The Influence of Thyroid Pathology on Osteoporosis and Fracture Risk: A Review

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.

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The Impact of Diabetes and Diabetes Medications on Bone Health

Endocrine Reviews ◽

10.1210/er.2012-1042 ◽

2015 ◽

Vol 36 (2) ◽

pp. 194-213 ◽

Cited By ~ 83

Author(s):

Matthew P. Gilbert ◽

Richard E. Pratley

Keyword(s):

Animal Models ◽

Fracture Risk ◽

Bone Metabolism ◽

Bone Health ◽

Limited Information ◽

Mineral Density ◽

Increased Risk ◽

Increase Fracture Risk ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

The Impact

Abstract Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures despite increased body weight and normal or higher bone mineral density. The mechanisms by which T2DM increases skeletal fragility are unclear. It is likely that a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality, contributes to the increased fracture risk. Drugs for the treatment of T2DM may also impact on the risk for fractures. For example, thiazolidinediones accelerate bone loss and increase the risk of fractures, particularly in older women. In contrast, metformin and sulfonylureas do not appear to have a negative effect on bone health and may, in fact, protect against fragility fracture. Animal models indicate a potential role for incretin hormones in bone metabolism, but there are only limited data on the impact of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists on bone health in humans. Animal models also have demonstrated a role for amylin in bone metabolism, but clinical trials in patients with type 1 diabetes with an amylin analog (pramlintide) have not shown a significant impact on bone metabolism. The effects of insulin treatment on fracture risk are inconsistent with some studies showing an increased risk and others showing no effect. Finally, although there is limited information on the latest class of medications for the treatment of T2DM, the sodium-glucose co-transporter-2 inhibitors, these drugs do not seem to increase fracture risk. Because diabetes is an increasingly common chronic condition that can affect patients for many decades, further research into the effects of agents for the treatment of T2DM on bone metabolism is warranted. In this review, the physiological mechanisms and clinical impact of diabetes treatments on bone health and fracture risk in patients with T2DM are described.

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Iatrogenic lesions of the skeleton

Osteoporosis and Bone Diseases ◽

10.14341/osteo12249 ◽

2017 ◽

Vol 20 (4) ◽

pp. 19-25

Author(s):

Galina A. Melnichenko ◽

Elizaveta O. Mamedova

Keyword(s):

Risk Factors ◽

Fracture Risk ◽

Bone Metabolism ◽

Negative Impact ◽

Public Health Problem ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Level Of Evidence ◽

Important Public Health Problem

Osteoporotic fractures are an important public health problem due to their negative impact on the quality of life and life expectancy, as well as high cost of treatment and rehabilitation. Along with the major risk factors for osteoporotic fractures, such as low bone mineral density (BMD), age, low body weight, frequent falls and previous fractures, an important secondary risk factor, especially among susceptible individuals, is taking certain medications. The difficulty in assessing fracture risk when taking various drugs, as well as the development of appropriate methods of prevention and treatment, is often due to the absence of large randomized trials with a sufficient level of evidence, as well as the heterogeneity of the main risk factors for fractures in studied groups of patients. We focus on the main groups of drugs for which there is evidence of a negative impact on bone metabolism, BMD and fracture risk. In addition to drugs, bone metabolism is also influenced by bariatric surgery, transplantation of solid organs, gonadectomy for various diseases. This article is the RePrint from the original publication in Obesity and Metabolism 2016; 13(2); pp. 41-47. doi: 10.14341/omet2016241-47

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Selenium: A Trace Element for a Healthy Skeleton - A Narrative Review

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200628030913 ◽

2020 ◽

Vol 20 ◽

Author(s):

Fabio Vescini ◽

Iacopo Chiodini ◽

Andrea Palermo ◽

Roberto Cesareo ◽

Vincenzo De Geronimo ◽

...

Keyword(s):

Bone Mass ◽

Bone Metabolism ◽

Bone Cells ◽

Fragility Fractures ◽

Serum Selenium ◽

Mineral Density ◽

Increased Risk ◽

Serum Selenium Levels ◽

Essential Nutrient ◽

The Relationship

: 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.

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Bone Health in Adults Treated with Endocrine Therapy for Early Breast or Prostate Cancer

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2015.35.e567 ◽

2015 ◽

pp. e567-e574 ◽

Cited By ~ 7

Author(s):

Catherine H. Van Poznak

Keyword(s):

Prostate Cancer ◽

Vitamin D ◽

Bone Resorption ◽

Endocrine Therapy ◽

Sex Hormones ◽

Bone Health ◽

Estrogen Therapy ◽

Fragility Fractures ◽

Mineral Density ◽

Increased Risk

Bone is a hormonally responsive organ. Sex hormones and calcium regulating hormones, including parathyroid hormone, 1–25 dihydroxy vitamin D, and calcitonin, have effects on bone resorption and bone deposition. These hormones affect both bone quality and bone quantity. The sex hormone estrogen inhibits bone resorption, and estrogen therapy has been developed to prevent and treat osteoporosis. Androgens are an important source of estrogen through the action of the enzyme aromatase and may themselves stimulate bone formation. Hence, the sex steroids play a role in bone metabolism. Breast cancer and prostate cancer are frequently hormonally responsive and may be treated with antiestrogens or antiandrogens respectfully. In addition, chemotherapy and supportive medications may alter the patient's endocrine system. In general, the suppression of sex hormones has a predictable affect on bone health, as seen by loss of bone mineral density and increased risk of fragility fractures. The bone toxicity of cancer-directed endocrine therapy can be mitigated through screening, counseling on optimization of calcium and vitamin D intake, exercise, and other lifestyle/behavioral actions, as well as the use of medications when the fracture risk is high. Maintaining bone health in patients who are treated with endocrine therapy for breast and prostate cancer is the focus of this review.

