Calcium and Phosphate Metabolism Flashcards
Why is bone turnover important?
For homeostasis of serum calcium and phosphate
What affects the homeostasis of serum calcium and phosphate?
- Parathyroid Hormone (PTH) = increases Ca2+
- Vitamin D = Increases Ca2+
- Calcitonin = Decreases Ca2+
- FGF-23
What is the distribution of body calcium?
99% in the bone
1% intracellular
<0.1 extracellular (this maintains Ca2+ balance)
What maintains Ca balance?
Hormonal control of small extracellular fraction (<0.1%) of calcium
What is the composition of calcium in extracellular fluid?
Half is free (Ca2+) and physiologically active
Other half is protein bound (mainly albumin)
What is the distribution of phosphate?
85% of phosphate is in bone
Remainder is intracellular
Extracellular = H2PO4-, HPO4-
What are the clinical features of hypercalcaemia?
PAINFUL BONES, RENAL STONES, ABDOMINAL GROANS, PSYCHIC MOANS
- Depression, fatigue, anorexia, nausea, vomiting
- Abdominal pain, constipation
- Renal calcification (kidney stones)
- Bone pain
What are clinical features of severe hypercalcaemia?
- Cardiac arrthymias
- Cardiac arrest
What are the common causes of hypercalcaemia in ambulatory patients?
Primary hyperparathyroidism
- e.g tumour within the thyroid gland
What is the most common cause of hypercalcaemia in hospitalised patients?
Hypercalcaemia of malignancy
What are less common causes of malignancy?
Hyperthyroidism/ excessive intake of vitamin D
What would the serum biochemistry look like in someone with hypercalcaemia?
- Serum calcium = modest to marked increase
- Serum phosphate = low to low normal
- Serum alkaline phosphatase = 20% of cases due to increased bone turnover
- Serum creatinine = May be elevated in long standing disease
- Serum PTH = interpreted in relation to calcium
What does high alkaline phosphatase indicate?
Increase in bone remodelling
What is the function of PTH?
Secreted when blood calcium levels drop to prevent hypocalcaemi
What are the main actions of PTH?
- Promote release of Ca and Pi from bone
- Increases renal Ca reabsorption from DCT
- Decreases renal Pi reabsorption fromo DCT (increases excretion)
- Upregulates 1 alpha hydroxylase activity activating vitamin D
What are the main actions of PTH on bone?
- Will promote bone remodelling
- PTH receptors are present on osteoblasts and pre-osteclasts
- PTH will bind to osteoblast receptors activating pre-osteoblasts via RANKL and OPG inhibition (normally inhibits RANK)
- Osteoclasts will absorb bone and release more calcium and phosphate
How does PTH regulate itself?
As free Ca2+ levels are low serum PTH levels rise, as free Ca2+ levels are high serum PTH levels decrease.
What is hypercalcaemia of malignancy?
Most common cause of hypercalcaemia in HOSPITALISED PATIENTS
- humoural e.g lung carcinoma secreting PTHrP (PTH related peptide)
- Metastatic
- Haematological (e.g myeloma)
What is the most common cause of hypocalcaemia?
- Vitamin D deficiency
- Renal failure
What is a less common cause of hypocalcaemia?
Hypoparathyroidism
What can vitamin D deficiency result in?
Rickets (in children)
- failure in bone mineralisation and disordered cartilage formation
Osteomalacia (in adults)
- Impaired bone mineralisation (soft bones)
What are features of osteomalacia?
- Bone pain
- Waddling gait, muscle weakness
- On X-ray, stress fractures
What is the serum biochemistry of osteomalacia?
- Low/normal calcium
- Hypophosphataemia
- Raised alkaline phosphatase
- Secondary hyperparathyroidism (the low calcium would stimulate PTH release)
What is osteoporosis?
Loss of bone mass/density due to the thinning of both cortical bone and trabecular mesh
What are some causes of osteoporosis?
- Endocrine
- Malignancy
- Drug-induced
- Renal disease
- Nutritional
- Age
What is the difference between osteoporosis and osteomalacia?
Osteoporosis
- Loss of bone mass/ density
Osteomalacia
- Loss of bone mineralisation
First sign of osteoporosis
Sustaining a fracture, usually:
- Wrist
- Neck of the femur
- Intervertebral
How do we diagnose osteoporosis?
Dual Energy X-Ray Absorptiometry Scan (DEXA)
- Measures bone mass density
How does DEXA work?
- Bone mineral density is at its peak in a young adult (25 years old)
- after it will slowly decline
- With DEXA we will achieve a T score by taking the average bone density for a young adult and then interpreting your bone mineral density score in relation
- T score = Number of standard deviations below average bone mineral density for a young adult at peak bone density (- 25yo)
Endocrine causes of osteoporosis
- Hypogonadism = notably any cause oestrogen deficiency
- Excess gluocorticoids - endogenous or exogenous
- Hyperparathyroidism
- Hyperthyroidism
What are the treatments of osteoporosis treatments?
- · Hormone Replacement Therapy- effects well established but safety of long-term treatment has been questioned
-
Bisphosphonates
- · Inhibit function of osteoclasts (e.g. risedronate, alendronate)
-
PTH Analogues
- · Intermittent doses of PTH promote good bone remodelling- not an excess of osteoclast over osteoblast activity (whereas raised prolonged doses of PTH tend to favour osteoclast activity for bone reabsorption)
-
Denosumab
- · Antibody against RANK ligand
-
Romosozumab
- · Antibody against sclerostin protein (which usually inhibits osteoblast differentiation)
- Ensure adequate calcium and vitamin D intake, appropriate exercise
