Metabolic Bone Disease

Question 1

Describe the composition and function of bone (aside from movement and protection)

Answer 1

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)

Question 2

Where is PTH produced and what is its function?

Answer 2

Produced by the parathyroid glands in response to low Ca2+

Functions:

1. Increases serum Ca2+ in PCT (↑PO excretion, ↓ Ca reabsorption)
2. Osteoclast-mediated surface bone resorption (↑ serum Ca and PO),
3. Enhanced synthesis of 1,25-hydroxy-vitamin D

Net result ➞ increase in serum Ca2+ while keeping PO stable

Question 3

Explain the pathway of Vit D metabolism

Answer 3

1. Endogenous D3 is synthesised by skin when exposed to UV. Exogenous D2 comes from diet
2. These are converted by liver to 25-hydroxy-vitamin D
3. Then by kidney to active form 1,25-hydroxy-vitamin D (increased in hypophasphataemia and hypocalcaemia)

Question 4

List 4 ways in which Vitamin D increases both serum calcium and phosphate?

Answer 4

1. Bones ➞ transcription of osteocalcin, osteopontin and alkaline phosphatase to release Ca2+ and PO. This promotes maturation and mineralisation of osteoid matrix (requires PTH cofactor)
2. Gut ➞ production of calcium-binding protein
3. Kidney ➞ increases PO re-absorption (requires PTH cofactor)
4. inhibits release of PTH

Question 5

Where is Calcitonin produced and what is its function?

Answer 5

Produced primarily by parafollicular cells of thyroid

Acts as a physiologic antagonist to PTH

Question 6

What is osteoporosis?

Answer 6

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)

Question 7

What is osteomalacia?

Answer 7

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

Question 8

What is osteopenia?

Answer 8

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)

Question 9

When is peak BMD reached and when does it begin to decline?

What factors influence this?

Answer 9

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

Question 10

Why is plain radiograph not a sensitive modality for assessing BMD?

Answer 10

Because more than 30-50% bone loss is required to appreciate decreased bone density on radiograph. So early changes are not apparent

Question 11

How does vertebral and femur osteoporosis manifest?

Answer 11

vertebral osteoporosis manifests as:

• pencilling of vertebrae
• loss of cortical bone and trabecular bone compression fractures

Proximal femur area manifests as loss of trabecula

Question 12

How do we measure BMD?

Answer 12

DEXA scan - estimation of calcium hydroxyapatite

Question 13

What is shown on the image below

Answer 13

Question 14

What is Rickets?

Answer 14

Rickets, essentially refers to osteomalacia in the paediatric population that occurs before fusion of the growth plate

(less commonly known as rachitis)

Question 15

In children, which part of the bone is mineralisation deficiency most evident in?

Answer 15

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

Question 16

In which parts of the body is bone is mineralisation deficiency most evident?

Explain

Answer 16

• knee: distal femur, proximal tibia
• wrist: especially the ulna
• anterior rib ends: rachitic rosary

As these locations have growth plates where growth is greatest

Question 17

Why may a childs legs appear bowed even if bones appear mineralised on radiology?

Answer 17

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

…?

Question 18

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Question 19

What is the effect of Hyperparathyroidism on bone?

Answer 19

Excessive PTH causes osteoclastic resorption, osteoporosis, osteomalacia

Affects cortical bone more than cancellous bone

Question 20

Compare primary vs secondary hyperparathyroidism

Answer 20

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)

Question 21

List 4 radiographic features of Hyperparathyroidism and in where each is seen

Answer 21

1. subperiosteal bone resorption ➞ radial aspects of proximal + middle phalanges of 2nd and 3rd fingers
2. subchondral resorption ➞ lateral end of the clavicles, pubis symphysis and sacroiliac joints
3. subligamentous resorption ➞ ischial tuberosity, trochanters, inferior surface of calcaneus and clavicle
4. Brown tumors

Question 22

How does Hypoparathyroidism occur?

What are the consequences of this?

Answer 22

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)

Question 23

What is Renal osteodystrophy?

Answer 23

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

Question 24

What is characteristic of Renal osteodystrophy?

Answer 24

Must have sub-periosteal bone resorption