NICE clinical guideline [CG146] Osteoporosis: assessing the risk of fragility fracture. Last updated: Feb 2017.
NOGG Clinical guideline for the prevention and treatment of osteoporosis. Last updated: Dec 2024.
NICE BNF Treatment summaries. Osteoporosis.
Article Last Updated: 22 July 2025
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Background Information
Definition
Osteoporosis is defined by low bone mass and microarchitectural deterioration of bone tissue
Objectively, osteoporosis can be defined by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA):
T score less than -2.5: osteoporosis
T score between -1.5 and -2.5: osteopenia
T-score vs Z-score
DEXA scans report both a T-score and a Z-score.
Definitions:
T-score: number of standard deviations by which a patient’s BMD differs from the mean BMD of a healthy young adult reference population, typically aged 20–30 years.
Z-score: number of SDs by which a patient’s BMD differs from the mean BMD of an age-, sex-, and ethnicity-matched reference population.
Clinical use
T-score → Main score used to definitively diagnose osteoporosis in adults – especially useful in post-menopausal women and men ≥50.
Z-score → Cannot definitively diagnose osteoporosis in adults, but is indicated for premenopausal women, men <50, and children, to identify whether BMD is lower than expected for age and to prompt evaluation for secondary causes of osteoporosis if the Z-score is ≤-2.[Ref]
Including carbamazepine, phenytoin, phenobarbital, primidone, valproate, topiramate, gabapentin and levetiracetam
Medical conditions
Hyperparathyroidism and CKDChronic kidney disease
Hyperthyroidism
Hypercortisolism
Hypogonadism
RARheumatoid arthritis and other inflammatory arthropathies
Clinical Features
Osteoporosis on its own is asymptomatic.
Osteoporosis is only clinically noticeable, when a fragility fracture occurs.
Fragility fractures are fractures that occur from a low-energy mechanism
Fragility fractures should be suspected in adults (especially postmenopausal women and older men) who present with fractures after minimal trauma, such as a fall from standing height, or who have radiographic evidence of vertebral compression fractures, unexplained height loss, or kyphosis
They should also be considered in younger patients with risk factors for secondary osteoporosis, such as chronic glucocorticoid use, hypogonadism, or metabolic bone disorders
Assessment and Decision Algorithm
Disclaimer:
The structure of this section has been intentionally designed to support learning, revision, and exam-style application. At first glance, the layout may appear different from the way NICE and NOGG present their recommendations, as the information has been reorganised to improve clarity and usability.
For exam purposes, it is important to recognise the following few points:
BMD <-2.5 (i.e. osteoporosis) → bone-sparing treatment is indicated
One may notice that this is NOT included in the guidelines / section below, as BMD <-2.5 alone is NOT an indication to treat
Once BMD is available, it should be used to recalculate the 10-year risk of fragility fracture and plot it against the NOGG intervention threshold to guide management
However, in exams one would be expected to know that an osteoporotic BMD (<-2.5) would necessitate bone-sparing treatment (as it will almost certainly put you above the treatment threshold)
Following a fragility fracture (in post-menopausal women, and men >50 y/o) → start bone-sparing treatment immediately
Patients starting high-dose oral glucocorticoids (≥7.5 mg/day prednisolone or equivalent over 3 months) → start bone-sparing treatment at the same time as glucocorticoid therapy (without awaiting DEXA scan or calculating FRAX)
If all of the above do NOT apply → calculate the 10-year fragility fracture risk (with FRAX / QFracture) to inform management (i.e. the standard pathway)
Step 1 – Exclude Alternative Causes
Always exclude the following first:
Secondary causes of osteoporosis (via routine bloods)
Non-osteoporotic causes of fracture (e.g. Paget’s disease, bone metastases, multiple myeloma)
Step 2 – Assess Need For Bone-Sparing Treatment
Standard Pathway (Most Patients)
This applies to ANY of the following:
ALL women >65 y/o and men >75 y/o
Women <65 y/o and men <75 y/o with risk factors
<50 y/o only with major risk factors (previous fragility fracture / untreated premature menopause / current or frequent use of oral steroids)
The pathway is as follows:
Calculate the 10-year risk of fragility fracture
Both FRAX (more commonly used in practice) and QFracture tools are recommended
At this point, the 10-year risk of fragility fracture is calculated solely on clinical factors (no BMDBone mineral density results)
Plot the 10-year risk (%) against age into the NOGG intervention and risk thresholds (see image below)
Subsequent actions depend on the risk category
Risk
Subsequent action
Low risk
DEXA and bone-sparing drugs are not indicated
Advice on conservative management
Intermediate risk
Perform DEXA
Once BMD is available → recalculate FRAX score and compare against intervention threshold
High risk
Start bone-sparing drugs immediately, and
Perform DEXA (but do not delay treatment whilst awaiting DEXA results)
Very high risk
Start bone-sparing drugs, and
Consider specialist referral
Exceptions (The High-Risk Population)
There are 3 main exceptions:
Following a fragility fracture (in post-menopausal women, and men >50 y/o)
Start bone-sparing treatment promptly
