurements of this femoral geometry have been clinically shown to predict the risk of hip fracture[10].
Related conditions affecting the hip, such as hip osteoarthritis (OA), are characterized by distinct diagnostic criteria. These often include persistent pain experienced in the groin and hip region over an extended period, in conjunction with radiographic evidence[9]. Such evidence may manifest as femoral or acetabular osteophytes (bone spurs), or axial joint space narrowing observed on radiography[9]. In some cases, a history of joint replacement specifically due to osteoarthritis serves as a definitive diagnostic marker[9].
Diagnostic and Measurement Criteria for Fracture Risk
Section titled “Diagnostic and Measurement Criteria for Fracture Risk”The assessment of hip fracture risk largely relies on objective diagnostic and measurement criteria, primarily focusing on bone mineral density (BMD). BMD is typically measured at critical skeletal sites, namely the femoral neck of the hip and the lumbar spine[1]. These measurements are crucial because BMD at different skeletal sites is highly correlated and collectively predictive of fracture risk across the skeleton [1]. The clinical significance of BMD lies in its ability to quantify bone mass, a key factor in determining bone strength and resilience against fractures[1].
Beyond traditional BMD measurements, other quantitative approaches contribute to a comprehensive risk assessment. Quantitative ultrasound (QUS) measures, such as broadband ultrasound attenuation (BUA) of the calcaneus, offer an alternative, non-invasive method to evaluate bone quality[5]. Furthermore, specific femoral geometry measures, including the narrow neck section modulus (NeckZr) and narrow neck width (NeckWr), provide additional insights into the structural characteristics of the hip bone, which are independent of bone density and hip axis length[5]. These detailed geometric analyses contribute to a more nuanced understanding of an individual’s predisposition to hip fracture.
Classification of Bone Health and Osteoarthritis
Section titled “Classification of Bone Health and Osteoarthritis”Bone mineral density (BMD) is recognized as a complex and highly heritable trait, playing a fundamental role in classifying an individual’s overall bone health and predisposition to fractures[1]. The presence of reduced bone mass is a critical factor in categorizing individuals at elevated risk for osteoporotic fractures, which commonly affect the spine and hip[11]. This reduction in bone density is closely associated with an increased likelihood of experiencing these types of fractures[12].
For hip osteoarthritis (OA), a distinct classification system is employed, integrating clinical and radiological findings. Diagnostic criteria for hip OA often include a Kellgren-Lawrence (KL) grade of 2 or higher, which signifies observable degenerative changes on radiographs[9]. Alternatively, a minimal joint space width of 2.5 mm or less, or a combination of joint space narrowing grade of 2 or higher with any osteophyte of grade 1 or higher, are also used as definitive criteria for classifying the condition [9]. These classifications are essential for grading the severity and progression of hip OA, a condition that can significantly impact mobility and quality of life.
Bone Health Assessment and Fracture Prediction
Section titled “Bone Health Assessment and Fracture Prediction”The assessment of hip fracture risk and underlying bone health primarily relies on objective measurement approaches focusing on bone mineral density (BMD) and specific bone geometries. BMD, typically measured at the hip (specifically the femoral neck) and the lumbar spine, serves as a crucial diagnostic tool, as these are common sites for fractures . Genome-wide association studies (GWAS) have identified numerous common genetic variants and at least 71 loci associated with BMD, including specific genes like WLS and CCDC170/ESR1; however, these variants individually explain only a modest portion of the genetic variance[6]. Beyond BMD, genetic factors also govern bone geometry and size, such as the PLCL1 gene’s influence on hip bone size in females, and anthropometric traits like height, weight, body mass index (BMI), and body fat distribution, which are themselves highly heritable and genetically correlated with BMD[13]. These polygenic predispositions contribute to an elevated familial relative risk of fragility fracture for individuals with an affected first-degree relative [6].
