Metabolic Bone Disease

Question 1

Non-neoplastic bone pathology

Answer 1

Congenital/Acquired: trauma, infection, degeneration, inflammation, metabolic

Question 2

Neoplastic bone pathology

Answer 2

Benign/malignant tumours

Question 3

Function of bone

Answer 3

Mechanical - support and site for muscle attachment
Protective - vital organs and bone marrow
Metabolic - reserve of calcium

Question 4

Composition of bone

Answer 4

Inorganic - 65% (calcium hydroxyapetite, is storehouse for 99% of calcium in the body, 85% of the phosphorus, 65% of the sodium and magnesium)

Organic - 35% (bone cells and protein matrix)

Question 5

Bone structure medial to lateral

Answer 5

Medulla
Cortex
Periosteum

Question 6

Bone structure proximal to distal (e.g. arm)

Answer 6

Diaphysis
Metaphysis
Epiphysis (epiphyseal line, subchondral bone)
Articular cartilage

Question 7

Small synovial joints

Answer 7

Facet joints of fovea

Question 8

What percentage of mineralisation does bone need to have for it to be visible on X-ray

Answer 8

50%

Question 9

Types of bone

Answer 9

Cortical

Cancellous

Question 10

Features of cortical bones

Answer 10

Long bones 
80% of skeleton 
Appendicular 
80-90% calcified 
mainly mechanical and protective 
Less metabolically active

Question 11

Features of cancellous bone

Answer 11

Vertebra and pelvis 
20% of skeleton 
Axial skeleton 
15-25% calcified 
Mainly metabolic 
Large surface area

Question 12

Structure of cortical bone

Answer 12

Trabecular lamellae
Interstitial lamella
Concentric lamellae
Circumferential lamellae

Question 13

Bone cells

Answer 13

Osteoblasts
Osteoclasts
Osteocytes

Question 14

Features of osteoblasts

Answer 14

Build bone by laying down osteoid

Question 15

Feature of osteoclasts

Answer 15

Multinucleate cells of macrophage family

Resorb or chew bone

Question 16

Features of osteocytes

Answer 16

Osteoblast like cells which sit in the lacunae in bone

Question 17

Stain used to view osteocytes and canaliculae

Answer 17

Silver stain

Question 18

What promotes osteoblast activity

Answer 18

Osteoclast activity released matrix bound growth factors in bone, which allows osteoprogenitor cells to differentiate into osteoblasts.

NB: mechanical factors, hormones and cytokines activate surface osteoblasts which promote activity of osteoclasts

Question 19

Activation of osteoclasts

Answer 19

RANK is expressed on the surface of osteoclast lineage cells.
RANKL is expressed on multipotential stem cells (MSCs) of osteoblast lineage and on T- and B- lymphocytes.
When RANKL binds to RANK this causes the osteoclast precursor cell to differentiate and thus increase bone resorbtion.

OPG competes with RANK for RANKL. OPG is also expressed by MSCs and osteoblast cells.

Question 20

How are bony metastases formed

Answer 20

Oncogene products produced by tumour cells metastasising to bone influence the bone cells to resorb bone and promote local growth of the tumour. This is mediated by the RANK /OPG signalling pathway.
I.e. when tumour growth is promoted, the bone is destroyed.

Question 21

What can tumours do to bone

Answer 21

Induce bone resorption

Induce bone formation

Question 22

What cancer causes more bone growth than destruction

Answer 22

Metastatic prostate carcinoma

Question 23

Types of bone

Answer 23

Woven/lanellar
Anatomically - flat bones/long bones (intramembranous and endochondrial ossification)
Trabecular (cancellous)/compact (cortical)

Question 24

Features of lamellar bone

Answer 24

Cortical and cancellous bone are lamellar and this is particularly evident when viewed under polarised light
Collagen fibres are arranged in alternating orientations allowing for the highest density of collagen per unit of tissue

Question 25

Features of woven bone

Answer 25

In woven bone the lamellar are absent. Collagen fibres are laid down in a disorganized fashion: such as states of high bone turnover(Pagets disease of bone, certain stages of flouride treatment, tumours) not so tightly packed, random bundles

Question 26

Metabolic bone disease

Answer 26

Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc) Overall effect is reduced bone mass (osteopaenia) often resulting in fractures with little or no trauma

Question 27

Categories of bone disease

Answer 27

Non-endocrine (e.g. age related osteoporosis) Related to endocrine abnormality (vitamin D, parathyroid hormone) Disuse osteopaenia

Question 28

Diagnosis of metabolic bone disease

Answer 28

Histology requires bone biopsy from iliac crest, | processed undecalcified for histomorphometry.

Question 29

Studies performed on bone biopsy to diagnose metabolic bone disease

Answer 29

Static parameters: cortical thickness and porosity, trabecular bone volume, thickness, number and separation of trabeculae Bone mineralisation studied using osteoid parameters Histodynamic parameters obtained from fluorescent tetracycline labelling

Question 30

Aetiology of osteoporosis

Answer 30

Primary - age, post-menopausal Secondary - drugs, systemic disease 90% of cases are due to insufficiency calcium intake and post-menopausal oestrogen deficiency

Question 31

Pathogenesis of osteoporosis

Answer 31

Low initial bone mass or accelarated bone loss can reduce bone mass below the fracture threshold

Question 32

Turnover classification of osteoporosis

Answer 32

High turnover results from increased bone resorption | Low turnover results from reduced bone formation

