Bones and Calcium Flashcards
What is osteoporosis?
Disease characterised by low bone mass and micro architectural detonation of bone tissue leading to enhanced bone fragility and an increase in fracture risk.
BMD more than 2.5 below SD of young subjects
Risk factors for osteoporosis?
Increased age Gender- women particularly post menopausal Ethnicity- caucasians and asians more Previous fractures Family history Menopause under 45 Other diseases can predispose Alcohol excess Low weight Low Peak bone mass Smoking Physical inactivity Drugs
What disease can cause osteoporosis?
hyperthyroid, hyperparathyroid, cushings, coeliacs, IBD, chronic liver disease, chronic pancreatitis, CF, COPD and CKD
Does osteoporosis have symptoms?
No- it’s only the fracture that will present
How do you decide who to screen and treat for osteoporosis?
Generally people who have had 1st low trauma fractures are assessed. Risk calculator then if risk greater than 10% referred for DEXA to see if have osteoporosis.
Define a low trauma fracture?
A fall from standing height or less (or a fall you just wouldn’t expect someone to break a bone)
Describe what scores you get from DEXA scan?
Z score (you compared to your age) SD score (you compared to young peak bone mass people)
Overview of osteoporosis treatment?
Treat underlying conditions Lifestyle and diet changes Bisphosphonates Consider HRT Other drugs Those on steroids need bone protective measures
Lifestyle and diet changes for osteoporosis?
Diet: 700 mg calcium a day, 1000 mg for post menopausal women. Calcium is mainly in dairy- also fortified bread and cereals, fish with bones, nuts, green veg and beans. Supplements of calcium and vitamins D in those at risk of deficiency.
Lifestyle changes: high intensity strength training, low impact weight bearing exercises, avoid excess alcohol, stop smoking, fall prevention
Describe pharmacological treatment for osteoporosis?
Bisphosphonates are main drug used which cause osteoclast death inhibiting bone resorption, these are effective at all sites.
Consider HRT in those with menopause before 40
Bone protective agent sin those on oral steroids
Other drugs: denosumab and teriparatide.
What is Paget’s disease?
Focal disorder of bone remodelling. Increased osteoclastic bone resorption is followed by compensatory increase in new bone formation, bone blood flow and fibrous tissue in adjacent bone marrow. Ultimately formation exceeds resorption but the new woven bone is weaker than normal bone leading to deformity and increased fracture risk.
What causes Paget’s disease of bone?
Unknown trigger
Genetic factors? Maybe viral?
Uncommon under the age of 45
What bones does Paget’s disease effect?
long bones, pelvis, lumbar spine and skull
What is a rare but important complication of Paget’s disease?
Osteosarcoma
Presentation of Paget’s disease?
Bone pain, deformity, deafness, compression neuropathy
May be asymptomatic and incidental finding on X-ray or due to high ALP
Tests for Paget’s?
XR, isotope bone scan shows distribution, raised ALP but rest of LFTs normal
Treatment for Paget’s disease?
Orthotic devices, walkers
NSAIDs for pain
Treat with bisphosphonates if pain is not responding to analgesia
What is osteogenesis imperfecta?
Rare group of genetic disorders that results in bones that break easily. Lots of types with varying severity.
Most osteogenesis imperfecta is caused by…
autosomal dominant mutations in type 1 collagen
Presentation of osteogenesis imperfecta?
Fractures in childhood in severe forms- differential diagnosis for suspected NAI
May be associated with blue sclerae and detinogenesis imperfecta
Blue sclerae and dentinogenesis imperfecta?
Osteogenesis imperfecta
Old fractures on child’s x-ray think…
NAI or osteogenesis imperfecta
Treatment of osteogenesis imperfecta?
No cure only fracture fixation, surgery to correct deformities and bisphosphonates.
Calcium homeostasis is regulated by…
the effects of PTh and 1,25-dihydroxyvitamin D on gut, kidney and bone
Calcium sensing receptors are present in ….
parathyroid glands, kidneys and brain
What is osteomalacia and rickets?
Softening of bones due to Vit D deficiency
Treatment of osteomalacia and rickets?
Vit D supplements
Where do we get calcium and vitamin D from?
Calcium is primarily from dairy foods whereas Vit D is from photo activation in the skin of certain compounds
Parathyroid hormone is secreted from ….
chief cells in the parathyroid gland
Function of parathyroid hormone?
Increase serum calcium and decrease serum phosphate
Action of parathyroid hormone?
Increases plasma calcium by …
increasing osteoclastic activity in bone
Increasing intestinal absorption of calcium
Activation of Vitamin D
Increasing renal tubular absorption of calcium
Describe action of vitamin D?
Active vitamin D is a hormone and it helps increase the amount of calcium the gut can absorb from food into the bloodstream and also prevents calcium loss from the kidneys
Calcitonin is only secreted in _______ by _______
extreme cases of hypercalcaemia by thyroid C cells
Does calcitonin have significant effects on the body?
Although it inhibits osteoclastic bone resorption and increases the renal excretion of calcium and phosphate neither excess calcitonin or its deficiency following thyroidectomy has significant skeletal effects in humans
2 main causes of hypercalcaemia? Other causes?
main causes are primary hyperparathyroidism and malignancy
other causes: drugs (vitamin D and thiazides), granulomatous disease, FHCC, thyrotoxicosis, Paget’s tertiary hyperparathyroidism
Causes of primary hyperparathyroidism?
