Hormonal Regulation of Bone Growth

Introduction 

The skeleton comprises of locomotor and skeletal roles and is a mineral reservoir. Bone turnover by osteoblasts and osteoclasts represents a lifelong procedure that involves modeling, growth and remodeling. The process further incorporates repair of damages. Signaling that takes place between bone cells is fundamental for the integration of the procedures ( Cosman, et al., 2014 ). Osteoblasts control osteoclast via the receptor activator of nuclear element; kB (RANK)/RANK ligand also known as osteoprotegerin system. Osteocytes on the other hand control activities via the secretion of sclerostin. In case formation and reabsorption are equal, there is zero change in bone mass after cycles. Nonetheless, with older age, some diseases surpasses the formation and this results in remodeling imbalance, reduced bone density and a further loss of microstructural integrity ( Black, Reid, Cauley, Cosman, Leung & Lakatos, 2015 ).  The level of remodeling is ascertained by endocrine and loading influences. Oestrogen is the most crucial endocrine controller of bone turnover. However, other hormones controlling the metabolism of bones incorporate insulin growth factor, gut, and parathyroid and adipocyte hormones. 

Hormonal regulation of bone 

Oestrogen is the major endocrine regulator of bone remodeling both in men and women. The other fundamental regulators involve a number of sex hormones including PTH, IGF-1, cortisol and gut hormones. 

Estrogen: In a premenopausal female, approximately 96% of circulating estrogen is produced by the ovaries while the remainder is manufactured by the extra-gonadal change of other sex steroids. Accordingly, postmenopausal women are characterized by circulating estrogen that is gotten from an extra-gonadal translation of adrenal steroids ( Bliuc, Nguyen, Eisman & Center, 2014 ).  In men, estrogen is entirely gotten from extra-gonadal fusion. The estrogen receptor is witnessed on growth plate chondrocytes and contains duties in the bone development. Normal puberty entails the upgrade in estrogen and may heighten growth and IGF-1. Later stages are when estrogen causes epiphyseal amalgamation and the cessation of longitudinal development ( Bone, et al., 2013 ).  Lack of estrogen, for instance in men lacking functional alterations of the aromatase gene, there exist continuing development with low bone mineral mass and tall stature. This is a suggestion that estrogen is not fundamental in the process of bone growth, however, is necessary for the fusion of epiphyseal. 

Estrogen might further inhibit periosteal apposition in the process of growth and this can contribute to gender dissimilarities in the size of bones. The hormone constrains osteoclast operations thereby increasing osteoclast apoptosis via direct signaling and through the osteoblast manufacture of RANK and OPG laggard ( Bone, et al., 2013 ).  Oestrogen further decreases the manufacture of pro-resorptive cytokines including IL-1 as well as tumor necrosis element-a by bone marrow cells. Oestrogen also enhances the differentiation of osteoblast and the formation of bones, partly via inhibition of sclerostin production by osteocytes. The menopausal loss of estrogen is the chief cause of improved bone turnover as well as remodeling inequity in aged women. 

Testosterone 

Testosterone is the major gonadal androgen that can be found in men, and over 96% is attained from the synthesis of testicular. In premenopausal women, about 28% of flowing testosterone is ovarian, 20% adrenal with 55% from peripheral translation. There is a decrease in the ovarian production of testosterone in postmenopausal female ( Cosman, et al., 2014 ).  The androgen receptor is located in chondrocytes and bone cells. Testosterone is a hormone that reduces the reposition of bones and heightens their formation using similar mechanisms as those of estrogen. In the process of modeling and growth, testosterone enhances periosteal apposition while combining with the reticence of apposition by estrogen. This is a process that leads to gender dissimilarities in the size of bones after puberty. It is probable that a significant section of the anti-resorptive activity of testosterone in aged males is mediated via estrogen aromatization ( Cosman, et al., 2014 ).  

Growth hormone and IGF-1: Growth hormone has a direct operation on target tissues; however the bigger part of its development-promoting impact is via the action of IGF-1. The liver produces a majority of the synthesized IGF-1, which is further fused by bone cell tissues. IGF-1 in the liver tissues undergoes intracrine and paracrine action that increase osteoblast activity and consequently the formation of bones. The hormone is imperative for longitudinal expansion, but further acts on periosteal osteoblasts that enhance the production of periosteal bones. IGF-1 and numerous other growth hormones propel the formation of bones in childhood via the spur of growth plate chondrocytes ( Bonnet, et al., 2013 ).  Serum levels go up steadily in the puberty duration in response to elevating oestradiol. IGF-1 and growth hormone further play a crucial duty bone geometry maintenance as well as bone mineral intensity in older mature individuals. 

