Bone health Flashcards
What are the functions of calcium in the body?
Muscle contraction
Blood clotting
Nerve conduction
Bone mineralisation
Hormonal communication
Where does the total body calcium lie?
Bone - 99%
Body fluids - 1%
-> Ionised/free - 50%
-> Bound to anions - 10%
-> Protein bound - 40%
Which calcium store can be measured, and what is the normal level?
Ionised/free calcium in body fluids
4.64 - 5.28 mg/dL
What hormones and organs regulate calcium ion levels?
Hormones:
- Parathyroid hormone
- Calcitrol or vit D3
- Calcitonin
Organs:
- Intestines
- Kidneys
- Bone
What releases parathyroid hormone (PTH), and what stimulates its release?
From chief cells in the four parathyroid glands
Released in response to a decrease in Ca2+
Most important regulator ECF Ca2+
By which mechanisms does PTH raise calcium levels by?
- Resorption of calcium from bone
- Increasing renal reabsorption of calcium
- Absorption of calcium from GIT (indirect)
What is the bone reabsorption mechanism?
- PTH upregulates RANKL on osteoblasts on surface of bone
- Osteoclasts adhere to bone like a suction cup under influence of RANKL and integrins and forms sealing zone with a ruffled border
- OC secrete protons to decrease pH idssolving minerals
- Release of proteolytic enzymes and non-proteolytic enzymes degrade the bone matrix - make pits
How does vitamin D become active?
Vitamins D2 and D3 are both inactive until undergoing two hydroxylations
- First occurs in liver to form calcidol
- Second occurs in kidneys to form calcitriol - active form of vit D
What is the role of vitamin D?
Active vit D:
increases absorption of both calcium and phosphate in the intestine
works with PTH to reduce Ca2+ loss in urine and stimulate the release of calcium and phosphorus from the bone
Where is calcitonin released from?
Secreted by C cells in the thyroid gland in response to hypercalcemia
What is the action of calcitonin?
PTH antagonist
On bones: inhibits activity of osteoclast (responsible for bone formation)
On kidney: increase urinary excretion of phosphate and calcium
Summarise the hormonal regulation of high blood calcium levels
High blood calcium level > activates thyroid gland > calcitonin released > stimulates calcium deposition in bones, reduces calcium uptake in kidneys, reduces calcium uptake in intestines > normal calcium in blood
Summarise the hormonal regulation of low blood calcium levels
Calcium levels too low > parathyroid gland stimulated > releases parathyroid hormone > stimulates calcium release from bones, increases calcium uptake in kidneys > increased Ca2+ and increases calcium uptake in intestines > increased calcium
What hormones are involved in regulation of bone health? (by class)
Calcium regulating hormones:
- PTH
- Calcitonin
- Active vit D (Calcitriol)
Sex hormones:
- Testosterone
- Oestrogen
Other hormones:
- Growth hormone
- Thyroid hormone
- Cortisol
What function does growth hormone have on bone regulation?
Stimulates bone formation
Stimulates longitudinal growth
What function does thyroid hormone have on bone regulation?
Too much stimulates bone resorption
Activates osteoclastic activity
What function does glucocorticoid have on bone regulation?
Inhibits bone formation
Decreases calcium absorption form the intestines
What function does oestrogen/testosterone have on bone regulation?
Maintain bone density by inhibiting activity of osteoclasts
Stimulation of osteoblasts
Calcium absorption
Inhibit bone resorption
How can bone health maintained?
Calcium intake: particularly important during childhood, adolescence, pregnancy, and lactation
Vitamin D
Regular excercise: muscle strengthening, weight bearing
Avoid smoking and drinking to excess
Maintain a healthy body weight
Hormonal health
Primary hyperparathyroidism
- Level of parathyroid hormone
- Level of serum calcium
- Level of phoshate
- Causes
PTH= high
Serum calcium= increased
Phosphate= decreased
Causes: parathyroid tumour, ectopic parathyroid tissueP
Primary hyperparathyroidism symptoms and treatments
Symptoms:
- renal stones
- bone pain
- abdominal pain
- constipation
- Depression
Treatments:
parathyroidectomy
Secondary hyperparathyroidism
- Levels of parathyroid hormone
- Level of serum calcium
- Level of phosphate
- Causes
PTH: High
Ca2+: decreased/normal
Phosphate: Increased/normal
Causes:
- Vit D deficiency
- End stage kidney disease
Secondary hyperparathyroidism symptoms and treatments
Symptoms:
- Osteoporosis
- Renal stone
- Bone and joint pain
Treatments:
- Vit D supplement
- Treat underlying cause
What is the presentation of Vitamin D deficiency in children?
- Demineralisation of bone - soft pliable bones
- Characteristic bow-leg deformity
- Overgrowth at costochondral junction - rachitic rosary
- Pigeon chest deformity
- Frontal bossing
- Osteomalacia
What is the presentation of vitamin D deficiency in adults?
Softening of bones - frequent fractures
What can be tested and detected to diagnose vitamin D deficiency?
Hypocalcemia
Hypophosphatemia
Increased alkaline phosphatase
What is renal osteodystrophy/CKD mineral bone disorder? What is a key characteristic of this?
Incorporates all biochemical abnormalities and skeletal manifestations in patients with CKD or end-stage renal disease
GFR below 60 mL/min
What are the symptoms of renal osteodystrophy/CKD mineral bone disorder? (5)
- Bone pain and fractures
- Joint pain
- Bone deformation
- Slow bone growth
- Low bone mineral content
Why does renal osteodystrophy/CKD mineral bone disorder occur?
Failure to synthesise active vit D
Kidneys produce limited calcitriol which is normally used to convert vitamin D from inactive to active
Failure to excrete phosphate - hyperphosphatemia > bind to serum calcium resulting in decreased ionised free Ca2+ > increased PTH
What is FGF23 produced by and what is it’s function?
Produced by osteoblasts and osteocytes
- Increases urinary phosphate excretion
- Involved in vit D metabolism and regulation
What happens to FGF23 levels in CKD?
Rise 1000 fold to maintain a neutral phosphate distribution
Promotes the suppression of 1-25,dihydroxyvitamin D production > reduction of intestinal calcium absorption increase of PTH level and ultimately develop secondary hyperthyroidism
What is osteoporosis and what are the causes?
Literal meaning = ‘Porous bone’
Bones are fragile and more likely to break
Reduced mineral density and bone mass
Causes:
- Hormonal/postmenopausal
- Chronic steroid use
- Malabsorption disease
- Drug related
- Low BMI
What are the symptoms of osteoporosis?
Painless unless fractures occur
Coughing can produce enough force to fracture bones
Significant height loss and curvature of the spine - if compression fractures in spine
How may the severity of osteoporosis be measured?
Bone mineral density scan (BMD scan)
Measures bone density and bone loss
Bone densities given as a T score
Normal: -1.0
Low bone density: -1.0 to -2.5
Osteoporosis: -2.5 and lower
When may a BMD be carried out?
- For those with significant risk factors
- When it is uncertain if bones are fragile
- To decide whether drug treatment is necessary