More than 80% due to adenoma, hyperplasia 15% and carcinoma about 2%
How does malignancy cause hypercalcaemia?
metastatic bone destruction, PTHrp from solid tumours (e.g. squamous cell lung cancer), osteoclast activating factors
Acute presentation of hypercalcaemia?
Thirst, dehydration, confusion and polyuria
Symptoms of hypercalcaemia?
BONES: pain usually effects cortical bone and bone cysts and locally destructive brown tumours but only in advanced disease. In chronic disease can get osteoporosis and fractures
STONES: renal colic from stones, also polyuria, nocturne, haematuria and hypertension. Polyuria is due to hypercalcaemia reducing renal tubules concentration ability- so also get polydipsia
ABDOMINAL GROANS: Abdo pain
PSYCHIC MOANS: Chronic disease can cause depression and in acute scenario there may be confusion
Explain investigations for hypercalcaemia?
ASSUMING ALREADY MEASURED SERUM CALCIUM
Serum PTH- this will be raised or inappropriately normal in primary hyperparathyroidism. Undetectable PTH in hypercalcaemia may be cause by malignancy MUST INVESTIGATE
24hr urinary calcium excretion will be increased in primary hyperparathyroidism
Elevated ALP usually suggests cause other than primary hyperparathyroid
When no PHPT should measure TSH, ACTH/ cortisol, serum ACE, X-ray, CT, MRI, isotope bone scan.
Sestamibi scan for parathyroid imaging
What will investigation results be in primary hyperparathyroidism?
Serum PTH raised or inappropriately normal
24hr urinary calcium excretion is increased
No elevated ALP or not by very much
What sort of scan can look at the parathyroids?
Sestamibi
Treatment of acute hypercalcaemia?
Rehydrate 0.9% saline
Bisphosphonates
Treatment for primary hyperparathyroidism is surgery… what are the indications?
Parathyroidectomy for anyone with renal stones or impaired renal functino Bone disease or osteoporosis Gastric ulcers Very high calcium Young enough to gain benefit
Causes of hypoparathyroidism
surgery most common cause, congenital absence in Digeorge, idiopathic, severe hypomagnaesemia
Causes of hypocalcaemia
hypoparathyroidism
Vit D deficiency
Resistance to PTH- pseudohypoparathyroid
Drugs- calcitonin and bisphosphonates
Why may bisphosphonates cause hypocalcaemia?
They decrease bone resorption
How can hypomagnesemia cause hypocalcaemia?
Calcium release from cells is dependent on magnesium
Symptoms of hypocalcaemia?
Neuromuscular irritability and neuropsychiatric manifestations:
Paraesthesia (fingers toe perioral), muscle cramps, tetany, muscle weakness, fatigue
Bronchospasm or laryngospasm, convulsions follow
Severe hypocalcaemia can cause what change on ECG?
Prolongation of the QT interval
2 signs of hypocalcaemia?
Chvosteks sign: gentle tapping over facial nerve causes twitching over the ipsilateral facial muscles
Trousseaus sign: inflation of BP cuff causes tetanic spasm of fingers and wrist
Investigations for hypocalcaemia?
Serum urine creatinine for renal disease
PTH absent or low in hypo pTH or increased in other causes
25 hydroxyvitamin D for Vit D deficiency
Magnesium levels
X-rays of metacarpals for pseudohypoparathyroidism
Treatment of hypocalcaemia?
Acute treatment is IV calcium gluconate
Calcium supplements and Vit D
Describe familial hypocalcuric hypercalcaemia?
Familial autosomal dominant condition that causes chronically elevated serum calcium and reduced calcium excretion
Usually due to defect in calcium sensors so abnormal set point for PTH
Usually benign
What is secondary hyperparathyroidism? What will results of investigations be?
Physiological compensatory hypertrophy or all parathyroids because of hypocalcaemia such as occurs in chronic kidney disease or vitamin D deficiency.
PTH is raised by Calcium is decreased or normal. PTH falls back to normal if the cause is corrected.
What is tertiary hyperparathyroidism? What are results?Treatment?
Development of apparently autonomous parathyroid hyperplasia after longstanding secondary hyperparathyroidism most often in renal failure (basically development of an adenoma)
Plasma calcium is increased and phosphate is also increased (kidney disease)
Parathyroidectomy is necessary
What is pseudohypoparathyroidism? Results?
Resistance to PTH due to mutation in receptor. Associated with short stature, short metacarpals, subcutaneous calcification and sometimes intellectual impairment.
Decreased calcium but elevated PTH.
What is pseudopseudohypoparathyroidism? Results?
Phenotypic defects of pseudo but not abnormalities of calcium metabolism may share gene defect and be in same families.
What adds strength to bone?
Calcium phosphate
As well as maintaining bone strength what is calcium essential in?
Excitability of smooth and cardiac muscle
Secretion of peptides and hormones in the body
Excitability of skeletal NM junctions
Role in blood clotting
Calcitonin does what to osteoclasts?
Inhibits them
ALP is a marker of _______ and is due to ______ activity
bone turnover
osteoblast
For idiopathic osteoporosis would expect what biochem results?
Ca, Phosphate and ALP expect to be normal
What does raised calcium suggest?
Destructive bone lesions or hyperparathyroidism
What does raised ALP in relation to bones suggest?
Destructive tumour or metabolic bone condition
Test for coeliacs? Relevance to bones?
Tissue transglutaminase IgA
Causes malabsorption of ca and vit d
What cancer can present as osteoporosis particularly in the back?
Myeloma- cancer of plasma cells
In men with osteoporosis what should you check?
Testosterone
