11/14/24, 10\:53 AM Osteoporosis

Osteoporosis

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Key points ⚡
Succinct notes to superpower your revision
Osteoporosis\: progressive bone disorder with reduced bone density and increased fracture risk, often asymptomatic until a
fracture occurs.
Prevalence\: global prevalence ~18%, more common in women, older adults, and certain risk factors.
Aetiology\: imbalance between osteoclast and osteoblast activity leading to reduced bone density and quality.
Risk factors\: increasing age, female sex, post-menopause, reduced mobility, low BMI, smoking, alcohol intake >3 units/day,
parental history of hip fracture, previous fragility fracture.
Medical conditions which can increase risk of osteoporosis\: rheumatoid arthritis, primary hyperparathyroidism, chronic
kidney disease, gastrointestinal disease, hyperthyroidism, chronic liver disease.
Medications which can increase risk of osteoporosis\: corticosteroids, SSRIs, PPIs, anti-epileptics, anti-oestrogens.
Symptoms\: asymptomatic until fractures occur; common fracture sites include vertebrae, hip, and wrist.
Investigations\: FRAX or QFracture score to assess fracture risk, DXA scan to measure BMD, X-rays for fractures, and
relevant blood tests (bone pro
Diagnosis\: based on history of fragility fracture or low BMD on DXA scan (T-score \< -2.5 indicates osteoporosis).
Management\: lifestyle advice (exercise, smoking cessation, reduced alcohol intake, adequate calcium and vitamin D),
pharmacological treatment including bisphosphonates (typically for 5 years if oral), denosumab, teriparatide, addressing
modi
Complications\: fragility fractures (hip, rib, wrist, vertebral), chronic pain, atypical fractures, osteonecrosis of the jaw, venous
thromboembolism.
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A comprehensive topic overview

Introduction

Osteoporosis means "p o r o u s b o n e "
. It is a progressive, systemic skeletal disorder characterised by reduced bone density
and defects within the microstructure of bone. This means that patients with osteoporosis are at an increased risk of
fractures, although the condition remains asymptomatic until a fracture occurs.
The global prevalence of osteoporosis is around 18%, although it is more common in women, older adults, and people with
certain risk factors.
1
Osteopenia is a precursor to osteoporosis and refers to a less severe reduction in bone density.
You may also be interested in our OSCE guide to bisphosphonate counselling.

Aetiology

Many factors contribute to our bones' strength, such as the size and shape of the bone, the rate of bone turnover, and
mineralisation. Osteoporosis is a disease that a
to a reduction in bone mass and mineral density.
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Bone is constantly being remodelled based on mechanical stress and systemic factors in the body. The cells responsible
for the resorption of bone are osteoclasts, and osteoblasts are responsible for producing new bone matrix. Osteocytes
regulate the balance between the activity of these cells.
Osteoporosis occurs when there is a mismatch between the activity of these cells and the demand for bone remodelling,
either through increased activity of osteoclasts or reduced activity of osteoblasts.
This eventually leads to lower bone density and quality, which increases the risk of fractures. Osteoporotic fractures are
also known as "fragility fractures" because they occur from mechanical forces or trauma that would not normally cause a
fracture.

Risk factors

There are numerous risk factors for osteoporosis.
2
General risk factors include\:
2
Increasing age\: bone density naturally decreases with age, so older patients are more likely to have reduced bone
density (Figure 1)
Female sex
Post-menopause\: due to changes in oestrogen levels; the risk is highest post-menopause as the relative de
oestrogen leads to excess bone resorption
Reduced mobility and activity\: weight-bearing places stress on bones, which leads to increase bone strength through
remodelling, the less active a patient is, the less this occurs
2
Low BMI (\<18.5kg/m )
Smoking
Alcohol intake >3 units/day
Parental history of hip fracture
Previous fragility fracture
Medical conditions which increase the risk of osteoporosis include\:
2
Rheumatoid arthritis
Primary hyperparathyroidism
Chronic kidney disease
Gastrointestinal disease (e.g. Crohn's disease, ulcerative colitis, coeliac disease)
Hyperthyroidism
Chronic liver disease
Medications which increase the risk of osteoporosis include\:
2
Corticosteroids\: any dose orally for > 3 months, but the risk increases signi
Selective serotonin reuptake inhibitors (SSRIs)
Proton pump inhibitors (PPIs)
Anti-epileptics
Anti-oestrogens
Figure 1. Bone density peaks around age
30 and then reduces with age. The
menopause accelerates bone loss
leading to an increased risk of
osteoporosis.
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Clinical features

