Osteoporosis Epigenetics: Write a Background and Review the Case Study (Case Study Sample)

Osteoporosis Epigenetics
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Background and Rationale
In reference to Marini and Brandi (2010), osteoporosis is a lean condition with two major characteristics: low bone mass and bone microarchitectural damage. As a result, the patient is susceptible to spontaneous fractures due to the increased bone fragility hence affecting health regarding morbidity, mortality, and costs. The condition is multifactorial with the environmental factors and genes interacting to affect the bone strength and mass. Jintaridth et al. (2013) argue that fractures of the spine, hip and the wrist were the commonest clinical outcomes. The bone mass density is controlled by the genes with the impact varying across various ethnicities. Copy number variations and single nucleotide polymorphisms are behind the genetic basis of osteoporosis. The environment mediates the susceptibility to the condition at a later stage in life. Delayed menarche, low body weight, Vitamin D insufficiency, smoking, alcohol intake and physical inactivity are associated with reduced bone mass density.
Marini and Brandi (2010) report that the condition affects about thirty percent of women in their postmenopausal period in Europe and the USA. Fragility fracture affects 40% of the affected women in their lifetime compared to the 15-30% of injured men. To develop novel therapies and achieve disease prevention, understanding the individual factors behind the predisposition to osteoporosis is important. The risk factors are divided into modifiable risks depending on lifestyle habits and fixed risks that are innate and not modifiable.
Wu et al. (2013) argue that osteoporotic fractures result in not only increased mortality but also approximately 1% of disabilities caused by prevalent noncommunicable diseases globally. Some of the current interventions narrow down on antiresorptive treatment and hormone replacement therapy. In reference to Wu et al. (2013), in severe osteoporosis, parathyroid hormone peptides are used together with anabolic therapy. Dietary vitamin D and physical exercises are encouraged to reduce the lifetime risk of osteoporosis. For fracture prediction and diagnosis of osteoporosis, the bone mineral density (BMD) is used together with other traits such as bone size, bone geometry and the fracture resulting from the condition.
Osteoporosis is a metabolic bone disease causing devastating psychosocial, physical as well as economic consequences. The imbalance between the activities of the osteoblasts and osteoclasts determine bone remodeling that is controlled by environmental and genetic factors acting together. Despite the problems caused, it is often undertreated and overlooked mainly because it does not depict other prior signs before manifesting as a fracture. With the low rates of diagnosis and treatment, a deeper understanding of the pathophysiology and susceptibility factors is deemed necessary. This paper, therefore, seeks to provide a review of the condition in the United States to facilitate better management. The researcher will present a case study and propose the necessary therapeutic interventions, preventative measures, and implications for the study of current policies relating to osteoporosis.
Literature Review
In reference to Bonjour and Chevalley (2015), puberty maturation played a critical role in bone acquisition. The higher risk of osteoporotic fractures was associated with shorter periods of exposure to estrogen during puberty as peak bone mass is attained. However, the two researchers report that the hypothesis is not yet confirmed by recent prospective studies. Bonjour and Chevalley (2015) indicated that in young adulthood, later menarche was associated with reduced bone mineral density, lower mechanical resistance, and impaired microstructural bone components. The real bone deficit explained why later menarche increased the risk of fractures during adolescence. In healthy persons, bone development and puberty timing shared similar traits such as significant physiological variability and high expression of heritable factors. These are accompanied by the moderate influence of the environmental factors such as physical activity and nutrition. Various conditions modify the processes of bone acquisition and puberty timing that offer the key to understanding the epigenetic basis.
Karasik et al. (2010) examined the degree of similarity between quantitative bone phenotypes associated with the pleiotropic impacts of genetic variants genome-wide. The importance of their study emphasized the need to consider multiple traits to understand the specificity of the bone phenotypic as well as genetic determinants. The study, however, indicates that there is a challenge regarding identifying the reasonable proportion of the variation in different skeletal phenotypes regulated by the same gene.
