Osteoporosis
geekymedics.com/osteoporosis
Dr Jess Speller August 3, 2023
Key points
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.
1/13
Investigations: FRAX or QFracture score to assess fracture risk, DXA scan to
measure BMD, X-rays for fractures, and relevant blood tests (bone profile, vitamin D,
PTH, thyroid function, testosterone).
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
modifiable risk factors, regular follow-up and monitoring.
Complications: fragility fractures (hip, rib, wrist, vertebral), chronic pain, atypical
fractures, osteonecrosis of the jaw, venous thromboembolism.
Introduction
Osteoporosis means “porous bone“. 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.
🔥
Want discounted access to all Geeky Medics products, including our medicine flashcard
collection? Check out our bundles to save money and supercharge your learning
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 affects all of the
bones in the body and leads to reduced bone strength due to a reduction in bone mass
and mineral density.
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.
2/13
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 deficiency of 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
Low BMI (<18.5kg/m2)
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 significantly at
doses > 7.5mg prednisolone/day
Selective serotonin reuptake inhibitors (SSRIs)
Proton pump inhibitors (PPIs)
3/13
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.
Clinical features
History
Osteoporosis remains asymptomatic until a fracture occurs, meaning the disease can
become established before it is diagnosed.
A fragility fracture is defined as a low-impact fracture from a standing height or less. The
most common sites of fragility fracture are:3
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.
4/13
Figure 2. An osteoporotic vertebral wedge fracture
of T12.
Clinical examination
Osteoporosis itself will generally not cause specific findings on clinical examination. Patients
with vertebral fractures may 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:4
Age
Sex
BMI
5/13
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:3
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
significant risk factors, for example, 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.5
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.6
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:6
Low risk: measuring bone mineral density (BMD) is not required; give lifestyle advice
and reassurance and monitor risk factors
6/13
Intermediate risk: arrange a dual-energy x-ray absorptiometry (DXA) scan and
recalculate the risk score with BMD taken into account
High risk: offer treatment, and arrange a DXA scan to measure BMD to establish a
baseline and guide treatment
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 different scores:
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 profile has
changed significantly. They can also 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 differential diagnoses.
X-Rays are useful for detecting fragility fractures, particularly vertebral fractures, or can show
osteopenia.1
Relevant laboratory investigations include:
Bone profile: usually normal in osteoporosis, raised ALP/low phosphate can indicate
osteomalacia
Urea & electrolytes: screening for chronic kidney disease as a cause of osteoporosis
7/13
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 identified on a DXA scan.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 offered for those diagnosed with osteoporosis, and
various medications are available depending on the patient’s risk factors, history, and
personal preference.
It is also important to address any modifiable risk factors (e.g., offering hormone
replacement therapy for women with premature menopause).
Lifestyle advice
Lifestyle modifications which can increase BMD and decrease fracture risk include:
Regular exercise, particularly strength-based and weight-bearing exercise:
swimming and cycling do not improve bone density
8/13
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 effect on bone metabolism.
Vitamin D is especially important as many people in the northern hemisphere are deficient.
Patients with vitamin D levels. below 50nmol/L should be offered treatment:7
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).
Bisphosphonates
Oral bisphosphonates are generally considered the first-line treatment for patients with
osteoporosis:
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 effects. It is important to 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 effects include gastrointestinal upset (dyspepsia, reflux), atypical
fractures and osteonecrosis of the jaw (jaw pain, swelling and erythema)
9/13
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
effects, then a specialist referral 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 different options will be
available depending on the age, sex, and BMD of the patient.
Denosumab
Denosumab is a monoclonal antibody that binds to RANKL, reducing osteoclast activity. It
is given every six months as a subcutaneous injection.
It can be given as the first-line treatment for postmenopausal women who cannot take
bisphosphonates and in men who 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
effect). This means patients must 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 effective for those with existing vertebral fractures.
As with denosumab, there is also a risk of a rebound effect when stopping teriparatide,
meaning that patients will need to transition to an alternative treatment, usually
bisphosphonates or denosumab.
10/13
Other options
Other treatment options for osteoporosis include:
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 benefits of
treatment with the potential adverse effects, particularly the risk of atypical fractures.
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 five years for oral
bisphosphonates and three years for IV 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.8
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)
11/13
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 significantly increased risk of atypical fractures.
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 significant cause of disability and mortality, only 30% of patients fully
recover
Rib fractures
Wrist fractures
Vertebral fractures: a significant cause of long-term pain and disability, 80% of patients
with vertebral fractures still experience significant pain after 12 months. One vertebral
fracture also significantly increases the risk of subsequent vertebral fracture.
Patients can develop chronic pain due to fractures, significantly impacting their quality of
life.
Other treatment-related complications include:
Atypical fractures due to bisphosphonate treatment
Osteonecrosis of the jaw due to bisphosphonate treatment
Venous thromboembolism due to hormone replacement therapy or raloxifene treatment
Editor
Dr Chris Jefferies
References
1. BMJ Best Practice. Osteoporosis. Published 2023. Available from: [LINK]
2. Patient.co.uk. Osteoporosis (Causes, Symptoms, and Treatment). Published 2021.
Available from: [LINK]
3. NICE CKS. Osteoporosis – prevention of fragility fractures. Published 2023. Available
from: [LINK]
4. FRAX. Fracture Risk Assessment Tool. Published 2011. Available from: [LINK]
12/13
5. ClinRisk. QFracture 2016 risk calculator. Published 2016. Available from: [LINK]
6. Patient.co.uk. Osteoporosis Risk Assessment and Primary Prevention. Published 2023.
Available from: [LINK]
7. National Osteoporosis Society. Vitamin D and Bone Health: A Practical Clinical
Guideline for Patient Management. Published 2018. Available from: [LINK]
8. 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]
Copyright © Geeky Medics
13/13
