bones Flashcards
Hormones that increase calcium + how are they made?
PTH (parathyroid glands)
Calcitriol = activated Vit D = 1,25-hydroxy vitamin D (skin + UV light)
Hormone that decrease calcium + how is it made?
Calcitonin
Produced in parafollicular cells within thyroid)
Explain the steps of active Vit D synthesis
SKIN, INTESTINES
diet + UV -> vit D
LIVER
25-hydroxylase converts to 25-hydroxy vit D
KIDNEYS
1a-hydroxylase converts to calcitriol
Causes of raised prolactin - the 6 p’s
pregnancy prolactinoma physiological polycystic ovarian syndrome primary hypothyroidism phenothiazines, metoclopramide, domperidone
Compare the effects of PTH and calcitriol on calcium and phosphate
PTH:
↑ Calcium
↓ ↓ Phosphate (phosphate trashing)
CALCITRIOL:
↑ ↑ Calcium
↑ Phosphate
State 3 organs affected by PTH and the outcome for each
KIDNEYS- - 1α-hydroxylase stimulation - ↑ calcium reabsorption - ↑ phosphate excretion BONE- - ↑ bone reabsorption
SMALL INTESTINE
- ↑ calcium absorption
- (↑ phosphate absorption)
State 3 organs affected by calcitriol and the outcome for each
KIDNEYS- - ↑ calcium reabsorption -(↑ phosphate reabsorption) BONE- - ↑ bone reabsorption
SMALL INTESTINE
- ↑ calcium absorption
- ↑ phosphate absorption
Which hormone decreases blood calcium levels?
Calcitonin
Which hormone, out of PTH and calcitriol, raises blood calcium levels the most?
Calcitriol
Which enzyme does PTH activate in the kidneys?
1α-hydroxylase
Which hormone increases urinary phosphate excretion?
PTH (=phosphate trashing hormone)
briefly explain the parathyroid axis
- decreased calcium
- parathyroid glands produce PTH
- PTH stimulates 1-a hydroxylase to produce more calcitriol
calcitirol + PTH increase calcium - negative feedback on parathyroid glands
State 2 causes of primary hyperparathyroidism
Parathyroid adenoma
Parathyroid hyperplasia
State 2 causes of secondary hyperparathyroidism
Vitamin D deficiency
CKD
Liver disease
What is another term used for secondary hyperparathyroidism?
osteomalacia
What are calcium and phosphate levels in:
- Primary hyperPTH
- Secondary hyperPTH
- Tertiary hyperPTH
Primary hyperPTH
- ↑ calcium
- ↓ phosphate
Secondary hyperPTH
- ↓ calcium
- ↓ phosphate (unless CKD = ↑ phosphate)
Tertiary hyperPTH (autonomous PTH secretion)
- ↑ calcium
- ↑ phosphate
Which two forms of hyperPTH show a high phosphate?
Chronic kidney disease:
- Secondary hyperPTH
- Tertiray hyperPTH
Kidneys cannot excrete phosphate
What causes tertiary hyperPTH?
CKD
develops from secondary hyperPTH
Causes of high calcium?
HIGH PTH CAUSES
- Primary hyperPTH
- Tertiary hyperPTH
LOW PTH CAUSES
Malignancy: - Bone metastases - Haem (multiple myeloma) - Paraneoplastic e.g. lung SCC
Sarcoidosis
Thiazide diuretics
Symptoms of hypercalcaemia
“stones, bones, thrones, abdominal groans and psychiatric moans”
- Renal stones
- Fractures, bones
- Polyuria, polydipsia
- Abdo- nausea, constipation, pancreatitis
- Depression, anxiety
Causes of low calcium?
