Osteoporosis is a complex, progressive skeletal disease that leads to an increased risk of fragility fractures. It can be characterised by a reduced bone mineral density and defects in bone tissue micro-architecture.

Postmenopausal osteoporosis (type I) and age-related osteoporosis (type II) are the most common primary forms of osteoporosis. Secondary osteoporosis can arise due to:

• Hyperthyroidism
• Hyperparathyroidism
• Alcohol abuse
• Immobilisation

Osteoporosis is more common in women than men, highlighting that men have greater bone mass than women at any age and that men exhibit no physiological menopause equivalent. Due to the fact that post-menopausal women experience increased degradation of bone tissue as a result of decreased levels of oestrogen.

Fractures due to osteoporosis are a major cause of morbidity and mortality in elderly populations, with vertebral compression fractures causing acute pain, postural back pain and deformity.

Oral bisphosphonates and lifestyle modification, including exercises and vitamin D supplements, are the mainstays of management. Some patients may require monoclonal antibody treatment to prevent further reduction in bone mineral density.

Significantly, bone strength can be divided into bone density (determined by the amount of bone present) and bone quality (determined by the trabeculization of bone).


Many factors contribute to the risk of osteoporotic fractures, which should be taken into account in the assessment of fracture risk in patients.

Using the FRAX tool, the major risk factors associated with osteoporosis can be listed as:

• Age (between 40 and 90 years)
• Gender
• Previous fracture
• Parent fractured hip
• Smoking
• Glucocorticoids (more than 3 months at a dose of prednisolone 5mg daily)
• Rheumatoid arthritis
• Secondary osteoporosis
• Alcohol consumption
• BMD

Osteoporosis results from increased bone breakdown by osteoclasts + decreased bone formation by osteoblasts → loss of bone mass.

Bone mass typically decreases with age in all populations but the degree of osteoporosis depends on the 'peak' mass attained in adult life and the rate of loss in later life.

Multiple genes are involved including:

• Collagen type 1A1
• Vitamin D receptor
• Oestrogen receptor genes

Not all causes of osteoporosis alter bone micro-architecture and remodelling in the same way:

• Oestrogen deficiency
  • Increased numbers of remodelling units
  • Premature arrest of osteoblastic synthetic activity and perforation of trabeculae
  • Loss of resistance to fracture

• Glucocorticoids
  • Induce a high-turnover state initially (with increased fracture risk evident within 3 months of therapy initiation)
  • Prolonged use leads to a reduced-turnover rate with a net loss due to reduced synthesis by osteoblasts
  • Typically occurs with equivalent corticosteroid use of 10mg prednisolone once daily for 3 months or more

• Ageing
  • Increased turnover at the bone / vascular interface within cortical bone → weak structure for stresses in long bones (trabeculazation of cortical bone)

Osteoporosis often has a long latent period where it remains asymptomatic and bone mineral density continues to fall before fragility fractures occur, in contrast to many other bone disease.

Increasing age and female sex are significant risk factors for osteoporosis. The prevalence of osteoporosis rises from 2% at 50 years to 25% at 80 years in women.

Pathological or fragility fractures, often the result of a fall, are traditionally the first clinical presentation. Pervasive sequelae include fractures of the proximal femur, humerus, distal radius and compression fractures of the vertebral bodies.

The most common pathological fractures seen include:

Vertebral compression fractures

• Often a sudden episode of acute back pain occurring at rest, bending or lifting
• Restricted spinal flexion and intensified pain with prolonged standing
• Anterior compression fractures in the thoracic spine may lead to thoracic kyphosis (Dowager's hump)
• Paravertebral muscle spasm and tender upon deep palpation
• Only about 1 in 3 vertebral fractures are symptomatic

Appendicular fractures (fracture of the proximal femur or distal radius following a fall)

• Often occur in those with several pre-existing co-morbidities that complicate post-operative recovery (such as pneumonia and DVT)
• Neck of femur fractures present as hip pain, inability to bear weight and upon physical examination there is a shortened and externally rotated leg
• Colles fractures present after a fall on an outstretched arm, wrist pain and reduced range of movement

The diagnostic work-up of osteoporosis aims to evaluate the extent of bone density loss, exclude secondary causes of bone loss and prevent further bone destruction.

It is clinically warranted to assess bone density in patients at high risk of fractures or deformity using serial bone density measurements, to monitor the effectiveness of therapy or preventative interventions.

This can be achieved using dual-energy x-ray absorptiometry (DXA) using low doses of radiation to measure bone mineral density. Diagnosis is based on history of prior fragility fracture or low bone mineral density, which is defined as a T-score ≤-2.5.

T score: based on bone mass of young reference population. A score of -1.0 means bone mass of one standard deviation below that of young reference population.

• > -1.0 = normal
• -1.0 to -2.5 = osteopaenia
• < -2.5 = osteoporosis

Plain radiographs will highlight any fractures and reveal previously asymptomatic vertebral deformities.

