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Osteoporosis

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Overview

Osteoporosis is a skeletal disease characterised by reduced bone density and deterioration of the bone tissue micro-architecture, leading to increasingly fragile bone that is more susceptible to fractures.

Osteoporosis can lead to osteoporotic (fragility) fractures that result from mechanical forces that would not ordinarily result in a fracture. Osteoporotic fractures are fractures associated with low bone mineral density (BMD).

Epidemiology

  • Osteoporosis predominantly affects white postmenopausal women
  • Age-related osteoporosis is another common form

Risk Factors & Associations

The risk factors for primary osteoporosis are as follows:

  • Increasing age
  • Female sex
  • Low body mass (BMI <19kg/m2) and anorexia nervosa
  • Family history of osteoporotic fractures
  • Corticosteroid therapy
  • Cushing’s syndrome
  • Excess alcohol consumption
  • Smoking
  • Falls and conditions increasing the risk of falls such as:
    • Neuromuscular disorders
    • Sedation
    • Alcohol
    • Cognitive impairment
    • Visual impairment

Secondary osteoporosis can arise due to:

Presentation

Patients are often asymptomatic while BMD falls before an osteoporotic fracture occurs.

The presenting complaint of a patient is usually a result of an osteoporotic fracture, usually as a result of a fall. The signs differ according to the fracture site. The most common osteoporotic fractures seen are:

  • Vertebral compression fractures:
    • Patients may be asymptomatic
    • Sudden onset of back pain occurring at rest, lifting items, or bending
    • The pain may be worse with prolonged standing
    • Restricted spinal flexion
    • Kyphosis may be seen; this may be with or without pain
    • Paravertebral muscles may spasm and be tender on deep palpation
  • Neck of femur fractures:
    • Presents with hip pain and inability to bear weight
    • Patients may have a shortened and externally rotated leg on the affected side
  • Colles fracture:
    • Usually the result of a fall onto an outstretched arm
    • Wrist pain and reduced range of movement are seen

Differential Diagnoses

Osteomalacia

  • Difficult to clinically distinguish from osteoporosis
  • Osteomalacia often has bone pain and muscle tenderness
  • Osteomalacia shows increased ALP and increased PTH

Multiple myeloma

  • Anaemia present
  • Renal failure present
  • Bleeding may be present
  • Increased susceptibility to infection may be present

Metastatic bone malignancy

  • History of cancer may be present
  • Bone pain may be in atypical locations
  • DEXA might be normal
  • CT may show the tumour

Paget’s disease of the bone

  • Bone and joint pain present before fragility fractures
  • Bone deformities may be present – usually skull changes and bowed tibia
  • Neurological complications may be present from bone compression

Primary hyperparathyroidism

  • Signs of hypercalcaemia may be present e.g. nausea, constipation, abdominal pain, and anorexia

Investigations

Overview

To assess fracture risk, the Fracture Risk Assessment Tool (FRAX) may be used:

  • This uses clinical risk factors for fracture and BMD scores to calculate the 10-year fracture probability for men and women
  • The threshold that triggers treatment varies depending on location. Check local guidelines.

The first investigation to consider is a dual-energy x-ray absorptiometry (DEXA) scan:

  • This measures BMD which is then given a T-score. This is a score based on the BMD of a young reference population. A score of -1.0 means a BMD of one standard deviation below that of the reference:
    • >-1.0 is normal
    • -1.0 to -2.5 indicates osteopenia
    • <-2.5 is classed as osteoporosis

The next investigations are to identify or rule out any possible secondary causes:

  • X-ray of the wrist, heel, spine, and hip
  • CT if DEXA is not available
  • Bone profile – calcium, phosphate, albumin, and ALP
  • Serum PTH
  • Serum 25-hydroxyvitamin D
  • TFTs
  • U&Es
  • Serum testosterone
    • This should be considered in all men with osteoporosis
  • Urine and serum protein electrophoresis

Diagnosis

The World Health Organisation have the following diagnostic criteria, which are based on BMD measurements using DEXA:

  • Normal
    • T-score: >-1.0
  • Osteopaenia
    • T-score: -1.0 to -2.5
  • Osteoporosis
    • T-score: <-2.5
  • Severe osteoporosis
    • Osteoporosis + one or more fragility fractures

Management

Pharmacological treatment is indicated for patients with:

  • A FRAX 10-year probability of osteoporotic fracture >1%
  • A hip or vertebral fracture
  • T-score <-2.5
  • T-score between -1.0 and -2.5 and a FRAX 10-year probability of osteoporotic fracture >3%

Options include:

  • 1st line: bisphosphonates + calcium and vitamin D supplementation
    • Primary options are oral alendronate or oral risedronate 1-weekly
      • Must be taken in the morning on an empty stomach with water while sitting upright for 30 minutes before eating any food.
        • This is because food can reduce absorption
      • Patients may experience upper GI symptoms:
        • Difficulty swallowing
        • Oesophagitis
        • Gastric ulcers
        • Osteonecrosis of the jaw
      • The BNF states that “patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain.”
    • The secondary option is: zoledronic acid given as a 1-yearly infusion
  • 2nd line: denosumab + calcium and vitamin D supplementation
    • Only used if bisphosphonates are not tolerated/ineffective
    • Given as a subcutaneous injection every 6 months
    • Contraindicated if there is hypocalcaemia
    • Risk of osteonecrosis of the jaw or osteonecrosis of the external auditory canal
  • Hormone replacement therapy (HRT) is no longer considered due to the increased risk of breast cancer unless the patient is experiencing symptoms relating to menopause.

Patients who are taking long-term corticosteroids should be given bisphosphonates along with calcium and vitamin D supplementation.

Monitoring

There are no specific guidelines on how often the BMD of individuals on treatment should be measured. Generally, follow-up BMD measurements are between 3 and 5 years.

The NOGG has the clearest guidelines regarding the continuation of treatment:

  • Recurrent fractures present
    • Check adherence and exclude secondary causes
    • Consider treatment choice and continue treatment
  • If no fractures are present, re-measure BMD and FRAX
    • If the T score is -2.5 or less:
      • Check adherence and exclude secondary causes
      • Consider treatment choice and continue treatment
    • If the T score is more than 2.5:
      • Consider a “drug holiday”
      • Repeat BMD and FRAX in two years

When treatment is discontinued, reassess the fracture risk after two years or earlier if a fragility fracture happens.

Patient Advice

  • Patients should be encouraged to carry out daily physical activity that is not excessively strenuous e.g. 30 minutes of walking
  • High-impact exercises such as weight-lifting should be avoided
  • Patients should lower salt intake, maintain adequate dietary protein and increase fruit and vegetable intake to help lower urinary calcium losses and maintain bone mass

Complications

Besides fractures, osteoporosis can cause many indirect effects. For example, vertebral compression fractures can lead to:

  • Pain and morbidity and high analgesia doses being used
  • Loss of height
  • Difficulty breathing
  • Loss of mobility
  • GI symptoms
  • Difficulty sleeping
  • Depression

Prognosis

  • Hip fractures require hospitalisation and permanently disable 50% of those affected, and are fatal in 20% of cases.
  • Vertebral fractures are often undiagnosed and associated with long-term pain and disability

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