What is Bone and Bone Formation? 

Bone is the connective tissue that functions to provide support and protection to various organs of the body. It comprises mineral salts and collagen fibers. The formation of new bones is called ossification. The process of ossification is essential for the healing of fractured bones, bone remodeling and for the formation of new bones.

Ossification

The formation of bones by osteoblasts is known as ossification. It is also known as osteogenesis. Osteoblasts are the bone forming cells whereas osteoclasts are the cells that cause breakdown of the bone. Ossification of bones involves calcification, that is, deposition of calcium inside the bones. Bone formation for an embryo starts about six weeks after fertilization. Intramembranous ossification is the formation of bone from fibrous membranes and endochondral ossification is the formation of bone from hyaline cartilage. Bones generally develop until the age of 25, after which bones start to thicken.  

Intramembranous ossification 

Intramembranous ossification is the phase of bone formation from fibrous membranes. The flat bones of the skull, the mandible, and the clavicles are all shaped by it. Ossification starts with the formation of a blueprint for future bone by mesenchymal cells. At the ossification base, they differentiate into osteoblasts. The extracellular matrix is secreted by osteoblasts. The osteoblasts deposit calcium which hardens the matrix. Spongy bone is formed as the non-mineralized part of the bone, called the osteoid. Osteoid grows around blood vessels. In the fetus, the connective tissue in the matrix differentiates into the red bone marrow. On the surface of the spongy tissue, it is remodeled into a thin layer of compact bone. 

Endochondral ossification 

The phase of bone formation from hyaline cartilage is known as endochondral ossification. Except for the flat bones of the brain, mandible, and clavicles, all of the body's bones are developed by endochondral ossification.  

Chondrocytes serve as a template for the hyaline cartilage diaphysis in long bones. The matrix starts to calcify in response to complex developmental signals. This calcification prevents nutrients from diffusing into the matrix, causing chondrocyte death and cavities to form in the diaphysis cartilage. Osteoblasts and osteoclasts change the calcified cartilage matrix into spongy bone as blood vessels enter the cavities, and modify the calcified cartilage matrix into spongy bone. Osteoclasts then break down some of the spongy tissue, forming a marrow cavity, or medullary cavity, in the diaphysis' middle. Around the bones, a sheath (periosteum) of dense, irregular connective tissue forms. The periosteum connects the bone to the underlying tissues, tendons, and ligaments. As the cartilage cells at the epiphyses divide, the bone begins to expand and elongate. 

The epiphyses' centers begin to calcify in the final stages of prenatal bone formation. Blood vessels and osteoblasts join the epiphyses and transform hyaline cartilage to spongy tissue, forming secondary ossification centers. Hyaline cartilage remains at the epiphyseal plate (growth plate) until puberty, which is the region between the diaphysis and epiphysis that is responsible for the lengthwise growth of bone. 

Bone Growth 

Long bones begin to lengthen with the addition of bone tissue at the epiphyseal plate, possibly until puberty. They also gain width as a result of appositional development. 

Growing of Long Bones Lengthwise 

On the epiphyseal side of the epiphyseal plate, chondrocytes divide, with one cell remaining undifferentiated near the epiphysis and the other moving toward the diaphysis. Calcification destroys the cells that are pulled out of the epiphysis as they mature. On the diaphyseal side of the plate, this procedure replaces cartilage with bone, resulting in bone lengthening. 

In a mechanism known as epiphyseal plate closure, long bones stop developing about the age of 18 in females and 21 in males. Cartilage cells avoid dividing during this period, and bone replaces all of the cartilage. The epiphyseal plate fades away, leaving an epiphyseal line or epiphyseal remnant, and the epiphysis and diaphysis fuse together. 

Widening of Long Bones 

Appositional development is the process of adding bony tissue to the surface of bones to increase the diameter of the bones. Bone matrix is secreted by osteoblasts on the surface, and bone is broken down by osteoclasts on the inner surface. The osteoblasts become osteocytes as they mature. The bone will thicken without being too heavy if these two processes are balanced. 

Remodeling of Bone and its Repair 

After birth, bone regeneration continues into adulthood. The replacement of old bone tissue with new bone tissue is referred to as bone remodeling. It comprises bone forming by osteoblasts and bone resorption by osteoclasts. Vitamins D, C, and A, as well as calcium, phosphorous, and magnesium, are needed for normal bone development. Hormones like parathyroid hormone, growth hormone, and calcitonin are also essential for bone growth and maintenance.  

Five to seven percent of bone mass is recycled per week, indicating a high rate of bone turnover. Different regions of the skeleton and different areas of a bone have different turnover rates. The bone in the head of the femur, for example, can be completely replaced every six months, while the bone along the shaft changes much more slowly.  

When bones are stressed, bone remodeling helps them to adapt by becoming thicker and stronger. Bones that are not subjected to normal stress, such as those in a cast, tend to lose mass. A fractured or broken bone goes through four stages of healing: 

• Blood vessels in the fractured bone tear and hemorrhage, resulting in a blood clot, or hematoma, at the break location. The clotting mechanism seals the blood vessels at the broken ends of the bone, and the bone cells that are deprived of nutrients begin to die. 
• Capillaries develop into the hematoma within few days of the fracture, and phagocytic cells begin to clear away the dead cells. Fibroblasts and osteoblasts invade the region and begin to reform bone, even though remnants of the blood clot remain. Osteoblasts begin to form spongy bone after fibroblasts develop collagen fibers that bind the broken bone ends. Since it is made up of both hyaline and fibrocartilage, the repair tissue between the damaged bone ends is known as the fibrocartilaginous callus. At this stage, some bone spicules can appear. 
• The fibrocartilaginous callus transforms into a spongy bone callus. After a fracture, the fractured bone ends take about two months to permanently connect together. When cartilage becomes ossified, osteoblasts, osteoclasts, and bone matrix are present, similar to the endochondral formation of bone. 
• Osteoclasts and osteoblasts then remodel the bony callus, removing excess material on the outside of the bone and inside the medullary cavity. To produce bone tissue that is identical to the original unbroken bone, compact bone is inserted. This remodeling process takes months, and the unevenness of the bone lasts for years. 

Context and Applications 

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for       

• Bachelor of Science in Biochemistry and Molecular biology         
• Bachelor of Molecular and cellular biology        
• Master of Science in Biological science 
• Master of Science in Biomolecular chemistry 
• Masters in Biotechnology