Understanding Sclerotic Bone

This article is directed more toward university professors to assist them in understanding the bone tissue samples they view histologically.

Sclerotic bone is a common pathological finding in routine radiographs. A common type of sclerotic bone known to all dentists is condensing osteitis. However, there are many different causes of sclerotic bone and they include vascular infarct, infection such as osteomyelitis, neoplasms, inflammation, genetic mutations, trauma, and metabolic diseases such as hyperparathyroidism and Paget’s disease.

The term sclerosis is defined as

pathological hardening of tissue especially from overgrowth of fibrous tissue or increase in interstitial tissue
an inability to adapt

While there are many different causes of sclerotic bone and each of them have differing clinical characteristics, the most common cause of sclerotic bone in the human skeleton is inflammation. Osteoarthritis and atherosclerosis are inflammatory diseases, and both produce sclerotic bone lesions. In dentistry, the most common sclerotic lesions are caused by condensing osteitis and cadaver bone grafts.

A common denominator of sclerotic lesions caused by inflammation is that they are all protective. They are formed by the body in order to defend itself and contain the damage being caused by the inflammation. In coronary heart disease (atherosclerosis), the calcium deposits are not just areas of mineral deposition in the affected arteries, but actual bone formation. Atherosclerosis results in a buildup of fatty plaques in the artery wall. A coronary infarct occurs when fatty plaques rupture and the contents move into smaller vessels and cause a blockage. In order to stop the fatty plaques from rupturing, bone is formed around the plaques to prevent their rupture. The bone formed in atherosclerosis is a result of inflammation causing the conversion of smooth muscles cells in the artery wall to convert into mineralizing cells. The bone formed in our artery walls is irreversible due to the lack of cells that can resorb the sclerotic bone. If chelation therapy, which is designed to remove the bone mineral in the arterial wall, were successful it would likely result in a significant increase in the potential for a coronary infarct, which shows how a little knowledge can be dangerous.

Sclerotic bone has been researched extensively in osteoarthritis. Current thinking is that overload causes an inflammatory response in the subchondral bone. This inflammatory response causes the thickening and stiffening of the bone in order to support the cartilage lining the joint.

The nature of sclerotic bone has been studied extensively in atherosclerosis and osteoarthritis, but minimally in condensing osteitis and cadaver bone grafts, but we can use the knowledge gained in studying sclerotic bone in joints to gain an better understanding of sclerotic bone in the jaws.

Sclerotic bone is structurally and physiologically different from normal bone. Sclerotic bone has an increased trabecular number and thickness, decreased trabecular spacing, increased stiffness, and reduced hardness when compared to normal bone.

This microCT scan shows an increase in bone volume compared to total volume with an accompanying increase in mineral density and trabecular thickness.

Physiologically, there is an increase in molecular markers alkaline phosphatase, osteopontin, osteocalcin and a decrease in sclerostin, all of which are associated with increasing bone formation.

Osteocytes control bone formation and resorption and significant differences can be found in osteocytes in normal bone versus sclerotic bone.

Comparing normal osteocytes on the left and osteocytes from sclerotic bone on the right shows the osteocytes in normal bone are spindle in shape, have smooth walls, and are aligned. In sclerotic bone the osteocytes are round, rough and non-aligned.

The normal osteocyte on the left shows a spindle shape with regular extensive dendrites. The osteocytes found in sclerotic bone on the right shows a rounded body with decreased and disorganized dendrites.

Osteoblasts that form sclerotic bone are also very different form normal osteoblasts. First, let’s see what normal osteoblasts look like while forming normal bone.

This photomicrograph is from a socket grafted with Socket Graft after 6 weeks. The osteoblasts are lined up on the surface of bone secreting osteoid. The normal osteoblasts are cuboidal in shape and form sheets over the osteoid. Note the lack of inflammatory cells.

This photomicrograph is from a remodeling site in the mandible. The osteoblasts are again cuboidal in shape forming a sheet on the osteoid that is being secreted over the mineralized bone. No inflammation is present.

Again, normal osteoblasts line the upper portion of this photomicrograph. The cells are cuboidal in shape, forming a sheet over the mineralized bone. An osteoclast is found in the bottom of the soft tissue. Note its relative size compared to the osteoblasts. (New Zealand White rabbit at 6 weeks grafted with Socket Graft)

When osteoblasts form sclerotic bone, the cells are round and separated. The cells do not form sheets. The osteoblasts secrete osteoid around the entire cell and encapsulate each cells in mineralized tissue. Note the mineralized tissue with encased osteoblasts. The intense inflammation is obvious. (New Zealand white rabbit grafted with mineralized allograft)

Bone remodeling is very organized with close orchestration of bone formation by osteoblasts and bone removal by osteoclasts.

The bottom of the soft tissue in this photomicrograph is lined by osteoclasts. Note there is no inflammation.

In sclerotic bone, remodeling is disjointed. There is no communication between osteoblasts and osteoclasts. In the early phase of sclerotic bone formation, osteoclasts are huge and not associated with a basic multicellular unit. In the center of the photomicrograph is one osteoclast. This cell is the largest cell we ever identified.

