Calcium and phosphate metabolism Flashcards
Define Osteoporosis
Osteoporosis – the loss of bone mass/ density.
What are the causes of osteoporosis?
- Endocrine disorders
- Malignancy
- Drug-induced
- Renal disease
- Nutritional
- Age
Define Osteomalacia
loss of bone mineralisation
What do we need for bone mineralisation?
If you have an adequate supply what happens if you take supplements?
- Need adequate vitamin D and calcium in the diet for bone mineralisation – defective if inadequate
- If adequate in diet but take supplements – no benefit, instead you put more load on the kidney in calcium excretion
How can we diagnose osteoporosis?
Measurement of bone mineral density (BMD) to see if its reduced – done via X-ray
Dual energy X-ray absorbtionmetry (DEXA or DXA scan) – use of 2 beams: 1 measures density and 1 measures thickness: technology converts it into a measurement – get T and Z scores
T-scores – number of standard deviations below average for a young adult at peak bone density. If T=0 then the same and if T=-1 then 1 SD away
Z-scores – matched to age and/or group
- In X-rays, the denser the bone the more absorption occurs
- Typical output ox DEXA scan on right – there is an age related decline in bone density
- At the hip joint a density reading is taken. The mean values for density correspsonding to age is seen
- Can see patient has 2 readings below the mean (blue). If your bone density is below normal it is osteopenia and if it way below it is osteoporosis
- See table for terms
What are the endocrine causes of osteoporosis?
- Hypogonadism – notably a cause of oestrogen deficiency
- Excess glucocorticoids – endogenous or exogenous e.g in cushings
- Hyperparathyroidism
- Hyperthyroidism
- Oestrogen is important in bone health for both sexes
- Oestrogen form from conversion from androgens via the enzyme aromatase – inactivation of aromatase enzyme in males leads to young men developing osteoporosis and failure in closure of the epiphyseal plates; can be treated with exogenous oestrogen
- Osteoporosis is more prevalent in women post-menopause
- Any cause of oestrogen deficiency increases the chances of osteoporosis
Why are post-menopausal women prone to osteoporosis?
- Males have similar curve but with a higher peak bone density
- Around the age of 50 (menopausal onset) there is greater drop for females
- Source of oestrogen is dividing follicles – after menopause there aren’t any: only source of aromatase conversion of adrenal androgens
- Oestrogen levels in post-menopausal is similar/ lower in males
- Not inevitable that women will get osteoporosis post menopause but there are increased risks for its e.g lower beak bone mass in adulthood, early menopause, accelerated loss of bone for some women
What is the treatment for osteoporosis?
- Postmenopausal: HRT – effectiveness well established but safety of long term treatment has been questioned
- Not currently first line treatment for purely osteoporosis
- Has been associated with an increased risk in breast cancer; negative effects with this were overhyped
- Oestrogen replacement can be effective
- Bisphosphonates – drugs inhibit function of osteoclasts i.e bone resorption; risedronate, alendronate
- PTH analogues
- Denosumab – antibody against (neutralises) RANK ligand so inhibits osteoclasts
- Ensure adequate calcium and vitamin D intake and appropriate exercise (promotes good bobe health and anabolic functioning)
What are the signs and symptoms of Osteomalacia
- Permanent deformities in bone growth (rickets in children)
- Diffuse aches and pains
- Chronic fatigue
- Weak bones
- Low Ca, Pi
- Elevated alkaline phosphatase
- 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 – due to rare conditions
Treatment most commonly involves ensuring adequate Vit D and Ca
How is vitamin D (calcitriol) increased and decreased?
- PTH
- Low Ca
- Low Pi
Decreased by
• FGF-23
• High Ca
• High Pi
What does a 1 alpha hydoxylase mutation cause?
Alpha hydroxylase mutation – impacts calcitriol production, although vitamin D levels are normal (precursor) the active form is not being form or is being made at low levels. Low calcitriol leads to low phosphate and low calcium. This leads to high PTH levels
What does a Vit D receptor mutation do?
Vit D receptor mutation – vitamin D levels are normal, but calcitriol levels are high. Low calcium and phosphate will be stimulating calcitriol production as a normal response. However due to a receptor mutation the calcitriol is unable to work. So calcium and phosphate remain low and PTH is high. Secondary hyperparathyroidism
What is hypophosphataemia?
Low levels of phosphate in the blood
- High FGF-23 leads to low phosphate. The excess FGF-23 is due to a mutation or in the case of oncogenic osteomalacia is due to ectopic secretion from a benign tumour. The effect of high FGF is low levels of phosphate.
- The effects on calcium can be variable. This is the same with calcitriol, the active form of Vitamin D.
- FGF-23 inhibits calcitriol production, which would lower calcitriol. But on the other hand the low levels of phosphate stimulates calcitriol pushing levels upwards.
- Low calcium could promote PTH, but depending on calcitriol, calcium may not be reduced leaving PTH in the normal range.
What are the 3 disorders of FGF-23?
- Oncogenic osteomalacia (tumour secreting FGF-23)
- X-linked hypophophataemic rickets
- Autosomal dominant hypopho-phataemic rickets (gain of function mutation)