History

diagnosed.
Osteoporosis remains asymptomatic until a fracture occurs, meaning the disease can become established before it is
A fragility fracture is de
fracture are\:
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Vertebral\: although a large number of vertebral fractures are asymptomatic
Hip (proximal femur)
Wrist (distal radius)
However, they can occur at other sites, such as the humerus, pelvis, and ribs.
Important areas to cover in the history are the mechanism of injury and risk factors for osteoporosis.
Figure 2. An osteoporotic vertebral
wedge fracture of T12.

Clinical examination

Osteoporosis itself will generally not cause speci
have hyperkyphosis of the spine due to multiple vertebral body compression fractures ("Dowager's hump").
There may be signs of risk factors for osteoporosis (e.g. tar staining in patients who smoke or joint swelling in patients with
rheumatoid arthritis).

Investigations

Assessing fracture risk

The Fracture Risk Assessment Tool (FRAX®) score was developed to help assess the risk of fractures in patients
suspected of having osteoporosis, either due to risk factors or following a fragility fracture.
FRAX calculates the 10-year fracture probability, which can be used to help guide further investigation and management.
The FRAX score takes into account the following factors\:
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Age
Sex
BMI
Previous fractures
Parental hip fracture
Smoking status
Alcohol consumption
Glucocorticoid use
Rheumatoid arthritis
Secondary osteoporosis
If a patient has already had their bone density assessed, then the FRAX score considers this to better estimate fracture
probability.
When to assess fracture risk
NICE advises that the following patient groups should have a fracture risk assessment\:
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All women aged 65 years and over
All men aged 75 years and over
Women aged under 65 years, and men aged under 75 years with risk factors (those listed above)
Generally, risk assessment is not recommended for people under 50 unless they have signi
current/frequent use of oral glucocorticoids, untreated premature menopause, or previous fragility fracture.
An alternative to the FRAX score is the QFracture risk calculator, which considers similar risk factors.
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Interpreting fracture risk
FRAX and QFracture produce a risk score for hip fractures and other major osteoporotic fractures (spine, wrist, or shoulder)
over the next 10 years.
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Table 1. Fracture risk with QFracture and FRAX.
Risk QFracture FRAX
High risk >10% Red zone of risk chart
Intermediate risk Close to, but \<10% Orange zone of risk chart
Low risk \<10% Green zone of risk chart
This is used to guide the management plan\:
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Low risk\: measuring bone mineral density (BMD) is not required; give lifestyle advice and reassurance and monitor risk
factors
Intermediate risk\: arrange a dual-energy x-ray absorptiometry (DXA) scan and recalculate the risk score with BMD taken
into account
High risk\: o
Risk assessment tools may underestimate the fracture risk in certain populations\:
Patients over 80 years old,
Multiple previous fragility fractures
Patients taking oral glucocorticoids (>7.5mg prednisolone or equivalent for 3 months or more)

Bone density measurement

BMD can be measured using a DXA scan, a specialised type of X-Ray that can indicate the density of bone depending on
how much radiation is absorbed.
Any bone in the body can be used, but the two regions typically used for osteoporosis diagnosis are the femoral neck and
spine. The femoral neck BMD is generally considered the gold standard diagnostic test.
A DXA scan produces several di
T-score\: the number of standard deviations the patient's bone density is from the mean bone density of a 30-year-old
adult
Z-score\: the number of standard deviations the patient's bone density is from the mean bone density of age and
gender-matched control
Generally, a DXA scan should not be repeated for two years unless the risk pro
be used to monitor response to treatment in patients with known osteoporosis, with repeated scans taking place every 2-5
years.

