Metabolic Bone Disease Flashcards
Non-neoplastic bone pathology
Congenital/Acquired: trauma, infection, degeneration, inflammation, metabolic
Neoplastic bone pathology
Benign/malignant tumours
Function of bone
Mechanical - support and site for muscle attachment
Protective - vital organs and bone marrow
Metabolic - reserve of calcium
Composition of bone
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)
Bone structure medial to lateral
Medulla
Cortex
Periosteum
Bone structure proximal to distal (e.g. arm)
Diaphysis
Metaphysis
Epiphysis (epiphyseal line, subchondral bone)
Articular cartilage
Small synovial joints
Facet joints of fovea
What percentage of mineralisation does bone need to have for it to be visible on X-ray
50%
Types of bone
Cortical
Cancellous
Features of cortical bones
Long bones 80% of skeleton Appendicular 80-90% calcified mainly mechanical and protective Less metabolically active
Features of cancellous bone
Vertebra and pelvis 20% of skeleton Axial skeleton 15-25% calcified Mainly metabolic Large surface area
Structure of cortical bone
Trabecular lamellae
Interstitial lamella
Concentric lamellae
Circumferential lamellae
Bone cells
Osteoblasts
Osteoclasts
Osteocytes
Features of osteoblasts
Build bone by laying down osteoid
Feature of osteoclasts
Multinucleate cells of macrophage family
Resorb or chew bone
Features of osteocytes
Osteoblast like cells which sit in the lacunae in bone
Stain used to view osteocytes and canaliculae
Silver stain
What promotes osteoblast activity
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
Activation of osteoclasts
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.
How are bony metastases formed
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.
What can tumours do to bone
Induce bone resorption
Induce bone formation
What cancer causes more bone growth than destruction
Metastatic prostate carcinoma
Types of bone
Woven/lanellar
Anatomically - flat bones/long bones (intramembranous and endochondrial ossification)
Trabecular (cancellous)/compact (cortical)
Features of lamellar bone
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
Features of woven bone
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
Metabolic bone disease
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
Categories of bone disease
Non-endocrine (e.g. age related osteoporosis)
Related to endocrine abnormality (vitamin D, parathyroid hormone)
Disuse osteopaenia
Diagnosis of metabolic bone disease
Histology requires bone biopsy from iliac crest,
processed undecalcified for histomorphometry.
Studies performed on bone biopsy to diagnose metabolic bone disease
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
Aetiology of osteoporosis
Primary - age, post-menopausal
Secondary - drugs, systemic disease
90% of cases are due to insufficiency calcium intake and post-menopausal oestrogen deficiency
Pathogenesis of osteoporosis
Low initial bone mass or accelarated bone loss can reduce bone mass below the fracture threshold
Turnover classification of osteoporosis
High turnover results from increased bone resorption
Low turnover results from reduced bone formation
Influencing factors in osteoporosis
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)
Risk factors for osteoporosis
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
Osteoporosis in UK figures
1/3 women, 1/12 men >50
50% of fracture patients cannot live independently post fracture, 20% die
Osteoporosis presentation
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
Investigations in osteoporosis
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
DEXA scores for osteopaenia and osteoporosis
T score between -1 and -2.5 = osteopaenia
T score >-2.5 = osteporosis
What is required for proper evaluation of osteoporosis/metabolic bone disease
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.
Organs involved in Hypo/Hyper-PTH
Parathyroid glands
Bones
Kidneys
Proximal small intestine
Low vitamin D effect on PTH
Vit D deficiency from whatever cause results in increased parathyroid hormone (PTH) release and subsequent increased bone resorption.
Most common cause of hypocalcaemia
Low vitamin D
Hypocalcaemia clinical manifestation
Muscle twitching
Spasms
Tingling
Numbness
Osteomalacia
Defective bone mineralisation
Causes of osteomalacia
Deficiency of vitamin D
Deficiency of phosphate
Sequelae in osteomalacia
Bone pain/tenderness
Fracture
Proximal weakness
Bone deformity
Osteomalacia in children
Rickets - bowing of the legs and widening of the ephiphysis
What condition are looser’s zones seen in
Ostemalacia
Biochem of hyperparathyroidism
Excess PTH
Increased calcium and phosphate excretion in the urine
Hypercalcaemia
Hypophosphataemia
Skeletal changes of osteitis firbosa cystica
Causes of hyperparathyroidism
Primary: parathyroid adenoma (85-90%), chief cell hyperplasia
Secondary: chronic renal deficiency, vitamin D deficiency, malabsorption
Symptoms of hyperparathyroidism
Manifestation of hypercalcaemia
STONES (calcium oxalate renal stones)
BONES (osteitis fibrosa cystica, bone resporption)
Abdominal GROANS (pain, acute pancreatitis)
Psychic MOANS (psychosis and depression)
Bone lesion in hyperparathyroidism
Brown cell tumour
Renal osteodystrophy
Comprises all the skeletal changes of chronic renal disease:
Increased bone resportion (osteitis fibrosa cystica) Ostemalacia Osteosclerosis Growth retardation Osteoporosis
Biochem of renal osteodystrophy
Phosphate retention - hyperphosphataemia Hypocalcaemia as a result of decreased vitamin D Secondary hyperparathyroidism Metabolic acidosis Aluminium deposition
Stages of Paget’s disease
Osteolytic
Ostelytic-osteosclerotic
Quiescent osteosclerotic
Paget’s disease
Disorder of bone turnover
Who is affected by Paget’s disease
Onset >40 years M=F Rare in Asians and Africans Mono-ostotic 15% Remainder polyostotic
Aetiology of Paget’s disease
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
Sites affected in Paget’s disease
Skull Spine Pelvis Humerus Femur Tibia
Clinical presentation of Paget’s disease
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%
Indications for bone biopsy
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)
