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Lung disease
• COPD • Cystic fibrosis
Drugs associated with osteoporosis
• Corticosteroids
• Gonadotrophin-releasing
hormone (GnRH) agonists
• Aromatase inhibitors
• Thyroxine over-replacement
• Thiazolidinediones
• Sedatives
• Anticonvulsants
• Alcohol intake > 3 U/day
• Heparin
Clinical features
Patients with osteoporosis are asymptomatic until a
fracture occurs. Osteoporotic spinal fracture may
present with acute back pain or gradual onset of
height loss and kyphosis with chronic pain.
Peripheral osteoporotic fractures present with local
pain, tenderness and deformity, often after an
episode of minimal trauma. In patients with hip
fracture, the affected leg is shortened and
externally rotated.
Investigations
The pivotal investigation is dual energy X-ray
absorptiometry (DEXA) at the lumbar spine and hip.
WHO has published criteria for osteoporosis on the basis
of bone density:
1. Normal bone density: if the t score is greater than −1.
2. Osteopenia: a bone density measurement between 1
and 2.5 SD below the young-adult mean (t score between
−1 and −2.5).
3. Osteoporosis: a bone density measurement
less than 2.5 SD below that of young, healthy controls
(t score < 2.5).
Indications of DEXA scan:
• Low trauma fracture age > 50 years
• Clinical features of osteoporosis (height loss, kyphosis)
• Osteopenia on plain X-ray
• Corticosteroid therapy (> 7.5 mg prednisolone daily for
> 3 mths)
• Family history of hip fracture
• Low body weight (BMI < 18)
• Early menopause (< 45 yrs)
• Diseases associated with osteoporosis
• Increased fracture risk on risk factor analysis (FRAX or
QFracture)
• Assessing response of osteoporosis to treatment
Other investigations:
Renal function, liver function, thyroid function,
immunoglobulins and ESR, with screening for coeliac
disease should be performed.
Serum 25(OH) vitamin D and PTH measurements are
useful to exclude vitamin D deficiency and secondary
hyperparathyroidism.
Levels of sex hormones and gonadotrophins should be
measured in men with osteoporosis and women under
the age of 50.
Transiliac bone biopsy is sometimes required in early-
onset osteoporosis of unknown cause or when coexisting
osteomalacia is suspected.
Management:
Non-pharmacological interventions:
Advice on smoking cessation, moderation of alcohol
intake, adequate dietary calcium intake and exercise
should be given.
Drug treatment:
Drug treatment should be considered in patients
with BMD T-score values below −2.5 or below −1.5
in corticosteroid-induced osteoporosis, and in
vertebral fractures, irrespective of BMD, unless they
resulted from significant trauma.
Bisphosphonates
Bisphosphonates are synthetic analogues
of pyrophosphate with a high affinity for
hydroxyapatite crystals in bone,
suppressing bone turnover and increasing
BMD at the lumbar spine and other sites
via inhibition of osteoclast-mediated bone
resorption.
Alendronate and risedronate are usually
administered once weekly for greater convenience.
Ibandronate is a monthly therapy
at a dose of 150 mg and is also available as a 3 mg
intravenous injection every 3 months.
Alendronate and risedronate reduce the incidence
of vertebral, nonvertebral, and hip fractures.
Both etidronate and ibandronate have
been shown to reduce the incidence of vertebral
fractures, but their impact on non-vertebral and hip
fractures is less clear.
The use of bisphosphonates in patients receiving
chronic glucocorticoid therapy is beneficial for
both the prevention and treatment of
osteoporosis. The use of alendronate 5 mg/day
(35 mg/week) as prevention or 10 mg/day (70
mg/week) as therapeutic dose, while
risedronate 5 mg/day (35 mg/week) as
preventive and therapeutic doses.
Zoledronic acid is licensed for the treatment of
osteoporosis in both men and women as a 5 mg
intravenous infusion once yearly.
It has been shown to significantly reduce the risk
of vertebral and non-vertebral fractures and
mortality in both men and women following
surgical repair of hip fracture
Adverse effects of bisphosphonates
Common
• Upper gastrointestinal intolerance (oral)
• Acute phase response (intravenous)
Less common
• Atrial fibrillation (intravenous zoledronic acid)
• Renal impairment (intravenous zoledronic acid)
• Atypical subtrochanteric fractures
Rare
• Uveitis
• Osteonecrosis of the jaw
The most common adverse effect with
intravenous bisphosphonates is a transient
influenza-like illness characterised by fever,
malaise, anorexia and generalised aches, which
occurs 24–48 hours after administration. This is
self-limiting but can be treated with
paracetamol or NSAID if necessary.
Atypical subtrochanteric fractures have been
described in patients who have received long-
term bisphosphonates, and may be the result of
over-suppression of normal bone remodeling.
Osteonecrosis of the jaw
ONJ is characterised by the presence of necrotic bone in
the mandible or maxilla, typically occurring after tooth
extraction when the socket fails to heal. Most ONJ cases
have occurred in cancer patients with coexisting
morbidity, such as infection and diabetes, who have
received high doses of intravenous bisphosphonates.
All patients should be advised to pay attention to good
oral hygiene.
There is no evidence that temporarily stopping
medication in patients undergoing tooth extraction is
necessary or alters the occurrence of ONJ.
Other treatments:
Denosumab is a monoclonal antibody that
neutralises the effects of RANKL; it is
administered by subcutaneous injection every 6
months in the treatment of osteoporosis.
It has few adverse effects but there are isolated
reports of ONJ with long-term use.
Calcium and vitamin D have limited efficacy in the
prevention of osteoporotic fractures when given in
isolation but are widely used as an adjunct to other
treatments, most often as combination
preparations containing 500 mg calcium and 800 U
vitamin D.
They are of greatest value in preventing fragility
fractures in elderly or institutionalised patients who
are at high risk of calcium and vitamin D deficiency.
Strontium ranelate It has a weak inhibitory effect
on bone resorption, stimulates biochemical markers
of bone formation and is incorporated within
hydroxyapatite crystals in place of calcium.
It is contraindicated in patients with risk of
cardiovascular disease due to an increased
myocardial infarction. There is also an increased
risk of venous thrombosis. Rarely, a severe rash
occurs, and this is an indication to stop treatment.
Parathyroid hormone
PTH is an anabolic agent that works by stimulating new
bone formation. The most widely used preparation is the
1-34 fragment of PTH (teriparatide) given by single daily
subcutaneous injection of 20 μg.
It is also effective in corticosteroid-induced osteoporosis
and appears superior to alendronate in terms of BMD
gain and vertebral fracture reduction. It is also effective in
male osteoporosis.
PTH is expensive and is usually reserved for patients
with severe osteoporosis (BMD T-score of −3.5 to −4.0 or
below) and those who have failed to respond adequately
to other treatments.
Hormonal replacement therapy
cyclical HRT with oestrogen and progestogen prevents
post-menopausal bone loss and reduces the risk of
vertebral and non-vertebral fractures in post-menopausal
women.
It is primarily indicated for the prevention of
osteoporosis in women with an early menopause and for
treatment of women with osteoporosis in their early
fifties who have troublesome menopausal symptoms.
HRT should be avoided in older women with established
osteoporosis because it significantly increases the risk of
breast cancer and cardiovascular disease.
Raloxifene acts as a partial agonist at oestrogen
receptors in bone and liver but as an antagonist in
breast and endometrium, and is classified as a
selective oestrogen receptor modulator (SERM).
It increases the risk of VTE to a similar extent as
HRT but reduces the risk of breast cancer; it does
not influence the risk of cardiovascular disease.