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Genetics of osteoporosis

Proceedings of The Nutrition Society ◽

10.1017/s002966510700540x ◽

2007 ◽

Vol 66 (2) ◽

pp. 158-165 ◽

Cited By ~ 46

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.

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Bone Quality in CKD Patients: Current Concepts and Future Directions – Part I

Kidney Diseases ◽

10.1159/000515534 ◽

2021 ◽

pp. 1-10

Author(s):

Kamyar Asadipooya ◽

Mohamed Abdalbary ◽

Yahya Ahmad ◽

Elijah Kakani ◽

Marie-Claude Monier-Faugere ◽

...

Keyword(s):

Fracture Risk ◽

Bone Quality ◽

Bone Health ◽

New Technologies ◽

Trabecular Bone Score ◽

Qualitative Assessment ◽

Mineral Density ◽

Tissue Quality ◽

Ample Evidence ◽

Increased Risk

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD in CKD patients. Bone quality and fracture risk in CKD patients can be better assessed by utilizing new technologies such as trabecular bone score and high-resolution imaging studies. Additionally, invasive assessments such as bone histology and micro-indentation are useful counterparts in the evaluation of bone quality. Summary: A precise diagnosis of the underlying skeletal abnormalities in CKD patients is crucial to prevent further bone loss and fractures. We must consider bone quantity and quality abnormalities for management of CKD patients. Here in this part I, we are focusing on advances in bone quality diagnostics that are expected to help in proper understanding of the bone health in CKD patients. Key Messages: Assessment of bone quality and quantity in CKD patients is essential. Both noninvasive and invasive techniques for the assessment of bone quality are available.

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B-vitamins and bone in health and disease: the current evidence

Proceedings of The Nutrition Society ◽

10.1017/s0029665114000044 ◽

2014 ◽

Vol 73 (2) ◽

pp. 330-339 ◽

Cited By ~ 19

Author(s):

M. Clarke ◽

M. Ward ◽

J. J. Strain ◽

L. Hoey ◽

W. Dickey ◽

...

Keyword(s):

Fracture Risk ◽

Coeliac Disease ◽

Bone Health ◽

B Vitamins ◽

Current Evidence ◽

Mineral Density ◽

Vitamin Status ◽

Increased Risk ◽

Health And Disease ◽

B Vitamin

Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

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Thyroid Hormone Diseases and Osteoporosis

Journal of Clinical Medicine ◽

10.3390/jcm9041034 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1034 ◽

Cited By ~ 1

Author(s):

Alessandro P. Delitala ◽

Angelo Scuteri ◽

Carlo Doria

Keyword(s):

Bone Turnover ◽

Thyroid Hormones ◽

Bone Metabolism ◽

Postmenopausal Women ◽

Overt Hypothyroidism ◽

Subclinical Hyperthyroidism ◽

Mineral Density ◽

Risk Of Fracture ◽

Increased Risk ◽

Bone Structures

Thyroid hormones are essential for normal skeletal development and normal bone metabolism in adults but can have detrimental effects on bone structures in states of thyroid dysfunction. Untreated severe hyperthyroidism influences the degree of bone mass and increases the probability of high bone turnover osteoporosis. Subclinical hyperthyroidism, defined as low thyrotropin (TSH) and free hormones within the reference range, is a subtler disease, often asymptomatic, and the diagnosis is incidentally made during screening exams. However, more recent data suggest that this clinical condition may affect bone metabolism resulting in decreased bone mineral density (BMD) and increased risk of fracture, particularly in postmenopausal women. The main causes of exogenous subclinical hyperthyroidism are inappropriate replacement dose of thyroxin and TSH suppressive L-thyroxine doses in the therapy of benign thyroid nodules and thyroid carcinoma. Available data similarly suggest that a long-term TSH suppressive dose of thyroxin may decrease BMD and may induce an increased risk of fracture. These effects are particularly observed in postmenopausal women but are less evident in premenopausal women. Overt hypothyroidism is known to lower bone turnover by reducing both osteoclastic bone resorption and osteoblastic activity. These changes in bone metabolism would result in an increase in bone mineralization. At the moment, there are no clear data that demonstrate any relationship between BMD in adults and hypothyroidism. Despite these clinical evidences, the cellular and molecular actions of thyroid hormones on bone structures are not complete clear.

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Iatrogenic lesions of the skeleton

Obesity and metabolism ◽

10.14341/omet2016241-47 ◽

2016 ◽

Vol 13 (2) ◽

pp. 41-47 ◽

Cited By ~ 1

Author(s):

Galina A. Melnichenko ◽

Elizaveta O. Mamedova

Keyword(s):

Risk Factors ◽

Fracture Risk ◽

Bone Metabolism ◽

Negative Impact ◽

Public Health Problem ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Level Of Evidence ◽

Important Public Health Problem

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DXA parameters, Trabecular Bone Score (TBS) and Bone Mineral Density (BMD), in fracture risk prediction in endocrine-mediated secondary osteoporosis

Endocrine ◽

10.1007/s12020-021-02806-x ◽

2021 ◽

Author(s):

Enisa Shevroja ◽

Francesco Pio Cafarelli ◽

Giuseppe Guglielmi ◽

Didier Hans

Keyword(s):

Bone Mineral Density ◽

Trabecular Bone ◽

Bone Mineral ◽

Trabecular Bone Score ◽

Bone Microarchitecture ◽

Fragility Fractures ◽

Endocrine Disorders ◽

Mineral Density ◽

Increased Risk

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.

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