[Mondoshawan]

A 73-year-old female patient is currently being treated with bisphosphonate medication for osteoporosis. She takes this medication along with a vitamin D supplement in the morning, then a calcium supplement in the late afternoon. Bisphosphonates inhibit osteoclast activity and encourage their apoptosis. Osteoclasts decalcify the bone matrix by:

• Degrading the collagen of the matrix, releasing the mineral components of the bone
• Pumping out protons to create an acidic microenvironment that dissolves the mineral components of the bone.
• Releasing matrix metalloproteinases, which act on the mineral components of the bone.
• Releasing carbon dioxide, which combines with water in the bone to form carbonic acid.
• Secreting small matrix vesicles which absorb the mineral components from the bone matrix

 

[drahmednawaz]

Answer is A.

Osteoclasts themselves are very large cells, formed from the conjoining of several cells created by the bone marrow that travel in the circulatory system. As a result of this conjoining, osteoclasts are known as multinucleate cells, meaning that each cell has multiple nuclei. The average osteoclast has anywhere from five to 20 nuclei, although osteoclasts with up to 200 nuclei are possible. Osteoclasts can generally be found in tiny pits along the bone's surface. These pits, which are formed by the action of osteoclastic enzymes, are known as Howship’s lacunae, and can be found on virtually every bone in the skeletal system.


When the resorption process is initiated, the osteoclastic cell latches onto the bone to be resorbed, releases enzymes to deconstruct the tissue surface, and then breaks it down into calcium and phosphorus ions, which the cell eventually passes through the outer membrane and into the circulatory system. The process of resorption, from first osteoclastic contact to the release of ions into the blood, can take up to three weeks to complete. The resorption process is controlled by hormones in the bloodstream, which is why osteoporosis, a condition where the rate of bone loss exceeds the regrowth of bone tissue, is closely linked to hormonal changes

 

[aktorque]

C) Releasing matrix metalloproteinases, which act on the mineral components of the bone.

My Ans is C) Releasing matrix metalloproteinases, which act on the mineral components of the bone.

Osteoclast cell secretes acid to dissolve the bone mineral, and enzymes (metalloproteinases) to digest the collagen of the bone matrix. metalloproteinases found in the osteoclast lysosomes.

 

[drahmednawaz]

May be answer is B.

My Ans is C) Releasing matrix metalloproteinases, which act on the mineral components of the bone.

Osteoclast cell secretes acid to dissolve the bone mineral, and enzymes (metalloproteinases) to digest the collagen of the bone matrix. metalloproteinases found in the osteoclast lysosomes.

Do metalloproteinases act on mineral components??? They act on the organic component. Minerals are the inorganic component.

Once activated, they move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in a small cavity called Howship's lacunae, formed from the digestion of the underlying bone. The sealing zone is the attachment of the osteoclast's plasmalemma to the underlying bone. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin. The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3- + H+) through the ruffled border into the resorptive cavity, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped against a high concentration gradient by proton pumps, specifically a unique vacuolar-ATPase. This enzyme has been targeted in the prevention of osteoporosis. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease(MMP) groups , are released to digest the organic components of the matrix. These enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance.

 

[aktorque]

Wow... you just had explained the entire process that occurs during the osteoclast decalcification. What I know about osteoclast demineralization is that osteoclast cell releases many different catabolic enzymes to degrade bone matrix and dissolves the bone minerals. The qn is particularly asking you to identify the ans choice that explains the cause of bone matrix decalcification not the demineralization.

 

[usmle0987]

C Releasing matrix metalloproteinases, which act on the mineral components of the bone.

metalloproteinases degrades matrix of the bone.

 

[drahmednawaz]

Choice C is wrong, because it says metalloproteinases act on the mineral components of the bone. Actually they don't. Decalcification is synonymous with demineralization. In bone formation, organic matrix (collagen, etc) is laid down first, then that matrix is calcified with minerals. Acids help remove (decalcify) mineral (inorganic) component and enzymes digest organic matrix.

Q is asking about decalcification, so choice B is correct.

 

[aktorque]

Hmmm.. i'm thinking, i'm thinking.

 

[Mondoshawan]

) You guys are hilarious!

 

[Mondoshawan]

Answer is B

Everything we need to know is in aktorque's post...

Osteoclast cell secretes acid to dissolve the bone mineral, and enzymes (metalloproteinases) to digest the collagen of the bone matrix.

... but drahmednawaz drew the right conclusion about what the question was asking for: the demineralization rather than the breakdown of the matrix.

The correct answer is B: Pumping out protons to create an acidic microenvironment that dissolves the mineral components of the bone. Carbonic acid is formed in the cytoplasm of the osteoclast, and protons are pumped out of the cell. The osteoclast also releases enzymes, including matrix metalloproteases, that degrade matrix collagen after decalcification.

 

[apx85]

B

Here is what I understand:

Osteoclasts demineralize/decalcify bone by releasing both protons and proteolytic enzymes (including MMP's).

Bone is composed of two major components: Osteoid (organic) and Hydroxyapatite (mineral). Osteoid is synthesized and released by osteoblasts and is composed of fibers and ground substance. The predominant fiber-type is Type I collagen. The ground substance is mostly made up of chondroiton sulfate and osteocalcin. Hydroxyapatite is made up of calcium and phosphate, which is the mineral component of bone.

The proteolytic enzymes released by osteoclasts digest the osteoid, releasing hydroxyproline. Hydroxyproline (from collagen) can be detected in the urine and is a marker of osteoclast activity. On the other hand, the acid is used to demineralize the bone, releasing CaPO4 (Note: Mineralization is favored by a basic environment while demineralization is favored by an acidic environment)

Hope that helps, Great question!!

 

[aktorque]

Hmmm... that's a tricky one. I misunderstood the qn. This happens all the time when I see the tricky choices. Very confusing. Thanks to drahmednawaz and Mondoshawan, you guys cleared my doubt.

It's a great qn as usual. Thanks guyz

 

[Mondoshawan]

Hmmm... that's a tricky one. I misunderstood the qn. This happen all the time when I see the tricky choices.

It's funny - I wrote this question for class last year, and when I opened it up yesterday my eyes jumped to "metalloproteases", and I thought "oh, C"... and then I looked at the answer (which I had written) and then back at the question and thought, "Oh, yeah.." :redcheeks;

 

[aktorque]

It's funny - I wrote this question for class last year, and when I opened it up yesterday my eyes jumped to "metalloproteases", and I thought "oh, C"... and then I looked at the answer (which I had written) and then back at the question and thought, "Oh, yeah.." :redcheeks;

Are you serious!!!! man! I always tell myself to go for the first choice no matter what happens, second choice always wrong for me. So, when I looked at the choices at first, "C" was clicked on my mind, then I went on net to confirm it and stated to read some articles. Came back to the qn and read it once more, option "B" looked right to me, but I didn't trust myself. I stubbornly sticked with my first choice stupid "metalloproteases", sad ....:toosad:

 

[doctorsmonsters]

Great question! ever greater discussion, keep them coming guys!