Calcium and Phosphate Metabolism Flashcards
What is osteoporosis
Loss of bone mass (mineral and organic matrix)
What are the causes of osteoporosis
- Endocrine
- Malignancy
- Drug-induced
- Renal disease
- Nutritional
- Age
How is osteoporosis diagnosed
Measurement of bone mineral density (BMD)
Dual-energy X-ray absorptiometry (DEXA or DXA scan)
T score:
- Number of SDs below average for Young adult at peak bone density
Z score:
- Matched to age and/or group
What T-values are classified as normal and osteoporosis
Normal: -1 or above
Osteopenia: Lowe than -1 and greater than -2.5
Osteoporosis: -2.5 or lower
Severe osteoporosis: -2.5 or lower and presence of at least one fragility fracture
What are the endocrine causes of osteoporosis
- Hypogonadism – notably any cause of oestrogen
deficiency - Excess glucocorticoids - endogenous or exogenous
- Hyperparathyroidism
- Hyperthyroidism
What are the risk factors for osteoporosis
- Low peak bone mass
- Early menopause
- Faster post-menopausal decline
What are the 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
- Denosumab – human monoclonal antibody against RANK ligand
- Romosozumab – human monoclonal antibody against sclerostin (very recent)
What is osteomalacia
Loss of bone mineralisation (termed rickets in children)
Soft and pliable like cartilage
What are the signs and symptoms of osteomalacia?
- 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 are the causes of osteomalacia
- Vitamin D deficiency (most common) - Lack of sunlight, lack of Vitamin D supplementation
- Mutations leading to errors in vitamin D metabolism (rare)
- Hypophosphataemia
Treatment most commonly involves ensuring adequate Vit D and Ca
Describe 1a hydroxyls mutation
- The enzyme converts Vit D into calcitriol, here that doesn’t occur due to enzyme mutation
- Cause of Vit D dependant rickets type 1
- Excess Vit D but low calcitriol concentration
- High PTH
Describe Vit D receptor mutation
- Low Ca and Pi stimulate calcitriol production but the excess calcitriol has no effect as its receptor doesn’t work
- Cause of Vit D dependant rickets type 2
- High PTH
Describe how vitamin D is regulated
Increased by:
- PTH
- Low Ca
- Low Pi
Decreased:
- FGF-23 - Osteocytes secrete in response to rise in PO3
- High Ca
- High Pi
What is Autosomal dominant hypopho-phataemic rickets
Mutation leading to excess FGF-23 activity
What is Oncogenic osteomalacia
Ectopic FGF secretion (benign tumour)