Other investigations

Depending on the clinical context, other investigations may be useful to identify underlying causes of osteoporosis and
exclude di
X-Rays are useful for detecting fragility fractures, particularly vertebral fractures, or can show osteopenia.
1
Relevant laboratory investigations include\:
Bone pro\: usually normal in osteoporosis, raised ALP/low phosphate can indicate osteomalacia
Urea & electrolytes\: screening for chronic kidney disease as a cause of osteoporosis
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Vitamin D\: if low, can increase the risk of osteoporosis
PTH\: screening for hyperparathyroidism as a cause of osteoporosis
Thyroid function tests\: screening for hyperthyroidism as a cause of osteoporosis
Testosterone\: screening for hypogonadism as a cause of osteoporosis
Serum immunoglobulins and paraproteins\: if abnormal, may indicate myeloma

Diagnosis

Osteoporosis can be diagnosed based on a history of a previous fragility fracture or a low BMD identi
1
While both the T-score and Z-score are given on a DXA scan report, the T-score is used for diagnosis.
Table 2. T-score interpretation.
T-score Diagnosis
> -1 Normal bone mineral density
-1 to -2.5 Osteopenia
\< -2.5 Osteoporosis
\< -2.5 AND previous fracture Severe osteoporosis

Management

All patients who undergo fracture risk assessment should be given lifestyle advice, as this may help prevent osteoporosis
and fractures in low-risk patients.
Pharmacological treatment should be o
available depending on the patient's risk factors, history, and personal preference.
It is also important to address any modi
premature menopause).

Lifestyle advice

Lifestyle modi
Regular exercise, particularly strength-based and weight-bearing exercise\: swimming and cycling do not improve
bone density
Stopping smoking
Reducing alcohol intake to recommended limits
Adequate dietary calcium intake (minimum 700mg/day)
Adequate vitamin D intake
Maintaining a healthy weight

Calcium and vitamin D

It is important to ensure that patients with osteoporosis have adequate calcium and vitamin D levels, as the risk of fracture
increases when low due to their e
Vitamin D is especially important as many people in the northern hemisphere are de
Patients with vitamin D levels. below 50nmol/L should be o
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Rapid correction\: 300,000 IU vitamin D3 over 6-10 weeks in divided doses, followed by maintenance vitamin D
Maintenance\: 800-2,000 IU vitamin D3/day
Most patients can meet their calcium intake through diet. If not, this can be supplemented. Calcium is often combined with
vitamin D, such as Calcichew-D3 (1000mg calcium and 800 IU vitamin D).
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Bisphosphonates

Oral bisphosphonates are generally considered the
Alendronic acid (10mg daily or 70mg weekly)
Ibandronic acid
Risedronate sodium (5mg daily or 35mg weekly)
Alendronic acid is generally given initially. Alternatives can be tried if the patient experiences side e
counsel patients before starting any bisphosphonate treatment.
Bisphosphonate counselling
Important points to cover when starting patients on bisphosphonates include\:
Oral bisphosphonates should always be taken on an empty stomach
Tablets should be swallowed whole with a whole glass of water in an upright position, and remain upright for 30
minutes after taking the medication
Potential side e
jaw (jaw pain, swelling and erythema)
A dental check-up is advised before starting bisphosphonates\: any dental work should be performed before or as
soon as possible after starting bisphosphonates.
For more information, see the Geeky Medics guide to bisphosphonate counselling.
If a patient cannot take oral bisphosphonates due to contraindications or experiences side e
should be considered. Further treatment options include zoledronic acid (5mg), an IV bisphosphonate that can be given
once per year.

