Recent Advances in the Genetics of Fractures in Osteoporosis

Koromani, Fjorda; Trajanoska, Katerina; Rivadeneira, Fernando; Oei, Ling

doi:10.3389/fendo.2019.00337

Cited by 38 publications

(33 citation statements)

References 103 publications

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“…Early reports have indicated that hereditary factors may play a role in PLO. Osteoporotic fractures at younger age more often have a genetic cause (68,69), in contrast to osteoporotic fractures at older ages which are often due to simple postmenopausal osteoporosis. Remarkably, a high prevalence of fractures has been reported in cases of mothers with PLO (70).…”

Section: Geneticsmentioning

confidence: 99%

Pregnancy and lactation, a challenge for the skeleton

Winter

Ireland

Butterfield

et al. 2020

Endocrine Connections

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In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.

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Section: Geneticsmentioning

confidence: 99%

Pregnancy and lactation, a challenge for the skeleton

Winter

Ireland

Butterfield

et al. 2020

Endocrine Connections

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“…With more fracture-related genetic components being discovered, a more significant effect of PGS on fracture risk prediction should be foreseen. Another possible reason for the minor effect of PGS on fracture outcomes observed in the present study is that, similar to other age-related traits, the heritability of fracture risk decreases with age [32]. Since the analytic sample consisted of older women, the effect mediated through genetic influences on bone turnover, and bone geometry or non-skeletal factors such as cognitive function, neuromuscular control, visual acuity, or other factors related to the risk of falling might be more attributable to the predisposition of fracture [33].…”

Section: Discussionmentioning

confidence: 62%

“…However, in the multivariate analysis, genetic profiling was demonstrated not to be a significant predictor of MOF and any fracture, after T-score classification was adjusted for. Prior twin studies demonstrated that the heritable component of fracture is largely independent of BMD [30,31], whereas the reported fracture-related genetic variants are also associated with BMD [32]. Due to the study power issue, GWAS for dichotomous disease as a direct outcome has yielded relatively lower numbers of loci discovered, and this is also the concern for osteoporotic fracture studies as well.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Performance of the WHO International Reference Standard for Osteoporosis Diagnosis in Postmenopausal Women of Varied Polygenic Score and Race

Xiao

2020

JCM

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Background: Whether the bone mineral density (BMD) T-score performs differently in osteoporosis classification in women of different genetic profiling and race background remains unclear. Methods: The genomic data in the Women’s Health Initiative study was analyzed (n = 2417). The polygenic score (PGS) was calculated from 63 BMD-associated single nucleotide polymorphisms (SNPs) for each participant. The World Health Organization′s (WHO) definition of osteoporosis (BMD T-score ≤ −2.5) was used to estimate the cumulative incidence of fracture. Results: T-score classification significantly underestimated the risk of major osteoporotic fracture (MOF) in the WHI study. An enormous underestimation was observed in African American women (POR: 0.52, 95% CI: 0.30–0.83) and in women with low PGS (predicted/observed ratio [POR]: 0.43, 95% CI: 0.28–0.64). Compared to Caucasian women, African American, African Indian, and Hispanic women respectively had a 59%, 41%, and 55% lower hazard of MOF after the T-score was adjusted for. The results were similar when used for any fractures. Conclusions: Our study suggested the BMD T-score performance varies significantly by race in postmenopausal women.

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“…GWAS have revolutionized the field of genetics of complex traits and common diseases, where osteoporosis is no exception. There are several reviews describing in detail the findings arising from the Genetic Factors of Osteoporosis (GEFOS) consortium, and the UK Biobank ( 56 – 58 ). Currently, there are close to thousands of variants associated with increased risk of osteoporosis ( 12 , 59 – 62 ).…”

Section: What Have We Learned From Complex Skeletal Traits?mentioning

confidence: 99%

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Trajanoska

Rivadeneira

2020

Front. Endocrinol.

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Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the drug development process and a molecular redefinition of skeletal disease can help overcoming current shortcomings in pharmaceutical research, including failed attempts and appalling costs. This review summarizes the achievements of genetic studies in the bone field and their application to clinical care, illustrating the imminent advent of the genomic medicine era.

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Recent Advances in the Genetics of Fractures in Osteoporosis

Cited by 38 publications

References 103 publications

Pregnancy and lactation, a challenge for the skeleton

Pregnancy and lactation, a challenge for the skeleton

Evaluating the Performance of the WHO International Reference Standard for Osteoporosis Diagnosis in Postmenopausal Women of Varied Polygenic Score and Race

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

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