Normal bone physiology 

The skeleton incorporates locomotor, structural and protective roles and is a reservoir for calcium. The cortical bone provides protective and structural roles thanks to its heavy calcification. Trabecular bone minimally calcified but contains a bigger surface area that permits it to be metabolically vigorous. Generally, the adult skeleton is approximately 20% trabecular bone and 80% cortical bone ( Bone, et al., 2013 ).  The percentage of cortical and trabecular bone is not constant, for instance, vertebrae are rich in trabecular bone but contain less cortex. Long bones, on the other hand, are characterized by long bones containing thicker cortices and little trabecular phone. It is worth noting that growth is a procedure via which bones enlarge and become mineralized in the course of adolescence and childhood. Bone mass enhances from about 80g at conception to 3000g at about 25 years of age ( Bonnet, et al., 2013 ).  Flat bones, for instance, the skull grow by intramembranous ossification. On the other hand, long bones including the humerus and femur expand in length by endochondral ossification and in breadth by a process that is referred to as periosteal apposition. By definition, modeling is whereby bones are molded and acclimatize for loading or any other influences. The process can lead to variations in geometry, size, and mass of bones. Cortical modeling at the endosteal or periosteal surfaces varies the cortical thickness and the diameter of bones ( Cosman, et al., 2014 ).  

Bone matrix and hormonal mineralization 

The bone matrix comprises of type I collagen fibers, proteoglycans, glycoproteins, water and carboxylated (gla) proteins. A high number of the non-collagenous proteins contain physiological duties in controlling the activities of bone cells. Type I collagen represents a triple-helical molecule that encompasses two similar a1 and a2 chains. Collagen fibers that are found in mature bones are positioned in varying layers that confer full strength on the formation ( Bone, et al., 2013 ).  Bone matrix accurately laid down after healing of fractures, or in high turnover assemblages, such as the case of Paget’s sickness is unsystematic without woven bone and is weaker compared to lamellar bone. Calcium hydroxyapatite is the major mineral element of bone tissues. The components crystals are located along the collagen fibers particularly in the ground substance. This is mineral is essential in strengthening bones by in ramping up theautomatedopposition of bone materials. Mineral components and associated matrix both add to the bone’s material characteristic. Apparently, the collagen matter offers toughness while the mineral provides rigidity ( Bonnet, et al., 2013 ).  Collagen irregularities result in fractures in osteogenesis imperfect because of decreased rigidity. Over- or under-mineralization might cause fracture because of excess or loss of rigidity. 

Gigantism 

Gigantism is an endocrine syndrome that is caused by the long-term production of excess growth hormones that drives muscle growth, connective tissues, and bones in adolescence or childhood prior to the conclusion of puberty. The ramification is an accelerated rate of growth and enhanced height in addition to the number of extra soft changes in tissues. If the condition is not treated, some people suffering from the condition can grow over 2.45 meters tall. The most famous illustration of the same is Robert Wadlow who holds the record as the tallest human being at 8 feet and 111 inches tall. The condition can be equated to acromegaly. Acromegaly is further caused by secretion of extra growth hormones but this happens at an older age. This is an indication that height is normality as the growth plates have joined prior to the production of the growth hormone takes place ( Bonnet, et al., 2013 ).  Gigantism is caused by benign adenoma located in the pituitary glands. An adenoma can be defined as a non-cancerous tumor and in the case of Robert Wadlow, this caused secretion of excess growth hormones. Pituitary hormones can be miniature or large. Nonetheless, in the case of Wadlow, they were large and invaded the brain tissues. This directly affected the symptoms and signs the Alton Giant experienced. 

Summary 

Bone turnover by osteoblasts and osteoclasts is fundamental for the development of skeletons as well as maintaining the strengths of bones in older age. Disease and aging lead to remodeling imbalance and further loss of structural strength and bone mass. Comprehending the intellectual signs and endocrine impacts that control bone turnover has resulted in the development of numerous diverse therapeutic targets for the diagnosis of osteoporosis. 

References 

Black, D., Reid, I., Cauley, J., Cosman, F., Leung, P., Lakatos, P.. ( 2015 ).  The effect of 6  versus  9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT) . J Bone Miner Res 30:  934 – 944 . 

Bliuc, D., Nguyen, T., Eisman, J., Center, J. ( 2014 ).  The impact of nonhip nonvertebral fractures in elderly women and men . J Clin Endocrinol Metab 99:  415 – 423 . 

Bone, H., Chapurlat, R., Brandi, M., Brown, J., Czerwinski, E., Krieg, M.. ( 2013 ).  The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension . J Clin Endocrinol Metab 98:  4483 – 4492 . 

Bonnet, N., Lesclous, P., Saffar, J., Ferrari, S. ( 2013 ).  Zoledronate effects on systemic and jaw osteopenias in ovariectomized periostin-deficient mice . PLoS One 8:  e58726 . doi: 10.1371/journal.pone.0058726   

Cosman, F., Cauley, J., Eastell, R., Boonen, S., Palermo, L., Reid, I.. ( 2014 ).  Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment?  J Clin Endocrinol Metab 99:  4546 – 4554 .