Calcium Disorders and Metabolic bone disease

Question 1

Main hormones that regulate calcium homeostasis

Answer 1

Parathyroid hormone (PTH) and Vitamin D

Question 2

PTH and 1,25(OH)2D main sites of action?

Answer 2

Bone, Kidneys, Intestine

Question 3

1,25(OH)2D effect?

Answer 3

• stimulates gut absorption of calcium (and PO4)

- enables mineralisation of bone

Question 4

The effects of PTH

Answer 4

1. PTH reduces renal calcium excretion
2. Increases renal tubular reabsorption
3. PTH increases renal PO4 excretion
4. PTH releases Ca2+ from bone via osteoclasts
5. PTH stimulates 1,25[OH]2D synthesis in kidney

Question 5

Normal Calcium range in the blood?

Answer 5

Serum calcium normally maintained within a narrow range (2.20 to 2.60 mmol/L)

Question 6

Common causes of hypercalcaemia?

Answer 6

1. Cancer (Bone mets)
2. Chronic renal failure
3. Primary hyperparathyroidism

Question 7

Clinical Features of hypercalcaemia

Answer 7

1. Neurological (lethargy, confusion, psychosis, hypotonia)
2. Gastrointestinal (Anorexia, vomiting, constipation)
3. Renal (Polyuria, polydipsia, nephrocalcinosis, renal failure)
4. Cardiovascular (Arrythmias)

Question 8

Rare causes of hypercalcaemia?

Answer 8

1. Immobilisation
2. Thyrotoxicosis
3. Vitamin D toxicity
4. Lithium treatment
5. Sarcoidosis
6. Hypoadrenalism

Question 9

How to investigate suspected hypercalcaemia?

Answer 9

1. Bone profile: Ca, PO4, albumin, alk phos
2. FBC + ESR + LFTs
3. Renal Profile
4. PTH + Vit D
5. TFTs
6. X-ray - skull, hands, T-L spine, chest
7. Isotope bone scan for malignancy?

Question 10

Treatment for ill patient with hypercalcaemia?

Answer 10

Rehydrate with intravenous saline
Give IV bisphosphonates
Dialysis
Corticosteroids for myeloma and vit D toxicity

Question 11

Hypercalcaemia in chronic kidney failure

Answer 11

Low GFR, Ca2+ containing phosphate binders, Tertiary hyperparathyroidism, Vit D metabolites (iatrogenic), Calcitriol, Alfacalcidol.

Clinical features - Raised Ca2+/PO4- product leads to metastatic calcification, Conjunctivitis, Vascular Skin (pruritus)

Treatment- Parathyroidectomy if PTH very high
Cinacalcet

Question 12

Types of hyperparathyroidism?

Answer 12

4 parathyroid glands secreting 1-84 PTH

1. Primary - High Ca2+ and high PTH (inappropriate)
2. Secondary - Low Ca2+ and high PTH (appropriate)
3. Tertiary - Prolonged hypocalcaemia leads to hyperplasia of parathyroids – mimics primary hyperparathyroidism

Question 13

Primary hyperparathyroidism - clinical features

Answer 13

Often incidental finding, Renal calculi 10%, Bone pain due to cysts or fractures(rare),
Symptoms of hypercalcaemia,
Xrays: subperiosteal erosions of phalanges and pepperpot skull
Osteoporosis
chondrocalcinosis

Question 14

Hypocalcaemia

Answer 14

Less common than hyper. Usually due to a decrease in PTH or Vit D

Question 15

Cause of hypocalcaemia?

Answer 15

Hypoparathyroidism, Pseudohypoparathyroidism, Vit D deficiency, Magnesium deficiency, Malabsorption, Renal failure

Question 16

Investigations in hypocalcaemia?

Answer 16

Bone profile: Ca2+, PO4- , albumin, bicarbonate, alkaline phosphatase
Serum magnesium
FBC  
Liver profile
Renal profile
PTH + 25(OH) D

Question 17

Clinical features of hypocalcaemia

Answer 17

Nervous system - Paraesthesiae, Tetany = spontaneous muscle contractions eg carpopedal spasm, Seizures and psychosis
Ocular - Cataracts
Cardiac - Arrhythmias, heart block

Question 18

Treatment of severe hypocalcaemia

Answer 18

Tetany or seizures
10 ml IV calcium gluconate 10% + repeat as required
Start calcitriol
Oral Calcium supplements

Question 19

Hypoparathyroidism

Answer 19

Cause - Autoimmune or post thyroid surgery
Present with symptoms of hypocalcaemia
PTH low or unrecordable
Serum PO4- high but creatinine normal
Treat with calcitriol and thiazides
Thiazides reduce renal leak of Ca2+

Question 20

Pseudohypoparathyroidism

Answer 20

Inherited, defect of PTH receptor, High PTH, but low Ca and high PO4. Short stature, shortened metacarpals. Intellectual disability and other hormone resistance. Treat with Calcitriol

Question 21

Calcitriol

Answer 21

Hormonally active metabolite of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)2D3 or simply 1,25(OH)2D)

Question 22

Mg deficiency

Answer 22

Vomiting, diarrhoea, alcohol, drugs (PPIs, Cisplatin, Aminoglycosides) or renal tubular disease

Question 23

How to diagnose Osteomalasia

Answer 23

Defined histologically on bone biopsy: widened osteoid seams with impaired mineralisation

Question 24

Clinical features of osteomalasia

Answer 24

Proximal myopathy
Bone pains
Pseudofractures on Xray
Pubic rami, ribs, femoral neck
osteoporosis
High alkaline phosphatase
PTH high, 25[OH]D low
low Ca2+, low PO4-

Question 25

Treatment for osteomalasia

Answer 25

Oral calcium and vit D supplements

Calcitriol or alfacalcidol for renal failure or vit D resistance

Question 26

Pagets disease

Answer 26

Focal remodelling of the bone - excessive and disorganised bone turnover.

Clinical features: bone pain, pathological fracture, bone deformity, secondary OA, nerve/spinal cord compression,
immobilisation hypercalcaemia, osteosarcoma

Question 27

How to diagnose Pagets?

Answer 27

Serum ALP
Xrays
isotope bone scan

Question 28

Treating pagets?

Answer 28

Bisphosphonates:
IV zoledronate
IV pamidronate
oral risedronate
High dose short term. 
90% remission rates, Relieves pain, Normalises biochemistry

Question 29

Causes of osteoporosis

Answer 29

Endocrine : thyrotoxicosis, hypogonadism, hyperparathyroidism, Cushing’s disease
Gastrointestinal : malaborption
Drugs: steroids, alcoholism
Malignancy, myeloma
Rheumatoid arthritis

Question 30

Treatment of osteoporosis

Answer 30

Bisphosphonates
Denosumab
These agents reduce fracture rates by about 50% and increase bone density, osteoclast inhibitors
Most patients also require calcium and vitamin D supplements (especially the elderly)