MSK Diseases 2 Flashcards
Bone and soft tissue tumours
Hx
O/E
Hx
- Bone pain
- Night pain
- Previous history of Cancer
- Red flags: worsening pain, weight loss, night sweats
O/E
- Lump/ soft tissue mass
- Skin may be stuck to mass
- Lymph nodes
- nothing
Bone and soft tissue tumours
Ix
- Bloods: FBC, U&E, CRP, ESR
- Bone profile: Ca, Phosphate, albumin, ALP
- LFTs, LDH (lactate dehydrogenases)
Markers of bone tumours: LDH, ALP
-X-ray (rule of 2)
Whole bone, 2 views, 2 joints (above and below)
Bone and soft tissue tumours
Diagnosis?
Bone and soft tissue tumours
Benign more common in children
TRUE OR FALSE
TRUE
What is the malignant bone and soft tissue tumour in children
Ewing’s sarcoma most common
Compare and contrast well defined, ill defines and sclerotic bone and soft tissue tumours
Examples of benign tumours
Osteoma
Osteochondroma
Giant cell tumours
Bone cysts
endochrondromas
What is Osteoma?
- benign overgrowth of bone most typically occurring on the skull
- more common in children
- resolve by itself in about 18 months
- night pain relieved by NSAIDs
- associated with Gardner’s syndrome (a variant of familial adenomatous polyposis, FAP)
What is Osteochondroma?
exotosis
most common benign bone tumour
more in males, usually diagnosed in patients ages <20 years
cartilage-capped bony porkection on the external surface of a bone
WHat is a giant cell tumour?
- tumour of multinucleated giant cells within a fibrous stroma
- peak incidence 20-40 years
- occus most frequently in th epiphyses of long bones
- X-ray shows a “double bubble” or “soap bubble” appearance
Examples on malignant bone tumours
- Metastasis
- Multiple myelomas
Primary
- Osteosarcoma
- Chondrosarcoma
- fibrosarcoma
Haematological
- Leukaemia
- Lymphoma
Features of malignant bone tumours
More common in older (>40yr)
Hypercalcemia
Fractures
Cauda equina
Multiple myelomas are neoplastic plasma cells
TRUE OR FALSE
TRUE
How do you identify multiple myelomas
- Bence-jones proteins in urine
- Presentation: CRAB
HyperCalcaemia
Renal failure
Anaemia
Punced out Bony lesions
Pathological fractures
- Histology: round plasma cells, eccentric nucleus, clock face chromatin
Examples of primary bone tumours (malignant)
Osteosarcoma
Ewing’s sarcoma
Fibrosarcoma
Features of Osteosarcoma?
Features of Ewing’s sarcoma
Features of Fibrosarcoma
Which one is Sun burst appearance and which one is Codman’s triangle
Muscle and ligamentous injuries
How do you grade in muscle injuries
What is grading for ligamentous injuries like?
What is the healing potential for Ligaments
Depends upon grade of injury and ligament injured.
3 phases - same as bone.
- Inflammation.
- Repair - Type III collagen
- Remodelling - Type I collagen
What is the healing potential for Tendon
- Depend upon Grade of injury.
- Repairs weakest at 7 - 10 days.
- Regain most of original strength at 21 - 28 days.
- Maximum strength at 6 months
What is the importance of physio?
- Promote early function.
- Increase ROM.
- Encourage weight bearing.
- Improve muscular strength/endurance and control.
