Medicine Semester I Assignment Osteoporosis

Contents

Definition and Epidemiology

Aetiology

Pathophysiology

Clinical signs and symptoms

Differential diagnosis and investigations

Osteomalacia

Paget’s Disease (Osteitis Deformans)

Malignant Tumours

Orthodox medical treatment

Avoiding and recovering from fractures

Drug treatments

Lifestyle changes

Natural medicine

Prognosis

Resource list

References

Bibliography

Appendix A Tables from the World Health Organisation technical report, 1994

Appendix B Case study

Appendix C Table of orthodox treatments

Definition and Epidemiology

The World Health Organisation (WHO)defines osteoporosis as ‘a disease characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk.’ The WHO report published in 1994, says that a bone mineral density of more than 2.5 standard deviations less than young adult reference mean is the defined value for osteoporosis. The young adult reference takes into consideration the ethnicity of the patient.
Figure 1 shows the bone tissue for a normal adult female compared with bone tissue of a 70 year old woman. These images show that the trabecular bone structure of the older woman has become thinner and more connections between the structures are missing. /
Figure 1 – scanning electron micrographs to show the structure of L3 vertebra in a 31 year old woman (top) and in a 70 year old woman (bottom). Copyright British Medical Journal (BMJ), 2006

Osteopenia is a low bone density value which is not low enough to be classified as osteoporosis, although an osteopenic individual has a high risk of developing osteoporosis. Based on the 1994 WHO definition, a value of between 1 and 2.5 standard deviations from the young adult mean would be classed as osteopenia.

Established (or severe) osteoporosis is diagnosed osteoporosis with a fracture. This information is summarised in Table 1.

Table 1 – summary of bone mass values
Definition / Value
Normal / 0-1 standard deviation below young adult mean
Low bone mass (osteopenia) / 1-2.5 standard deviations below young adult mean
Osteoporosis / More than 2.5 standard deviations below young adult mean
Established (severe) osteoporosis / Osteoporosis + 1 or more fragility fractures

Based on information from WHO (1994) report – see reference list

There is a strong female bias for the condition with the highest incidence in white post-menopausal women, although it is possible for anyone to be affected by the condition, including children (O’Connor and Perkins, 2005). Figure 2 compares the incidence of osteoporotic fractures between men and women and shows that women are twice as likely to sustain wrist or hip fractures after 60, and vertebral fractures after 70 years of age.

Race has also been shown to be a factor for osteoporosis: negro races are less likely than Caucasians to have the disease because of higher initial skeletal mass (WHO, 1994).

Figure 2 – Epidemiology of osteoporotic fractures in men and women. Copyright Dennison, Cole and Cooper (2005), taken from BMJ, 2006. / As part of the aging process bone density naturally decreases which means that older people are more likely to have the condition. An older person is more likely to sustain a fragility fracture (a fracture caused by a minor trauma) and at this point be diagnosed with osteoporosis which partially explains the relationship between age and incidence (WHO, 1994).
The condition is often asymptomatic until a fragility fracture occurs which is why the condition is sometimes described as the ‘silent thief’ (WHO, 1994). In the UK, osteoporosis is responsible for over 60,000 hip, 50,000 wrist and 120,000 vertebral fractures each year (National Osteoporosis Society [NOS], 2006).

Aetiology

Osteoporosis can be primary or secondary which means it can result from another condition such as Cushing’s syndrome (Gould, 2006).

Figure 3 shows that bone mass naturally reduces after peak bone mass has been reached at around 35 years of age. In the primary form of the disease, the rate at which it diminishes with age is affected by many factors: genetic (vitamin D receptors, family history, ethnic origin, skeletal mass), nutrition (calcium intake, alcohol consumption), lifestyle (weight-bearing exercise, smoking). Secondary causes include diseases affecting hormone balance, drugs and conditions such as anorexia nervosa(WHO, 1994).

Figure 3 – Age related changes in bone mass throughout life in women and men, copyright BMJ, 2006. / The sex hormones, oestrogen and testosterone, play a significant part in the rate of bone formation because they stimulate osteoblast activity. During the menopause, oestrogen levels are greatly reduced which that bone mass is reduced. In addition to hormonal changes, women are more likely to have osteoporosis because they have lower peak bone mass (Tortora and Derrickson, 2006).

