Bone Conditions

Achondroplasia

This is the most common cause of dwarfism, which occurs due to a gene mutation in the receptor that converts cartilage to bone during development.

It is due to an activating mutation (usually sporadic) in FGF3 (autosomal dominant).

This gene is found in chondrocytes and inhibits growth favouring differentiation.

Whilst endochondral ossification is affected, there is normal intramembranous bone formation meaning that patients have a normal skull and torso but short limbs.

It leads to dwarfism with short limbs but a normal head and chest size.

Symptoms

Short limbs with normal head and chest

Management

Growth hormone therapy (somatotropin)

Osteogenesis Imperfecta

This is a congenital defect of bone formation due to an autosomal dominant mutation in collagen type 1 synthesis.

This results in very weak bones structurally, which predisposes to fracture.

Symptoms

Multiple fractures in bones

Skin that bruises easily

Blue sclera

Hearing loss due to inner ear bone fractures

Management

No cure, but fractures are managed and lifestyle changes

Osteopetrosis

This is an inherited defect of bone resorption which causes abnormally thick, heavy bone which often fractures

Mutations in genes lead to poor osteoclast function, shift balance to bone formation

It is often caused by mutation of carbonic anhydrase II, leads to decreased resorption of bicarbonate, leading to renal tubular acidosis type II 

Symptoms

Multiple fractures

Anemia, leukopenia – due to bone marrow being replaced with hard bone

Vision and hearing impairment – due to pressure on cranial nerves

Hydrocephalus – due to narrowing of the foramen magnum which occurs with skull enlargement

Management

Bone marrow transplant can be used to regenerate functioning osteoclasts 

Paget’s Disease of Bone

This is a condition due to an imbalance between osteoclast and osteoblast function.

There is increased bone turnover due to higher numbers of osteoblasts and osteoclasts leading to bone remodeling, often caused by mutations in RANK ligand.

This gives rise to a thick, sclerotic bone that fractures easily.

It is usually seen in late adulthood and is more common in cooler climates.

It usually involves one or more bones, rather than the entire skeleton.

Symptoms

Deep, bone pain caused by microfractures

Enlargement of pelvis, femur, tibia and skull – increases hat size and can cause hearing loss

Can lead to osteosarcoma and high output heart failure – due to AV shunts within bone

Key tests

Normal Calcium, phosphate and PTH, but ALP is markedly raised

X-ray shows bone enlargement and cortex thickening with sclerosis and deformity

Management

Medical management includes bisphosphonates (e.g., alendronate to inhibits osteoclasts) and calcitonin (inhibits osteoclast functioning)

Osteoporosis

This is a reduction in overall bone mass, which increases the risk of bone fracture.

Women lose trabecular bone with age, but men have more stable trabeculae during their lifetime, reducing the risk of osteoporosis.

Osteoporosis leads to the majority of fragility fractures in the elderly, e.g., vertebrae, hip and distal radius.

Causes

Can by primary (age-related) or secondary to other conditions or drugs. A useful mnemonic to remember is (SHATTERED)

Key tests

Blood tests show normal Ca2+, PO43-, PTH and ALP levels

DEXA scan measures bone density to give a T-score, a statistical score of how many standard deviations bone density is away from normal

T score between -2.5 and -1 is suggestive of osteopenia

T score < -2.5 suggests osteoporosis

Management

Lifestyle – stop smoking and drinking and increase weight bearing exercises

Ensure levels of vitamin D and calcium are optimised

Medical management is bisphosphonates (e.g., alendronate)

If unsuitable, options include denosumab, strontium ranelate (stimulates osteoblasts) or raloxifene (if post-menopausal).

Hormone replacement therapy can be used in younger postmenopausal women.

Rickets/Osteomalacia

This is a disease which occurs due to defective mineralisation of osteoid with calcium.

It occurs due to low levels of vitamin D resulting in low serum Ca2+ and PO43-.

In children, it causes the disease rickets, which causes symptoms like growth retardation and bowing of the legs.

Causes

Decreased sun exposure, poor diet, malabsorption (coeliac disease) and renal failure

Vitamin D-resistant rickets – due to low renal 1a-hydroxylase activity or receptor resistance

X-linked hypophosphateaemic rickets – dominantly inherited, defect in renal phospate handling

Symptoms

Bone pain and weak bones increasing risk of fracture

Key tests

Blood tests show low Ca2+, low Phosphate, high PTH and ALP levels

X-ray show loss of cortical bone and partial non-displaced fractures on the scapulaand femoral shaft (Looser’s zones)

Management

Vitamin D supplements

Osteomyelitis

This refers to inflammation of bone tissue, usually due to an infection of the bone.

Bacteria can enter the bone from the blood, from local skin infections (cellulitis) or from trauma (such as surgery/fractures).

The most common pathogen is Staphylococcus aureus, but others include Pseudomonas, E. coli as well as N. gonorrhoeae (in sexually active adults).

Causes

Staph Aureus (90%)

N gonorrhoeae (sexually active adults)

Pseudomonas (diabetes)

Symptoms

Bone pain with systemic signs of infection (High WBC and fever)

Key tests

Bloods show raised inflammatory markers. Blood cultures to assess for bacteraemia

X-ray and CT can be used, but MRI is the best imaging modality

Management

IV antibiotics (often prolonged course). May require surgery in severe cases.