HIGH PTH CAUSES
- Secondary hyperPTH
- aka osteomalacia
- aka vit D deficiency
LOW PTH CAUSES
- surgical complications- post thyroidectomy for Grave’s
- autoimmune hypoparathyroidism (rare)
Symptoms of hypocalcaemia
‘Cats go numb’
Convulsions
Arrhythmias (eg prolonged QT)
Tetany
Parasthesia (hands, mouth, feet, lips)
2 clinical signs of hypocalcaemia
Trousseau’s sign (carpopedal spasm caused by inflating BP cuff above SBP)
Chvostek’s sign (twitching of the facial muscles in response to tapping over facial nerve)
Which is more likely to be found in a pancreatitis patient: hypercalcaemia or hypocalcaemia?
Hypocalcaemia- due to saponification
Damage to pancreas leads to autodigestion of pancreas (autolysis)
Calcium binds to digestive ‘gunk’ + this draws out of blood
Will bone cancer cause high PTH or low PTH
Low PTH (due to negative feedback)
Risk factors for PT gland hyperplasia
MEN-1 or MEN-2
Hypertension
Which conditions come up in:
MEN-1 (PPP)
MEN-2 (PTP)
MEN-1:
- PT hyperplasia
- Pituitary tumours
- Pancreatic tumours
MEN-2:
- PT hyperplasia
- medullary Thyroid cancer
- Phaeochromocytoma
signs and symptoms of hyperPTH
Often asymptomatic
Hypercalcaemia:
”Stones, bones, thrones, abdominal moans, psychiatric overtones”
Define secondary hyperPTN
disorder of bone mineralisation
Causes of secondary hyperPTH
Vitamin D deficiency - Poor dietary intake - Poor sunlight - Malabsorption Chronic kidney disease Liver disease
Signs and symptoms of secondary hyperPTH
ADULTS Fractures/bone pain Proximal myopathy Fatigue Hypocalcaemia:”CATs go numb”
CHILDREN (Rickets)
Bowed legs
Knock knees
3 endocrine causes of proximal myopathy (COT)
Cushing’s
Osteomalacia
Thyrotoxicosis
Investigations for hyperparathyroidism
Physical examination (cardio/resp/abdo/neuro) Basic observations
Bloods
- (FBC, CRP)
- U&E
- LFTs - ALP
- Calcium
- Phosphate
- PTH
Imaging
- X-rays/CT (extent of bone disease)
- Cervical U/S (before surgery, adenoma)
State the level of: Calcium Phosphate PTH ALP in primary hyperPTH
Calcium ↑
Phosphate ↓
PTH ↑ (or ↔)
ALP ↔
State the level of: Calcium Phosphate PTH ALP in secondary hyperPTH (osteomalacia)
Calcium ↓
Phosphate ↓
PTH ↑ (↓ in CKD)
ALP ↑
What 3 signs might you see of primary hyperPTH on xray?
- Subperiosteal bone resorption (usually radial)
- Acro-osteolysis (resorption of distal phalanges)
- Pepper pot skull (resorption by PTH)
What do you see in x-rays of children with secondary hyperPTH?
Rachitic rosary = nodularity at costochondral junctions
What do you see in x-rays of adults with secondary hyperPTH?
Looser’s pseudofractures
Wide, transverse lucencies with sclerotic borders traversing partway through a bone, usually perpendicular to the involved cortex
Management of acute hypercalcaemia
IV fluids
Bisphosphonates (if calcium remains high)
Management of primary hyperPTH (associated risk)
Total parathyroidectomy
- risk of recurrent laryngeal nerve damage (hoarseness)
If unsuitable for surgery
- Cinacalcet
- calcimemetic- acts to negatively feedback on PTH axis
Management of secondary hyperPTH
IV calcium infusion (calcium gluconate)
also used to treat hyperkalaemia
Management of acute hypocalcaemia
Medical:
- Calcium
- Inactive vitamin D (ergocalciferol)
- Active vitamin D (alfacalcidol) in CKD as cannot complete second hydroxylation step
Which hyperPTH is ALP high?
