12.10 Metabolic Bone Diseases

Question 1

Different bone cells that provide metabolic activity

Answer 1

• osteoblasts (4-5%) – make new bone (build)
• osteoclasts (1-2%) – resorb old bone (chew)
• osteocytes (90-95%) – “mechano-sensing” & regulatory functions

Question 2

Intracellular signalling

Answer 2

• mevalonate pathway and bone
  ➡️ prenylation (addition of hydrophobic molecules to protein
• RANK (receptor activator of nuclear kappa beta) – ligand
  ➡️bind to RANK receptor on OC (osteoclasts)
  ➡️ produced by osteoblasts
  ➡️promotes osteoclastogenesis (enhance bone resorption)
  ➡️ regulator: OPG (osteoprotegerin)
• osteoprotegerin
  ➡️block RANK-ligand RANK interaction
  ➡️ produced by osteoblasts and osteocytes
  ➡️may thus decrease osteoclastogenesis (protects against bone resorption)
• sclerostin
  ➡️inhibit bone formation
  ➡️ produced by osteocytes

Question 3

Define metabolic bone disease

Answer 3

Broad umbrella term for wide spectrum of diseases associated with disturbance of normal bone remodeling, bone metabolism and bone integrity.

Question 4

Define osteoporosis

Answer 4

Metabolic bone disease characterized by:
- decreased bone strength (⬇️ ability of skeleton to withstand trauma)
- with increased bone fragility
- susceptibility to fracture due to a decrease in the amount of normally mineralized bone
- a decrease in micro-architectural integrity.
- ⬇️ quantity of bone

Question 5

High risk category pt for developing osteoporosis

Answer 5

Normal physiology of ageing - highest risk category
- older postmenopausal female (≥ 65 yrs) and the elderly male (≥ 70 yrs) based on physiology per se
➡️ lower peak bone mineral density in women compared to men
➡️increased bone resorption at menopause in women (accelerated bone loss at menopause)
➡️decreased bone formation and bone quality with ageing in both genders

External (contributing) factors
- adult patients with significant clinical risk factors or a secondary cause of excessive bone loss.

Question 6

Two main categories of contributors to low bone mass & skeletal fragility

Answer 6

1. clinical risk factor (CRF)
- contributor to bone loss that is not a specific disease or a bone unfriendly pharmacological agent and may be non-modifiable or modifiable

2. secondary causes
- specific systemic disease or bone toxic medication responsible for adverse bone effects

Question 7

Non-modifiable clinical risk factors for low bone mass & skeletal fragility

Answer 7

• age: (fracture risk 2-5 fold higher in elderly than in the young)
• genetics: parental history of hip fracture (maternal) - is a largely BMD independent RF for all fractures
• gender and ethnicity: OP and fractures occur more frequently in women than men as previously noted with marked ethnic variation and in SA highest in Indian and white populations
  previous low trauma fracture: very important risk factor for subsequent fracture, best defined in age groups 40-50 yrs and older, risk is highest within 12 months after injury and dependent on site involved

Question 8

Modifiable clinical RF for low bone mass and skeletal fragility

Answer 8

• excessive leanness (BMI 22-18kg/m2): lean vs fat mass, mechanical, hormones
• excess alcohol (> 3U daily): direct toxin, nutrition, gonadal, cortisol, falls
• smoking: low weight, low estrogen, early menopause, nutrition
• nutritional risk factors: low calcium intake, hypovitaminosis D, protein-energy malnutrition – restrictive diets
• hypogonadism: use of progesterone contraceptives, athletes amenorhoea, delayed puberty (also regarded as specific disease / secondary cause if premature ovarian failure)

Question 9

Secondary causes of low bone mass and skeletal fragility

Answer 9

• Long-term glucocorticoid therapy
• Alcoholism
• Hypogonadism including hormone deprivation Px
• Rheumatoid arthritis
• Chronic lung diseases
• Inflammatory GI disorders
• Hypercalciuria
• Renal failure
• Cancers (myeloma…..)
• Medication (other)
• HIV and HIV treatment

Question 10

Osteomalacia

Answer 10

• in adulthood mostly associated with phosphate or severe vitamin D deficiency
• state of decreased mineralization or softening of bone
• normal unmineralized quantity of organic bone matrix
• DXA-BMD measurement low in these patients due to suboptimal mineralization
• to consider in patient who presents with bone and muscle pain, marked proximal muscle weakness and skeletal fragility
• renal phosphate loss consequence of some of ARV regimens
• distinguish from OP via clinical features, biochemical findings and unique radiological findings

Question 11

Paget’s disease

Answer 11

• sclerotic bone disease, cause focal abnormalities in the skeleton that may be unifocal or multicentric and often affect pelvis, skull and long bones
• only focal sclerotic bone disease that cause bony expansion (enlargement)
• thought to be due to a slow viral infection in genetically susceptible person with distortion of normal bone remodeling
• may present with pain, deformity and even fracture in the affected area
• serum ALP high in active disease and best marker of disease
• consider if focal sclerosis of skeleton noted on radiology, certain malignancies cause sclerotic bone metastases and can be distinguished from Paget’s on basis of bony enlargement