Osteoporosis

Original article by Tom Leach | Last updated on 27/5/2015
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Introduction

Osteoporosis is the most common bone disorder. It is a reduction in bone mass and alteration of bone structure, not just a reduction in bone density. The easiest way to measure the extent of the disease is with bone density scans.

The condition in itself is clinically silent, however, it massively increases the risk of fractures, which increases the risk of mortality.
 

Epidemiology

  • Most common bone disorder
  • Genetic factors are very important – in twins, concordance is 60-90%. Many genes have been implicated, and it is likely that numerous genes are involved.
    • Osteogenesis imperfecta is a type of monogenic osteoporosis that has been well described, but is rare compared to multigenic and multifactorial causes. OI actually comprises of 4 subtypes, which are classified by the presence of a blue sclera. In some cases, this is apparent in childhood, but may resolve with age. In some cases, affected children are born with multiple fractures. There is also often joint hypermobility, aortic root dilation (causing aortic regurg) and hearing loss. These secondary features are related to defects in collagen.
  • More common in women (4:1)
  • More common in Caucasian population than in other races
  • Affects 35% of the over 50s in the UK
 

Causes

  • Post menopausal bone loss is the most common cause – this is related to oestrogen deficiency
  • Hyperparathyroidism
  • Malabsorption (e.g. coeliac disease)
  • Osteomalacia
    • Most commonly the result of vitamin D deficiency
  • Multiple myeloma
  • Hypopituitarism
 

Aetiology

  • Family history
  • Alcohol excess
  • Smoking
  • Amenorrhoea
  • Late menarche
  • Early menopause – including surgical menopause
  • Lack of weight bearing exercise
  • Drugs:
    • Corticosteroids
      • Including Cushing’s disease
    • Anticonvulsants
    •  Heparin
    • Thyroxine
    • Extreme alcohol excess
  • Low calcium and/or vitamin D intake
 

Clinical features

  • Fracture
  • Reduced height (vertebral fracture)
  • Stooping posture – kyphosis, aka dowager’s hump – as a result of wedge shaped fractures of the vertebral bodies.      
 

Pathology

Essentially, there is loss of bone mass, despite normal mineralisation.
  • As opposed to osteomalaciawhich occurs when bone is not being properly mineralised, despite the normal production of bone matrix.
Caused by a loss of coupling between bone deposition and bone absorption mechanisms. This can result in excess osetoclast activity, decreased osteoblast activity, or both. The process of mineralisation of new bone matrix remains normal.
 
Osteoporosis affects both trabecular (long thick bones, e.g. femur) and cortical bone (high surface area, thin bones, e.g. spine). When it affects trabecular bones, reabsorption of bone is the main mechanism. 
 
Post menopausal osteoporosis
This is the most common type of osteoporosis. Bone mass naturally declines with age. Peak bone mass occurs several years after puberty, and then steadily declines. In women, this decline is increased during and after menopause. This, coupled with the fact that women have a lower peak bone mass than men, means post-menopausal women are at particularly high risk.
 
Reduced levels of oestrogen mean that normal osteoclast and osteoblast activity is no longer in conjunction, and osteoclast activity slightly exceeds osteoblast activity, so that over time, bone mass is reduced.
 
Corticosteroid induced osteoporosis
Steroids affect bone density regulatory mechanisms at several places:
  • Decreased absorption of calcium from the gut
  • Decrease muscle mass – which can affect bone remodelling by altering the normal weight bearing stressors normally exerted on bone
  • Increasing osteoclast activity
 

Diagnosis

  • Bone mineral density two standard deviation BELOW the mean value for young adults of the same sex. This is assessed using a DEXA scan.
    • More mild reduction in bone density are classed as osteopenia. This is likely to progress to osteoporosis, so preventative measures may be initiated at this stage.
    • The BMD is assessed on a scale relative to 0.
    • >0 – better BMD than the reference
    • 0 to -1 – in the top 84% of the population
    • -1 to -2.5 – osteopenia
    • <-2.g - osteoporosis
  • Thyroid Function Test
  • Vitamin D levels
  • Myeloma screen
    • ESR
    • Serum immunoglobulins / electrophoresis
    • Urinary Bence Jones Protein
  • X-ray – not very sensitive or specific. Often osteoporosis only presents with a fracture, so you will end up doing one anyway!
  • Screening programs are not widely undertaken, as their efficacy is not proven
 

