Calcium and phosphate metabolism Flashcards
What is osteoporosis and what can cause it?
Osteoporosis: loss of bone mass (mineral and organic matrix) Causes can include: Endocrine Malignancy Drug-induced Renal disease Nutritional Age
How is osteoporosis diagnosed?
Osteoporosis can be diagnosed by taking a measurement of bone mineral density (BMD)
using Dual-energy X-ray absorptiometry (DEXA or DXA scan) (uses 2 x ray beams essentially)
T score
Number of Standard Deviations (SDs) below average for young adult at peak bone density
Z score
Matched to age and/or group
T score of -1 or above= normal
T-score lower than -1 and greater than -2.5= osteopenia
T-score of -2.5 or lower= osteoporosis
T-score of -2.5 or lower, and presence of at least one fragility fracture= severe osteoporosis
What do endocrine causes of osteoporosis include?
Hypogonadism – notably any cause of oestrogen deficiency
Excess glucocorticoids – endogenous or exogenous (eg cushing’s syndrome left untreated)
Hyperparathyroidism lead to excess bone reabsorption over bone formation
Hyperthyroidism
What do treatments of osteoporosis include?
Ensure adequate calcium and vit D intake, appropriate exercise
Postmenopausal: Hormone Replacement therapy – effects well established but safety of long term treatment was questioned in early 2000s
Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate usually first line in therapy
PTH analogues
Denosumab – human monoclonal antibody against RANK ligand
Romosozumab – human monoclonal antibody against sclerostin (very recent)
What is osteomalacia? What are some 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 PTH may be elevated
What can cause 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 can Vitamin D (calcitriol) be increased and decreased by?
Increased by
PTH
Low Ca
Low Pi
Decreased by
FGF-23
High Ca
High Pi
What is FGF-23?
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 hypopho-phataemic rickets (gain of function mutation)
What can an imbalance of calcium and phosphate lead to?
Renal disease- calcium low, phosphate high
What is renal osteodystrophy?
Spectrum of conditions associated with bone lesions in renal failure 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)
