Calcium and Phosphate Metabolism Flashcards
Bone turnover serves as homeostasis of serum calcium and phosphate, in conjunction with …?
- Parathyroid hormone (PTH)
- Vitamin D (1,25-dihydroxy D3)
- Calcitonin
- FGF-23
Briefly, describe calcium homeostasis.
99% of body calcium is in bone, the remaining 1% is mainly intracellular.
Hormonal control of the tiny (<0.1%) extracellular fraction is what maintains Ca balance.
Extracellular: plasma Ca 2.2-2.6 mmol L-1
About half is free [Ca2+] (physiologically active), half protein bound (mainly albumin).
Describe phosphate hoemostasis.
85% of body phosphorus is found in bone, the remainder is mainly intracellular.
Extracellular: H2PO4-, HPO42-, 2.5-4.5 mg dL-1 (0.75-1.45 mmol L-1).
Phosphate levels may fluctuate more than Ca.
List some clinical features of hypercalcemia.
- Depression, fatigue, anorexia, nausea, vomiting,
- Abdominal pain, constipation
- Renal calcification (kidney stones)
- Bone pain
“painful bones, renal stones, abdominal groans, and psychic moans,”
Severe: cardiac arrhythmias, cardiac arrest
List some causes of hypercalcemia.
MOST COMMON CAUSES
In ambulatory patients: primary hyperparathyroidism
In hospitalized patients: malignancy
LESS COMMON CAUSES:
Hyperthyroidism
Excessive intake of vitamin D
Describe the serum biochemistry of hyperparathyroidism.
Serum calcium - modest to marked increase
Serum phosphate - low or low normal
Serum alkaline phosphatase raised in ~ 20% of cases
Serum creatinine may be elevated in longstanding disease (kidney damage)
Serum PTH concentration should be interpreted in relation to calcium
Describe hypercalcemia of malignancy.
It is the most common cause of hypercalcemia in hospitalised patients. The malignancy can be:
- humoural (e.g. lung carcinoma secreting PTHrP)
- metastatic
It can also have a haemotological cause (myeloma).
List some causes of hypocalcemia.
MOST COMMON CAUSES:
- Vitamin D deficiency
- Renal failure
LESS COMMON CAUSES:
- Hypoparathyroidism
What is the difference between rickets and osteomalacia?
It is a bone disease associated with vitamin D deficiency.
RICKETS - in children, failure of bone mineralisation and disordered cartilage formation
OSTEOMALACIA - in adults, impaired bone mineralisation
What are some features of osteomalacia?
- Diffuse bone pain
- Waddling gait, muscle weakness
- On X-ray, stress fractures
Serum biochemistry:
- Low/normal calcium
- Hypophosphataemia
- Raised alkaline phosphatase
What is the difference between osteoporosis and osteomalacia?
OSTEPOROSIS: loss of bone mass/density due to:
- endocrine
- malignancy
- drug-induced
- renal disease
- nutritional
OSTEOMALACIA: loss of bone mineralization
How would you diagnose osteoporosis?
You would measure bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA or DXA scan).
Two beams are used: one to measure thickness of bone and one to measure density.
T SCORE:
- number of SDs below average for young adult at peak bone density
Z SCORE:
- matched to age and/or group
List some endocrine causes of osteoporosis.
- Hypogonadism – notably any cause of oestrogen deficiency
- Excess glucocorticoids – endogenous or exogenous
- Hyperparathyroidism
- Hyperthyroidism
What are some treatments for osteoporosis?
Postmenopausal: HRT (hormone replacement therapy) – effects well established but safety of long term treatment has been questioned
Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate
PTH analogues
Denosumab – antibody against RANK ligand
Ensure adequate calcium and Vitamin D intake, appropriate exercise
After long research and study, what are the modified HRT guidelines?
- Short-term therapy (3-5 years) for treating vasomotor symptoms
- Lowest effective dose to be used
- Long term use not recommended
