Calcium Homeostasis and Bone Disorders Flashcards
what contributes to calcium homeostasis
diet
gut absorption
PTH
Vit D
what are the 4 key components of calcium homeostasis
serum calcium, serum phosphate, 1,25-dihydroxyvitamin D-3 (vit D) and PTH
why does serum phosphate play a part
99% of the total body calcium is stored in bone in the form of phosphate and hydroxide salts
how is vitamin D made
Dehydro-cholesterol >> from sunlight Cholecalciferol (D3) >> converted in the liver 25 (OH) Vit D >> converted in the kidney 1,25 (OH) Vit D
what is the primary action of Vit D
promote gut absorption of calcium
what are the other roles of Vit D
works in conjunction with PTH
increase of Vit D causes increase in calcium transport within the intestine, bone, and kidney
symptoms of hypercalcaemia
Stones, groans, bones, psychic moans
Acute - Thirst, dehydration, confusion, polyuria
Chronic - myopathy, osteopenia, fractures, depression, hypertension, pancreatitis, ulcers, renal stones
if you can do one test with suspected hypercalcaemia what is it
PTH levels
what does high PTH levels suggest
hyperparathyroidism is the cause of the hypercalcaemia
what are causes of hypercalcaemia
- Primary hyperparathyroidism
- Malignancy
- Drugs - Vit D, Thiazides
- Granulomatous Disease e.g. TB, Sarcoid
- Familial Hypocalciuric hypercalcaemia
- Tertiary hyperparathyroidism
what is suggestive of hyperparathyroidism
Raised serum Calcium
Raised serum PTH (or inappropriately normal)
Increased urine calcium excretion
why do you get hypercalcaemia in malignancy
Metastatic Bone destruction
PTHrp from solid tumours
Osteoclast activating factors
what is suggestive of malignancy
raised calcium and alk phosphatase
decreased albumin
Ix for malignancy causing hypercalcaemia
Isotope bone scan
Acute Tx of hypercalcaemia
IV fluids
Consider loop diuretics once rehydrated
Bisphosphonates e.g. Pamidronate
what are function of bisphosphonates
prevent bone reabsorption by inhibiting osteoclast activity
what genetic syndromes are linked with hypercalcaemia
MEN 1/2 Familial hyperparathyroidism (FHPT)
what is Familial Hypocalciuric Hypercalcaemia
condition that can cause hypercalcemia
reduced calcium in urine
usually due to fault in Ca sensing receptor
why do you get hypercalcaemia in Familial Hypocalciuric Hypercalcaemia
perceived lack of calcium levels by the parathyroid leads to constitutively high levels of parathyroid hormone, and therefore hypercalcemia
what does PTH do
increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate.
what are symptoms of Hypocalcaemia
Paraesthesia - fingers, toes, perioral Muscle cramps and weakness Fatigue Bronchospasm or Laryngospasm Fits
what are signs of hypocalcaemia
Chovsteks sign
- corner of the mouth twitches when the facial nerve is tapped over the parotid
Trousseau’s sign
- in inflating the cuff, the wrist and fingers flex and draw together
what are signs on an ECG of hypocalcaemia
QT prolongation
causes of hypocalcaemia
Hypoparathyroidism
Vit D Deficiency (osteomalacia, rickets)
Chronic renal failure
what other blood abnormality is seen in hypocalcaemia
raised phosphate
Tx of acute hypocalcaemia
Emergency
- IV 10% calcium gluconate 10 ml
what are causes of hypoparathyroidism
Congenital absence (DiGeorge syndrome) Destruction (surgery, radiotherapy, malign) Autoimmune Hypomagnesaemia Idiopathic
Mx of hypoparathyroidism
Calcium supplements 1-2g a day
Vit D supplements
tablets - 1alpha calcidol 0.5-1mcg
injection - Cholecalciferol 300,000 units 6 monthly
what is calcium release from cells dependent on
magnesium
what is hypomagnesaemia
low Mg in the blood
what is seen in hypomagnesaemia
high intracellular calcium
PTH release inhibited
Skeletal and muscle receptors less sensitive to PTH
Tx of hypomagnesaemia
Magnesium salts
what causes hypomagnesaemia
Alcohol Drugs - thiazide, PPI GI illness - short gut Pancreatitis Malabsorption
what is Pseudohypoparathyoidism
genetic defect - dysfunction of G protein in GNAS1
failure of target cell to respond to PTH
signs and symptoms of Pseudohypoparathyoidism
Brachydactyly - seen in 4th and 5th metacarpal of
Round face
Short stature
Learning Disability
what is Brachydactyly
shortening of the fingers and toes due to unusually short bones
what are the test results of Pseudohypoparathyoidism
Decreased serum Calcium
Increased PTH
Alk phos normal or raised
what is Pseudo-pseudohypoparathyroidism
the morphological features of pseudohypoparathyroidism but with NORMAL BIOCHEMISTRY
can patents can from pseudo to pseudo-pseudo?