Bone structure
- Outer= inner=
- ECM=
- Bone is layer down in lamellae
- Osteon-=
- Volkmann’s cannal=
- Woven bone=
- Outer= cortex, inner=trabecular
- ECM= osteoclasts, osteoblasts and osteocytes
- Bone is layer down in lamellae
- Osteon-= concentric lamellae with central haversian canal
- Volkmann’s cannal= in between osteons
- Woven bone= immature bone
Normal function of bone
- Support
- Movement
- Protects organs
- Hematopoiesis
- Mineral homeostasis
Bone remodelling
RANKL-RANK-OPG:
RANK binds to osteoclast precursor
RANKL binds to RANK->stimulates NFkB-> activates osteoclast formation
OPG inhibits RANK/RANKL binding-> inhibiting osteoclast formation
WHat is Reverse RANK-RANKL signaling
RANK binds to extracellular vesicle-> attaches to RANKL on osteoblast-> stimulates RUNX2-> osteogenesis
Sclerostin inhibits Wnt-> inhibiting osteogenesis
Bone mineralisation is associated with?
calcium and phosphate
Ca2+ regulated by ____ cells of the Parathyroid gland
Ca2+ regulated by chief cells of the Parathyroid gland
What happens if there is a decrease in calcium?
If decrease in Ca2+-> PTH-> decrease PO4 & increase Ca2+
What happens next after increase in calcium and decrease in phosphate
binds to osteoblasts-> promotes osteoclastogenesis via RANKL upregulation-> excess Ca2+ ( CKD -> 2dary hyperparathyroidism)
stimulates production of calcitriol-> promotes synthesis of calbindin in intestinal epithelial cells-> increased absoprtion of Ca2+ in GI tract
promotes Ca2+ reabsorption in kidneys
What does oestrogen inhibit
sclerostin
inhibition of sclerostin allows?
osteoblastogenesis
+ inhibits RANKL-> no osteoclastogenesis
What happens when there is oestrogen deficiency?
Oestrogen deficiency-> osteoclastogenesis, no inhibition of sclerostin-> inhibited osteoblastogenesis
Perimenopause/Childbearing-> estrogen-> osteoblastogenesis
Postmenopausal-> problems start – osteoporosis/ osteopenia
What is osteoporosis?
- Porous bones- reduced trabecular bone à increased risk of fracture (50 y/o female = 50% lifetime risk of fragility fractures)
- resorption>formation
- Most common metabolic bone disease
Osteoporosis RF
- Affects women more after menopause à less oestrogen àosteoclastogeneis + uninhibited sclerostin à deceased osteoblastogenesis
- Affects old people more (senile osteoporosis) à impaired osteoblast function à more resorption
- Older age
- Female
- Reduced mobility and activity
- Low BMI (<18.5 kg/m2)
- Rheumatoid arthritis
- Alcohol and smoking
- Long term corticosteroids. NICE suggest the risk increases significantly with the equivalent of more than 7.5mg of prednisolone per day for more than 3 months)
- Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens
What is the determinant of osteoporosis
•Determinants of peak bone mass: genetics, body weight, sex hormones, diet, exercise
Determinants of bone loss: sex hormone deficiency, genetics, diet, immobility, diseases, drugs (corticosteroids, aromatase inhibitors, glitazones
CF of osteoporosis
- height loss
- thoracic kyphosis or lumbar lordosis
- protuberant abdomen
- decreased lung capacity
- early satiety, weight loss, oesophageal reflux
Ix for osteoperosis?
-DEXA scan
- Compares pts bone density to that of a normal adult
- Produces a T-score = 2.5 è osteoporosis
- X ray
- PTH, TFTs, vit D, urinary calcium (24hr), bone turnover markers- CTX & P1NP
Treatments for osteoporosis
Antiresorptive:
- Bisphosphonates eg alendronic acid
- Anti-RANKL ab eg Denosumab
Anabolic:
- recombinant PTH eg teriparatide
- Anti-sclerostin Ab eg Romosozumab
What is pagets disease
- Disorder of bone remodelling – focally increased and disorganised bone turnover
- driven by abnormal osteoclasts à increased and haphazard osteoblast activity à formation of poor quality woven bone
Paget’s disease of bone refers to a disorder of bone turnover. There is excessive bone turnover (formation and reabsorption) due to excessive activity of both osteoblasts and osteoclasts. This excessive turnover is not coordinated, leading to patchy areas of high density (sclerosis) and low density (lysis). This results in enlarged and misshapen bones with structural problems that increase the risk of pathological fractures. It particularly affects the axial skeleton (the bones of the head and spine).
