Bone Histology

Question 1

Osteoporosis

Answer 1

• Dysregulation of RANK, RANK ligand, and OPG interactions is likely a major contributor in the pathogenesis of osteoporosis.
• Such dysregulation can occur for a variety of reasons, including aging, changes in cytokine environment, and estrogen deficiency .
• The final common pathway in osteoporosis involves an imbalance of osteoblast bone formation, osteoclast bone resorption, and osteoblast (and stromal cell) regulation of osteoclast activation.

Question 2

Osteopetrosis

Answer 2

• Osteopetrosis (stone bone) is a group of rare genetic disorders characterized by reduced osteoclast-mediated bone resorption and therefore defective bone remodelling.
• Carbonic anhydrase II deficiency that makes excellent pathogenic sense because this enzyme is required for the osteoclast hydrogen ion excretion and, therefore, for acidification of the site of bone resorbtion.
• Thus, defective bone remodeling in these patients is directly attributable to reduced bone demineralization.
• The affected bone is grossly dense and stone-like.
• Paradoxically, the bone is architecturally unsound and fractures as readily as a piece of chalk.

Question 3

Osteogenesis Imperfecta “Brittle bone disease”

Answer 3

• Is a hereditary disorders caused by defective synthesis of type I collagen.
• Because type I collagen is a major component of extracellular matrix in other parts of the body, there are also numerous extraskeletal manifestations (affecting e.g., skin, joints, and eyes).
• The molecular pathology underlying OI characteristically involves gene mutations in the coding sequences for α1 or α2 chains of type I collagen.
• Because successful collagen synthesis and extracellular export require formation of a complete and intact triple helix, any primary defect in a collagen chain tends to disrupt the entire structure and results in its premature degradation.

Question 4

Achondroplasia

Answer 4

• Achondroplasia is a major cause of dwarfism.
• The underlying etiology is a point mutation in the fibroblast growth factor receptor 3 (FGFR3) that results in its constitutive activation.
• Unfortunately, activated FGFR3 inhibits chondrocyte proliferation; as a result, the normal epiphyseal growth plate expansion is suppressed and long bone growth is severely stunted.
• Because the most common mutation leads to ligand-independent FGFR3 activation, the disorder is typically autosomal dominant.
• Achondroplasia affects all bones that form from a cartilaginous framework.
• The most conspicuous changes include marked, disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic (sway-backed) posture.
• The cartilage growth plates are disorganized and hypoplastic, in contrast to the expanded, orderly columns normally seen at the epiphyses.

Question 5

Hyperparathyroidism

Answer 5

• PTH excess is increased osteoclastic activity, with bone resorption.
• Cortical and trabecular bone are lost and replaced by loose connective tissue.
• Bone resorption is especially pronounced in the subperiosteal regions and produces characteristic radiographic changes, best seen along the radial aspect of the middle phalanges of the second and third fingers.
• Microscopically, excessive resorptive activity is manifested by the presence of increased numbers of osteoclasts and accompanying erosion of bone surfaces

Question 6

Brown tumor of hyperparathyroidism

Answer 6

In some instances, collections of osteoclasts, reactive giant cells, and hemorrhagic debris form a distinct mass, termed a brown tumor of hyperparathyroidism

Question 7

Osteitis fibrosa cystica (osteodystrophia fibrous, Von Reklinghuasen’s disease of bone)

Answer 7

In some instances, collections of osteoclasts, reactive giant cells, and hemorrhagic debris form a distinct mass, termed a brown tumor of hyperparathyroidism.
Cystic change is common in such lesions (hence the name osteitis fibrosa cystica (osteodystrophia fibrosa ,Von Reklinghuasen’s disease of bone), and they can be confused with primary bone neoplasms.

Question 8

Rickets

Answer 8

• Is a manifestations of vitamin D deficiency or its abnormal metabolism.
• The fundamental change is defective bone mineralization resulting in overabundant nonmineralized osteoid.
• This contrasts with osteoporosis, where the mineral content of the remaining bone is normal, but the total bone mass is decreased
• Refers to a childhood disorder in which deranged bone growth produces distinctive skeletal deformities.
• A disease in which the bone matrix does not calcify normally and the bone spicules formed by the epiphyseal plate become distorted by the normal strains of body weight and muscular activity.
• Ossification processes at this level are consequently hindered, and the bones not only grow more slowly but also become deformed.

Question 9

Osteomalacia

Answer 9

• Is a manifestations of vitamin D deficiency or its abnormal metabolism.
• The fundamental change is defective bone mineralization resulting in overabundant nonmineralized osteoid.
• This contrasts with osteoporosis, where the mineral content of the remaining bone is normal, but the total bone mass is decreased
  is the adult counterpart; bone that forms during the remodeling process is undermineralized, resulting in osteopenia and predisposition to fractures.
• Characterized by deficient calcification of recently formed bone and partial decalcification of already calcified matrix.
• Since adults have no epiphyseal cartilage, the deformation of long bones and retardation of growth that is characteristic of rickets in children does not occur; growth is, of course, not affected.
• Osteomalacia may be aggravated during pregnancy, since the developing fetus requires a great deal of calcium.
• Osteomalacia should not be confused with osteoporosis. In the former (osteomalacia), there is a decrease in the amount of calcium per unit of bone matrix