Bone and bone marrow disruption by endocrine‐active substances

Abstract

Bone is a multifaceted dynamic tissue, involved in mobility, mineral metabolism, and mesenchymal or stromal and hematopoietic progenitor or stem cells breading. Recently, an endocrine role has been attributed to bone due to its ability to produce at least two hormones (osteocalcin and fibroblast growth factor 23) and to participate directly or indirectly in leptin, insulin, estrogens, and serotonin signaling; regulation; and action. Also, bearing in mind the enormous amounts of substances secreted by the different bone marrow cell types, it becomes understandable the contribution of bone tissue to systemic homeostasis. Besides, bone is a well-known estrogen-responsive tissue, reacting to environmental influences. Thus, it has been coined as a critical target of environmental xenoestrogens, known as endocrine-disrupting chemicals (EDCs). The exposure to EDCs results to disruption or imbalance of the systemic hormonal regulation of the skeleton including bone modeling and remodeling, local hormones, and cytokine or chemokine release. The present report highlights the harmful EDCs effects on bone tissue and provides up-to-date information of xenoestrogen action on proliferation, maturation, and homing of bone marrow inhabitants.

Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications

“…Bone mineral mass is acquired relatively slowly throughout childhood, with no substantial sex difference in the axial (lumbar spine) or appendicular (radius and femur) skeleton, when adjusted for age, nutrition and physical activity [ 21 ]. Estrogen and androgen regulation is at the basis of the development and maturation of the adult skeleton until epiphyseal fusion, usually by the end of the second decade of life [ 22 ]. The peak in bone accretion is reached shortly after peak height gain, at 12.5 ± 0.90 years in girls and 14.1 ± 0.95 years in boys of European ancestry.…”

Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors

“…Endocrine-disrupting chemicals are substances with an endocrine mode of action that adversely interfere with the activity of the endocrine system ( 55 ). Among the numerous ones contaminating our everyday environment, some have been proved to interfere with bone remodeling leading to osteoporotic lesions including phthalates (present in plastics and cosmetics), alkylphenol ethoxylates or APE (added to detergents, additives for fuels and lubricants, perfume fragrances, chemical oils, and flame retardants), perfluoroalkyls (PFAs) (used in the industry of cookware, clothes, carpets, electronics, mechanics), bisphenol A or BPA (present in plastics, food containers, and materials for dental medicine), diethylstilbestrol (DES) (a synthetic estrogen considered in the treatment of selected prostate cancer cases), organotin compounds (used as industrial antifungal agents in textiles, agricultural fungicides, wood preservatives, and antibiofouling agents), and dioxin/dioxin-like compounds (primarily detected in pesticides, waste incineration, and different processes of combustion and paper fabrication) having high affinity for fat stores in animals and humans ( 9 ).…”

“…A similar mechanism is possibly at work also with 2,3,7,8-tetrachlorodibenzo- p -dioxin, which blocks the ability of HSC and progenitors to complete a normal differentiation cycle ( 66 ). Table 1 summarizes known effects of these and other EDs on cells residing in different bone compartments [from ( 9 , 56 , 57 , 60 , 62 , 64 – 66 )], whereas Table 2 provides a tentative integrated view of primary sites of early bone involvement during an inflammatory and/or ED-dependent bone insult based on location and osteomodulatory effects of BM immune cells.…”

“…Immune cells residing in the bone may contribute to development of both primary (postmenopausal, senile) and secondary (autoimmune, infective, vascular, neurological, endocrine, and multiorgan failure) osteoporosis acting on the progenitors of osteoblasts (OBs) and osteoclasts (OCs) (8). Finally, beyond pharmacological treatments well-known to interfere with OBs and OCs, endocrine-disrupting chemicals (EDs) may affect the activity of the immune cells in bone, leading to bone weakness (9).…”

Serum Osteocalcin, P1NP, Alkaline Phosphase, and CrossLaps in Humans.The relationship with body mass index

“…Skeleton is a dynamic complex organ with a permanent balance between bone formation and bone resorption [1,2]. Some pathological conditions like Paget's disease, primary and secondary osteoporosis, primary hyperparathyroidism first affect the bone turnover in different ways [3][4][5][6].…”