Osteoporosis

Definition:

• ‘A disease characterised by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and susceptibility to fracture’
• The bone that is present is normally mineralised but is deficient in quantity, quality and structural integrity.
• The WHO defines osteoporosis as a bone density > 2.5 SDs below the young adult mean value for individuals matched for sex and race. Values between 1 and 2.5 are termed ‘osteopenia’.

Incidence:

• Over 1.3 million osteoporotic fractures in the USA each year, approximately:
• 50% vertebral
• 25% hip
• 25% Colles’ fractures

Pathogenesis:

• Bone mass increases rapidly up to the age of puberty, rises slightly in the 20s and 30s and then begins to decline around age 40
• In men there is a gradual decline, reaching moderate levels of fracture risk in the 70s and 80s, but a subset of women show a very accelerated loss in the 10 years following the menopause
• Osteoporosis arises as the end-result of many years of mismatch between the rates of bone resorption and bone formation during the remodelling process. This can arise from ‘high turnover’ osteoporosis (from such conditions as the postmenopausal state, hyperparathyroidism and hyperthyroidism) while others may be due to ‘low turnover’ osteoporosis (e.g. as in anorexia nervosa and liver disease)

Risk factors:

• Age
• Gender (women more susceptible)
• White race
• Late menarche/early menopause
• Smoking
• Low calcium intake
• Low BMI

Signs and symptoms of osteoporosis:

• Asymptomatic (most commonly)
• Fractures (e.g. vertebrae, hip and wrist)
• Bone pain
• Loss of height
• Kyphosis (excessive outward curvature of the spine – causes a hunched back)

Causes of osteoporosis:

Endocrine:

• Postmenopausal (especially premature menopause)
• Cushing’s syndrome
• Hyperthyroidism
• Male hypogonadism

Drugs:

• Corticosteroid osteoporosis
• Heparin osteopenia

Miscellaneous:

• Simple osteoporosis of ageing
• Immobilisation
• Dietary deficiency of Ca²⁺, protein or vitamin C
• Malabsorption syndrome
• Idiopathic juvenile osteoporosis
• Idiopathic adult osteoporosis

Fracture investigations:

X-rays:

• May show the fracture and/or earlier, unrecognised, fractures
• X-rays showing pedicle destruction are suggestive of malignant destruction
• Osteopenia is used to describe a non-specific generalised or regional rarefaction of the skeleton on X-ray

Bone scans:

• Are sometimes useful to demonstrate fractures
• An osteoporotic fracture can be distinguished from a Metastatic lesion, as the latter is often associated with multiple lesions elsewhere

X-rays are of limited value in evaluating bone density because up to 30-40% of the bone mineral content has to be lost before any change in radiological bone density is detectable

Bone density investigations:

• Dual Energy X-ray Absorption scanning – DEXA
• CT scanning (higher radiation dose than DEXA)
• Ultrasound (of the calcaneum is used occasionally)

Other investigations:

• Iliac crest bone biopsy

• Serum Ca²⁺, PO₄^3- and ALP (will be normal in osteoporosis as no disorder of calcium metabolism is involved)
• Biochemical markers of bone resorption:
• Urinary hydroxyproline (not very sensitive)
• Urinary pyridinoline
• Urinary collagen cross-links

Non-drug therapy of osteoporosis:

Diet:

• At least 1000mg of calcium daily (ideally 1500mg postmenopausally)
• 400-800 IU of vitamin D daily
• adequate weight gain in a thin person is necessary, as a low bodyweight is itself a risk factor for further fractures

Exercise

Smoking cessation

Common drug therapy:

Oestrogen therapy as HRT:

• Is the treatment of choice for postmenopausal women
• The potential side-effects (breast cancer and thrombosis) remain controversial
• Selective oestrogen receptor modulators (SERMs) such as Raloxifene are under trial; they do not stimulate the endometrium but do stimulate oestrogen receptors in bone, thereby increasing bone mass. They also lower total and LDL cholesterol

Androgens:

• Should be given to hypogonadal men (although prostatic hypertrophy may sometimes be a limiting factor)

Bisphosphonates:

• Are analogues of normal bone pyrophosphate
• They adhere to hydroxyapatite and inhibit osteoclastic bone resorption
• Alendronate 10mg daily has been shown to increase bone mass substantially and reduce the incidence of fractures
• The only main side-effect of alendronate is oesophageal ulceration (which can be minimised if the patient takes the tablet before breakfast with a full glass of water and remains upright for 30 mins

Lesser used agents:

Calcitriol:

• This is the active metabolite of vitamin D
• Produces some small improvement in bone density, but not as much as HRT or bisphosphonates

Calcitonin:

• Can administer human calcitonin nasally or (the more potent) salmon calcitonin subcutaneously
• Good for patients who experience vertebral fracture pain

Fluoride:

• Has been shown to increase bone density
• Is current concern about the quality of the bone formed
• Not currently recommended