Osteoporosis – clinical manifestations

• fractured spine / wrist (post-menopausal woman)
• fractured hip (age-related)
• pain – mid-thoracic, lower back
• height loss
• osteopaenia noted on X-Ray (incidental finding)
  • bone mass 3-4 standard deviations below normal
    • late sign
      • ± bone scan

Note: acute onset of back pain in a woman with a history of compression fracture often indicates  a new fracture.

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Osteoporosis – epidemiology

The incidence of osteoporosis is rising, even after taking into account for the ageing of the population. The increasing life expectancy has predicted a doubling in the number of hip fractures which will bee seen in the next 50 years.

• > 50 year-old, life-time risk of osteoporotic fracture is 40% in women and 13% in men
  • women
    • > 45 years – forearm fracture
    • > 65 years – hip fracture (and risk increases exponentially, thereafter, with advancing age)
  • men
    • > 75 years
    • > 85 years – hip fracture (predominately)
• Risk in Asian, Caucasian >> Black

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Osteoporosis – risk factors

• hypogonadism
• glucocorticoid treatment
• previous fragility fracture
• low body weight
• cigarette smoking
• excess ethanol consumption
• low dietary Ca++ intake
• vitamin D deficiency
• late menarche
• physical inactivity
• high caffeine intake
• maternal history of hip fracture
• haematological malignancy
  • multiple myeloma, lymphoma, leukaemia

Although persistent bone loss (hormonal environment) is a feature in most patients with osteoporosis, impaired acquisition of peak bone mass (genetics, Ca++) is responsible for 60-70% of the variance in bone mass at any age.

∴ Bone mass measurement will predict the risk of fracture more accurately than calculation of risk factor scores.

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Osteoporotic Fracture – treatment

1. Analgesia – NSAIDs, paracetamol, opioids
2. Surgical stabilisation of fracture
3. Salmon calcitonin (intranasal or subcutaneous) – reduces bone pain
4. epidural glucocorticoid injection – hospitalised patients
5. ? admit

Osteoporotic fracture – prognosis

• hip fracture can be related to up to 20% 6-month mortality
• long, complicated rehabilitation
• reduction in quality of life

∴ aggressive strategy to prevent further fracture

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Osteoporotic fracture – pathophysiology

1.  reduced bone mass
   1. genetics, exercise, + dietary factors → lowered peak bone mass (PBM)
   2. menopause, age (reduced vitamin D, reduced Ca++) → subsequent bone loss
2. falls – neurological, musculoskeletal, environmental factors

Peak bone mass (PBM) occurs between 20 and 30 years of age with an increased number of remodelling units with age, favouring a remodelling unit where bone resorption ≠ bone formation.

Prior vertebral fracture ⇒ 2 x increased Relative Risk for spinal fracture

Low Bone Mass + prior spinal fracture ⇒ 4 x increased Relative Risk for new spinal fracture

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Osteoporosis – investigations to exclude secondary causes

• FBC & ESR
• serum Ca++, PO4, alkaline phosphatase (ALP)
• liver function tests (LFTs)
• thyroid function tests (TFTs)
• serum protein immuno-electrophoretogram (IEPG)
• urinary Bence-Jones proteins – occasionally normal in myeloma
  • need bone-marrow trephine biopsy to make diagnosis
• thoracic / lumbar spine lateral X-Ray
• ± isotopic bone scanning – ? malignancy
• ± bone biopsy – ? osteomalacia

Considerations of osteoporosis in men – possible causative factors:

1. secondary hypogonadism
2. ethanol
3. glucocorticoid treatment

∴ the following tests may prove useful

• serum testosterone / gonadotrophins
• ± serum prolactin

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Osteoporosis – indications for Bone Mineral Density (BMD) assessment

• recent evidence of osteopaenia and/or vertebral deformity
• previous fragility fracture of hip, spine, or wrist
• corticosteroid treatment: > 7.5 mg per day for ≥ 1 year
• premature menopause: < 45 years old
• prolonged secondary amenorrhoea
• primary hypogonadism
• anorexia nervosa
• malabsorption
• primary hyperparathyroidism
• post-transplantation
• chronic renal failure (CRF)
• hyperthyroidism
• prolonged immobilisation
• family history of osteoporosis, particularly maternal hip fracture

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Osteoporosis – differential diagnosis (secondary causes)

• endocrine disorders
  • primary / secondary hypogonadism
  • thyrotoxicosis
  • hyperparathyroidism
  • Cushing’s syndrome
  • hyperprolactinaemia
• malignant disease
  • myelomatosis
  • leukaemia
  • lymphoma
  • mastocytosis
• connective tissue disorders
  • osteogenesis imperfecta
  • Marfan’s syndrome
  • Ehlers-Danlos syndrome
  • homocystinuria
• drugs
  • ethanol
  • glucocorticoids
  • heparin
• others
  • malabsorption / bowel disease
  • post-gastrectomy
  • chronic liver disease
  • chronic renal disease
  • rheumatoid arthritis
  • immobilisation

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Osteoporosis – protective doses of menopausal hormone therapy (MHT)

• 15 mcg ethinyl oestradiol, oral daily
• 1 mg 17-β–oestradiol, oral daily
• 0.625 mg conjugated equine oestrogen, oral daily
• 50 mcg ethinyl oestradiol, transdermal daily
• 50 mg oestradiol, over 6 months as implant

Oestrogen effects

• 35% Relative Risk reduction of non-vertebral fracture, starting MHT < 60 years old
• 50% Relative Risk reduction of wrist / hip fracture in younger female
• less effect on femoral neck than on spine
• once MHT is ceased, bone loss resumes with little long-term benefit gained

Monitoring of MHT

• MHT in patients with secondary osteoporosis
• newer drugs – e.g.:
  • bisphosphonates
  • calcitonin
  • vitamin D metabolites
  • sodium fluoride

Osteoporosis – comprehensive management

• lifestyle
• activity
• diet
• treat risk factors
• bone mineral density (BMD) measurements
  • + repeat 1-2 yearly