Calcium and Phosphate Metabolism Flashcards
What is osteoporosis and its causes?
Osteoporosis: loss of bone mass (mineral and organic matrix) Causes: - Endocrine - Malignancy - Drug-induced - Renal disease - Nutritional - Age
How does one diagnose osteoporosis?
Based on measurement of bone mineral density (BMD)
Done using dual-energy X-ray absorptiometry (DEXA or DXA scan)
Uses two X ray beams and uses them to calculate bone density
T score
- Number of SDs below average for young adult at peak bone density
Z score
- Matched to age and/or group
What are the endocrine causes of osteoporosis?
Hypogonadism – notably any cause of oestrogen deficiency (can also happen in males as they also need oestrogen)
- E.g. a genetic aromatase mutation causes impaired conversion of oestrogens from androgens and that present with osteoporosis in young men
Excess glucocorticoids – endogenous or exogenous
- E.g. glucocorticoid therapy
Hyperparathyroidism- lead to increased bone remodelling and excess bone resorption over bone formation
Hyperthyroidism- increases bone metabolism so can contribute to oesteoporosis
What are the different treatments for osteoporosis?
Ensure adequate calcium and vit D intake, appropriate exercise
Postmenopausal: HRT – effects well established but safety of long term treatment was questioned in early 2000s
Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate
PTH analogues- you still get more bone resorption but also bone formation (as long as its not a prolonged treatment)
Denosumab – human monoclonal antibody against RANK ligand
Romosozumab – human monoclonal antibody against sclerostin (very recent)
What is osteomalacia and its signs and symptoms?
Loss of bone mineralization (termed rickets in children)
Signs and symptoms :
- Permanent deformities in bone growth (rickets)
- Diffuse aches and pains
- Chronic fatigue
- Weak bones
- Low Ca, Pi
- Elevated alkaline phosphatase (an enzyme which is a marker of bone turnover)
- PTH may be elevated
What are the causes of osteomalacia?
- Vitamin D deficiency (most common)
- Mutations leading to errors in vitamin D metabolism (rare)
- Hypophosphataemia
Treatment most commonly involves ensuring adequate Vit D and Ca
What are the two types of rickets?
- Vitamin D dependent rickets type 1
So in alpha-hydroxylase mutation, this impacts calcitriol production
Even though vitamin D levels are normal, calcitriol is low- Vitamin D dependent rickets type 2
With a vitamin D receptor mutation, the calcitriol is very high as a response to low calcium and phosphate, but calcitriol is ineffective due to the vitamin D receptor mutation
- Vitamin D dependent rickets type 2
How is vitamin D (calcitriol) regulated?
The conversion from 25 OH D3 to 1,25(OH)2 D3 is increased by: - PTH - Low Ca - Low Pi Decreased by: - FGF-23 - High Ca - High Pi
What do osteomalacia and hypophosphatemia have in common?
Elevated FGF-23 hormone
This leads to low phosphate due to:
1. Mutation leading to excess FGF-23 activity
2. Ectopic FGF secretion (benign tumour)
Calcium and calcitriol may be in the low or normal range
FGF-23 decreases calcitriol but low Pi increases it
PTH is high/normal as low calcium promotes PTH production but depending on calcitriol which determines calcium it might be normal
What is FGF-23 and what disorders can it lead to?
FGF-23; a hormone secreted by osteocytes
Phosphate balance: increases renal excretion
Disorders:
- Oncogenic osteomalacia (tumour secreting FGF-23)
- X-linked hypophophataemic rickets
- Autosomal dominant hypophophataemic rickets (gain of function mutation)
What are the conditions associated with osteodystrophy?
- Impaired Pi excretion
- High plasma Pi
- Impaired Vit D activation
- Low plasma Ca
- PTH rises
- Excess bone resorption
- May be augmented by acidosis (impaired renal H+ excretion)
