Metabolic Bone Disease

Question 1

Pathophysiology of MBD

Answer 1

-Imbalance in bone remodelling
=More mone formation than resorption (Paget’s)
=Increased phosphate excretion (FGF-23)

Question 2

Clinical features of Paget’s

Answer 2

-Affects about 1% of people over 55yrs in the UK
-Increased bone turnover in affected sites
-Strong genetic component
-Bone enlargement and deformity
-Bone pain, osteoarthritis deafness and pathological fractures
-Osteosarcoma (rare)
-Osteoarthritis
-Many people have no symptoms
-Bone deformity usually affecting tibia, skull or femur (bowed legs)

Question 3

Diagnosis of Paget’s

Answer 3

-Biochemistry
=High alkaline phosphatase, normal LFT, calcium and U&E

-X-ray
=Osteolysis & Osteosclerosis
=Bone expansion, pseudofractures (stress fractures)
=Trabecular thickening, expansion of pelvis and proximal femur

-Radionuclide bone scan
=Intense tracer uptake
=Most sensitive test

Question 4

Management of Paget’s

Answer 4

Symptomatic
-Analgesia/ NSAIDs

Inhibitors of bone resorption
-IV Bisphosphonates
=Risedronate
=Pamidronate
=Zoledronic acid (1)
-Calcitonin (seldom used)

Surgical
-Joint replacement
-Fracture fixation
-Spinal Surgery (spinal stenosis)

Question 5

When should bisphosphonates be used in Paget’s?

Answer 5

-Pain localised to an affected site with evidence of increased metabolic activity
=Raised ALP
=Uptake on bone scan

-No evidence that treating asymptomatic disease to alter natural history is of benefit

Question 6

Clinical features of Osteomalacia (prolonged vit D deficiency)

Answer 6

-SOFTENING OF BONES SECONDARY TO LOW VIT D LEVELS= DECREASED BONE MINERAL CONTENT AS RESORBED BONE REPLACED WITH UNMINERALISED OSTEOID

-Diffuse bone pain / muscle weakness and tenderness (lower back pain, shoulder, ribs, pelvis, legs)
-Proximal myopathy: waddling gait
-Malaise, lethargy
-Fractures & pseudofractures (especially femoral neck)

-People at risk:
=Muslim women
=Housebound elderly
=Malabsorption (coeliac)
=Cirrhosis, CKD
=Age

Question 7

Diagnosis of osetomalacia

Answer 7

-Biochemistry
=Raised ALP
=Calcium - normal or low-normal, low 24-hr urinary calcium
=Phosphate – low
=25(OH)D low
=PTH raised (secondary parathyroidism)

-X-ray= translucent bands (Looser’s zones/ pseudofractures)

-Bone Biopsy
=If diagnosis is in doubt
=Increased extent and thickness of osteoid

Question 8

Treatment of osteomalacia

Answer 8

-Vitamin D
=Several regimens can be used successfully
=10,000 IU daily for 2-3 months
=Maintenance 800-3200 IU daily or 10,000 weekly

-Monitoring
=Renal function and calcium biochemistry 2 weekly, then 3 monthly
=Expect a raised ALP initially, increase serum phosphate and Calcium
=ALP falls to normal by 3-6 months as osteomalacia heals

Question 9

Clinical significance of low Vit D

Answer 9

-Common but clinical significance not clear
-Associations observed with many diseases
=Sick people have low vitamin D
-Benefits of vitamin D supplementation in healthy individuals unknown (even though advised by CMO!)
-Response to osteoporosis treatment better in
patients with higher vitamin D levels
-Measuring vitamin D is of limited clinical value in most patients

Question 10

Presentation of Primary hyperparathyroidism

Answer 10

-Most common presentation
=Incidental finding

-Symptoms of hypercalcemia
=Thirst, polyuria
-Osteoporosis
-Renal stone disease
-Parathyroid bone disease (high bone turnover, fractures)

Question 11

Pathophysiology of primary hyperparathyroidism

Answer 11

-Parathyroid adenoma= secrete PTH= stimulates bone turnover, increased calcium reabsorption from renal tubules= increased serum calcium= increased activated vit D production so increased gut calcium absorption

Question 12

Diagnosis of Primary hyperparathyroidism

Answer 12

-Biochemistry
=Raise serum calcium
=Low serum phosphate
=Raised PTH
=(rarely) raised ALP (parathyroid bone disease)

-X-ray
=Subperiosteal erosions

-Imaging (localise adenoma)
=Sestamibi 99mTc
=Choline PET-CT

Question 13

Management of Primary hyperparathyroidism

Answer 13

-Parathyroidectomy
=Osteoporosis, bone disease
=Renal stones, serum calcium >3.0mM

-Observation
=Older patient with mild hypercalcaemia who is asymptomatic

-Medical
=Cinacalcet (reduces PTH by binding to CaSR)
=Frail patient, unsuitable for surgery

Question 14

Describe hypophosphatemic rickets

Answer 14

-Orphan disease (1 in 20,000)
-Inherited disorder of renal phosphate reabsorption
-Caused by elevated FGF23
-Growth retardation and deformity
-Stress fractures, myopathy, dental abscess.
-Joint pain due to enthesopathy in adults

Question 15

Traditional management of hypophosphatemic rickets

Answer 15

-Phosphate supplements
=Replace losses from kidney

-Active vitamin D metabolites
=Compensate for defective 1,25(OH)2D3 synthesis
=Increase phosphate absorption from the gut

-Downside of current therapy
=Adherence challenging especially in children
=Difficult to correct metabolic abnormality even with careful monitoring
=Risk of hypercalcaemia and nephrocalcinosis

-Burosumab (anti FGF23)= superior

Question 16

Describe Osteogenesis Imperfecta

Answer 16

-Inherited disorder of type 1 collagen
-Presents with multiple low fractures especially in childhood and adolescence, with continued fractures during adult life
-Fractures more common in males

=Blue sclera (thinning of sclera)
=Hypermobility
=Bone deformity
=Fractures (bilateral femoral)
-Back pain or height loss
-Deafness
-Soft tissue injuries
-Positive family history

-Vit D biochemistry, X-ray thoracic and lumbar spine if height loss, DEXA

Question 17

Management of osteogenesis imperfecta

Answer 17

-Bisphosphonates often used
=Evidence base poor
=Increase BMD but little evidence that fractures are prevented

-Calcium and vit D

-Orthopaedic surgery
=Fracture fixation
=Correction of deformity

-Physiotherapy and occupational therapy
=Important role