Causes for pagets disease
Genetics
- Fx
- Mutations- SQSTM1 most common
- Ethnicity
Environmental
- Involvement of paramyxovirus
- Mechanical loading of affected bone
- Poor nutrition in childhood
CF of pagets disease
- Early – asymptomatic
- Bone Pain= bone impinges on nerves
- Overgrowth of bone
- Facial deformity- leontiasis
- Hearing loss- impingement on auditory nerve
- Vision loss – impingement on optic nerve
- Osteosarcoma à pagets sarcoma
- Kyphosis
- Lower limb muscle weakness
- Pelvic asymmetry
- Bow legs
- Arthritis
- Fractures
- Bone deformity
- Fractures
- Hearing loss can occur if it affects the bones of the ear
Ix for pagets disease
- Elevated ALP (isolated)
- Elevated bone turnover markers à P1NP and CTX
- X ray- osteolysis, osteosclerosis, chaotic bone architecture, bone expansion and deformity
- Radionucleotide bone scan- increase in tracer uptake in affects bones
Pagets disease treatment
•Bisphosphonates eg Zoledronate and risedronate – they cause osteoclast dysfunction/death
Other measures include:
- NSAIDs for bone pain
- Calcium and vitamin D supplementation, particularly whilst on bisphosphonates
- Surgery is rarely required for fractures, severe deformity or arthritis
What is rickets
- decreased serum calcium/phosphate à widening and delay of mineralisation of growth plates in bones
- Associated with osteomalacia
Causes for Rickets
•Causes bowing deformity of bones, rachitic rosary, Harrison sulcus, widened wrist
Rickets
other features
- Widening gair/ delay in walking
- Bone pain, fatigue
- Fractures
- Short stature
- Tetany/ seizures
- Cardiomyopathy
What can you see radiologically with rickets
What other types of rickets
Vitamin d dependent rickets
Hypophosphatemic rickets
Vitamin d dependent rickets
Causes?
Types?
Caused by
- Deficiency in 1 alpha hydroxylase
- Inactivating mutations in the vit D receptor
VDDR type I:
- Deficiency in 1-alpha hydroxylase ( converts into calcitriol)
- 25(OH) will be normal/high but 1,25(OH) will be low
VDDR type II:
- Inactivating mutations in Vit D receptor- VDR
- Both 25(OH), 1,25(OH) will be normal or high
Hypophosphatemic rickets
WHat is it
subtypes?
- Excessive renal phosphate losses
- Low serum phosphate for normal bone mineralisation
- Excess in FGF23 expressed by osteocytes
- PHEX, DMP1 normally inhibit FGF23-> mutations increase FGF23
- Subtypes:
- XLH: X-linked, PHEX- more common
- ADHR:AD, FGF23
- ARHR:AR, DMP1
What is osteomalacia?
causes
- Softening of bones dues to defective mineralisation of newly formed bones
- Mainly caused by vit D deficiency, Hypophosphatemia, inhibitors of mineralisation
CF for osteomalacia
- Bone pain
- Bone tenderness
- Fractures
- Muscular weakness
- Malaise
- Tetany
- Fatigue
Looser zones are fragility fractures that go partially through the bone.
Ix for osteomalacia?
Treatment for Rickets and osteomalacia
- Vitamin D and calcium
- Active vit D metabolites (+/- calcium infusions) for VDDR
- Phosphate supplements for hypophosphataemic rickets, plus active vitamin D metabolites
- Burosumab (anti FGF23 ab) for children with XLH
What is FRAX Tool
The FRAX tool gives a prediction of the risk of a fragility fracture over the next 10 years. This is usually the first step in assessing someone’s risk of osteoporosis.
