Basic bone metabolism Flashcards
Describe the basic structure and cells of bone
Bone= specialized connective tissue consists of :
* a dynamic matrix undergoing continuous remodeling
The basic structure of bone can be divided into two types: cortical bone, which is the dense outer layer providing structural integrity and mechanical support, and cancellous or trabecular bone, characterized by a spongy architecture with a high surface-area-to-volume ratio that is critical for metabolic activity.
The bone matrix is primarily composed of type I collagen fibers, providing a framework for the deposition of hydroxyapatite crystals, which confer rigidity and strength. This mineralized matrix is interspersed with three principal cell types:
Osteoblasts: bone-forming cells responsible for the synthesis and secretion of the organic components of the bone matrix. Upon completion of their bone-forming activity, osteoblasts either become entrapped within the matrix to become osteocytes, line the bone surfaces as lining cells, or undergo apoptosis.
Osteocytes: These are former osteoblasts that have become embedded within the bone matrix. They reside in lacunae and maintain connections with each other and with cells on the bone surface via a network of canaliculi. Osteocytes are mechanosensitive and play a pivotal role in the regulation of bone remodeling by orchestrating the activities of osteoblasts and osteoclasts in response to mechanical stress.
Osteoclasts: These are large, multinucleated cells that are responsible for bone resorption. They attach to the bone surface, creating a sealed zone where they secrete protons and lytic enzymes such as cathepsin K, which dissolve the mineral and degrade the organic matrix, respectively.
The vascular supply to bone is essential, providing nutrients, oxygen, and regulatory factors, in addition to housing the bone marrow where hematopoiesis occurs. The periosteum, a dense fibrous membrane covering the outer surface of cortical bone, serves as a source of progenitor cells for bone growth and repair and contains a rich sensory nerve supply contributing to pain perception in various bone pathologies.
1) what are the reasons for bone remodelling and 2) how much faster does trabecular bone remodel compared to cortical bone
3) how it is linked to calcium homeostasis
1) reasons for bone remodelling:
* renews bone before detrioration
* redistributes bone matrix along lines of mechanical stress
2) Trabecular bone remodells 3-10 times quicker than cortical bone
* large SA
* responds to stresses on the bone quicker
3)The relationship between bone remodeling and calcium homeostasis is mediated through a tightly regulated feedback loop involving parathyroid hormone (PTH), vitamin D, and the calcium-sensing receptor (CaSR). When serum calcium levels drop, parathyroid cells increase the synthesis and release of PTH. PTH acts on osteoblasts to stimulate the expression of RANKL (receptor activator of nuclear factor kappa-B ligand), which in turn promotes osteoclast differentiation and activity, leading to increased bone resorption. The release of calcium from the bone matrix into the bloodstream elevates serum calcium levels.
Conversely, when serum calcium is elevated, the secretion of PTH is suppressed, reducing osteoclast activity and promoting bone formation by osteoblasts. Calcitonin, secreted by the thyroid gland when calcium levels are high, further inhibits osteoclastic bone resorption.
Describe the process of bone remodelling
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.
(1) CELL ACTIVATION
(2) BONE RESORPTION= osteoclast comes in clamps itself to resorption bay, forming leak proof seal starts vomiting enzymes (proteases that digest collagens and other proteins) + acid (HCl + citric). We end up with this soup of digested and semi digested stuff, now osteoclast leaves.
(3) ‘REVERSAL’ Osteoblast comes and takes over; called ‘reversal line’ it marks the cessation of osteoclast activity from the commencement of osteoblast activity at a remodeling site in bone.
(4) BONE FORMATION; Osteoblasts fill lacuna + releases osteoid, after 7-10 days osteoid is fully mineralised and osteoblasts will be surrounded by their own mineralised matrix= these osteoblasts have now become OSTEOCYTES.
this whole process can take uo to 3 months from activation to final bone minerilisation
Bone remodeling is a tightly regulated process that involves the coupled activities of osteoclasts and osteoblasts, often referred to as the Basic Multicellular Unit (BMU). The regulation of this process involves systemic hormones such as parathyroid hormone (PTH), calcitriol, and sex hormones, as well as local factors including cytokines and growth factors like RANKL, OPG, and M-CSF.
Describe the hormonal regulation of normal bone metabolism
Normal bone metabolism is regulated by a complex interplay of hormones, primarily including parathyroid hormone (PTH), calcitriol (the active form of vitamin D), and calcitonin. These hormones work together to maintain a balance between bone formation and bone resorption, ensuring skeletal integrity and calcium homeostasis.
Parathyroid Hormone (PTH):
Secreted by the parathyroid glands in response to low blood calcium levels.
Increases bone resorption by stimulating osteoclasts, the cells that break down bone tissue. This releases calcium and phosphate into the bloodstream.
Enhances renal reabsorption of calcium and stimulates the kidneys to convert inactive vitamin D into its active form, calcitriol.
Reduces renal reabsorption of phosphate to mitigate hyperphosphatemia, which would otherwise accompany increased bone resorption.
Calcitriol (Active Vitamin D):
Produced in the kidneys from vitamin D, with its synthesis stimulated by PTH.
Increases intestinal absorption of calcium and phosphate, boosting their serum levels.
Works synergistically with PTH to mobilize calcium from bone and enhance renal reabsorption of calcium.