Investigations to exclude any secondary causes of osteoporosis include:

• Quantitative CT and US of the heel
• History and physical examination
• FBC
• U&Es (serum calcium, creatinine, phosphate)
• LFTs (ALP, transaminases)
• TFTs
• 25-OH vit D & 1,25-OH vit D
• Serum testosterone & prolactin
• Lateral radiographs of lumbar and thoracic spine
• Protein immunoelectrophoresis and urinary Bence-Jones protein

The World Health Organisation (WHO) have published diagnostic criteria for osteoporosis. This is based on bone density measurements determined by dual-energy x-ray absorptiometry (DXA).


According to the criteria, by 75 years-old, an estimated 38% of women will have osteoporosis and 94% will have low bone mass. Although this tool is useful to establish prevalence of osteoporosis, it should not guide treatment. As the risk of osteoporotic fractures in many elderly patients during their lifetime is sufficiently low to avoid intensive treatment.

Therefore, the FRAX tool can be used to evaluate fracture risk of patients and guide clinical treatment. It is based on patient models that integrate clinical risk factors and bone mineral density (BMD) at the femoral neck to give the 10-year probability of fracture at the hip or major osteoporotic fracture.

Clinical risk factors used in FRAX include:

• Age (between 40 and 90 years)
• Gender
• Previous fracture
• Parent fractured hip
• Smoking
• Glucocorticoids (more than 3 months at a dose of prednisolone 5mg daily)
• Rheumatoid arthritis
• Secondary osteoporosis
• Alcohol consumption
• BMD

Osteoporosis may easily be confused with other metabolic or neoplastic bone disease.

Possible differential diagnoses:

• Osteomalacia
  • Osteoporosis is associated with a decreased density of normally mineralized bone matrix
  • Osteomalacia may have increased, normal, or (most commonly) decreased bone mineral density, but there is insufficient bone mineralisation
  • In contrast to osteoporosis (which remains asymptomatic until fractures occur) osteomalacia may cause generalised bone pain, tenderness and myopathy.
  • Osteomalacia may caused by vitamin D deficiency due to malabsorption or medication so it is important to measure levels of Calcidiol (25-hydroxyvitamin D) and Calcitriol (1,25-dihydroxyvitamin D)

• Paget disease of bone
  • Increased osteoclastic bone resorption and compensatory increase in osteoblast bone formation
  • Formation exceeds resorption but new woven bone ('mosaic' architecture) is weaker than trabecular bone, leading to an increased fracture risk
  • In contrast to osteoporosis, patients with Paget's disease may have bone pain, joint pain, bone deformities (such as bowed tibia and skull changes) and neurological complications from nerve compression

• It is also important to consider other bone disease, including neoplastic bone disease such as myeloma, primary and metastatic bone tumours, lymphoma

• As well as secondary causes of osteoporosis such as:
  • Hyperparathyroidism
  • Mastocytosis
  • Sickle cell anaemia

Diagnostic investigations should be completed in order to guide the management of osteoporosis.

Lifestyle modification for the prevention of osteoporotic fractures is the mainstay initial management, this includes:

• Falls risk assessment
• Weight-bearing and muscle strengthening exercises
• Optimum daily calcium (800-1200mg) and vitamin D (400-800 IU) intake through sunlight and diet or supplements
• Calculation of 10-year probability of osteoporotic fragility fracture

Pharmacological therapy using oral bisphosphonates should be reserved for those with a 10-year probability of osteoporotic fragility fracture > 1%, or :

• A hip or vertebral fracture
• T-score <2.5 or less at the femoral neck
• T-score between -1.0 and -2.5 and a 10-year probability of a hip fracture >3% using FRAX

Bisphosphonates:

• First line medication to treat osteoporosis
• Adhere to hydroxyapatite and inhibits osteoclasts thereby reducing bone resorption
• Oral Alendronate and risedronate are given as 1-weekly doses, whilst zoledronic acid as a 1-yearly infusion
• They should be taken fasting, with water whilst standing or sitting upright for 30 minutes
• May be associated with upper-GI side effects such as oesophagitis
• Careful monitoring is required in those with CKD4 or 5

Denosumab, a monoclonal antibody, should only be used in extensive osteoporosis:

• Given as a subcutaneous injection every 6 months
• Anti-resorptive agent that increases BMD and reduces fracture risk at the spine
• Adverse effects are infrequent but serious:
  • Dysuria
  • Cellulitis
  • Osteonecrosis of the jaw

Hormone replacement therapy (HRT) is reserved for early postmenopausal women due to its adverse effects on breast cancer and cardiovascular disease risk.

New vertebral fractures may require:

• Bed rest for 1-2 weeks
• Strong analgesia
• Muscle relaxants (i.e. diazepam 2mg TDS)
• Gradual physiotherapy

There are also treatments for specific patient demographics:

In addition to the increased risk of fractures, osteoporosis can lead to other direct or indirect complications, such as:

Limited mobility

• Osteoporosis can limit physical activity that may result in weight gain and increase the risk of the long-term sequelae of heart disease and diabetes

Depression

• Commonly seen with the loss of independence and isolation

Pain

• Fractures of osteoporosis in the spine in particular can lead to a loss of heigh, stooping posture and persistent back pain

Complications of medication

• Oral bisphosphonates can lead to oesophagitis
• Teriparatide increases the risk of osteonecrosis of the jaw and atypical femoral fractures