Karasik et al. (2010) report that contrasting the non-pleiotropic and pleiotropic genes for skeletal phenotypes yields new molecular insights into the fundamental biology of the bone. The genetic relationships within the BMD phenotypic group exceeded the genetic correlations between BMD and heel ultrasound and femoral geometric characteristics. In this case, assumptions made are that the sets of genes contributing to the BMD of the spine and that of the hip and heel geometry were different.
Delgado-Calle and Riancho (2012) report that the cellular expression of OPG and RANKL in the osteoblastic lineage is controlled by the methylation of the genes’ promoter regions. The epigenetic mechanisms define the inheritable variations in the DNA and do not impair the base sequence, hence, can be reversed and are expressed as distinct rhythms of gene expression. The epigenome is the combination of the epigenetic marks, it is dynamic and changes in response to the surrounding at the cellular and individual level.
In reference to Delgado-Calle and Riancho (2012), the three types of epigenetic mechanisms described this far include DNA methylation, microRNAs and the post-translational modification of the histone proteins. DNA methylation plays a repressor role in the CpG islands promoter regions hence blocking the expression of genes. The moment the mechanisms modulate gene expressions are unknown but data seems to suggest the presence of methyl groups inhibits the binding of transcription factors to the targeted sequences. Delgado-Calle and Riancho (2012) argue that the presence of the methyl groups promoted changes in the chromatin hence minimizing the accessibility of critical regions required to initiate the transcription process.
Bocheva and Boyadjieva (2012) argue that the accumulation of minerals is influenced by several factors such as diet, heredity, physical activity, gender, endocrine functions and risk factors such as drug abuse. During intrauterine life, the transfer of nutrients from the placenta has a great influence on the development of bones in fetuses. Several factors such as maternal stress and nutritional state affect the epigenetic state of genes in the fetal development of bones. Histone modifications occur as histone hypermethylation, Histone hypomethylation, and hypoacetylation all involved in the process of remodeling chromatin. In reference to Bocheva and Boyadjieva (2012), chromatin remodeling contributed to the chromosomal epigenetic landscape that influences the bone fetal bone development and osteoporosis. The study found a relationship between epigenetic changes and the transfer of nutrients such as Vitamin D and Calcium and the abnormal fetal bone development and osteoporosis pathogenesis.
Case study
A.L is a 37-year-old African-American female who complains of diffuse brain pain for the last two years. She has a background of fractures on her left arm and right hip. She narrates that the pain has become worse hence preventing her from doing her daily activities as any weight-bearing exercise causes serious discomfort. About 40% of persons diagnosed with fractures complain of constant pains while others have difficulties leading their routine lives. About 80% are unable to provide for themselves followed by reduced quality of life. The incidence of fractures varies with the ethnicity where there is a greater frequency in white women compared to African-American women. The rates of hip fractures in women of Hispanic and Asian decent are lower than the recorded rates in white women (Wright et al., 2012).
This tally is, however, greater than those of black females and the differences are mainly attributed to the differences in skeletal size, microarchitecture, and BMD. Compared to the other ethnicities, African-American women possess greater bone area, enhanced trabecular thickness, cortical thickness and cortical area when compared to Caucasian women thus accounting for more resistance to fracture and increased bone strength (Manolagas, 2010).
The patient is not on any medication or hormone replacement therapy but is well conversant with the need for preventative care. As a result, the patient is vitamin E 400 IU on a daily basis and soy herbal supplements. She does not use alcohol or smoke. She is updated with past mammograms and gynecological exams which indicate standard health maintenance exams. Today is her first complaint. Fragility structures possess a heritable component where the risk of fractures is higher in persons whose patients have had a history of similar conditions. However, the condition itself presents an interplay of genetic inheritance, intrauterine and other shared environmental factors. In her family, her mother has a history of osteoporosis, anxiety, and hypertension and non-insulin dependent diabetes. Her father, though in good health, also has hypertension. The family has no history of arthritis, breast disorders, thyroid or other metabolic diseases.


Hypertension Osteoporosis