Flashcards in Metabolic Bone Disease – Biochemistry Deck (56)
What is metabolic bone disease?
A group of disease that cause a change in bone density and bone strength by increasing bone resorption, decreasing bone formation or altering bone structure
What are the five main metabolic bone disorders?
What are the main components of bone strength?
When is peak bone mass reached?
Around 25 years
When does bone mass begin to decline?
Around 40 years
NOTE: in women, the decline in bone mass accelerates after menopause
How are microfractures repaired?
Briefly describe the bone remodelling cycle.
A microcrack crosses the canaliculi and severs the osteocyte processes, inducing osteocyte apoptosis
This signals to the surface lining cells, which release factors to recruit cells from the blood and marrow to the remodelling compartment
Osteoclasts are generated locally and resorb the matrix and the mitrocrack
Then osteoblasts deposit new lamellar bone
Osteoblasts that become trapped in the matrix become osteocytes
What is the normal range for serum calcium concentration?
Describe the distribution of calcium.
46% plasma protein bound (albumin)
47% free calcium
7% complexes (with phosphate or citrate)
What is the ‘corrected’ calcium level?
This compensates for changes in protein level (if proteins are high, itcompensates down)
Corrected calcium = [Ca2+] + 0.02(45-[albumin])
Describe the effect of metabolic alkalosis on calcium distribution.
It makes more calcium bind to plasma proteins thus reducing the free calcium levels
NOTE: venous stasis may elevate free calcium
What are the two main targets of PTH?
Describe the effects of PTH in:
Acute release of available calcium (not stored in hydroxyapatite crystal form)
More chronically, increased osteoclast activity
Increased calcium reabsorption
Increased phosphate excretion
Increased stimulation of 1-alpha hydroxylase (thus increasing calcitriol production)
Where does the PTH-mediated increase in calcium reabsorption take place in the nephron?
DISTAL convoluted tubule
Where does the PTH-mediated increase in phosphate excretion take place in the nephron?
PROXIMAL convoluted tubule
How many amino acids make up PTH and which part of this is active?
What is PTH dependent on?
What is the half-life of PTH?
What else can the PTH receptor be activated by other than PTH?
PTHrP (PTH related protein)
This is produced by some tumours
What does the parathyroid gland use to monitor serum calcium?
Describe the relationship between PTH level and calcium in vivo.
Steep inverse sigmoid function
NOTE: there is a minimum level of PTH release (it can’t get below this even in the case of hypercalcaemia)
What are the causes of primary hyperparathyroidism?
Parathyroid adenoma (80%)
Parathyroid hyperplasia (20%)
What biochemical results are diagnostic of primary hyperparathyroidism?
Elevated total/ionised calcium
With PTH levels frankly elevated or in the upper half of the normal range (negative feedback should drop PTH if there is hypercalcaemia)
What are the clinical features of primary hyperparathyroidism?
Stones, Bones, Abdominal Groans and Psychic Moans
Stones – renal colic, nephrocalcinosis
Bones – osteitis fibrosa cystica
Abdominal moans – dyspepsia, pancreatitis, constipation
Psychic groans – depression, impaired concentration
NOTE: patients may also suffer fractures secondary to the bone resorption
IMPORTANT NOTE: hypercalcaemia also causes diuresis (polyuria and polydipsia)
What is the main site of action of calcitriol and what effect does it have?
Small intestine – increases calcium and phosphate absorption
Describe the effects of calcitriol on bone and in the kidneys.
Facilitates PTH effect on the DCT in the kidneys (increased calcium reabsorption)
Synergises with PTH in the bone to increase osteoclast activation/maturation
Which receptors/proteins are involved in mediating the effects of calcitriol on the intestines?
What parameter is used to determine whether a patient is vitamin D deficient?
Deficient < 20 ng/M (50 nmol/L)
Normal > 30 ng/M (75 nmol/L)
What is Rickets?
Inadequate vitamin D activity leads to defective mineralisation of the cartilaginous growth plate (before a low calcium)