Further complexity arises from sex-specific genetic regulation of bone mass and density, with studies identifying distinct genetic loci, such as SPTB and IZUMO3, that influence pediatric bone mineral density at multiple skeletal sites in a sex-dependent manner[14]. Genetic variants related to obesity and body fat distribution have also been identified in various populations, including Hispanic and African ancestries, highlighting the diverse genetic architecture underlying these traits that can indirectly impact bone health and fracture susceptibility[4]. The interplay of these numerous genetic factors, potentially involving pleiotropic effects where single genes influence multiple traits, contributes to an individual’s overall skeletal fragility and susceptibility to hip fracture[6].
Developmental and Early Life Determinants
Section titled “Developmental and Early Life Determinants”Early life conditions and developmental processes lay the foundation for bone health and can significantly influence hip fracture risk later in life. Developmental dysplasia of the hip (DDH), a condition characterized by abnormal formation of the hip joint, is a significant risk factor for subsequent hip osteoarthritis and potentially fracture[15]. Both genetic and environmental factors are known to contribute to the etiology of DDH, with specific genetic variants, such as a common variant of the ubiquinol-cytochrome c reductase complex, having been associated with its occurrence [15]. Perinatal risk factors also play a role in the development of DDH, underscoring the importance of early life events in shaping hip joint integrity [15]. Additionally, bone mineral density established during childhood, which exhibits sexual dimorphism even in newborn vertebrae, can set a trajectory for skeletal strength throughout life, implying that early influences on bone accrual are critical[14].
Lifestyle, Comorbidities, and Age-Related Changes
Section titled “Lifestyle, Comorbidities, and Age-Related Changes”Environmental and lifestyle factors significantly modulate hip fracture risk, often interacting with an individual’s genetic predispositions. Age is a primary and unavoidable risk factor, as bone mass and geometry naturally change over time, leading to increased fragility[7]. Lifestyle choices such as physical activity levels, dietary habits, and exposure to factors like smoking can influence anthropometric traits such as adiposity and overall bone health[16]. Comorbidities also play a crucial role; for instance, hip osteoarthritis, which itself is influenced by genetic variants, is a known risk factor for hip fracture[2]. While specific medication effects are not detailed, the collective impact of an individual’s health status and environmental exposures throughout life critically shapes their susceptibility to hip fractures.
Interplay of Genes and Environment
Section titled “Interplay of Genes and Environment”The etiology of hip fracture is complex, resulting from intricate gene-environment interactions where genetic predispositions are modulated by lifestyle and environmental exposures. Research indicates significant genetic and environmental contributions to bone mass and related traits, emphasizing that neither factor acts in isolation[5]. For example, genetic variants influencing adiposity can interact with physical activity levels, demonstrating how lifestyle choices can modify genetically influenced traits relevant to fracture risk[16]. The overall risk of hip fracture is thus a product of an individual’s inherited skeletal architecture, their developmental history, and the cumulative impact of their environment and health behaviors over time[6].
Biological Background
Section titled “Biological Background”Hip fractures represent a significant public health concern, often resulting from a complex interplay of biological factors that compromise bone strength and structure. These factors range from fundamental molecular and cellular processes governing bone health to systemic influences from other organs and genetic predispositions. Understanding these intricate biological mechanisms is crucial for comprehending the susceptibility to hip fractures.
Bone Homeostasis and Structural Integrity
Section titled “Bone Homeostasis and Structural Integrity”Bone is a dynamic tissue continually undergoing remodeling, a process vital for maintaining its mechanical strength and structural integrity. This involves a delicate balance between bone-forming osteoblasts, which synthesize new bone matrix, and bone-resorbing osteoclasts, which break down old bone. Disruptions in this homeostatic balance, such as an imbalance favoring resorption, can lead to reduced bone mass and increased fragility, a primary factor in hip fracture susceptibility[5]. For instance, the fibroblast growth factor-2 (FGF-2) gene plays a role in bone formation, and its disruption can result in decreased bone mass, highlighting the importance of growth factors in bone health[15].
The structural properties of the hip, including femoral geometry and hip bone size, are critical determinants of fracture risk. Genetic variations can influence these structural aspects; for example, thePLCL1gene has been identified in association with hip bone size variation in females[7]. Understanding the molecular and cellular pathways that regulate bone formation, resorption, and overall bone architecture is essential for comprehending the biological underpinnings of hip fracture.
