Metabolic Bone Disease

Question 1

Describe the metabolism of vitamin D

Answer 1

Sources: sunshine + diet (fish, meat, supplements). Storage form (25(OH)Vitamin D) is in liver (and also fat and muscle). This is what is measured when assessing vitamin D levels. Metabolised further in kidney active form, 1,25(OH)2Vitamin D. Vitamin D main action is absorption of calcium from the gut. Works with PTH to move Ca in and out of tissues. Essentially maintains calcium balance in body.

Question 2

Describe the metabolism of calcium

Answer 2

ECF calcium level maintenance is important for physiological processes. Moved in and out of cell, bones, kidneys, under the action of PTH & absorbed from the gut under the action of vitamin D. ECF Ca level needs to be kept under tight limits, may be at the expense of Ca held in bone (largest store).

Question 3

What is the definition of osteoporosis?

Answer 3

A metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.

Question 4

What are the endocrine causes of osteoporosis?

Answer 4

Thyrotoxicosis. Hyper/hypoparathyroidism. Cushing’s. Hyperprolactinaemia. Hypopituitarism. Low sex hormone levels.

Question 5

What are rheumatic causes of osteoporosis?

Answer 5

RA. Ankylosing spondylitis. Polymyalgia rheumatica.

Question 6

What are the gastroenterological causes of osteoporosis?

Answer 6

Inflammatory diseases: UC + Crohn’s. Liver diseases: PBC (primary biliary cirrhosis), CAH (chronic active hepatitis), alcoholic cirrhosis, viral cirrhosis (hep C). Malabsorption: CF, chronic pancreatitis, coeliac disease, Whipple’s disease, short gut syndromes + ischaemic bowel.

Question 7

Describe the role of falls, trauma and osteoporosis in causing fractures

Answer 7

Relevance of osteoporosis is increased risk of fracture. Risk of fracture is related to: age, BMD, falls, and bone turnover.

Question 8

What investigations may be used in diagnosing osteoporosis?

Answer 8

• X-ray (low sensitivity/specificity, often w/ hindsight after fracture)
• Bone densitometry (DEXA/dual-energy x-ray scan)
• Bloods: Ca2+, PO43-, and ALP (alkaline phosphatase level) usually normal in osteoporosis
• Consider specific investigation for secondary causes if history suggests

Question 9

What types of drugs are used to prevent and treat osteoporosis?

Answer 9

Hormone replacement therapy (post-menopausal). Selective oestrogen receptor modulator (post-menopausal). Bisphosphonates – main treatment/first line, requires adequate renal function, calcium, vit D status + good dental health/hygiene advised. Denosumab – reduces osteoclastic bone resorption, safer in patient’s w/ sig renal impairment than bisphosphonates. Teriparatide.

Question 10

What are the side effects of hormone replacement therapy?

Answer 10

Increased risks of blood clots. Increased risk of breast cancer with extended use into late 50s/early 60s. Increased risk of heart disease and stroke if used after large gap from menopause.

Question 11

What are the side effects of selective oestrogen receptor modulator?

Answer 11

Hot flushes if taken close to menopause. Increased clotting risk. Lack of protection at hip site.

Question 12

What are the possible side effects of bisphosphonates?

Answer 12

Oesophagitis. Iritis/uveitis (iris/eye). Possible osteonecrosis of jaw. Possible atypical femoral shaft fractures

Question 13

What are the side effects of denosumab?

Answer 13

Allergy/rash. Symptomatic hypoglycaemia if given when vitamin D depleted. Possible osteonecrosis of the jaw. Possible atypical femoral shaft fractures.

Question 14

What are the side effects of teriparatide?

Answer 14

Injection site irritation. Rarely hyperglycaemia. Allergy.

Question 15

Describe the pathogenesis of osteomalacia and rickets

Answer 15

Severe nutritional vitamin D or calcium deficiency causes insufficient mineralisation and thus rickets in a growing child and osteomalacia in the adult when the epiphyseal lines are closed. Vitamin D stimulates absorption of calcium and phosphate from the gut and calcium and phosphate then become available for bone mineralisation. Muscle function is also impaired in low vitamin D states.

Question 16

What investigations are used to confirm the diagnosis of osteomalacia?

Answer 16

Plasma (bloods, urinalysis): Mildly increased Ca2+ (but may be severe). Decreased PO43-. Increased ALP (alkaline phosphatase level). PTH high. Decreased 25(OH)-vitamin D, except in vitamin D resistance. In renal failure, decrease 1,25(OH)2-vitamin D
Biopsy: incomplete mineralisation, muscle biopsy (if proximal myopathy) is normal.
X-ray – loss of cortical bone; also partial fractures without displacement may be seen esp. on lateral border of scapula, inferior femoral neck, and medial femoral shaft. Cupped, ragged metaphyseal surfaces are seen in rickets.

Question 17

Describe the clinical features of osteomalacia

Answer 17

• Bone pain and tenderness. Muscle weakness.
• Fractures (esp. femoral neck), proximal myopathy (waddling gait)
• Increased falls risk

Question 18

Describe the clinical features of rickets

Answer 18

Growth retardation, hypotonia (floppy baby), apathy (lack interest) in infants. Once-walking: knock kneed (angling), bow legged (curve outward at the knees, ankles touch), deformities of the metaphyseal-epiphyseal junction. Illness.
Wide joints at elbow/wrist, wide bones/ankles, large abdomen, odd shaped ribs/breast bones, large forehead, odd curve to spine.

Question 19

What are the principles of prevention and treatment of osteomalacia?

Answer 19

Increased vitamin D intake via diet or oral supplements. Increase calcium intake through supplements. Increase phosphorous intake through supplements. Treat conditions that can affect vitamin D metabolism.

Question 20

What is Paget’s disease

Answer 20

Localised disorder of bone turnover. Increased bone resorption followed by increased bone formation. Leads to disorganised bone: bigger, less compact, more vascular and more susceptible to deformity and fracture.

Question 21

Describe the epidemiology/aetiology of Paget’s disease

Answer 21

Strong genetic component (15-30% familial). Restricted geographical distribution – Anglo-Saxon origins. Environmental trigger – possibility of chronic viral infection within osteoclast.

Question 22

Describe the presentation of Paget’s disease

Answer 22

Presents in patient > 40 years with bone pain. Occasionally presents with bone deformity/fracture. Excessive heat over Pagetic bone. Nerve deafness/hearing loss. Isolated elevation of serum alkaline phosphatase (ALP) – commonest presentation. Rare development of osteosarcoma in affected bone.

Question 23

What investigations are used to confirm the diagnosis of Paget’s disease

Answer 23

X-ray. Liver function tests (increased serum alkaline phosphatase (ALP)). Bone scan.

Question 24

What are the principles of management of Paget’s disease?

Answer 24

No evidence to treat asymptomatic Paget’s unless in skull or in area requiring surgical intervention. Don’t treat based on raised ALP alone. IV Bisphosphonate therapy – one off IV zoledronic acid.

Question 25

What is Osteogenic Imperfecta and how is it managed?

Answer 25

Genetic disorder of connective tissue characterised by fragile bones from mild trauma and even acts of daily life. Features: growth deficiency/deformities, defective tooth formation, scoliosis/barrel chest, blue sclera, hearing loss. Surgical – treat fracture; medical – prevent fracture, IV bisphosphonates; social – educational + social adaptations; genetic – genetic counselling.