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- See:
      - osteoblasts
      - osteocytes

- Discussion:
    - osteoclast is a large multinucleated cell that plays an active role in bone resorption;
    - monocytes from the marrow or the blood serve as precursors of osteoclasts;
    - osteoclasts are found in notches or indentations of bone surfaces called Howship's lacunae;
           - lacunae are 100 or more microns in length, just bit larger than associated cell, & appear to have been excavated by osteoclast;
    - osteoclasts contain substantial amounts of the enzyme acid phosphatase;
    - evidence that mitochondria play a role in osteoclasts' resorptive activity stems from microscopic data demonstrating that there is
           significant increase in number of electron-dense mitochondrial granules during states of active bone resorption;
    - misc: osteoclasts are rich in acid phosphatase, which can be used as an identifier;
    - receptors:
           - calcitonin:
                  - calcitonin is a polypeptide hormone that is a potent inhibitor of osteoclastic bone resorption, but effects are only transient;
                  - the calcitonin receptor is specific for osteoclasts;
                  - calcitonin causes rapid shrinkage of the osteoclasts w/ initial exposure;
                  - osteoclasts escape inhibitory effects of calcitonin following continued exposure;
           - estrogen (indirect)
           - PTH, 1-25 Vit D & prostaglandin E, do not have receptors on osteoclasts (which is strange since these are bone resorption hormones)
    - osteoclast dysfunction:
           - osteopetrosis;
           - paget's disease;
           - gorham-stout syndrome:
                  - condition in which there is progressive bone resorption;
                  - Moller G, et al report that this condition may be due to an increased number of osteoclasts and may respond to calcitonin
                            or bisphosphonates;
                  - ref: The Gorham-Stout syndrome (Gorhams' massive osteolysis). A report of 6 cases with histopathological findings

- Resorption:
    - opposite of bone formation is bone resorption, which involves hydrolysis of collagen and the dissolution of bone mineral;
    - cell primarily responsible for bone resorption is the osteoclast;
    - actual amount of bone resorbed is dependent upon number of osteoclasts present and each osteoclast's activity;
    - although precise functional organization & structure of ruffled border is yet unknown, it is of primary importance to osteoclast
           during bone resorption since it is this portion of osteoclast that secretes acid, collagenases, pyrophophatases, and other enzymes
           that partially decalcify and hydrolyze organic matrix;
    - when osteoclasts are defective, bone resorption will be defective;
           - an example of this involves osteopetrosis;
           - further, the fact that osteopetrosis can often be cured w/ a bone marrow transplant, indicates that circulatory monocytes serve
                     as the  precursor to monocytes;

- Micro-scopic Features:
    - surface of osteoclast adjacent to bone has striated or brush border;
          - this ruffled border apparently plays an important role in resorption of the underlying bone;
    - large cells are multinucleated, w/ cytoplasm full of mitochondria, free ribosomes, vesicles, prominent Golgi apparatus and lysosomes;
    - osteoclasts have three cellular organelles that are believed to be involved in resorption:
          - mitochondria, lysosomes, and a ruffled or brush border;
    - lysosomes are membrane-bound vesicles which contain a wide spectrum of acid hydrolase enzymes;
    - these organelles are found in almost all cells and are capable of absorbing, digesting, and breaking down material;

- Osteocalcin
    - vit K dependent protein which regulates the rate of bone synthesis;
    - osteoclacin is the only protein made by osteoblasts exclusively;
    - levels of osteocalcin and other gamma carboxylated glutamic acid containing proteins have been shown to be elevated in serum &
                urine of pts w/ Pagets disease, primary hyperparathyroidism, renal osteodystrophy, and high turn over osteoporosis

Cathepsin K:
    - involved in degradation of type I collagen:

Membrane-bound carbonic anhydrases in osteoclasts.

Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+.

Recent advances toward understanding osteoclast physiology.

Cellular biology of bone-resorbing cells.      

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

The Deceiving Appearances of Osteoclasts