Details of the factors associated with osteoporotic fractures and causes of osteoporosis in adults can be found in Appendix A.

Risk and predisposing factors are varied so that cause of the disease process in an individual is often complex and not definitive. For example, Liz Larsson was diagnosed as osteopenicin 2006 at the age of 44 although her lifestyle and family history did not indicate she was particularly at risk. The mostly likely reason for her condition was that she had started the menopause approximately 18 months previously. However, there were other things which could have contributed to her low bone density such as prolonged use of the contraceptive injection depo-provera. There may also have been a genetic element as a younger sister has subsequently been told that her bones are thinner than expected. See Appendix B for her case study.

Pathophysiology

Normal bone tissue is constantly being broken down and then rebuilt. During childhood and early adulthood, more bone is built than is broken down. After peak bone mass has been reached, bone loss starts in the fourth or fifth decade of life (Poole and Compston, 2006).

The normal process for remodelling bone is described in Figure 4. In an osteoporotic patient, osteoclasts are more active and / or osteoblasts are less active with the result that more of the internal structure and therefore strength of bone tissue is reduced (see Figure 1, page 2)

A
trabecular bone surfaces are covered by resting osteoblasts (cells which create bone matrix) / B
osteoclasts (cells which break down bone matrix) migrate to a dormant bone surface / C
osteoclasts excavate a resorption cavity / D
mononuclear cells smooth the cavity
E
osteoblasts are attracted to the site where they synthesize bone-like matrix / F
synthesis of the new matrix continues / G
Newly formed bone calcifies / H
When the process is complete, lining cells overlie the trabecular surface

Figure 4 – Steps in the remodelling sequence of trabecular bone, adapted from 1994 WHO report

Bones consisting of proportionally higher cancellous (trabecular)bone are particularly likely to be affected because this type of bone is relatively more hollow than compact or cortical bone. It also regenerates quickly which means that there is more opportunity for problems with remodelling to have an effect (Gould 2006) (Reister O’Connor and Perkins, 2005).

Emily Greenslade (Bristol), Medicine Semester I Assignment – Osteoporosis page 1 of 17

Figure 5 - A man aged 78 presented with an acute onset of thoracic kyphosis over a period of 10 weeks. The differential diagnosis on magnetic imaging included the possibility of a neoplasm, but further investigations confirmed osteoporotic collapse.

Copyright: Shergill, I and Wilson-Macdonald, J, Nuffield Orthopaedic Centre NHS Trust, Oxford OX3 7LD

Emily Greenslade (Bristol), Medicine Semester I Assignment – Osteoporosis page 1 of 17

The effect of these changes on the body is that the patient’s bones are more prone to fracture. This results in pain for the patient either through fracture or pressure on nerves through vertebral collapse. Spinal fractures may cause loss of height and spinal deformity such as kyphosis (increased thoracic flexion, see Figure 5) or scoliosis (increased lateral curvature). Spontaneous or fragility fractures occur most commonly in the hip, wrist or vertebrae (Gould, 2006).

Clinical signs and symptoms

Reister O’Connor and Perkins (2005) describe osteoporosis as ‘a silent disease’ which means individuals are likely to be asymptomatic until a fragility fracture occurs.They suggest that any fracture which happens from a very minor trauma should be investigated as a fragility fracture, as should ‘multiple fractures, even with significant trauma’.

Given that the definition of established osteoporosis according to the WHO study group report in 1994 includes a clinically apparent fracture, this type of break can be considered a pathognomonic sign. Presentation of a fragility fracture, particularly if the patient history includes risk factor or factors listed in Appendix A should be treated as a red flag and further diagnostic tests carried out.ity fr

Vertebral compression fractures may present as ‘nagging’ back pain initially but as the disease progresses a patient will show clinical signs such as loss of height and deformity of the spine (Reister O’Connor and Perkins, 2005). Figure 5 shows an example of kyphosis caused by osteoporotic vertebral fractures.

Osteoporosis is likely to cause fractures in specific areas because of the higher proportion of cancellous bone particularly if it is under pressure from supporting the body (vertebrae, hip) or from protecting against falls. A wrist or Colles’ fracture is a typical sign of osteoporotic fracture which occurs in the distal radius, ulna or smaller wrist bones. It is often a protective injury when an individual puts out a hand to break a fall and should be treated as a red flag (Reister O’Connor and Perkins, 2005).