Question 33

Influencing factors in osteoporosis

Answer 33

Nutrition & social practices (etoh, smoking, malabsorption, vit C&D deficiency) Endocrine abnormalities (menopause, hyperthyroidism, hyperparathyroidism, cushings, DM) Immobilisation Iatrogenic (corticosteroids, long-term heparin or phenytoin therapy, castration, XS thyroid therapy)

Question 34

Risk factors for osteoporosis

Answer 34

``` Advanced age Female Smoking Alcohol Early menopause Long-term immobility Low BMI Poor diet (low vitamin D, low calcium) Malabsorption Thyroid disease Low testosterone Chronic renal disease Steroids ```

Question 35

Osteoporosis in UK figures

Answer 35

1/3 women, 1/12 men >50 50% of fracture patients cannot live independently post fracture, 20% die

Question 36

Osteoporosis presentation

Answer 36

Patients commonly present with back pain and # wrist (Colles’), hip (NOF and intertrochanteric) & pelvis may be the first sign of disease > 60% vertebral # are asymptomatic Compression # usually in T11-L2 distribution

Question 37

Investigations in osteoporosis

Answer 37

Lab investigations: serum calcium, phosphorus and alkaline phosphate (usually all normal) Imaging Bone density: T score between -1 and -2.5 = osteopaenia T score >-2.5 = osteporosis

Question 38

DEXA scores for osteopaenia and osteoporosis

Answer 38

T score between -1 and -2.5 = osteopaenia | T score >-2.5 = osteporosis

Question 39

What is required for proper evaluation of osteoporosis/metabolic bone disease

Answer 39

Quantitative analysis. Parameters measured are percentage of bone tissue as opposed to marrow and the percentage of bone tissue actively laying down bone or resorbing bone compared with inactive surfaces.

Question 40

Organs involved in Hypo/Hyper-PTH

Answer 40

Parathyroid glands Bones Kidneys Proximal small intestine

Question 41

Low vitamin D effect on PTH

Answer 41

Vit D deficiency from whatever cause results in increased parathyroid hormone (PTH) release and subsequent increased bone resorption.

Question 42

Most common cause of hypocalcaemia

Answer 42

Low vitamin D

Question 43

Hypocalcaemia clinical manifestation

Answer 43

Muscle twitching Spasms Tingling Numbness

Question 44

Osteomalacia

Answer 44

Defective bone mineralisation

Question 45

Causes of osteomalacia

Answer 45

Deficiency of vitamin D | Deficiency of phosphate

Question 46

Sequelae in osteomalacia

Answer 46

Bone pain/tenderness Fracture Proximal weakness Bone deformity

Question 47

Osteomalacia in children

Answer 47

Rickets - bowing of the legs and widening of the ephiphysis

Question 48

What condition are looser's zones seen in

Answer 48

Ostemalacia

Question 49

Biochem of hyperparathyroidism

Answer 49

Excess PTH Increased calcium and phosphate excretion in the urine Hypercalcaemia Hypophosphataemia Skeletal changes of osteitis firbosa cystica

Question 50

Causes of hyperparathyroidism

Answer 50

Primary: parathyroid adenoma (85-90%), chief cell hyperplasia Secondary: chronic renal deficiency, vitamin D deficiency, malabsorption

Question 51

Symptoms of hyperparathyroidism

Answer 51

Manifestation of hypercalcaemia STONES (calcium oxalate renal stones) BONES (osteitis fibrosa cystica, bone resporption) Abdominal GROANS (pain, acute pancreatitis) Psychic MOANS (psychosis and depression)

Question 52

Bone lesion in hyperparathyroidism

Answer 52

Brown cell tumour

Question 53

Renal osteodystrophy

Answer 53

Comprises all the skeletal changes of chronic renal disease: ``` Increased bone resportion (osteitis fibrosa cystica) Ostemalacia Osteosclerosis Growth retardation Osteoporosis ```

Question 54

Biochem of renal osteodystrophy

Answer 54

``` Phosphate retention - hyperphosphataemia Hypocalcaemia as a result of decreased vitamin D Secondary hyperparathyroidism Metabolic acidosis Aluminium deposition ```

Question 55

Stages of Paget's disease

Answer 55

Osteolytic Ostelytic-osteosclerotic Quiescent osteosclerotic

Question 56

Paget's disease

Answer 56

Disorder of bone turnover

Question 57

Who is affected by Paget's disease

Answer 57

``` Onset >40 years M=F Rare in Asians and Africans Mono-ostotic 15% Remainder polyostotic ```

Question 58

Aetiology of Paget's disease

Answer 58

Aetiology is unknown Familial cases show autosomal pattern of inheritance with incomplete penetrance (mutation 5q35-qter - sequestosome 1 gene) Parvomyxovirus type particles have been seen on EM in Pagetic bone

Question 59

Sites affected in Paget's disease

Answer 59

``` Skull Spine Pelvis Humerus Femur Tibia ```

Question 60

Clinical presentation of Paget's disease

Answer 60

Pain Microfractures Ner compression (including spinal nerves and cord) Skull changes may put medulla at risk +/- haemodynamic changes, cardiac failure Development of sarcoma in area of involvement in 1%

Question 61

Indications for bone biopsy

Answer 61

Suspected osteomalacia Diagnostic classification of renal osteodystrophy Osteopaenia in young patients <50y Osteopaenia associated with abnormal Ca metabolism Classification of hereditary childhood bone disease Evaluation of treatment (osteomalacia, hypophosphatasia)