Osteoporosis
Oteoporosis is characterised by reduced
bone mass and increased bone fragility. It is very common in postmenopausal females. Up to one in three women
over 80 years have an osteoporotic hip fracture. Fragility fractures also occur
in the spine and distal radius. Osteoporosis, defined according to T score,
occurs when bone density is >2.5 standard deviations below normal peak bone
mass (T ≤2.5). When the T score is between –1 and –2.5, p ified as osteopenic
(orborderline osteoporosis).
Causes
Primary osteoporosis
This is multifactorial, usually resulting from a
combination of oestrogen deficiency and ageing. Osteoporosis is commonly
familial so genetic factors are important. Vitamin D deficiency, smoking and
alcohol are significant risk factors for primary osteoporosis (Figure 18.1a).
Secondary osteoporosis
This suggests a potentially reversible cause of
osteoporosis. It should be considered when osteoporosis occurs in non-‘at risk’
groups including men and pre-menopausal women. Endocrine causes of secondary
osteoporosis include hyperthyroidism, hyperparathyroidism, Cushing’s syndrome,
hypogonadism and hyperprolactinaemia. Exogenous steroids commonly cause
osteoporosis (Figure 18.1b).
Clinical features
Osteoporosis only causes symptoms when a fracture
occurs. Typically, osteoporotic fractures occur after minimal trauma, termed
low fragility fractures (Figure 18.1b). Hip fractures usually occur following a
fall, leading to severe pain and a shortened externally rotated leg on
examination. The 6-month mortality following a hip fracture is up to 20%
because of associated frailty and co-morbidities. Vertebral fractures occur
spontaneously or following lifting, leading to sudden onset of severe back pain
at the level of the fracture. Vertebral wedge fractures can cause loss of
vertical height and kyphosis. Falling on the outstretched hand can cause
fracture of the distal radius (Colles’ fracture).
Investigation
A basic screen for secondary osteoporosis includes
full blood count (FBC), liver function tests (LFTs), calcium, phosphate, ALP
and thyroid function (Figure 18.1c). Bone densitometry, measured by dual energy
X-ray absorptiometry (DXA) scan; Figure 18.2, is the mainstay of diagnosis.
However, many elderly inpatients have clear osteoporosis on plain X-ray, and do
not require a DXA scan if they have had a low trauma fracture. Biochemical
markers of bone resorption and formation are not useful in establishing the
diagnosis.
Assessing fracture risk
Clinical risk prediction of fracture is a better guide
to treatment than DXA scanning alone. Algorithms exist to calculate the 10-year
fracture risk. An example is the FRAX score, which takes into account age, sex,
weight, height, previous fracture, parent with fractured
hip, smoking, treatment with glucocorticoids, the presence of rheumatoid
arthritis, alcohol intake, the presence of secondary osteoporosis and bone
density.
Treatment
Non-pharmacological treatment
Lifestyle measures include adequate calcium and
vitamin D intake, exercise, smoking cessation, falls prevention and avoidance
of excessive alcohol intake (Figure 18.1d). Supplements of 500–1000 mg
calcium/day and 800–1000 IU vitamin D are recommended. Weight-bearing exercise
for at least 30 minutes three times per week reduces the risk of osteoporosis.
Avoidance of drugs that cause osteoporosis is important, particularly corticosteroids.
Pharmacological treatment
Drug treatments for osteoporosis predominantly act by
inhibiting osteoclastic bone resorption, termed anti-resorptive agents. Some
drugs increase osteoblastic bone formation, such as parathyroid hormone.
Bisphosphonates
These are used first line, and are given once a week
or less often. The main side effects are gastrointestinal, typically
oesophagitis. They should therefore be taken with fluid while sitting upright
for 30–60 minutes. Intravenous bisphosphonates are options if gastrointestinal
side effects are intolerable. Long-term use can cause long bone mid-shaft
fractures and osteonecrosis of the jaw. Although the risk is small, a drug
holiday is recommended after several years.
Monoclonal antibodies
Denosumab is a monoclonal antibody that binds to RANK
ligand, which is essential for osteoclastic bone resorption. This reduction in
bone resorption improves bone density and treatment should be considered in
patients with severe osteoporosis who cannot tolerate bisphosphonates.
Parathyroid hormone
PTH (teriparatide) stimulates bone formation and
activates remodelling of bone. It is expensive and only used in patients with
severe osteoporosis who are unable to tolerate, or who have contraindications
to bisphosphonates, or who do not respond to other treatment.
Hormone replacement therapy
HRT in peri-menopausal women can prevent or delay
osteoporosis. HRT is particularly useful when women have other significant
vasomotor symptoms. The pros and cons of HRT should be discussed with the
patient because of the small increased risk of thrombotic disease and
oestrogen-sensitive tumours.
Other agents
Strontium ranelate has weak anti-resorptive activity
and can be used as an alternative in elderly patients who cannot tolerate
bisphosphonates. Calcitonin has a small effect in reducing but the evidence
base is limited and it is not commonly used in clinical
practice.