Differential diagnosis and investigations

Osteoporosis is often asymptomatic, particularly if vertebrae are affected where approximately two thirds of patients do not present a clinically evident fracture. When a patient has spinal deformity or sustains a fragility fracture further investigation is required to confirm a diagnosis of osteoporosis (Poole and Compston, 2006).

The primary investigative tooloften seen as a gold standard is a dual energy x-ray absorptiometry (DXA) scan(Reister and Perkins, 2005). It measures bone density using two sources of x-rays. The scan can be carried out at any site but most commonly the test is used to measure the lumbar spine (L2-L4 or L1-L4) and hip. This technique is easy to use and has a high level of precision (WHO, 1994). See Appendix A (table 7) for other investigative tools.

There are other causes of fragile bones and deformity which would need to be ruled out:

Osteomalacia

• Characterised by demineralisation related to vitamin D deficiency.
• Weaker bones result in compression fractures especially in the vertebral body and femoral neck (Thibodeau and Patton, 2007).
• Signs including site of fracture, and symptoms are very similar to osteoporosis and the two disorders can co-exist.
• Diagnosed by x-rays – bone demineralisation will be seen in the spine, pelvis and lower extremities. Fibrous lamellae and incomplete areas of demineralisation are apparent in the cortex (Merck, 2008)

Paget’s Disease (Osteitis Deformans)

• Characterised by more osteoclasts and compensatory osteoblast activity.
• Bones are remodelled in a disorganised way which can cause weakness in some areas of bone and additional strength in other areas.
• Commonly affects the skull, humerus, femur, vertebrae and pelvic bones. Weakness can cause fragility fractures similar to osteoporosis (Thibodeau and Patton, 2007)
• Diagnosis is confirmed through x-ray (Figure 6) which would show abnormal architecture (cortical trabeculation or thickening) and serum levels of alkaline phosphate, calcium and phosphate (Merck, 2008).

Figure 6 – X-rays of bones affected by Paget’s Disease. Copyright BMJ, 1996

Malignant Tumours

• Osteosarcoma (osteogenic sarcoma) is the most common malignant bone tumour and most often in the metaphysic of the tibia, femur (see Figure 7) and humerus.
• Presents as bone pain and sometimes pathological fracture. This would need to be ruled out because it can quickly metastasise to the lungs, although peak incidence is between 10 and 25 years (Gould, 2006).
• Diagnosed through bone biopsy (Merck, 2008).

/
Figure 7 - Osteosarcoma of the distal femur in a young patient treated with pre-operative chemotherapy and a limb-sparing surgical procedure. Copyright Cancer Research Norway

Orthodox medical treatment

Once the diagnosis of osteoporosis has been confirmed, the disease is managed according to the specific requirements of the individual patient. The following strategies from Reister O’Connor and Perkins, 2005 and National Osteoporosis Society leafletsmight be used in a management programme:

Avoiding and recovering from fractures

An individual with osteoporosis is very likely to sustain a fracture from a fall and may even fall due to a spontaneous fracture (stress fracture). Precautions such as installing grab bars and hand rails in the home, sufficient lighting, taking extra care in snow/icy conditions as well as in the home can reduce the number of falls.

Femoral fractures may require surgery and hip replacement. Vertebral compression fractures can be left untreated if the fracture is stable. If the vertebra is unstable percutaneous vertebroplasty (injecting acrylic cement into the vertebra) or kyphoplasty (injecting a small balloon) may be used for pain relief. Colles’ fractures (wrist) are treated by realigning the bones and then splinting to immobilise while the bone heals.

Drug treatments

There are many drug treatment options but the biosphosphonates are the most common group. They are given in tablet form and work by inhibiting osteoclast activity which allows osteoblasts to work more effectively. There are several licensed in the UK including Alendronate, Cyclical Etidronate, Ibandronate and Risedronate.

Hormone replacement and hormone mimicking drugs are also available. These work by either stimulating osteoblasts (parathyroid hormone treatment) or inhibiting osteoclasts (oestrogen and testosterone replacement therapies, raloxifene). Stronium ranelate works by both stimulating osteoblasts and inhibiting osteoclasts.

