Osteoporosis

Definition

• The composition of bone is normal, but the amount of bone per unit volume is less than normal
• Defined as a bone density below the 95th percentile of the young normal range
• By this definition, everyone from 40’s on becomes increasingly osteoporotic
• This process is accelerated after the climax (~ 50 years in women and ~ 65 in men)
• Osteoporosis in people under 45 should be investigated to exclude malignant disease, dietary deficiency, etc.

Aetiology

Nutritional

• Scurvy
• Malnutrition
• Malabsorption

Malignant disease

• Carcinomatosis
• Multiple myeloma
• Leukaemia

Endocrine disorders

• Hyperparathyroidism
• Gonadal insufficiency
• Cushing’s disease
• Thyrotoxicosis

Non malignant disease

• Rheumatoid arthritis
• Ankylosing spondylitis
• Tuberculosis
• Chronic renal disease

Drug induced

• Corticosteroids
• Alcohol
• Heparin
• Idiopathic Juvenile osteoporosis
• Post climacteric osteoporosis

Mechanical

• Disuse
• Immobilisation

Haematological

• Thalassaemia
• Sickle cell disease

Incidence

• Commonest of the metabolic bone disorders
• All women over the age of 65 have suffered vertebral crush fractures (many of them minor)
• White women particularly of north western European ethnic background have a much higher incidence than do those of Mediterranean descent

Classification

• Type I Idiopathic
• Type II Females between menopause and 65 years (10 – 15% loss of bone in first 5 years)
• Type III Males and females > 65 years (1% / year bone loss)

Clinically

• Only becomes symptomatic when it leads to structural failure of the bone
• Fractures occur with minimal force especially in the spine (thoracic wedge and lumbar crush fractures), distal radius (Colles’), femoral neck fractures, and unsuspected rib fractures may cause chest pain
• Unless there is an associated metabolic disorder biochemical tests are normal

Risk factors

• Early or surgically induced menopause (not in the long term)
• Family history
• Low weight and small build
• Sedentary lifestyle
• Excessive alcohol intake causes direct depression of osteoblast function
• Steroids cause decreased formation and increased resorption

X-Rays

• General loss of bone density may be obvious, but does not differentiate osteoporosis from osteomalacia
• Wedging and biconcave indentation of the vertebrae is common, but isolated fractured in the upper thoracic spine suggest malignancy
• In long bones the cortex is unduly thin
• At least 30% of the bone mass must be lost before rarefaction is evident on X-Ray
• Singh index uses femoral neck trabecular patterns as index of osteoporosis

Investigations

• Blood and endocrine screens to exclude metabolic bone disorders
  • Serum calcium, phosphorus, alkaline phosphatase
  • 24 hour urinary calcium, creatinine and hydroxyproline (fasting).
  • Pyridinoline cross links of Type 1 collagen and tartrate resistant acid phosphatase assess bone destruction
  • Plasma cortisol, 1,25-OHD3, PTH, T3 and T4, serum electrophoresis, blood count and ESR also useful
• Bone biopsy after double labelling with tetracycline 10 – 14 days apart yields meaningful interpretation of bone dynamics
• Radiographic evaluation using photodensitometry estimates mass by measuring optical density of the radiograph, but does not take account of soft tissue thickness
• Quantitative CT scanning
• Single and dual photon absorptiometry (densitometry) makes use of difference ion photon absorption between bone and soft tissue to determine bone mineral content
  • Single photon : Immersion in water bath to subtract soft tissue component
  • Dual photon uses an isotope with emission of two energy levels (dual photon looks at lumbar spine or femoral neck)

Pathology

• Peak bone mass achieved in mid 30’s in both sexes, the value influenced by sex, nutrition, race, exercise and overall health (being 30% higher in men than women)
• Women lose 10 – 15% of their bone mass in the first 5 years after menopause
• After the age of 65 it makes no difference when the menopause occurred, approximately 1% bone mass lost per year
• Menopause increases bone resorption (i.e. increased osteoclastic activity) and further loss may be related to decreased formation
• Trabecular bone with its higher surface area and greater metabolic activity is first area to be resorbed
• Colles and vertebral fractures early (soon after menopause) and the incidence of hip fractures increases slowly with age due to loss of cortical bone
• 75% of osteoporotic fractures occur in bone with density 3 standard deviations below the pre-menopausal mean
• Fat people protected somewhat due to peripheral conversion of androgens to oestrogen and increased strain on the skeleton

Treatment

• If there is a specific underlying cause it may be correctable
• Bone density 75 – 100% of normal needs no treatment required
• Bone density 50 – 75% of normal needs re-scan in 12 months
• Bone density less than 50% of normal needs treatment
• Treatment directed towards one or more of the following
  • Calcium intake
  • Calcium absorption
  • Bone formation
  • Bone resorption
  • Urinary calcium
• Important to correct dietary deficiency and keep the patient active
• Daily requirement of calcium in Australia is 800 mg
• Pre-menopausal women daily allowance 1.2 gm / day
• Menopausal women daily allowance 1.5 gm / day
• Extra gram of calcium per day may decrease bone loss
• Vitamin D may be needed if deficient or lack of sun exposure
• Anabolic steroids may be used (e.g. deca durabolin)
  • Can stimulate bone formation but also increases hair and voice changes
  • The only treatment that will increase bone density
  • Dose 50 mg monthly with 6/12 treatment and 6/12 no treatment
• Bone mass once lost is extremely difficult to restore
  • Give calcium supplement and if still bone loss persists, measure urinary calcium and if still high, restrict salt (as salt excretion carries out calcium)
  • May also try thiazide as this decreases urinary calcium
  • If still bone loss add oestrogen
  • If still bone loss may add calcitonin
  • Fluoride may be used in combination with vitamin D and calcium (triple therapy) but fluoride has high incidence of side effects (40%)

Prevention

• Now, there is good evidence that hormone replacement (oestrogens) given from the onset of the menopause can prevent progressive bone loss
• Benefit maximised when treatment begins within 6 years of the menopause
• There is still consideration for possible harmful side effects of long term oestrogen therapy
• Prospective studies have demonstrated that one hour of impact exercise 2 – 3 times per week can maintain or slightly increase bone mass in lumbar spine compared to sedentary controls

Side Effects

• Endometrial hyperplasia and cancer; use cyclical oestrogen and progesterone
• Worsening of pre-existing breast Ca
• Aggravation of DVTs (? effect of low dose post-menopausal estrogen)
• Potentiation of gallstones

Contraindications

• Breast Ca (regardless of oestrogen receptor status)
• Any other oestrogen sensitive tumour
•  Past history of PE
• Acute or chronic liver disease or low grade chronic hepatitis
• Severe uncontrolled hypertension

Dose

• 0.625 mg conjugated estrogen/day first 25/7 of month 10 mg medroxyprogesterone/day for 10/7 (days 16 – 25 each month)
• Modify the dose to suit the patient, could start with 0.3 mg estrogen

Differential diagnosis

Osteomalacia	Osteoporosis
Unwell	Not unwell
General bone ache	Pain only after fracture
Muscles weak	Muscles normal
Looser’s zones	No Looser’s zones
ALP increased	ALP normal
Serum phosphorous and calcium decreased	Serum calcium and phosphorous normal
Urine calcium low	Urine calcium normal or high

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