Metabolic bone disease: Biochemistry Flashcards
What are biochemical investigations used in bone disease?
Bone profile: calcium, albumin, phosphate, alkaline phosphate
Renal function: PTH, 25-OH vitD
Urine: Calcium, phosphate, NTX
What 3 systems control calcium?
Kidney
GI tract
Bones
How do we correct serum calcium calculations?
[calcium] + 0.02(45-[albumin])
How does PTH control calcium?
Low plasma Ca -> Release of PTH
PTH increases bone resorption
Acts on the kidney to increase calcium absorption/reabsorption and increase calcitriol formation, while increasing phosphate excretion in the urine
How does parathyroid gland monitor serum Ca?
Via calcium-sensing receptor
Diagnosis of Primary hyperthyroidism?
Hypercalcaemia with PTH in the upper half of the normal range
Chronically elevated PTH causes?
Gall stones
Increased cortical bone resorption
Increased fracture risk
Biochemical findings in Primary HPT?
- Increased serum calcium (by absorption from bone/gut)
- Decreased serum phosphate (renal excretion in proximal tubule)
- PTH in the upper half of the normal range or elevated
- Increased urine calcium excretion
- Cr may be elevated
What are the actions of vitamin D in the intestine, bone and kidney? What is its feedback mechanism?
Intestine: activates Ca/P absorption
Bone: Synergises with PTH - act on osteoblasts, increases formation of osteoclasts via RANKL. Also increases osteoblast differentiation/bone formation
Kidney: Facilitates PTH action to increase Ca reabsorption in DCT
Direct feedback on parathyroid to reduce PTH secretion
Feedback on bone to increase FGF-23 production
How is vit D deficiency defined?
Serum 25(OH)D = 21-29ng/ml
Define rickets
Vit D deficiency leading to defective mineralisation of growth plates (BEFORE hypocalcaemia)
Severe rickets may have hypocalcaemia
Biochemical findings in rickets/osteomalacia
Serum: Ca NORMAL (low in osteomalacia) Phosphate NORMAL (low in osteomalacia) Alk Phosphates HIGH 25(OH)D LOW PTH high (secondary effect, to compensate)
Urine:
Phosphates HIGH
Where is FGF-23 produced and what does it do?
Produced by osteoblast lineage cells in long bones
Causes LOSS of phosphates in PCT -> phosphaturia (same as PTH)
Inhibits 1-alpha hydroxylase -> inhibits vit D activation (unlike PTH)
Name conditions which involve loss of phosphate leading to osteomalacia
X-linked hypophosphataemic Rickets
- High levels of FGF-23
Autosomal Dominant Hypophosphataemic Rickets
- High FGF-23
Oncogenic osteomalacia - mesenchymal tumours producing FGF-23 (phosphaturia + inhibit 1a-hydroxylase)
PCT damage -> phosphaturia and stops activation of vit D
What are the 4 Ms that make a bone strong?
Mass
Material properties
Microarchitecture
Macroarchitecture
Describe changes in bone mass with age in men and women
Women have lower bone mass in general
Both attain Peak bone mass at around 28-30yrs age
Followed by consolidation stage until early 40s (i.e. no change in BM)
Then age-related bone loss
Women have further decrease in bone mass (endocortical bone resorption) during menopause, meaning they could go below the fracture threshold at EARLIER age than men
Significance of Peak Bone Mass? What factors affect it?
Important predictor of osteoporosis
Genetics, gender, nutrition (Ca), exercise levels, ethnic origin
Lifespan of remodelling units, osteoclast, osteoblasts? How long does it take to replace whole skeleton?
remodelling units = 6-9 months
Osteoclast = 2 weeks
Osteoblast = 3 months
10 years
What causes menopausal bone loss?
Estrogen deficiency
Increases number of remodelling units
Causes increased bone resorption (bone formation also increased but only half as much)
Causes remodelling errors - more/deeper remodelling pits
Decreased osteocyte sensing
What is the likelihood of women having osteoporotic fracture?
HALF of women aged over 50
Biochemical findings of osteoporosis
Serum should all be NORMAL if primary osteoporosis If secondary: 1. Check Vit D deficiency 2. Check secondary endocrine causes 3. Exclude multiple myeloma 4. May have high urine Ca
Diagnosis using bone density DEXA scan
T score less than -2.5 = Osteoporosis
Which bone is measured for Fracture Risk Assessment Tool? (FRAX)
Hip bone
Commonest fractures?
- Vertebral - measure of cancellous bone
2. Hip
What are the bone formation/resorption markers?
Formation markers: P1NP - propeptide formed during collagen synthesis by osteoblasts
Resorption markers: Serum CTX, urine NTX
3-hydroxylysine condenses to form PYRIDINIUM linkage