Genetic and Epigenetic Determinants of Bone Health
Section titled “Genetic and Epigenetic Determinants of Bone Health”Genetic mechanisms significantly contribute to an individual’s susceptibility to hip fractures by influencing bone mineral density (BMD), bone geometry, and overall bone strength. Genome-wide association studies (GWAS) have identified specific genes and regulatory elements associated with these traits. For example, sequence variants in thePTCH1gene have been linked to spine bone mineral density and osteoporotic fractures, demonstrating a direct genetic influence on bone fragility[8].
Furthermore, genetic influences on bone mass can exhibit sex-specific patterns, indicating sexual dimorphism in bone regulation. Research has identified sex-specific loci, such asSPTB and IZUMO3, that influence pediatric bone mineral density at multiple skeletal sites from early life[14]. This dimorphism extends to anthropometric traits and body fat distribution, where distinct genetic loci are found to operate differently between sexes, impacting overall skeletal loading and fracture risk [17].
Systemic Metabolic and Adipose Tissue Influences
Section titled “Systemic Metabolic and Adipose Tissue Influences”Beyond direct bone-related genes, systemic metabolic processes and the biology of adipose tissue play a crucial role in hip fracture risk. New genetic loci have been identified that link adipose and insulin biology to body fat distribution, suggesting that metabolic health and how fat is stored can influence skeletal health[18]. For instance, traits like waist-hip ratio, a measure of body fat distribution, are influenced by genetic variants, with some loci showing sexual dimorphism[17].
Obesity, characterized by excess adipose tissue, is a complex trait with genetic underpinnings[4]. While increased body weight might initially seem protective for bone density due to increased mechanical loading, the metabolic consequences of obesity, including altered insulin sensitivity and inflammation, can negatively impact bone quality and contribute to fracture risk. Anthropometric traits, encompassing body size and composition, are also influenced by numerous genetic loci and can indirectly affect bone loading and fracture susceptibility[13].
Pathophysiological Processes Leading to Bone Fragility
Section titled “Pathophysiological Processes Leading to Bone Fragility”Hip fractures are often the culmination of various pathophysiological processes that compromise bone integrity over time. Osteoporosis, characterized by low bone mass and microarchitectural deterioration of bone tissue, is a primary contributor to increased fracture risk[5]. The molecular and genetic mechanisms underlying osteoporosis involve complex regulatory networks affecting bone cell function and overall bone architecture.
Conditions such as osteoarthritis of the hip also contribute to fracture susceptibility by altering joint mechanics and potentially influencing surrounding bone quality[2]. Additionally, developmental processes, such as developmental dysplasia of the hip (DDH), which has been linked to variants in the ubiquinol-cytochrome c reductase complex, can predispose individuals to abnormal hip structure and subsequent fracture risk [15]. Cellular functions like apoptosis, mediated by factors such as STAT1, can also play a role in bone health by influencing bone cell survival and turnover[15].
Genetic Regulation of Bone Structure and Density
Section titled “Genetic Regulation of Bone Structure and Density”Genetic factors play a fundamental role in determining bone mineral density (BMD) and overall bone integrity, directly impacting the risk of hip fracture. Variants within genes such asPTCH1have been associated with spine BMD and susceptibility to osteoporotic fractures . These genetic insights are valuable for identifying individuals at a higher predisposition for hip fracture, allowing for targeted early intervention.
Furthermore, the prognostic value of genetic profiling is evident in assessments of compound allelic scores and their association with fracture risk, suggesting that genetic markers can help predict an individual’s susceptibility to fractures [1]. This enables personalized medicine, where individuals are stratified based on their genetic risk profile, guiding tailored preventive strategies. The discovery of sex-specific genetic loci influencing pediatric bone mineral density at multiple skeletal sites also underscores the importance of considering sex-specific genetic factors in comprehensive risk assessment and prevention across different life stages[14].
Clinical Applications in Diagnosis and Treatment
Section titled “Clinical Applications in Diagnosis and Treatment”Genetic discoveries hold promise for enhancing the diagnostic utility in assessing hip fracture risk. Identifying specific genetic variants linked to bone mineral density and hip geometry can supplement conventional clinical evaluations, offering a more thorough risk profile for patients[5]. For instance, insights into genetic influences on anthropometric traits and body fat distribution, which are recognized risk factors for falls and can impact bone health, contribute to a more holistic diagnostic framework[13].
