Hyperparathyroidism

Rickets is a condition that causes a child’s bones to soften and weaken. This makes them bend and warp, often leading to bowed legs. It also causes bone pain and makes them break more easily. The most common cause of rickets is a vitamin D deficiency. This occurs when a child doesn’t get enough vitamin D from the foods they eat or exposure to the UV radiation from the the sun.

​​            Endochondral ossification =  b0ne replaces cartilage
1. within cartilage model, chondrocytes (cartilage cells) enlarge and die in cartilage cavity 
​2. blood vessels invade cavity and perichondrium converts to periosteum
3. osteoblasts move via blood into cavity and produce spongy bone. this is the 
     primary ossification center
4. bone growth continues in both width and length
5. secondary ossification centers form in epiphyses form spongy bone
​6. ossification centers meet at epiphyseal plate where epiphyseal cartilage remains.
    epiphyseal "closure" occurs when cartilage production slows and bone production                 accelerates. the epiphyseal plate then becomes the epiphyseal line when all of the                 cartilage is replaced ​ with bone (post puberty). this is when long bones stop elongating.
7. Cartilage remaining on ends of bone serves as articular cartilage. 

​ Just an FYI re actual complexity of process...yikes! 

Excessive production of GH in children (before the epiphyseal plates fuse) results in  gigantism and continued growth of long bones.

 Hormonal control of bone remodeling:
Calcitonin and Parathyroid Hormone (PTH)

OPG acts as a decoy receptor that inhibits RANKL's signaling. The balance between RANKL and OPG affects bone mass.

When the area around the osteoblast calcifies into this matrix, the osteoblast becomes trapped in this bony matrix within a space called the lacuna and transforms into an osteocyte. 

 pathology

bone mass determinants

 Bone marrow
 is the tissue found in the medullary cavities and spongy bone of long bones.
There's red bone marrow (myeloid tissue) and yellow bone marrow (fatty tissue). 
Red marrow houses stem cells which are able to differentiate into WBCs used to fight infections, RBCs which carry O2 and platelets which participate in clot formation. 
Yellow marrow is stored fatty tissue but also contains stem cells which give rise to fat, cartilage, and bone.

​   how long bones
            thicken

Thyroid hormone T3/T4 balance is important for bone integrity

RANKL stands for
​ 'Receptor Activator of NF-κB Ligand'.
It is a cytokine (cell messenger) crucial for bone resorption. It acts as a ligand, binding to its receptor RANK on
stem cells. This triggers them to  differentiate into osteoclasts
leading to bone resorption.

 80% of the skeleton is compact bone while 20% is spongy bone

​overactivation of osteoclasts due to  parathyroid tumors stimulating the over secretion of PTH leading to
very high blood Ca+ levels

the bone remodeling process

​​ Osteoblasts secrete a new matrix of collagen and calcium salts. 

Glucocorticoids = ​stress

OPG is stimulated by estrogen.
​OPG blocks RANKL from binding to RANK so decreases osteoclast activity.
low estrogen levels leads to increased osteoclast activity and weaker bones. 

          The Skeletal System

PTH stimulates the secretion of RANKL

​the softening  of bones in children. Rickets occurs often because of extreme
vitamin D deficiency.

Finding a match for a bone marrow transplant involves identifying a donor with compatible Human Leukocyte Antigens (HLAs), which are proteins found on the surface of white blood cells. The ideal match has the same HLA markers as the recipient.

Rickets 

how a bony  skeleton is made from an embryonic scaffold...

endochondral ossification 

GH imbalance

    compact bone structure

 Osteoclasts 
​release enzymes that release calcium from bone, decalcifying the matrix.

 osteoporosis

vitamin C and K also stimulate osteoblast differentiation

​   how long bones
            lengthen

    compact v spongy bone 

 The synthesis and degradation of bone is controlled by the RANKL system. RANKL is released by osteoblasts. RANKL binds to RANK receptors on the surface of stem cells and triggers them to differentiate into osteoclasts.

This is a another example of a ligand/receptor system.

 The human body has 206 bones   
            There are 26 bones in the foot
​                        The hand and wrist contains 54 bones
                                  The femur is the longest and strongest bone
                                           The stapes, in the middle ear, is the smallest and lightest bone
                                                     Only the hyoid bone isn't connected to another bone
                                                              Only 10% of the world's animals have an internal skeletal system

          bone remodeling

ossification

 Calcitonin and PTH are antagonists

Bone marrow transplants are used to treat conditions where the bone marrow isn't functioning properly, such as leukemia, aplastic anemia, and sickle cell anemia. They can also be used to restore bone marrow function after high-dose chemotherapy or radiation therapy.  

 Calcitonin acts to reduce blood Ca+ levels.
Calcitonin inhibits the activity of osteoclasts and decreases the resorption of calcium by the kidneys. 
Parathyroid hormone (PTH) acts to resorb calcium from the bone and increase calcium resorption by the kidneys increasing
blood Ca+ levels.