Metabolic Bone Disease Flashcards
Describe the composition and function of bone (aside from movement and protection)
Bones made up of calcium hydroxyapatite mineral deposited on a matrix/osteoid of primarily collagen
Bone is a reserve for calcium and phosphate, helping to keep serum levels constant (also maintained by gut absorption and renal tubules)
Where is PTH produced and what is its function?
Produced by the parathyroid glands in response to low Ca2+
Functions:
- Increases serum Ca2+ in PCT (↑PO excretion, ↓ Ca reabsorption)
- Osteoclast-mediated surface bone resorption (↑ serum Ca and PO),
- Enhanced synthesis of 1,25-hydroxy-vitamin D
Net result ➞ increase in serum Ca2+ while keeping PO stable
Explain the pathway of Vit D metabolism
- Endogenous D3 is synthesised by skin when exposed to UV. Exogenous D2 comes from diet
- These are converted by liver to 25-hydroxy-vitamin D
- Then by kidney to active form 1,25-hydroxy-vitamin D (increased in hypophasphataemia and hypocalcaemia)
List 4 ways in which Vitamin D increases both serum calcium and phosphate?
- Bones ➞ transcription of osteocalcin, osteopontin and alkaline phosphatase to release Ca2+ and PO. This promotes maturation and mineralisation of osteoid matrix (requires PTH cofactor)
- Gut ➞ production of calcium-binding protein
- Kidney ➞ increases PO re-absorption (requires PTH cofactor)
- inhibits release of PTH
Where is Calcitonin produced and what is its function?
Produced primarily by parafollicular cells of thyroid
Acts as a physiologic antagonist to PTH
What is osteoporosis?
Reduced quantity in otherwise normal bone quality. Bone loss exceeds bone production.
(USMLE: Trabecular (spongy) and cortical bone lose mass despite normal bone mineralization and lab findings)
What is osteomalacia?
Osteomalacia is bone softening due to insufficient mineralisation of the osteoid
Occurs secondary to any process that results in vitamin D deficiency or defects in phosphate metabolism:
- high remodelling rate: excessive osteoid formation with normal/little mineralisation
- low remodelling rate: normal osteoid production with diminished mineralisation
What is osteopenia?
reduced bone mineral density (BMD) (encompassing osteoporosis and osteomalacia)
(Stage before osteoporosis - lower BMD than the average for your age, but not low enough to be classed as osteoporosis)
When is peak BMD reached and when does it begin to decline?
What factors influence this?
Peak bone mass between 25-30
At age 40 we slowly begin to lose bone mass
Magnitude depends on genes, physical activity, muscle strength, diet, hormonal state
Why is plain radiograph not a sensitive modality for assessing BMD?
Because more than 30-50% bone loss is required to appreciate decreased bone density on radiograph. So early changes are not apparent
How does vertebral and femur osteoporosis manifest?
vertebral osteoporosis manifests as:
- pencilling of vertebrae
- loss of cortical bone and trabecular bone compression fractures
Proximal femur area manifests as loss of trabecula
How do we measure BMD?
DEXA scan - estimation of calcium hydroxyapatite
What is shown on the image below
What is Rickets?
Rickets, essentially refers to osteomalacia in the paediatric population that occurs before fusion of the growth plate
(less commonly known as rachitis)
In children, which part of the bone is mineralisation deficiency most evident in?
Metaphyseal zones of provisional calcification
Here an excess of non-mineralised osteoid will be seen, resulting in growth plate widening and metaphysis flares out and appears frayed
In which parts of the body is bone is mineralisation deficiency most evident?
Explain
- knee: distal femur, proximal tibia
- wrist: especially the ulna
- anterior rib ends: rachitic rosary
As these locations have growth plates where growth is greatest
Why may a childs legs appear bowed even if bones appear mineralised on radiology?
As osteomalacia co-occurs with rickets, It is important to remember that even bones that appear mineralised are weak
This results in bowing, most commonly seen in the lower limbs once the child is walking
…?
???
What is the effect of Hyperparathyroidism on bone?
Excessive PTH causes osteoclastic resorption, osteoporosis, osteomalacia
Affects cortical bone more than cancellous bone
Compare primary vs secondary hyperparathyroidism
Primary ➞ from parathyroid adenomas/hyperplasia
Secondary (more common) ➞ Mostly from renal failure
Reduced capacity to excrete PO result in elevated serum PO and reduced Ca promoting PTH secretion (milder than primary HPT)
List 4 radiographic features of Hyperparathyroidism and in where each is seen
- subperiosteal bone resorption ➞ radial aspects of proximal + middle phalanges of 2nd and 3rd fingers
- subchondral resorption ➞ lateral end of the clavicles, pubis symphysis and sacroiliac joints
- subligamentous resorption ➞ ischial tuberosity, trochanters, inferior surface of calcaneus and clavicle
- Brown tumors
How does Hypoparathyroidism occur?
What are the consequences of this?
Parathyroid gland deficiency from parathyroid gland resection
Hypocalcaemia and hyperphosphataemia with irritability, seizures, tetany.
Occasional calvarial thickening, subcutaneous and basal ganglia calcification, osteosclerosis (localised or generalised)
What is Renal osteodystrophy?
A constellation of MSK abnormalities that occur in patients with chronic renal failure, due to concurrent and superimposed:
- osteomalacia (adults)/rickets (children)
- secondary hyperparathyroidism
- aluminium intoxication, e.g. if the patient is on dialysis
What is characteristic of Renal osteodystrophy?
Must have sub-periosteal bone resorption
