Why is bone resorption important

It also results in facial changes, with the lips and cheeks sinking and shifting over time. For most, treating bone resorption is placing dental prosthetics to reintroduce a stimulus. Dental implants are a great way to stimulate bone and stop the resorption. JavaScript is Disabled For the best experience and to ensure full functionality of this site, please enable JavaScript in your browser.

Understanding born resorption in our dental health is important because it provides a better picture of why we need our teeth or prosthetics. The Two Sites Of Dental Resorption We know resorption can happen at the root, but it can happen both internally and externally.

How can you treat bone resorption in these areas? Sclerostin, a protein product of the SOST gene, inhibits osteoblast activity via antagonism of the Wnt signaling pathway and plays a key role in the cycle of bone growth and resorption. As the population continues to age, so does the prevalence of chronic diseases such as obesity, type 2 diabetes and osteoporosis. A number of recent reports have shown that sclerostin levels are increased and bone turnover markers decreased in type 2 diabetes.

Bone metabolism is regulated by a complex array of hormonal influences and growth factors that foster communication between osteoclasts and osteoblasts and which have profound effects on the skeleton. Wnt modulators in the biotech pipeline. Developmental Dynamics. Mar ; Vol No 3: Gaudio et al.

Skeletal health is maintained by bone remodeling, a process in which microscopic sites of effete or damaged bone are degraded on bone surfaces by osteoclasts and subsequently replaced by new bone, which is laid down by osteoblasts.

This normal process can be disturbed in a variety of pathologic processes, including localized or generalized inflammation, metabolic and endocrine disorders, primary and metastatic cancers, and during aging as a result of low-grade chronic inflammation. TRAF3 also limits osteoclast formation induced by TNF, which mediates inflammation and joint destruction in inflammatory diseases, including rheumatoid arthritis. Chloroquine and hydroxychloroquine, anti-inflammatory drugs used to treat rheumatoid arthritis, prevent TRAF3 degradation in osteoclast precursors and inhibit osteoclast formation in vitro.

Chloroquine also inhibits bone destruction induced by ovariectomy and parathyroid hormone in mice in vivo. Mice genetically engineered to have TRAF3 deleted in osteoclast precursors and macrophages develop early onset osteoporosis, inflammation in multiple tissues, infections, and tumors, indicating that TRAF3 suppresses inflammation and tumors in myeloid cells.

Mice with TRAF3 conditionally deleted in mesenchymal cells also develop early onset osteoporosis due to a combination of increased osteoclast formation and reduced osteoblast formation. TRAF3 protein levels decrease in bone and bone marrow during aging in mice and humans. Development of drugs to prevent TRAF3 degradation in immune and bone cells could be a novel therapeutic approach to prevent or reduce bone loss and the incidence of several common diseases associated with aging.

The skeleton provides support for propulsion by skeletal muscles as well as vital protection for internal organs, including the brain and heart. It is also a repository for calcium and other elements that get deposited in bone as it mineralizes during bone formation and are released from bone when it is being remodeled. In this way, bone participates in the control of calcium levels in the blood and tissues 1 to mediate numerous cellular functions, including contraction of skeletal and cardiac muscles 2.

Bone remodeling is a normal physiological process that maintains skeletal integrity after skeletal development by removing small foci of damaged or effete bone from bone surfaces and replacing them with new bone 3 , 4. By this mechanism, the skeleton is continuously renewed throughout life. During embryonic development, bone is formed by osteoblasts, specialized mesenchyme-derived cells that lay down layers lamellae of matrix composed of mainly type 1 collagen 3 , 5 , which is mineralized a few days later.

These proteins and minerals are released from bone during bone resorption and in increased amounts in numerous pathologic processes in which bone destruction is elevated. They can influence the behavior of cells in the bone microenvironment and outside the skeleton, particularly in pathologic processes in which remodeling is increased 5 , 8 , 9. During development, long bones are formed initially in cartilage molds roughly in the shape that the bones will have before birth 3.

Growth plates form at the proximal and distal ends of embryonic long bones. These plates consist of columns of small resting proliferating chondrocytes and larger hypertrophic chondrocytes, which lay down matrix that calcifies at the interface between them and the bone marrow 3. This calcified matrix is resorbed and replaced by bone, which also is calcified. Figure 1. In the adult skeleton, bone remodeling begins with removal of microscopic foci of calcified bone matrix by osteoclasts, which form trenches on bone surfaces, called resorption lacunae.

Signaling downstream from these receptors regulates the differentiation of osteoclast precursors into osteoclasts as well as the resorptive activity and survival of osteoclasts. The M-CSF receptor is a tyrosine kinase that phosphorylates and activates downstream signaling molecules TRAFs play important positive and negative regulatory roles in RANKL-induced osteoclast formation and activation 16 , 17 in normal bone remodeling and in many pathologic processes affecting the skeleton in which bones can weaken to the point where they can fracture readily.