Non-bisphosphonate treatment

There are several other specialist treatment options available, and di
sex, and BMD of the patient.
Denosumab
subcutaneous injection.
Denosumab is a monoclonal antibody that binds to RANKL, reducing osteoclast activity. It is given every six months as a
It can be given as the
cannot take bisphosphonates or teriparatide. It is generally considered a third-line treatment for glucocorticoid-induced
osteoporosis.
Calcium and vitamin D levels must be adequate before starting denosumab, and it carries the risk of osteonecrosis of the
jaw.
When stopping denosumab, there is a large increase in osteoclast activity (the rebound e
take a bisphosphonate for 1-2 years after stopping denosumab to prevent rapid bone loss and subsequent fractures.
Teriparatide
Teriparatide is a synthetic form of parathyroid hormone which increases new bone formation. It is given as a daily
subcutaneous injection and can generally be given for up to 2 years. A course of teriparatide can only be given once to a
patient and should not be repeated.
It is generally given as second-line treatment for patients at very high risk of fracture or who have continued to sustain
fractures or experience further decreases in BMD while on treatment for osteoporosis (bisphosphonates or denosumab).
Teriparatide is generally thought to be most e
As with denosumab, there is also a risk of a rebound e
transition to an alternative treatment, usually bisphosphonates or denosumab.
Other options
Other treatment options for osteoporosis include\:
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Raloxifene\: a selective oestrogen receptor modulator (SERM) that can be prescribed for postmenopausal women who
cannot tolerate other treatment options. It also reduces the risk of oestrogen receptor-positive breast cancer but has an
increased risk of venous thromboembolism (VTE).
Hormone-replacement therapy\: should be considered to prevent osteoporosis in women who undergo premature
menopause. However, it is important to remember that it does come with associated risks, such as increased VTE, and
patients who have a uterus should only use oestrogen in combination with progestins to prevent the increased risk of
endometrial cancer.
Romosozumab\: a recently approved monoclonal antibody that increases new bone formation and decreases bone
resorption. It is given as a monthly subcutaneous injection for 12 months. Once the treatment course is complete, the
patient will need to transition to an alternative therapy, such as bisphosphonate.

Treatment duration

When considering the duration of treatment, there is a need to balance the bene
adverse e
Factors that can be taken into consideration when deciding on the duration of treatment include\:
Which anti-osteoporosis treatment the patient is taking
The continuing presence of risk factors
Repeat BMD measurements\: DXA scans are generally repeated every 2-5 years
Measurement of bone turnover markers
Incidence of any new fragility fractures
For bisphosphonates, the initial length of treatment is typically
zoledronic acid.
At this point, the patient should be reassessed. If the patient falls below the treatment threshold (e.g. no further fractures,
BMD T-score > -2.5), a drug holiday can be considered, with another review after two years.
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Otherwise, the patient should continue treatment (up to 10 years for oral treatments and up to 6 years for IV). The following
patients are likely to require ongoing treatment\:
Age >75
Previous hip or vertebral fracture
Taking oral glucocorticoids (7.5mg prednisolone/day or equivalent)
One or more low-trauma fractures during treatment (once poor adherence is excluded)
BMD T-score \< -2.5
Bisphosphonate treatment can potentially continue under specialist guidance, but the patient should be aware of the
signi
Treatments such as denosumab and teriparatide should not be stopped without specialist input due to the risk of rebound
fractures.

Complications

The major complication of osteoporosis is fragility fractures\:
Hip fractures\: a signi
Rib fractures
Wrist fractures
Vertebral fractures\: a signi
experience signi
vertebral fracture.
Patients can develop chronic pain due to fractures, signi
Other treatment-related complications include\:
Atypical fractures due to bisphosphonate treatment
Osteonecrosis of the jaw due to bisphosphonate treatment
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Venous thromboembolism due to hormone replacement therapy or raloxifene treatment

References

BMJ Best Practice. Osteoporosis. Published 2023. Available from\: [LINK]
Patient.co.uk. Osteoporosis (Causes, Symptoms, and Treatment). Published 2021. Available from\: [LINK]
NICE CKS. Osteoporosis - prevention of fragility fractures. Published 2023. Available from\: [LINK]
FRAX. Fracture Risk Assessment Tool. Published 2011. Available from\: [LINK]
ClinRisk. QFracture 2016 risk calculator. Published 2016. Available from\: [LINK]
Patient.co.uk. Osteoporosis Risk Assessment and Primary Prevention. Published 2023. Available from\: [LINK]
National Osteoporosis Society. Vitamin D and Bone Health\: A Practical Clinical Guideline for Patient Management. Published
2018. Available from\: [LINK]
Royal Osteoporosis Society. Duration of Osteoporosis Treatment. Published 2018. Available from\: [LINK]

Image references

Figure 1. OpenStax College. Age and Bone Mass. License\: [CC BY]
Figure 2. Adapted by Geeky Medics. Case courtesy of Usman Bashir, Radiopaedia.org, rID\: 19198. License\: [CC BY-NC-SA]

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Contents

Introduction
Aetiology
Risk factors
Clinical features
Investigations
Diagnosis
Management
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