Bone Remodeling
- Total bone mass remains constant in adults; however, bones are not static:
- Bone deposition and resorption are constantly occurring.
- Deposition and resorption occur at the surfaces of both periosteum and endosteum.
- Bone deposition:
- Done by osteoblasts
- Osteoid seam: unmineralized band of matrix deposited by osteoblasts
- Calcification front: abrupt separation between old bone and osteoid seam
- Bone resorption:
- Done by osteoclasts: lysosomal enzymes and protons (H+) to break down bony matrix
- Once resorption is complete, osteoclasts undergo apoptosis.
- Initial signal:
- Microdamage is sensed by osteocytes.
- Damaged osteocytes undergo apoptosis, releasing intracellular components → bone-lining cells sense apoptosis and send chemoattractants
- Control of remodeling:
- Calcium levels control parathyroid hormone (PTH) levels, which in turn control osteoclast activity.
- Response to mechanical stress (Wolff’s law): A bone remodels in response to the force applied to it.
- Curved bones are thicker where they can bend.
- Trabeculae align along lines of compression.
- Bones on the dominant hand are thicker.
- Large bony projections appear where muscle pull is greater.
Bone anatomy:
Bones are covered in a layer called the periosteum, composed of fibrous and cellular layers. Below the periosteum is the endosteum, a complex architecture constructed on a mineral scaffold (the bony matrix) and composed of osteocytes, osteoclasts, and osteoblasts.
Bone-remodeling diagram
Image by Lecturio.
Bone remodeling begins with the osteocytes sensing microdamage. This process causes their apoptosis, which is concurrently sensed by bone-lining cells. These cells release chemoattractants, and osteoclasts group together in the damaged area to release calcium and phosphate. As soon as osteoclasts finish their work, osteoblasts begin recruiting the bone tissue. The process also traps some of the cells and forms a new lining by converting osteoblasts into osteocytes and bone-lining cells.
Signaling microdamage and activation:
Image by Lecturio.
Osteocytes at the site of microdamage undergo apoptosis.
Bone-lining cells then digest underlying osteoid to expose mineral and lift off the surface.
Osteoclast precursor recruitment:
Image by Lecturio.
Osteoclast precursors bind receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and coalesce to form an osteoclast.
Absorption:
Image by Lecturio.
Osteoclasts digest minerals with acid, releasing Ca2+ and PO43–.
Deposition:
Image by Lecturio.
Osteoblast precursors become osteoblasts and lay down new osteoid. Osteoid mineralizes and forms new bone.
New bone:
Image by Lecturio.
Trapped osteoblasts become osteocytes and extend dendrites.
Bone Repair
- After a fracture occurs, healing and repair take around 6–8 weeks.
- Steps of repair:
- Hematoma formation/bone tissue death
- Fibrocartilaginous callus formation:
- Soft granulation tissue (blood vessels grow into the hematoma, phagocytic cells start clearing the tissue remnants)
- Fibroblasts, chondroblasts, and osteogenic cells invade the area.
- Fibroblasts produce collagen that reunites the 2 separated bone ends.
- Chondroblasts form cartilaginous matrix.
- Osteoblasts start forming spongy bone.
- Bony callus formation:
- After a week, trabeculae form in the callus.
- After a few months, the callus becomes bone.
- Bone remodeling:
- Excess material on the diaphysis is removed.
- Compact bone will form the shaft.
Hormonal Control of Bone Remodeling
Parathyroid hormone (PTH)
- Secreted by parathyroid glands
- Raises blood calcium levels by releasing it from bone:
- Indirect activation of osteoclasts
- Also acts on kidneys and intestine to regulate calcium secretion/absorption
Calcitonin
- Released by thyroid C cells
- Down-regulates bone resorption by inhibiting osteoclasts
- Often supplemented to treat osteoporosis
Growth hormone
- Secreted by pituitary gland
- Stimulates release of insulin-like growth factor (IGF)
- Causes both osteoblast and osteoclast release, but net effect is bone growth
Estrogen
- Secreted by ovaries in females and testes in males
- Blocks osteoclast proliferation/activity
- Absence leads to decrease bone mass.
Clinical Relevance
- Bone fractures: break in a bone that results from accidental trauma, falls, or sports injuries. Fractures may even arise spontaneously in weakened bones, such as bones of low density and osteoporotic bones, or during overuse and stress. Fractures are classified into 4 categories: comminuted, impacted, greenstick, and oblique. Bone remodeling is activated in response to fractures and leads to repair.
- Osteomalacia and rickets: caused by insufficient dietary calcium or by vitamin D deficiency. In these conditions, the bones are poorly mineralized. Rickets affects the cartilage of the epiphyseal growth plates in children, while osteomalacia affects the sites of bone turnover in children and adults. As an end result, the patient’s bones are poorly mineralized. The osteoid scaffold is assembled, but calcium salts do not fill this matrix sufficiently resulting in brittle bones that deform easily. Usually, taking vitamin D restores the homeostasis of bone formation and calcium deposition.
- Osteoporosis: disease process in which bone resorption is greater than bone deposition. Etiologies may vary, but estrogen deficiency after menopause is a common cause. The composition of the matrix remains normal but bone mass declines, and the bones become porous and light. People with osteoporosis become prone to fractures with even slight trauma. Treatment/prevention can be done with exercise, hormone replacement therapy, bisphosphonates, and statins.
References
- Gallagher, J.C. (2018). Advances in osteoporosis from 1970 to 2018. Menopause 25:1403–1417 https://pubmed.ncbi.nlm.nih.gov/30489459/
- Kenkre, J.S., Bassett, J. (2018). The bone remodelling cycle. Ann Clin Biochem 55:308–327. https://pubmed.ncbi.nlm.nih.gov/29368538/
- Bakr, M.M., et al. (2019). Single injection of PTH improves osteoclastic parameters of remodeling at a stress fracture site in rats. J Orthop Res 37:1172–1182. https://pubmed.ncbi.nlm.nih.gov/30816593/
- Parfitt, A.M. (1994). Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286. https://pubmed.ncbi.nlm.nih.gov/7962158/
