HD 7 - Metabolic bone disorders Flashcards
How much Ca does the kidney filter and excrete per day?
Glomerular filters 10g a day
0.2g out of kidneys
How much Ca is needed for bone remodelling/repair per day?
0.5g per day
How much Ca is found in the body?
1kg
Where is the vitamin D3 found?
Formed from action of sunlight in the skin with cholesterol, some from meat + fish
How does the liver process vitamin D3?
Liver hydroxylates vit D3 + stored in the liver as 25-vit D3
What forms of vitamin D3 does the kidney convert?
Conversion of 25-D3 –> 1,25-D3 (ACTIVE hormonal form)
What happens to PTH levels when Ca is low and high?
Low Ca –> Increased PTH
High Ca –> Decreased PTH
What happens to the bone health in chronic high PTH?
Bones gradually deteriorate and release Ca
Where is the biggest source of Ca in the body?
BONES
What is the function of osteoclasts?
Absorb bone (and apoptose after function fulfilled)
What is the function of osteoblasts?
Reform new bone with calcium
What is the function of osteocytes?
Resting bone
What is Ca bound to in the body?
1/2 bound to albumin (protein)
1/2 ionised (active form regulated by PTH)
What biochemistry is increased in fracture healing?
Alkaline phosphatase, due to increased osteoblast
When is alkaline phosphatase raised in the body?
In fracture healing, due to increased osteoblast activity
Also in liver problem
What is the function of albumin in the blood?
Ca transporter
Low albumin can result in lower Ca levels
What are the phosphate levels in kidney failure?
High
Where is phosphate found?
Meat
What are examples of bone turnover markers in blood/urine?
DPD or CTX
What do beta cross laps levels measure?
Measure osteoclastic activity and breakdown product of bone collagen
What do x-rays show in bones?
Metastases, deformities & fractures
What does a MRI show in bones?
Water not Ca
What does radioisotope scanning show in bones?
Taken up by osteoblasts, shows hotspot areas of increased turnover
Not diagnostic but can indicate an abnormality
What does DEXA stand for?
Dual energy X ray absorptiometry
What does DEXA measure?
Assesses bone mineral density for diagnosis of osteoporosis
What is the main cause for primary hyperparathyroidism?
Adenoma
What does secondary hyperparathyroidism mean?
PTH working normally
Low normal calcium, high PTH = normal response
What does a vitamin D deficiency cause in kids and in adults?
Kids - rickets
Adults - osteomalacia
What can cause rickets?
Vitamin D deficiency
Phosphaturia (genetics)
Low Ca intake
Poor diet and sunlight exposure
What happens to the bones in rickets?
Swollen bones at epiphyses
Enlarged costalchondral junction
Harrison’s sulcus - ribs deformed - diaphragm pulled in on the ribs
What are the symptoms of osteomalacia?
Bone pain, muscular weakness, malaise, rarely tetany
Why would tetany present in osteomalacia?
Tetany = calcium stabilises muscles membranes – pain and tremors
Hand of obstetrician
What are the levels of Ca, PTH, Phosphatase and ALP in osteomalacia?
Ca - low
PTH - high
Phosphatase - low
ALP - high
How is osteomalacia treated?
Vitamin D replacement and rectifying underlying cause – normally given orally
What vitamin D medications are available?
- Vitamin D depot injection 300,000 units every 6-12 months
- Dekristol (trade name) – 20,000 units of vit D
- Big dose – severely deficient or building up stores
- Given weekly or monthly; increasingly used in our area.
• Fultium D3 – formulation of 800 units – smaller tablet you can chew (1/2 a day)
What is Paget’s disease?
Uncoordinated bone re-modelling and disorganised bone turnover
What are the symptoms of Paget’s disease?
- Pain, deformity, increased fracture risk, compression of nerves
- In skull, causes cranial nerve palsies. Can also cause fuzzy and thickened skull on x-ray
- Commonest nerve problem is in the auditory nerve = causing deafness
What is the treatment for Paget’s disease?
Bisphosphonates
Most commonly alendronic/ risedronic acid
What is the function of bisphosphonates?
Inhibit osteoclastic activity and prevent bone resorption
What is osteoporosis?
Reduced bone density impaired structure and increased risk of fracture
What are common fracture sites in osteoporosis?
Wrist, vertebrae and neck of femur
Why is osteoporosis more common in women?
Menopause, lacking oestrogen causing more rapid bone deterioration
What causes osteoporosis?
- Age
- Post-menopausal, early menopause
- Steroid treatment = Cushing syndrome (most often cause - iatrogenic)
- Chronic liver, kidney, nutritional disorders affecting Ca and vit D
What are the treatments for osteoporosis?
• Bisphosphonates (low dose)
– Alendronate or risedronate orally weekly
– Ibandronate or zoledronate by injection quarterly or annually
• HRT and oestrogen analogues
- Help prevent the effect of menopause
- Controversial due to breast cancer/thrombosis risk
- Ca and D3 in malnourished elderly
- Denosumab – monoclonal antibody against cytokine, sc injection 6 monthly (BIOLOGIC) = causes hypocalcaemia
- PTH injections – daily s-c injection, expensive – puts calcium into bones
How do bone metastases develop?
Development of secondary malignant growths at a distance from a primary site of cancer
Where is the most common site of bone metastases?
Breast, lung and phosphate
What is myeloma?
Malignancy of plasma cells in bone marrow
What occurs to the bone in myeloma?
Stimulates osteoclasts but not osteoblasts
What are the symptoms associated with myeloma?
- Causes bone pain, fracture, pressure on adjacent nerves, spinal cord
- Spinal cord compression – paraplegia – medical emergency
- Hypercalcaemia of malignancy can occur with or without bone metastases
What presents in the pelvis from breast cancer metastases?
Holes in pelvis, lytic in bone
What is the treatment of bone metastases?
• Radiotherapy – relieve bone pain
• Surgery for complications – fracture/ compression
• Pain relief for symptoms
• High dose IV bisphosphonates can reduce progression in myeloma, breast and prostate cancer
- Can use Denosumab in a similar way
How does phossy jaw come about in the body?
Exposed to phosphorus
When does osteonecrosis of the jaw occur?
- Case series of cancer patients
- All on high dose bisphosphonates for Paget’s disease, myeloma, hypercalcaemia
- Can occur with Denosumab
- Majority had had dental or maxillo-facial surgery
