Rare metabolic bone diseases Flashcards
What is cortical bone and trabecular bone?
- Cortical bone → the dense outer surface of bone that forms a protective layer around the internal cavity.
- Trabecular bone → hierarchical, spongy, and porous material composed of hard and soft tissue components which can be found at the epiphyses and metaphyses of long bones and in the vertebral bodies.
In the early stages of embryonic development, the embryo’s skeleton consists of fibrous membranes and hyaline cartilage. By the sixth or seventh week of embryonic life, the actual process of bone development, ossification (osteogenesis), begins. There are two osteogenic pathways—intramembranous ossification and endochondral ossification—but in the end, mature bone is the same regardless of the pathway that produces it.
What is intramembranous ossification?
During intramembranous ossification, compact and spongy bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue.
What is endochronal ossification?
Here, bone develops by the replacement of hyaline cartilage. Note: cartilage does not become bone, but it serves as a template to be completely replaced by new bone.
What is the effect of aging on bones?
Bones lose their load baring function due to increasing osteoporosis.
- Bones must be as light as possible, while being as strong as possible. In osteoporosis, bone is no longer able to withstand the loads placed upon it.
Name three factors that determine bone strenght (and fracture resistance)?
- Amount of bone material
- Quality of bone material
- Structural organisation
- Around what mean age is the amount of bone mass highest (peak bone mass)?
- Is there a difference in bone mass between men and women?
- Around 30 years
- Men have a higher bone mass
What factors determine the quality of the bone matrix?
The presence of:
- Anorganic material
- Organic material
- Cells (amount of turnover and repair)
What is Wolff’s law?
Bone structures orient themselves in form and mass to best resist extrinsic forces (i.e. form and mass follow function).
What determines the bone turnover?
The balance and ongoing dynamic process of bone resportion and formation.
What bone cells are responsible for:
- bone resorption
- bone formation
- osteoclasts digest type I collagen of bones
- osteoblast form new bones
What signalling pathway is important for bone formation?
Wnt signalling
What is the Bone (or Basic) Multicellular Unit (BMU)?
A team of cells that dissolves the area of the bone surface and then fills it with new bone/
Name characteristics associated with metabolic bone diseases.
- Dysfunctional bone cells
- Dysbalanced bone turnover
- Increased bone turnover
What is glucocorticoid induced osteoporosis?
Glucocorticoid medications have both direct and indirect effects on bone tissue that lead to bone loss. These drugs have a direct negative effect on bone cells, resulting in a reduced rate of forming new bone. Also, they can interfere with the body’s handling of calcium and affect levels of sex hormones. Either of these problems can lead to increased bone loss.
What type of bone is predominantly affected by corticosteroids?
The trabecular bone
What is pycnodysostosis?
An autosomal recessive mutation in Catepsin K, this causes osteoclasts to appear normal but inactive (so decreased bone turnover and normal bone formation).
What is sclerosteosis?
An autosomal recessive disorder characterized by bone overgrowth as a result of a mutated gene encoded for the sclerostin protein. This protein is necessary for the inhibition of Wnt signaling. Normally, Wnt signalling increases osteoblasts activity and RANKL synthesis. Mutated sclerostin thus results in increased expression of RANKL synthesis and osteoclasts activation. This results in:
- High trabecular bone volume
- High or low turnover
- Sclerostin expression normal
Osteoporosis is characterized by a low (trabecular) bone volume with few/thin trabeculae. What does this lead to?
It leads to vulnerable bones with increased fracture risk.
Describe the pathophysiology of osteoporosis regarding:
- what factors play a role in the pathophysiology of osteoporosis.
- what the result is of these factors at play that eventually lead to increased bone resorption and reduced bone formation and thus osteoporosis.
- hormones, nutrition, mechanical loading, diseases, medication, genetic predisposition, etc.
- factors at play lead to production of certain cytokines and growth factors that lead to increased bone resorption and decreased bone formation.
