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Bone Metabolism

The skeleton is a metabolically active organ that undergoes continuous remodeling throughout life. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through the osteoblasts that subsequently become mineralized. The remodeling cycle consists of three consecutive phases: resorption, during which osteoclasts digest old bone; reversal, when mononuclear cells appear on the bone surface; and formation, when osteoblasts lay down new bone until the resorbed bone is completely replaced.  Bone remodeling serves to adjust bone architecture to meet changing mechanical needs and it helps to repair micro damages in bone matrix preventing the accumulation of old bone.


Bone metabolism is regulated by many systemic hormones and locally acting substances. Systemic hormones can be divided into two groups: hormones affecting the metabolism of calcium and phosphates and other systemic hormones.


Hormones affecting the metabolism of calcium and phosphates

In the human body parathormone, calcitriol and calcitonin play a key role in the regulation of calcium and phosphate content.

1)Parathormone

Parathormone stimulates the resorption of bone by increasing the activity of osteoclasts (stimulates transformation of monocytes to osteoclasts). The result is an increased release of Ca2+ and phosphates from the bone.

2)Calcitonin

Calcitonin inhibits osteoclast activity (inhibits transformation of monocytes to osteoclasts), thereby reduces bone resorption and it results in an increased deposition of Ca2+ in bones.

3) Calcitriol (1, 25-dihydroxycholecalciferol, vitamin D derivative)

Calcitriol stimulates synthesis of proteins allowing the absorption of Ca2+ and phosphates in the small intestine. Thus calcitriol ensures the availability of Ca2+ and phosphates for bone formation. Simultaneously activates osteoblasts to synthesize collagen.


Other systemic hormones

1)Estrogens

Estrogens act like calcitonin. Therefore they inhibit bone resorption – inhibit osteoclast activity through local factors.

2)Growth hormone

Growth hormone stimulates bone formation mediated through the formation of local growth factors – insulin-like growth factors (somatomedins – IGF-1 and IGF-2).

3)Insulin

Insulin increases the synthetic activity of osteoblasts. Bone loss can occur in an untreated diabetes mellitus.

4)Glucocorticoids

Glucocorticoids reduce the formation of new bone (they inhibit proteosynthesis in osteoblasts and their differentiation).

5)Thyroid hormones

Thyroid hormones stimulate osteoclasts, activate bone remodeling. At their overproduction an osteoporosis may develop.


Local factors regulating bone metabolism

1) Factors stimulating osteoblast differentiation

a) Bone morphogenic factor (BMF)

b) Insulin-like growth factor 1 (IGF-1)

c) Platelet-derived growth factor (PDGF)

d) Fibroblast growth factor (FGF)

2) Factors stimulating osteoclast differentiation

a) M-Colony stimulating factor (M-CSF)

b) Interferons (INF-γ) and interleukins (IL-1, IL-6 etc.)


Bone Related Diseases

Osteoporosis

Osteoporosis is systemic bone disease characterized by low bone density and altered bone microarchitecture with consequent increase in fragility. Its substrate is the loss of inorganic and organic bone matter which leads to increased fracture risk. Osteoporosis is divided into two types – primary osteoporosis (cause is unknown, e.g. postmenopausal or senile osteoporosis) and secondary osteoporosis (cause is known, e.g. endocrine problems, medicaments, immobilization).


Fasciitis

Fasciitis is an inflammation of the fascia, which is the connective tissue surrounding muscles, blood vessels and nerves, an inflammation of the connective tissue that may be caused by streptococcal or other types of infection, an injury, or anautoimmune reaction, an abnormal benign growth (pseudosarcomatous fasciitis) resembling a tumor that develops in the subcutaneous oraltissues, usually in the cheek. Commonly growing rapidly and then regressing, it consists of young fibroblasts and many capillaries.


Arthritis

Arthritis is a medical condition that damages the body’s joints, causing discomfort and pain. It can range from mild to severe and can affect people of all ages. Arthritis is not one disease alone, but an umbrella term for more than 100 conditions that affect the joints of the body. Joints are points where two or more bones meet, such as in the wrist, knuckles, hips, knees and ankles.


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