Dietary supplementation of calcium and vitamin D is often recommended in conjunction with other medication and for elderly people.

Medication such as nonsteroidal anti-inflammatory drugs are prescribed or suggested for acute or chronic pain associated with osteoporotic fracture. More information about drug treatments can be found in Appendix C.

Lifestyle changes

Smoking, excessive alcohol intake, unbalanced diet and a sedentary lifestyle can all contribute to bone mass loss. Management of osteoporosis is likely to include keeping active but this will depend on the severity of the condition.

Natural medicine

There are not many natural treatments recommended for this condition. Natural treatments for pain managementsuch as acupuncture or massage (although this is not recommended for severely osteoporotic patients) could be considered to mediate nerve pain from any spinal damage or other fractures (Reister O’Connor and Perkins, 2005).

Diet, lifestyle changes and vitamin supplementation are often prescribed as part of orthodox management for the condition (see ‘Orthodox Medical Treatment’ above).

Prognosis

The first stages of the disease are asymptomatic so the condition is often untreated until the patient has a fragility fracture.Once diagnosed, ‘drug treatments have been shown to reduce the risk of fractures by up to 50%’(NOS, 2006).

According to the NOS (2006) the likely outcomes of osteoporosis in the UK are:

• significantly reduced quality of life with 60% of patients limited in class I (e.g. feeding, dressing) and 80% limited in class II activities (e.g. shopping, gardening) 12 months after a hip fracture
• 18% mortality in the first three months following hip fracture
• 55% of patients require assistance at home in the first 12 months following a hip fracture
• 40% of patients with vertebral fractures will have constant pain
• loss of height, kyphosis and severe back pain lead to a lack of mobility which can worsen the osteoporosis

Reister O’Connor and Perkins (2005) include constipation, weight loss and possible lung compression leading to lung disease as outcomes of spinal deformity following vertebral compression.

Resource list

National Osteoporosis Society (NOS)

Camerton, Bath, BA2 0PJ

tel: 01761 471771, helpline: 0845 450 0230

website: email:

NOS Regional Support Groups:

Cardiff and District –

Bridgend and District –

Useful websites:

British Orthopaedic Association –

British Geriatric Society (Falls and Bone Health Special Interest Group) –

British Medical Journal –

National Institute for Clinical Excellence (NICE) –

NHS Direct -

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This figure does not include contents page, section headings, appendices, reference list or bibliography.

References

Page numbers in brackets refer to pages of this assignment.

Gould, B E (2006)

Pathophysiology for the Health Professions, Third Edition, Saunders Elsevier, Pages: 657-659 (4, 6 & 9)

National Osteoporosis Society (January 2006) Osteoporosis Facts and Figures Version 1.1,Pages: 2-4 (6, 11)

Merck Online, accessed 13 March, 2008:

Osteosarcoma:

Paget’s disease:

Vitamin D deficiency (osteomalacia):

Osteomalacia and osteoporosis:

Poole, K E S and Compston, J E (2006)

Osteoporosis and its management, British Medical Journal Volume 333; Pages: 1251 (5),1252 (7)

Reister O’Connor, C and Perkins, S (2005)

Osteoporosis for Dummies, First Edition, Wiley Publishing, Pages: 63-67 (3), 23, 107, 109 (6), 109-110, 114-115, 136-137 (7), 107-117, 145-160, 161-175, 180-186,194-196 (9-10)

Thibodeau, G A and Patton, K T (2007)

Anatomy and Physiology, Sixth Edition, Mosby Elsevier, Page:248 (8)

Tortora, G J and Derrickson, B (2006)

Principles of Anatomy and Physiology, Eleventh Edition, John Wiley & Sons, Inc., Pages:189-190 (4)

WHO Study Group (1994)

Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis, World Health Organisation Technical Series (843), Pages: 3, 5-6 (2), 7-8, 62 (3), 15, 59-61 (4), 19 (5), 5-6, 29-30 (7)

Bibliography

Compston, J (1999)

British Medical Association - Family Doctor Guide to Osteoporosis, First Edition, Dorling Kindersley

Epstein, O et al (2004)

Pocket Guide to Clinical Examination, Third Edition, Mosby Elsevier