It involves inputting information such as their age, BMI, co-morbidities, smoking, alcohol and family history. You can enter a result for bone mineral density (from a DEXA scan) for a more accurate result but it can also be performed without the bone mineral density.
It gives results as a percentage 10-year probability of a:
- Major osteoporotic fracture
- Hip fracture
What does DEXA SCAN show
WHO Classification
Bone mineral density (BMD
What is FRAX assessment
Assessing For Osteoporosis
The first step is to perform a FRAX assessment on patients at risk of osteoporosis:
- Women aged > 65
- Men > 75
- Younger patients with risk factors such as a previous fragility fracture, history of falls, low BMI, long term steroids, endocrine disorders and rheumatoid arthritis.
FRAX outcome without a BMD result will suggest one of three outcomes:
FRAX outcome with a BMD result will suggest one of two outcomes:
FRAX outcome without a BMD result will suggest one of three outcomes:
- Low risk – reassure
- Intermediate risk – offer DEXA scan and recalculate the risk with the results
- High risk – offer treatment
FRAX outcome with a BMD result will suggest one of two outcomes:
- Treat
- Lifestyle advice and reassure
Management for osteoporosis
Lifestyle Changes:
Vitamin D and Calcium:Calcichew-D3, which contains 1000mg of calcium and 800 units of vitamin D (colecalciferol).
Bisphosphonates are the first-line treatment for osteoporosis.
- Alendronate 70mg once weekly (oral)
- Risedronate 35 mg once weekly (oral)
- Zoledronic acid 5 mg once yearly (intravenous)
Simplified Pathophysiology Osteomalacia
Patients with darker skin require a longer period of sun exposure to generate the same quantity of vitamin D. A standard diet contains inadequately levels of vitamin D to compensate for a lack of sun exposure. Reduced sun exposure without vitamin D supplementation leads to deficiency. Patients with malabsorption disorders (such as inflammatory bowel disease) are more likely to have vitamin D deficiency. The kidneys are essential in metabolising vitamin D to its active form, therefore vitamin D deficiency is common in chronic kidney disease.
Vitamin D is essential in calcium and phosphate absorption from the intestines and kidneys. Vitamin D is also responsible for regulating bone turnover and promoting bone reabsorption to boost the serum calcium level.
Inadequate vitamin D leads to a lack of calcium and phosphate in the blood. Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation. Low calcium causes a secondary hyperparathyroidism as the parathyroid gland tries to raise the calcium level by secreting parathyroid hormone. Parathyroid hormone stimulates increased reabsorption from the bones. This causes further problems with bone mineralisation.
Patients with osteomalacia are likely to have risk factors such as darker skin, low exposure to sunlight, live in colder climates and spend the majority of their time indoors.
TRUE OR FALSE
TRUE
Investigations Osteomalacia
Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D. The interpretation of the results is as follows:
- <25 nmol/L – vitamin D deficiency
- 25 – 50 nmol/L – vitamin D insufficiency
- 75 nmol/L or above is optimal
Other investigation results include:
- Serum calcium is low
- Serum phosphate is low
- Serum alkaline phosphatase may be high
- Parathyroid hormone may be high (secondary hyperparathyroidism)
- Xrays may show osteopenia (more radiolucent bones)
- DEXA scan shows low bone mineral densit
Ix Pagets disease
Bone enlargement and deformity
- “Osteoporosis circumscripta” describes well defined osteolytic lesions that appear less dense compared with normal bone
- “Cotton wool appearance” of the skull describes poorly defined patchy areas of increased density (sclerosis) and decreased density (lysis)
- “V-shaped defects” in the long bones are V shaped osteolytic bone lesions within the healthy bone
Biochemistry
- Raised alkaline phosphatase (and other LFTs are normal)
- Normal calcium
- Normal phosphate
Complications Paget’s Disease
- Osteogenic sarcoma (osteosarcoma)
- Spinal stenosis and spinal cord compression
