Metabolic bone disease: biochemistry Flashcards
what is metabolic bone disease?
A group of diseases that cause a change in bone density bone strength by 1. INCREASING bone resorption 2. DECREASING bone formation 3. Altering bone structure
And may be associated with disturbances in mineral metabolism
What are the 5 common metabolic bone disorders?
Primary hyperparathyroidism
Rickets/ Osteomalacia
Osteoporosis
Paget’s Disease
Renal osteodystrophy
symptoms in these disease:
- metabolic
- specific to bone
Metabolic
- Hypocalacaemia
- Hypercalcaemia
- Hypo/Hyperphosphataemia
Specific to bone
- Bone Pain
- Deformity
- Fractures
what does the bone calcium do?
-hydroxyapatite
-cancellous bone metabolically active
remodelling
continuous exchange of ECF with bone fluid reserve
What makes a bone strong?
-the 4 Ms
Mass
Material properties (matrix and mineral)
- collagen
- woven versus lamellar
- mineralisation
- microcracks
microarchitecture
- trabecular thickness
- trabecular connectivity
- cortical porosity
microarchitecture
- hip axis length
- diameter
what might be used to assess bone structure and function?
Bone histology
Biochemical tests
Bone mineral densitometry, e.g. osteoporosis
Radiology
what is the age related changes in bone mass like?
Men have greater bone mass than women
bone mass increases, no increase from 27 to 42 (called consolidation), then decreases. For women there is a sharp drop in bone mass during menopause
how can growth and exercise change peak bone mass?
change in bone dimensions
change in bone shape
change in trabecular volumetric BMD
what is bone remodelling
bone has a structure designed to absorb energy
irreversible PLASTIC deformation does occur resulting in microfractures, which dissipate the excess energy, generally limited to the interstitial bone between osteons . If these accumulate bone strength will be compromised.
Bone remodeling is the process by which these areas are repaired, each osteon essentially represents a previous remodelling event.
describe the bone remodelling cycle
Bone remodelling occurs in the basic multicellular unit, seen here.
Activation occurs
A microcrack crosses canaliculi, so severing osteocyte processes causing osteocytic apoptosis. This is thought to act as a signal to the connected surface lining cells (which are osteoblast lineage), which along with the osteocytes release local factors that attract cells from blood and marrow into the remodeling compartment. For the resorption phase to start osteoclasts are generated locally and resorb matrix and the offending microcrack, then successive teams of osteoblasts deposit new lamellar bone. Osteoblasts that are trapped in the matrix become osteocytes; others die or form new, flattened osteoblast lining cells.
what are the biochemical investigations that can be used in bone disease?
Serum Bone profile -calcium - corrected calcium (albumin -phosphate -alkaline phosphatase
Renal function
- creatinine
- parathyroid hormone
- 25-hydroxy vitamin D
Urine
- Calcium/ Phosphate
- NTX
biochemical changes table
see ppt
calcium balance systems
Calcium is most abundant mineral in body; 1kg
Mainly in BONE
Huge fluxws in /out of bone; it is not a metabolicaaly inert tissue
Cancellous bone has a huge blood supply; respiratory physiologists tell you the alveolar surface area for gas exchange is TENNIS court; bone is many times greater.
Thinking about calcium is easy
GUT whats comig in; 1g day recommended intake
Kidney whats going out
BONE flux; your compensatory mechanism
how do serum calcium measurements need correction?
We measure in serum is a TOTAL calcium
free; the active form
complexed; to P and citraate
protein-bound to ALBUMIN
So the corrected calcium a lab gives you compensates for the protein level; if protein levels are HIGH they compensate down; o.o2 for each g/l of albumin PROBLEMS occur in acid-base disturbance
If HYPERVENTILATE; get alkalosis which causes more ca to bind to prtotein so that free levels drop; all experienced this;tingling
venous stasis may falsely elevate LEVELS
How does PTH regulate serum calcium levels?
If plasma calcium drops within seconds have secretion of PTH from pre-formed stores
Acts on 2 systems
1.Bone acute release of available calcium; not in hydroxyapatite crystals
more chronically INCREASED osteoclast activiyty to re-absorb bone
- Kidney Increased ca re-absorption in the distal conv tubule; the only site where ca re-absorption is under active hormonal controlStimulation of 1alpha Ohase activity , so increasing actiavated vit D production, which leads to increased gut re-abs of ca;
Decreases 24 oh ase activityIncreases p excretion by inhibiting the NAP cotransporter in the proximal tubule
clinically relevant points about PTH
- 84 amino acid peptide
but N1-34 active - Mg dependent
- T 1/2 8 min
- PTH receptor is activated
also by PTHrP
how does the parathyroid gland monitor serum Ca through the calcium-sensing receptor?
A steep inverse sigmoidal function
relates PTH levels and Cao2+ in vivo.
MINIMUM: even at high calcium levels
there is base-line PTH secretion
SET-POINT: point of half maximal
suppression of PTH; steep part of slope;
Small perturbation causes large change PTH
**MINIMUM This is important in diagnosis.
Even in Hyperacalcaemia of malig PTH will be detectable; lower half normal rangs
PTH drives active calcium absorption in
the distal tubule of the kidney
how does PTH cause bone resorption?
RANK system
how is primary HPT diagnosed?
Primary hyperparathyroidism is diagnosed by
‘an elevated total/ionised calcium with PTH levels frankly elevated
or in the upper half of the normal range’
(ie. Corrected Calcium > 2.60 mmol/l with PTH > 3.9 pmol/l (nr 1.0 - 6.8))
Subjects with hypercalcaemia and a PTH in the upper half of the normal range are physiologically not normal
It is important to note that such ‘non-suppressed’ concentrations are entirely compatible with the diagnosis of Primary HPT
clinical features of primary HPT
Thirst, polyuria
Tiredness, fatigue, muscle weakness
“Stones, abdominal moans and psychic groans”
Renal colic, nephrocalcinosis, CRF Dyspepsia, pancreatitis Constipation, nausea, anorexia Depression, impaired concentration Drowsy, coma
Patients may also suffer fractures secondary to bone resorption