In the realm of treatment selection and monitoring, genetic information can facilitate the development of tailored interventions. Individuals with particular genetic predispositions to lower bone density might benefit from more aggressive prophylactic treatments or specialized monitoring protocols. The identification of sex-specific loci affecting bone mineral density suggests that treatment strategies could be optimized based on an individual’s unique genetic and sex-specific characteristics, moving towards more precise and effective patient care[14].
Comorbidities and Genetic Associations
Section titled “Comorbidities and Genetic Associations”Hip fracture frequently occurs in conjunction with or is influenced by other medical conditions and underlying genetic predispositions. For example, a meta-analysis of genome-wide association studies has pinpointed novel genetic variants associated with osteoarthritis of the hip, indicating an overlapping genetic architecture between these conditions[2]. Recognizing these associations is vital for improving patient care by addressing comorbidities that may elevate fracture risk or complicate the recovery process.
Beyond direct bone health, anthropometric traits and body fat distribution, which are significantly shaped by genetics, also play a relevant role. Genome-wide studies have identified numerous loci influencing these traits, noting sex-specific effects and variations across different ancestries[13]. These factors can indirectly affect hip fracture risk by influencing bone loading, the likelihood of falls, and overall metabolic health, thereby illustrating the complex interplay of genetic and environmental elements in an individual’s vulnerability.
Frequently Asked Questions About Hip Fracture
Section titled “Frequently Asked Questions About Hip Fracture”These questions address the most important and specific aspects of hip fracture based on current genetic research.
1. My mom fractured her hip; does that mean I will too?
Section titled “1. My mom fractured her hip; does that mean I will too?”Your mom’s hip fracture does indicate a potentially higher risk for you, as bone mineral density (BMD), a major factor in fracture risk, is highly heritable. This means you might share some of the genetic predispositions that influenced her bone strength. However, it’s not a guarantee, and other factors also play a role.
2. Can I make my bones stronger even if my family has weak ones?
Section titled “2. Can I make my bones stronger even if my family has weak ones?”While genetics strongly influence your bone mineral density and hip structure, you can absolutely take steps to support your bone health. Maintaining a healthy lifestyle, including weight-bearing exercise and a diet rich in bone-supporting nutrients, can help optimize your bone strength and potentially lower your risk, even with a family history.
3. Why might my bone density be different from my brother’s?
Section titled “3. Why might my bone density be different from my brother’s?”There are sex-specific genetic factors that influence bone mass. Research shows different genetic loci can affect bone density in males and females. So, even within the same family, genetic differences related to sex can contribute to variations in bone density.
4. Does my ancestry change my hip fracture risk?
Section titled “4. Does my ancestry change my hip fracture risk?”Yes, your ancestry can influence your genetic risk. Many large-scale genetic studies have focused mainly on populations of European ancestry, meaning the identified risk factors might not be equally relevant or effective in other populations like African or Hispanic ancestries. This ancestral bias limits the generalizability of findings, making ancestry an important consideration.
5. Is there a special test to know my hip fracture risk?
Section titled “5. Is there a special test to know my hip fracture risk?”Yes, the primary diagnostic tool is a bone mineral density (BMD) measurement, typically taken at your hip and lumbar spine. This measurement helps identify individuals at higher risk. Future genetic tests might offer even more precise risk prediction.
6. Why do some people seem to have naturally strong bones?
Section titled “6. Why do some people seem to have naturally strong bones?”Bone mineral density (BMD) is a complex and highly heritable trait, meaning a significant portion of your bone strength is determined by your genes. Individuals with naturally strong bones often have genetic variations, including in genes likeZBTB40 or GPR177, that contribute to higher BMD and robust bone metabolism.
7. Are women just more prone to hip fractures genetically?
Section titled “7. Are women just more prone to hip fractures genetically?”Studies have shown there’s sex-specific genetic regulation of bone mass. This means certain genetic factors influence bone density differently in males and females. While hip fractures are more common in older women, some of this difference is rooted in these distinct genetic influences on bone health.
