Abnormalities of Bone Structure Flashcards
What is normal compositon of bone
90% type 1 collagen (contains glycoproteins and proteoglycans)
Osteoid (protein matrix of bone secreted by osteoblasts)
Hydroxyapatite (mineral component of calcium and phosphate)
State the properties of the two structural forms of bone
Woven bone:
Weak
Rapid osteoid production
Collagen in an unorganised structure
Normally seen in growth and repair of bone
Lamellar bone:
Strong
Parallel collagen fibres (lamellae)
Normal (adult) stable form of bone
What factors can cause disruption to the structure of bone?
Over active or underactive osteoblasts or osteoclasts (Change in bone turnover)
Renal disease
Hyperparathyroidism
Loss of mineralisation (rickets due to lack of vitamin D)
Tumours (affect activity of osteoclasts and osteoblasts)
What biochemical tests can you do to assess bone structure?
Blood test and U+E analysis for biochemical markers.
Calcium homeostasis (Ca2+, PO4-, vitamin D, PTH)
Bone turnover (Alk phos, osteocalcin, collagen breakdown)
What investigations could you do to assess bone structure?
Plain X-ray
MRI/CT/ultrasound
Tc radionucleotide scans
Bone biopsy - histology
Bone density (diagnostic for osteoporosis)
What are osteochondrodysplasias?
group of conditions among the skeletal dysplasias characterised by abnormal growth or development,
e.g. osteogenesis imperfecta (OI)
What are the signs and symptoms associated with osteogenesis imperfecta?
‘Brittle bone disease’
multiple fractures
deformed teeth (dentinogenesis imperfecta)
growth retardation
hearing loss
blue/grey sclera
Presentation varies because all areas of the body with type 1 collagen are affected
What investigations would you carry out in suspected OI?
Physical examination (blue sclera, hearing loss, dentition)
Genetic analysis
What are the main abnormalities seen in the four most common types of osteogenesis imperfecta?
type 1: mild bony deformities, normal stature blue sclerae, defective dentine, early-onset deafness, hypermobility of joints, and heart valve disorders.
type 2: lethal in the perinatal period
type 3: severe bone deformities, defective dentine, short stature, deformity at birth
type 4: mild/moderate deformity, short stature, tooth problems
What s the treatment given to patients with osteogensis imperfecta?
Bisphosphonates
Inhibits osteoclast activity and increases the cortical thickness of bone
What are the common signs and symptoms associated with Paget’s Disease?
Begins late in adulthood (70 years)
fractures
pain (microfractures of bone or bone overgrowth that compresses the nerves, localised to the affected bone)
deformities in bone (bowing, increased skull size, spinal curvature)
arthritis
deafness
cardiac
Describe the underlying pathology Paget’s Disease
Paget’s disease is a disorder of bone remodelling.
The initial event of excessive resorption (osteolytic stage) followed by a compensatory increase in new bone formation by osteoblasts (mixed stage).
Formation then exceeds resorption as osteoblastic activity predominates, however this progresses to a burnt-out osteosclerotic stage. The new lamellar bone is disordered, and has a mosaic pattern with coarse thick trabeculae and a soft, porous cortex that lacks stability and is therefore prone to fractures under stress.
How is Paget’s disease diagnosed?
X-ray: Bone is typically enlarged with thick, coarsened cortices and cancellous bone.
Isotopic bone scans can indicate areas of active bone formation
Many affected individuals have elevated serum alkaline phosphatase levels
Describe the underlying pathology of osteogenesis imperfecta
OI is caused by deficiency in the synthesis of type 1 collagen, and primarily affects bone.
Results from autosomal dominant mutations that involve the substitution of glycine residues in the alpha chains of collagen. This disrupts is secondary and tertiary structure , making the triple helix unstable. The collagen produced is weaker and the resulting bone is brittle - therefore more likely to fracture.
Describe the histological appearance of bone in a patient with Paget’s disease
Mosaic pattern of lamellar bone
Bone is larger than normal
Has thick coarse trabeculae and porous cortex
More vascular
Describe the pathophysiology of osteoporosis
As an individual ages, there is decreased replicative activity of osteoprogenitor cells and decreased activity of osteoblasts and growth factors.
Reduced physical activity also reduces mechanical stress on the bone which encourages remodelling.
In women, decrease in oestrogen also removes inhibiton of osteoclasts.
Overall increase in osteoclast activity which promotes resportion of bone, particularly in bones with a large surface area e.g. vertebral bodies
Trabecular bone becomes thin and perforated, and cross-linking is lost. Bone becomes weak.
