Metabolic Bone Disease - Biochemical (13.01.2020) Flashcards
What are the 5 common metabolic bone disorders?
- Primary hyperparathyroidism
- Rickets/ Osteomalacia
- Osteoporosis
- Paget’s Disease
- Renal osteodystrophy
Symptoms of these diseases
Metabolic
- Hypocalacaemia
- Hypercalcaemia
- Hypo/Hyperphosphataemia
Specific to bone
- Bone Pain
- Deformity
- Fractures
What makes bone strong?
4 M’s:
- mass
- material properties
- microarchitecture
- microarchitecture
Ways to asses structure and function of bone?
- Bone histology
- Biochemical tests
- Bone mineral densitometry, e.g. osteoporosis
- Radiology
Exercise and bone
- can increase bone mass
- can increase bone density
- in young age
- changes shape and bone dimensions depending in where strength is needed
- change in trabecular volumetric BMD
Sexual dimorphism in bone growth
- Men: bigger bones under the influence of testosterone
- Women: lower bone mass than men
- steroids and IGF-1 play a role here.
life spans of osteoclasts and osteoblasts
c: weeks
b: months
Biochemical investigations 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
Alkalosis and calcium levels
alkalosis makes more calcium bind to albumin
Clinical feature of 1* HPT
- Thirst, polyuria (hypercalcaemia causes diuresis)
- 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 (Chronically elevated PTH causes increased cortical bone resorption cortical>cancellous)
- Acute/ pulsed PTH : anabolic
- Chronic: catabolic
Biochemical findings in PHT
- 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
Where in the gut is calcium reabsorbed under the actions of vitamin D3?
20-60% in duodenum, jejunum and colon
Passive: Paracellular
linear
Active: up to 40%
saturable
duodenum
1,25 Vit D
Dangers of rickets becoming severe
- bronchospasm
seizures
echopic calcification in basal gangla -> PD - dementia
- cataracts
- muscle twithcing
- NM irritability (e.g. chvosteks sign, trousseaus sign -> spasm after BP cuff put on for a few minutes)
What are the causes of Ricktes/osteomalacia?
- dietary
- GI
- Small bowel malabsorption/ bypass (very common in gastrectomies; coeliac)
- Pancreatic insufficiency
- Liver/biliary disturbance
- Drugs- phenytoin, phenobarbitone
- Renal (chronic renal failure)
- Rare hereditary
- vitamin D dependant rickets
- T1: deficiency of 1 alpha hydroxylase
- T2: defective VDR for calcitriol
- vitamin D dependant rickets
Lack of sunlight!
Not added to foods except in USA.
Decreased production with age.
FGF 23
- 32KD protein
- Produced by osteoblast lineage cells, long bones
- LIKE PTH causes P loss
- UNLIKE PTH inhibits activation of Vit D by 1 α OH ase
-> decreases levels of P043-
Can cause rickets or osteomalacia
What are phosphate wasting hormones?
PTH and FGF-23
Fanconi syndrome - causes
- multiple myeloma
heavy metal poisoning: lead, mercury
drugs: tenofovir, gentamycin
congenital disease: Wilsons, glycogen storage diseases
Commonest causes of phosphate related osteomalacia
Kidney proximal tubule damaged -> causes phosphaturia and stops 1α hydroxylation of Vit D