secondary
Define Paget’s
disorder of bone remodelling (i.e. formation and resorption) – genetic factors play a role
3 phases of Paget’s
LYTIC PHASE- hyperactive osteoclasts > resorption
SCLEROTIC PHASE- compensation by osteoblasts
MIXED PHASE- hyperactive osteoblasts > formation
(woven bone, not lamellar)
So you get lots of immature bone leading to pain, fragility fractures
RF for Paget’s
Elderly
FHx
Number of bones affected by Paget’s
25% of cases: monostotic
75% of cases: polyostotic
Symptoms of Paget’s
Often asymptomatic
- Fragility fractures
- Bone pain (insidious onset)- skull, pelvis, femur
Nerve compression- due to narrowing of foramina
- Hearing loss (sensorineural- vestibulococular nerve)
- Sciatica
Signs of Paget’s
Bone enlargement/bossing
Warm skin over painful area (high metabolic activity)
Investigations for Paget’s
Bloods
- (FBC, CRP)
- U&E
- LFTs (ALP)
- Calcium
- Phosphate
- PTH
- Serum CTX (bone resorption marker)
- Serum P1NP (bone formation marker)
Imaging
- X-rays
- Bone scan- a type of nuclear medicine imaging test- using Tech99 tracer
Looks at areas of increased metabolic activity
State the level of: Calcium Phosphate PTH ALP in Paget's
Calcium ↔
Phosphate ↔
PTH ↔
ALP ↑↑
define osteoporosis
low BMD
RF for osteoporosis (primary and secondary causes)
PRIMARY
Post-menopausal
Elderly
SECONDARY
Drugs – steroids, thyroxine, alcohol
Endo – Cushing’s disease, hyperPTH, hyperT
GI – coeliac disease, IBD (malabsorption > low vitD)
Signs and symptoms of osteoporosis
Often asymptomatic
Fragility fractures
Back pain
Classic fractures in osteoporosis
Hip – neck of femur (NOF)
Wrist – Colles’ fractures
Lumbar spine - vertebral wedge fractures (these can be asymptomatic- explain why older people ‘shrink’)
Shoulder - neck of humerus
State the level of: Calcium Phosphate PTH ALP in osteoporosis
EVERYTHING NORMAL
Investigations for osteoporosis
Bloods (FBC, CRP) U&E LFTs (ALP) Calcium Phosphate PTH
Imaging
- X-rays
- DEXA scan
2 scores used to diagnose osteoporosis. Which one is more useful?
T-score: Patient’s BMD compared to young, healthy adult
Z-score: Patient’s BMD compared to age-matched BMD
T-score is used more often:
>-1.0 = normal
-1.0 and -2.5 = osteopaenia
What is T score used to calculate?
FRAX score:
10 year risk of developing fragility fractures
Which can help decide if Tx is required
A 42 year old Pakistani woman attends her GP appointment. She has been experiencing non-specific pain in her legs alongside muscle weakness for a month. Her X-ray shows Looser’s pseudofractures
What is the most appropriate treatment option?
A Increase calcium intake in diet B Bisphosphonates C Calcium and vitamin D supplements D Total parathyroidectomy E Recombinant PTH
Calcium and vitamin D supplements
diagnosis = osteomalacia
“Pakistani/Arabic women” is a common buzzword for vitamin D deficiency (due to the unfair generalisation that these women will be wearing hijabs and thus will not produce enough vitamin D from sunlight)
Treatment of osteoporosis/pagets
bisphosphonates (alendronic acid)
A 58 year old post-menopausal woman was diagnosed with a fragility fracture. Her past medical history includes a myocardial infarction at the age of 47, and rheumatoid arthritis for which she is taking prednisolone. Her blood results are normal
What is the most likely underlying diagnosis?
A Osteomalacia B Primary hyperparathyroidism C Paget’s disease D Tertiary hyperparathyroidism E Osteoporosis
osteoprosis- RF:
Steroids can cause osteoporosis
Menopause can cause osteoporosis (since oestrogen is protective of bones)
In which 2 bone conditions is calcium normal?
osteoporosis
Pagets
In which bone condition is calcium low?
osteomalacia / secondary hyperPTH
In which bone conditions is calcium high?
primary/tertiary hyperPTH, malignancy