This review will briefly describe the mechanisms that regulate bone remodeling, with emphasis on osteoclast formation in normal and pathologic processes, and the roles that TRAFs play in osteoclast and osteoblast formation and function, focusing on the evolving roles of TRAF3.

In response to normal wear and tear and mechanical forces and the aging process, bone is continuously remodeled in the adult skeleton by a process in which damaged or effete microscopic portions of bone are removed by osteoclasts and subsequently are replaced by new bone, which is laid down by osteoblasts 3 , 18 , On trabecular surfaces of spongy cancellous bone, bone remodeling units BRUs are trench-shaped structures that osteoclasts form by degrading the matrix.

Osteoclastic resorption is less orderly in pathologic processes in which resorption rates are increased, resulting in reversal lines that are typically irregular and can give the bone a mosaic pattern, seen most classically in Paget's disease of bone Osteoclasts also remodel the more dense cortical bone that encases and protects spongy bone by forming roughly circular tunnels through it.

These tunnels are almost completely filled in with new bone to form structures called osteons, which have a small central nutrient artery and vein. This remodeling process involves complex interactions between osteoclastic and osteoblastic cells that couple bone formation to these sites of resorption where coupling factors released from the bone matrix and by osteoclasts attract osteoblast precursors to the site 5.

To initiate bone resorption, osteoclasts first produce hydrochloric acid, which dissolves the mineral in bone, and then they secrete metalloproteases, which breakdown the collagenous matrix Mutations in the genes involved in matrix demineralization and dissolution account for the majority of human cases of osteopetrosis 3 , 10 , 21 , The osteoclast cell membrane folds to form finger-like processes called the ruffled border that greatly increases the cell surface area for secretion of bone-degrading acid and enzymes 10 , The main osteoclast proteolytic enzyme, cathepsin K, functions most effectively at this pH to degrade the matrix after the mineral has been dissolved 10 , Degraded matrix particles are passed through the osteoclast cytoplasm to the outer surface of the cell from which they are released into the resorption lacunae 23 , where there are nutrient-carrying afferent sinusoids as well as efferent sinusoids that remove these particles to the bloodstream The lacunae appear to be covered by a thin collagenous membrane called a canopy that isolates the lacunae to protect the adjacent bone marrow from the resorptive process Osteoclasts are multinucleated cells that form by fusion of hematopoietic myeloid precursors typically in the bone marrow adjacent to bone surfaces.

Osteoclast precursors are formed in the bone marrow and are attracted from there into the bloodstream by sphingosine-1 phosphate S1P 37 , which is produced in large amounts by red blood cells.

They are attracted back into the bone marrow to resorption lacunae by RANKL 10 , 38 expressed by osteoblastic and immune cells. Osteoclasts can also form outside the skeleton in a variety of pathologic lesions in humans, including the relatively common giant cell tumor of tendon sheath and the closely related pigmented villonodular tenosynovitis [ 41 ; Figure 2 ].

Mesenchymal cells in these soft tissue lesions express RANKL and M-CSF 42 , which presumably attract osteoclast precursors from the bloodstream and induce their differentiation into osteoclasts. Osteoclasts can also be observed, sometimes in large numbers, in a small percentage of primary carcinomas 43 , 44 , including breast, lung, pancreas, and bladder, and in some soft tissue sarcomas, but the molecular mechanisms that induce their formation in these lesions are unknown.

Tumor cells attract and activate these macrophages 45 , which are called tumor-associated macrophages TAMs. TAMs have multiple functions, some supportive of tumor cell growth and invasion 46 , others inhibitory Some of these cells fuse to form the multinucleated osteoclasts in these lesions, but others can fuse to form TRAP-negative polykaryons [Figure 2 ; 48 ] and these multinucleated cells do not resorb bone.

TRAP-negative giant cells can form in numerous other pathologic settings in response to a variety of factors, including cholesterol from dead normal or tumor cells Figure 2 , foreign agents, such as some bacteria and viruses, and surgically implanted graft materials, and their function in these conditions is to degrade them.

It is possible that osteoclasts and their mononuclear precursors, like TAMs, have positive or negative influences on the behavior of malignant cells in tumors outside the skeleton, but this has not been studied to date.

Figure 2. Osteoclasts and multinucleated foreign-body type giant cells in giant cell tumor of tendon sheath. The right-hand panels show low and high power images of the lesion with TRAP-positive osteoclasts and TRAP-negative multinucleated giant cells associated with the cholesterol clefts. M-CSF is expressed by osteoblast lineage cells in the bone marrow and induces expression of RANK by osteoclast precursors, which further differentiate and fuse with one another to form osteoclasts in response to RANKL 5 , RANKL is also expressed and secreted by osteocytes 52 , 53 , the most abundant cells in bone.