This is a higher power of the osteoclast identified in the previous photomicrograph. The cell is many times the size of a normal osteoclast. The cell is resorbing a mineralized allograft particle. Normal osteoclasts most often form layers and work together. However, in early sclerotic bone formation the osteoclasts are usually seen individually. After sclerotic bone has formed and has encased the allograft particles, osteoclasts are no longer found in the sclerotic bone.

As mentioned earlier, sclerostin is a negative regulator of bone formation. In sclerotic bone, sclerostin is decreased and results in the increased bone volume found in sclerotic bone. However, by contrast, there is an increased expression of DMP1 which impairs mineralization and results in poorly organized mineral composition found in sclerotic bone. A histological characteristic of sclerotic bone is a significant reduction in vascular supply. There is a decrease in arterial inflow of sclerotic bone when compared to normal bone combined with a decrease in outflow. Very few capillaries are found in sclerotic bone. Sclerotic bone osteoblasts express high levels of inflammatory cytokines such as transforming growth factor b1 (TGFb1) and prostaglandin E2 (PGE2). Overexpression of inflammatory cytokines is thought to contribute to sclerotic bone disturbance. In mature sclerotic bone, the number of CD68+ macrophages and CD20+ B lymphocytes are significantly higher as can be found in the previous slides. B cells and their secretion of IL-10 are associated with delayed bone fracture healing. The macrophages are believed to affect the recruitment of osteoprogenitor cells and their differentiation into the strikingly altered osteoblast, osteocyte, and osteoclast phenotype in sclerotic bone. Wnt/β-catenin signaling is one of the pathways that are a normal response to mechanical loading in bone cells. In sclerotic bone, loading has been found to suppress osteoclastogenesis by the Wnt signaling pathway. The results indicated that mechanical loading increased the expression of Wnt3a, and reduced expression of NFATc1 (a master transcription factor for development of osteoclasts), RANKL, TNF-α, and Cathepsin K in sclerotic bone. It has previously been shown that Wnt signaling inhibited osteoclastogenesis by decreasing the expression of genes that were involved in osteoclast development. The combination of increased bone forming cytokines and reduced bone resorbing cytokines explains why osteoclasts are never found in mature sclerotic bone and why the remaining cadaver bone graft particles and sclerotic bone that surrounds the particles are never resorbed.

The following graphic explains the differences seen in early and late sclerotic bone formation. In the early stages of sclerotic bone formation, there is an uncoupling of bone formation and resorption. Both bone formation and resorption are significantly altered in the presence of inflammation that results in osteocytes, osteoblasts, and osteoclasts that have a significantly altered appearance and cytokine profile. The image on the left matches the cellular activity of the histology of sclerotic bone produced at 6 weeks after grafting with a mineralized allograft that was shown previously. On the right in late stage sclerotic bone, osteoclasts are absent which results is a high percentage of mineralized tissue and no resorption of the sclerotic bone.

Let’s now apply what we have learned and move into the oral cavity and look at sclerotic lesions of the oral cavity.

An obvious sclerotic lesion is found mesial to the molar.

A bone core sample is taken from the lesion. As is typical of sclerotic lesions, very little blood is present in the sample tissue.

The histology is typical of sclerotic bone that is produced by an inflammatory reaction to the implanted foreign proteins found in cadaver bone grafts. In this case, the sclerosis was created by a xenograft. The characteristics that allows the diagnosis as sclerotic bone is the lack of vascular supply, absence of osteoclasts, and absence of remodeling. Upon communication with the treating clinician, it was confirmed that the site was grafted with Bio-Oss 10 years prior.

Sclerotic bone lesions present with varying amounts of radiopacity. Typical of sclerotic lesions this lesion is surrounded by a distinct radiolucent border.

The histology from this sclerotic lesion is again typical of all sclerotic bone lesions. Very little vascular supply is found, no osteoclasts are found, and no bone remodeling is present. The bone core sample has a high mineralized tissue percentage. Upon communication with the treating clinician, it was confirmed that the site was grafted with a mineralized allograft 6 months prior to this bone core sample.

In the presence of inflammation, our skeleton forms sclerotic bone. The sclerotic bone is a protective mechanism. In arteries, sclerotic bone prevents fatty plaques from causing a coronary infarct. In the joint, the sclerotic bone supports the cartilage in an effort to limit the loss of cartilage and thinning of the joint space. In condensing osteitis, sclerotic bone is formed to isolate the pulpal inflammation. Sclerotic bone formation around cadaver bone grafts isolates the body from the inflammation caused by foreign proteins. Sclerotic bone found in atherosclerosis, osteoarthritis, and cadaver bone grafts is irreversible because the cause of inflammation cannot be removed. In condensing osteitis, sclerotic bone is reversible upon removal of the inflamed pulp.

In an upcoming article, we will discuss how the characteristics of sclerotic bone affect clinical outcomes.

MEMBER:

American Society for Bone and Mineral Research (ASBMR)

Tissue Engineering and Regenerative Medicine International Society (TERMIS)