Complications

Fractures mainly depend on the type of bone affected by the osteoporosis. The lumbar vertebrae, wrist and the hip are the most commonly affected bones.
Vertebral fractures.
  • This can present ‘silently’, perhaps as an exaggerated kyphosis – Dowager’s Hump. This is particularly common in elderly women, and can also cause a reduction in height.
    • Only 30% of vertebral fractures are symptomatic
  • It may also present as acutely, especially when the nerves and nerve roots are involved.
    • Thoracic spine – pain radiates around the front of the torso
    • Lumbar spine – sciatic and femoral nerves may be involved.
    • Sudden onset back pain
    • 25% may feel nauseous and/or vomit
    • Localised tenderness
  • Management
    • Bed rest (1-2 weeks) may be helpful
    • TENS can relieve pain
    • Diazepam (muscle relaxant) may also be helpful
    • Initiate preventative treatments (calcitonin, bisphosphonates)
    • Physiotherapy

 

Non-spinal fractures

  • Managed in the standard way
 

Treatment

The aim of treatment is to reduce the risk of fracture.
 

Lifestyle changes

May be sufficient for some patients. Measures include:
  • Sufficient daily calcium intake – the equivalent to 1 pint of milk per day (1200-1500mg)
  • Smoking cessation
  • Reduction in alcohol intake
  • Increase weight bearing exercise
    • Not only increases bone density, but also helps to prevent falls.
    • At least 30 minutes weight bearing exercise 3x per week is needed to increase bone density
 

Drug treatments

NICE guidelines:

  • 1st line – use a bisphosphonate
  • 2nd line – if no improvement, try a different bisphosphonate
  • 3rd line – if no improvement, try strontium
Drug treatments can reduce the risk of fracture by up to 50%
 

Supplements

Many patients also receive dietary supplements as adjuncts to their pharmacological therapy:
Used alone, they reduce the risk of fracture only by 4%! In very elderly patients, for whom vit D deficiency is the main mechanism of bone density loss, they may be sufficient
 

Bisphosphonates

e.g. alendronic acid, risedronate, clodronate, pamidronate, etidronate
The different drugs have similar mechanisms, but different efficacy. The most effective is usually pamidronate given IV. Etidronate is the least effective, and has to be given in higher doses, which increase the side effects.
 
The drugs are essentially analogues of pyrophosphate.
 
Mechanism
  • Bind to hydroxyapatite crystals in the bone, and are then taken up by osteoclasts – resulting in a high concentration of the drugs in these particular cells. Once within the cell they:
    • Cause apoptosis – by acting as analogues to ATP
    • Inhibit cholesterol synthesis mechanisms – which eventually results in apoptosis
    • Inhibit binding of the osteoclasts ruffled border to the bone surface – and thus the osteoclast cannot resorb the bone.
 
Pharmacokinetics
  • Usually taken weekly, and with plenty of water.
  • Poorly absorbed from the gut
    • Should be taken on an empty stomach – as they can bind to calcium in food, after which, the drug cannot be absorbed.
    • Only about 10% of the oral dose is absorbed under normal circumstances
  • Pamidronate is only available IV, all other agents only available as oral preparations
  • They are rapidly removed from the blood by the kidney, but as they bind to salts, they stay deposited in bone for long periods
 
Unwanted effects
  • GI upset – which can be severe!
  • Bone pain
  • Oesophagitis – to reduce the risk, the patient should take the drug:
    • With a full glass of water
    • At least 30 minutes before food
    • And stay stood or sat upright for at least 30 minutes after the tablet is taken
  • Headache
 
Uses
As well as osteoporosis, bisphosphonates are used in Paget’s disease, and sometimes used against bone metastases.
 

HRT

No longer used as mainstream treatment, but if other treatments are not tolerated or effective, then it may be useful in women in post-menopausal osteoporosis.
  • Most effective when started early in menopause, and continued for >5 years
  • Bone loss continues, and is possibly increased upon stopping HRT
  • Also increases the risks of cardiovascular disease and stroke
 
Strontium
Sometimes used as an alternative to bisphosphonates
 
Calcitonin
Sometimes used in those for whom bisphosphonates are not very effective