Osteocytes start their existence as matrix-forming osteoblasts on bone forming surfaces. Most osteoblasts die by apoptosis when their matrix forming mission has been completed 26 , but some of them become embedded within the uncalcified matrix, called osteoid, as it is being formed, and the others remain on the bone surface as flat lining cells. Osteocytes have numerous dendritic processes that allow them to communicate with each other within the bone and with lining cells on the surfaces of fully calcified bone It is believed that, as a result of this syncytial arrangement, osteocytes can respond to mechanical forces and detect areas of bone that have become damaged and need to be removed by osteoclasts Interestingly, osteocyte-derived RANKL is not required for the formation and activation of osteoclasts that resorb bone during embryonic development in mice, but it is required for normal bone remodeling in the adolescent and adult mouse skeleton 53 , Mice and humans deficient in RANKL, RANK or M-CSF or its receptor c-fms develop osteopetrosis 10 , 22 , which is characterized by failure of removal of mineralized bone matrix from the medullary cavities of long bones and vertebrae during embryonic development Figure 1.

Consequently, osteopetrotic bones are radio-opaque on X-ray and have a typical diagnostic club-shape to their ends because the resorption of cortical bone on the periosteum at metaphyses that gives the ends a concave configuration does not occur. Despite their sclerotic appearance, osteopetrotic bones are weaker than normal bones 22 , because the bone formed during development is typically composed of woven, rather than lamellar bone, which is stronger than woven bone.

Osteoblast precursors, like osteoclast precursors, appear to circulate in the blood and are attracted to BMUs by molecules released during bone resorption, including various cytokines, chemokines and growth factors 56 , and other osteoclast products, including S1P and collagen fragments Osteoblasts, derived from mesenchymal precursors in the bone marrow, positively and negatively regulate osteoclast formation and activation: osteoblast precursors presumably at the advancing edges of BMUs and osteocytes express M-CSF and RANKL to drive and maintain resorption 5 , Osteoblast precursors destined to become osteoblasts appear to be attracted to the deeper parts of BMUs after osteoclasts undergo apoptosis.

At this site, they form a layer of cells on the lacunar surface and lay down lamellae of bone matrix. The precise details of which subsets of osteoblastic cells promote and inhibit osteoclast formation and where they are located precisely in resorption lacunae remain to be determined. Osteoclasts and their precursors can also positively and negatively regulate osteoblast formation 3 , 5 , but exactly where these subsets of cells are located in BMUs also remains to be determined.

Many of the accessory cells that express RANKL also express OPG to limit osteoclast formation, and the relative concentrations of these cytokines appear to be a major determinant of the level of bone resorption in normal and disease states 3 , A human monoclonal antibody to RANKL has been approved by the FDA for the treatment of a variety of osteolytic bone diseases, including osteoporosis, metastatic bone disease, and multiple myeloma 66 , RANK is expressed by a growing number of cell types in addition to immune cells in bone marrow.

For your jawbone, when you chew and bite, the force you exert through your teeth into your jaws sends signals to osteoblasts to keep that bone strong. If you're missing a tooth due to tooth extraction, gum disease, or injury, the jawbone in the area of loss no longer receives stimuli, osteoclasts will begin to break down the jawbone, and osteoblasts will no longer prioritize rebuilding the bone structure there.

According to Frontiers in Physiology , new bone will still form, but at a slower rate than the bone that is being destroyed. Wearing dentures may increase the rate at which the bone deteriorates. If you wear dentures and they've become loose, it may be a result of bone loss, and they may require refitting. In addition to the symptoms noted above, jawbone loss can cause you to lose teeth and make it difficult or impossible to give you replacement teeth implants, removable bridges, or dentures without an oral surgeon first performing a bone graft.

Jawbone loss can also lead to facial collapse, in which your mouth seems to fall back into your face, your chin becomes more pointed, and your facial muscles weaken.

This will cause premature wrinkling around your mouth and a thinning of your lips. All of these changes tend to make you appear older than your actual age. If you're experiencing bone loss in your jaw, your treatment will largely depend on what's causing it, and your dental professional is best positioned to help you determine the source of the abnormal resorption.

If you have one or more missing teeth and still have enough bone density, it may be recommended that you get dental implants. Implants not only replace teeth but also stimulate the bone and can restore the natural balance of osseointegration and resorption in your jaw. If you've already experienced significant bone loss, bone grafting may be necessary before your dental professional can place an implant in your jaw.

If your bone loss isn't related to tooth loss, bone grafting is still a treatment that can do more than replace bone, but stimulate bone growth, too. If your high level of resorption is due to a condition like osteoporosis, your healthcare professional and dental professional may need to collaborate on treatment for you.

The Mayo Clinic notes that bone loss caused by osteoporosis can be treated with various medications or hormone therapies depending on your age, gender, and whether or not you have other medical conditions. Bone loss in your jawbone can seem frightening, but no matter what's causing your resorption, your dental professional can work with you to develop the best approach for treatment.