8. Does aging automatically mean my bones will weaken?
Section titled “8. Does aging automatically mean my bones will weaken?”While hip fractures are more common in older adults, it’s not an automatic guarantee of severe bone weakening for everyone. However, age is a significant risk factor, and maintaining good bone mineral density throughout life becomes increasingly important to counteract age-related bone changes and reduce fracture susceptibility.
9. If my family has weak bones, can I still prevent a fracture?
Section titled “9. If my family has weak bones, can I still prevent a fracture?”Yes, absolutely. While your genetic background, including genes like CTNNB1 or ESR1, heavily influences your bone mineral density, you can still take proactive steps. Regular physical activity, a balanced diet, and discussing your family history with your doctor for appropriate screenings can help manage your risk.
10. Why do doctors focus on my hip’s shape and size for risk?
Section titled “10. Why do doctors focus on my hip’s shape and size for risk?”Beyond just bone density, the actual geometry of your hip, including factors like the neck-shaft angle, femoral neck length, and width, also contributes to how susceptible you are to a fracture. These structural elements can be influenced by genetics and are important predictors of risk.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Rivadeneira F et al. “Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.”Nat Genet, vol. 41, no. 10, Oct. 2009, pp. 1199-206. PMID: 19801982.
[2] Evangelou E et al. “A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip.”Ann Rheum Dis, vol. 73, no. 7, July 2014, pp. 1321-28. PMID: 23989986.
[3] Liu CT et al. “Genome-wide association of body fat distribution in African ancestry populations suggests new loci.” PLoS Genet, vol. 9, no. 8, Aug. 2013, e1003681. PMID: 23966867.
[4] Comuzzie AG et al. “Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.”PLoS One, vol. 7, no. 12, 2012, e51954. PMID: 23251661.
[5] Kiel DP et al. “Genome-wide association with bone mass and geometry in the Framingham Heart Study.”BMC Med Genet, vol. 8, 2007, p. 62. PMID: 17903296.
[6] Mullin, B. H., et al. “Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.”BMC Genomics, vol. 17, 2016, p. 165. PMID: 26911590.
[7] Liu, Y. Z. et al. “Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study.”PLoS One, vol. 3, no. 9, 2008, e3160. PMID: 18776929.
[8] Styrkarsdottir, U. “Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.”Nat Commun, vol. 7, 2016, p. 10428.
[9] Castano-Betancourt, M. C., et al. “Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.”PLoS Genetics, vol. 12, no. 10, 2016, p. e1006276.
[10] Faulkner, K. G., et al. “Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures.”Journal of Bone and Mineral Research, vol. 8, no. 10, 1993, pp. 1211-1217.
[11] Kroger, H., et al. “Bone density reduction in various measurement sites in men and women with osteoporotic fractures of spine and hip.”Osteoporosis International, vol. 7, no. 5, 1997, pp. 390-406.
[12] Cummings, S. R., et al. “Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group.”Lancet, vol. 341, no. 8837, 1993, pp. 72-75.
[13] Berndt SI et al. “Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.” Nat Genet, vol. 45, no. 5, May 2013, pp. 501-12. PMID: 23563607.
[14] Chesi A et al. “A Genomewide Association Study Identifies Two Sex-Specific Loci, at SPTB and IZUMO3, Influencing Pediatric Bone Mineral Density at Multiple Skeletal Sites.”J Bone Miner Res, vol. 33, no. 6, June 2018, pp. 1047-56. PMID: 28181694.
[15] Sun, Y. et al. “A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.” PLoS One, vol. 10, no. 4, 2015, e0121110. PMID: 25848760.
[16] Graff, M., et al. “Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.”PLoS Genet, vol. 13, no. 4, 2017, e1006528.
[17] Heid, I. M. et al. “Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.”Nat Genet, vol. 42, no. 11, 2010, pp. 949-60. PMID: 20935629.
[18] Shungin D et al. “New genetic loci link adipose and insulin biology to body fat distribution.”Nature, vol. 518, no. 7538, Feb. 2015, pp. 187-96. PMID: 25673412.