yes
what is osteomalacia know as in children
rickets
what can cause Rickets and Osteomalacia
Vit D deficiency due to
- Dietary deficiency
- Malabsorption: gastric surgery, coeliac disease, liver disease, pancreatic failure
- Chronic renal failure
- Lack of sunlight
- Drugs eg anticonvulsants
what is osteomalacia
normal amount of bone but the mineral content is low
opposite of osteoporosis
symptoms of osteomalacia
bone pain and tenderness fractures esp femoral neck rib deformity limb deformity proximal myopathy dental defects
what x-ray sign is seen commonly in rickets and osteomalacia
Loosers zones
- pseudofractures
symptoms of rickets
growth retardation
knock knees
bow legs
children are ill
lab results seen in rickets/osteomalacia
low calcium - often mild in rickets decrease phosphate increase alk phos PTH high decreased 25(OH) vit D
what does chronic renal disease cause in the body
vit D deficiency
secondary hyperparathyroidism
what are lab results seen in chronic renal disease
low 1,25-OH Vit D
Tx for rickets/osteomalacia
Vit D supplements
if vit D deficiency due to chronic renal disease what is the Tx
Alfacalcidol
OR
Calcitriol
what are side effects of Calcitriol and Alfacalcidol
can cause dangerous hypercalcaemia
what is vitamin D resistant rickets
X-linked hypophosphatemia (i.e. low phosphate levels)
Defect in PHEX gene
High Vit D levels
Ix findings of vitamin D resistant rickets
low phosphate
high vit D
phosphaturia - too much phosphorus in urine
Tx of vitamin D resistant rickets
Phosphate
Vit D supplements - Calcitriol
what is osteoporosis
progressive skeletal disease
low bone mass
deterioration of bone tissue
increase in bone fragility and susceptibility to fracture
common fracture sites seen in osteoporosis
neck of femur
vertebral body
distal radius
humeral neck
when is a patient assessed for risk factors of osteoporosis
Anyone >age 50 years with risk factors
Anyone under 50 years with very strong clinical risk factors
Early menopause
Glucocorticoids
when to refer for DEXA
If there is a 10 year risk assessment for any OP fracture of at least 10%
what are risk factors for osteoporosis
SHATTERED
Steroid use
Hyperthyroidism/hyperparathyroidism
Alcohol and tobacco use
Thin (BMI
what are the BMD scores suggestive of bone pathology
Osteopenia BMD > 1 SD below mean
Osteoporosis BMD > or equal to 2.5 SD below mean
Severe Osteoporosis BMD > or equal to 2.5 below mean with fragility fractures
what will the blood results be in osteoporosis
normal
Tx of osteoporosis
Biphosphonate
Calcium and Vit D supplements
Strontium ranelate - 3rd line
HRT
what is given for premature osteoporosis
HRT or Testosterone
examples of biphosphonates and what do they do
Alendronate or Risedroante
Are anti-resorptive agents
Prevent bone loss at all sites vulnerable to osteoporosis
Ingested by osteoclasts leading to cell death thereby inhibiting bone resorption
why is Strontium ranelate third line and when is it contraindicated
- fracture risk reduction slightly less than bisphosphonate
- history of thromboembolic disease, IHD, peripheral arterial disease, uncontrolled hypertension
relationship between corticosteroids and bone
Reduction of osteoblast activity and lifespan
Suppression of replication of osteoblast precursors
Reduction in calcium absorption
Inhibition of gonadal and adrenal steroid production
what is Paget’s disease
increased bone turnover associated with increased numbers of osteoblasts and osteoclasts
what does Paget’s disease cause
bone enlargement, deformity and weakness
bone pain
deafness
compression neuropathies
blood chemistry of Paget’s disease
alk phos very raised
normal calcium and phosphate
Tx of Paget;s
Analgesia
Is that fails bisphosphonates
what is osteogenesis imperfecta
genetic disorder of type I collagen
results in fragile, low density bones
what are the types of osteogenesis imperfecta
Type I - Mild
Type III and IV - very severe
Type II - neonatal lethal
what is osteogenesis imperfecta associated with
blue sclerae
hearing loss
dentinogenesis imperfecta - disorder of tooth development
how does the most severe form of osteogenesis imperfecta present
fractures in childhood
progressive spinal and limb deformity
when might mild osteogenesis imperfecta present
may not present till adult life
Tx of osteogenesis imperfecta
fracture fixation
surgery to correct deformities
bisphosphonates
prevent injury