Plays a role in bone formation by promoting the differentiation and activity of osteoblasts, the cells responsible for bone formation.
Calcitonin:
Secreted by the C-cells of the thyroid gland in response to high blood calcium levels.
Counteracts the action of PTH by inhibiting osteoclast activity, thereby reducing bone resorption and lowering blood calcium levels.
Its role in normal physiology is less pronounced than that of PTH and calcitriol.
Additional hormones also influence bone metabolism, including:
Sex Hormones (Estrogen and Testosterone): Essential for the maintenance of bone density. Estrogen, in particular, inhibits bone resorption. Post-menopausal decreases in estrogen levels are a major factor in the development of osteoporosis in women.
Growth Hormone and Insulin-Like Growth Factor 1 (IGF-1): Promote bone growth and remodeling.
Corticosteroids: In high levels, can lead to increased bone resorption and decreased bone formation.
This hormonal regulation ensures a dynamic balance between bone deposition and resorption, which is crucial for maintaining bone strength and mineral homeostasis throughout life. Disruptions in this system can lead to metabolic bone diseases such as osteoporosis, osteomalacia, and hyperparathyroidism.
Describe bone formation + postnatal growth
Postnatal bone growth involves both the increase in length (longitudinal growth) and the increase in diameter (appositional growth).
Longitudinal Growth: Growth in length is facilitated by the activity in the epiphyseal plate (growth plate). Chondrocytes undergo a lifecycle of proliferation, maturation, and ossification, pushing the diaphysis away from the epiphysis and lengthening the bone. The rate of longitudinal growth is significantly influenced by systemic endocrine factors including growth hormone, thyroid hormone, and sex steroids.
Appositional Growth: Growth in width is achieved through the process of periosteal expansion. Osteoblasts beneath the periosteum secrete bone matrix, adding new layers to the outer bone surface, while osteoclasts at the endosteal surface resorb bone, expanding the medullary cavity. This coordinated process allows for the increase in girth without compromising the bone’s integrity or increasing its mass disproportionately.
As the individual reaches adulthood, the epiphyseal plates close, signifying the cessation of longitudinal bone growth. However, bone remodeling continues throughout life, a dynamic process involving bone resorption by osteoclasts and bone formation by osteoblasts. This remodeling is essential for the maintenance of skeletal strength and mineral homeostasis, as well as the repair of micro-damages to prevent stress fractures.
what collagen is the bone made up of
1) type 1
2) type 2
3) type 3
Bone is made up of type 1 collagen
type 2= cartillage
type 3= smooth muscle e.g. blood vessels
how many bones do we have at birth vs how many bones does an adult have
275 bones (lots of cartillage think of it as babies got a lot of collagen they young) at birth become 206 bones (less cartillage) by adulthood.
baby’s bones will fuse together as they grow. Kids have a lot of WOVEN bone (their bones are bendy and disorganised layers)
what are the 2 tissue types lamellar bones are made up of
- compact/cortical bone = (80%) hard outer layer which is strong and dense
*n.b. cortical bone is much thicker around the diaphysis of a long bone than it is of epiphysis
*cancellous/trabecular bone= (20% mass. 80% surface area) this spongy inner layer network of trabeculae is lighter + less dense than cortical bone constantly modified to accomodate load {cancellous bone is ike honey comb it has lots of gaps in. and it is constantly remodelled}
what is endosteum
Endosteum: A membrane lining the inner surface of the bony wall also identified as the lining membrane of the Bone marrow cavity is endosteum; The endosteum lines the Haversian canal and all the internal cavities of the bone
endosteum (covers bone marrow) is where the osteoprogenitor cells (type of stem cell) produce different type of bone cells
osteoclasts are derived from which cell progeny ?
osteoblasts, osteocytes + osteoprogentior cells are derived from where?
Osteoclasts are multinucleated cells that derive from hematopoietic progenitors in the bone marrow (monocytes)
osteoblasts, osteocytes + osteoprogentior cells are from immature mesenchymal stem cells
describe the stages which form an activated osteoclast
granulocyte-macrophage colony forming unit (CFU-GM) thanks to macrophage colony stimulating factor (M-CSF) forms a –> osteoclast precursor–> these fuse to form an osteoclast which is then activated by receptor activator RANKL–> activated multinucleated osteoclast
where are osteoprogenitor cells (aka bone stem cells) located
osteoprogenitor cells (aka bone stem cells) are located in the periosteum + endosteum
osteocytes are bone _____ that ____ the state of bone matrix
osteocytes are bone MAINTAINERS that SENSE the state of bone matrix
we are born with ____ ____ _____ (haemopoietic stem cells)
The epiphyses + diaphysis (medullary cavity) gradually contain ____ _____ (adipocyte cells)
____ ____ ____ remains in vertebrae, ribs, skull, pelvis + epiphyses of femur
The _____ _____ is preferred for bone marrow transplantation
we are born with RED BONE MARROW (haemopoietic stem cells)
The epiphyses + diaphysis (medullary cavity) gradually contain YELLOW MARROW (adipocyte cells)
RED BONE MARROW remains in vertebrae, ribs, skull, pelvis + epiphyses of femur
The ILIAC CREST is preferred for bone marrow transplantation
why do chondrocytes die
Chondrocytes die when they can no longer receive nutrients or eliminate wastes via diffusion. This is because the calcified matrix is much less hydrated than hyaline cartilage.