Fracture risk assessment (informed by DEXA) is performed to guide the choice of drug treatment, not primarily to determine the necessity of intervention
Starting high-dose oral glucocorticoids (≥7.5 mg/day prednisolone or equivalent over 3 months)
Start bone-sparing treatment at the same time as glucocorticoid therapy
Fracture risk assessment (informed by DEXA) should be performed, but should NOT delay initiating bone-sparing treatment
Starting treatment that may have a rapid adverse effect on bone density
Notable treatments include androgen deprivation therapy for prostate cancer and aromatase inhibitors for breast cancer
Baseline fracture risk assessment (including DEXA) is necessary
Management
Conservative / General Management
The following should be given to ALL patients (even those with low fracture risk):
Lifestyle advice
Healthy, balanced diet rich in calcium and vitamin D
Weight-bearing and muscle-strengthening exercise
Smoking cessation and reducing alcohol intake
Assess and address the risk of falls
Calcium intake
Dietary sources are preferred, do not routinely give supplements
Only give supplements if intake is <700mg/day
Vitamin D intake
Give supplements if there are insufficiencies or risk factors (e.g. housebound)
Bone Sparing Treatment
Choice of Bone-Sparing Treatment
BNF-oriented recommendations:
1st line
Oral bisphosphonates
Preferred: alendronic acid or risedronate sodium
Alternative: ibandronic acid
2nd line (usually if oral bisphosphonates are contraindicated or not tolerated)
Parenteral bisphosphonates (e.g. IV zoledronic acid)
Denosumab injection
3rd line (specialist only)
Raloxifene – for post-menopausal women (not approved for use in men)
HRTHormone replacement therapy– generally restricted to younger post-menopausal women with menopausal symptoms + at high risk of fractures
Anabolic agents – only reserved for very high-risk patients (see green box)
Teriparatide
Romosozumab
Strontium ranelate – rarely used due to concerns with its safety profile
It is worth noting that NOGG recommends annual IV zoledronic acid infusion as 1st line therapy in patients with osteoporosis following a hip fracture
Anabolic agents (teriparatide or romosozumab) may be considered for very high-risk patients; they are typically initiated by specialists
Definition of very high-risk patients: recent vertebral fracture (within the last 2 years) or ≥2 vertebral fractures or BMD T-Score ≤−3.5
Anabolic therapy should be followed by anti-resorptive treatment (bisphosphonate or denosumab) to maintain the gains in bone mineral density
Sclerostin is a glycoprotein primarily produced by mature osteocytes in bone tissue. It acts as a potent inhibitor of bone formation.
→ increases bone formation and reduces resorption
Subcutaneous injection
Once monthly for 12 months
Information on Specific Bone-Sparing Treatments
Information on bisphosphonates is by far the most important and high-yield one to learn. Denosumab is also included as it’s safety profile is similar to bisphosphonates, and is a commonly used 2nd line bone-sparing treatment.
Bisphosphonates Therapy
Administration Instructions
The following applies only to oral bisphosphonates:
The tablet should be taken after an overnight fast
Take the tablet at least 30 min before the first food or drink or any other medications / supplementation (including calcium and vitamin D)
Swallow the tablet with a glass of plain water, while the patient is sitting or standing in an upright position
Do NOT lie down (stay in sitting or standing position) for 30-60 min after taking the tablet
Alendronate and risedronate: 30 min
Ibandronate: 60 min
Adverse Effects and Complications
Common
With oral tablets:
GI effects
Oesophagitis (or rare ulceration)
Heartburn / reflux
Epigastric pain
MSK (bone / joint / muscle pain)
IV drug form mainly causes an acute phase reaction 24-72 hours after the infusion:
Fever
Myalgia and arthralgia
Flu-like symptoms
Fatigue
Rare but serious (both oral and IV drug forms)
Osteonecrosis of the jaw (patients should be advised to maintain good oral hygiene, receive routine dental check-ups, and immediately report any oral symptoms like dental mobility, pain or swelling)
Atypical femoral fractures (often bilateral, affecting the subtrochanteric and diaphyseal regions of the femoral shaft) (prodromal pain is typically felt before the actual fracture occurs)
Caution and Contraindications
There are 2 main things to consider before starting bisphosphonates:
Hypocalcaemia
Pre-existing hypocalcaemia and vitamin D deficiency must be investigated and treated BEFORE starting bisphosphonates (esp. IV bisphosphonates)
Adequate dietary calcium and vitamin D intake must be ensured (if insufficient, give supplements if appropriate)
Rationale: Bisphosphonates inhibit osteoclast-mediated bone resorption, which ↓ release of calcium from bone into the circulation. If bisphosphonates are started in someone with low baseline calcium (or vitamin D), this can precipitate hypocalcaemia.
Renal impairment
Assess renal function before starting bisphosphonates:
Zoledronate: contraindicated if eGFR ≤35
Risedronate: contraindicated if eGFR ≤30
Alendronate: cautioned against if eGFR ≤35
Ibandronate: cautioned against if GFR ≤30
Oesophagus abnormalities
Examples include:
Oesophageal stricture
Achalasia and other oesophageal motility disorders
Inability to stand or sit upright for at least 30-60 min
Examples include:
Extremely frail patients
Bed-bound patients
Follow Up
Initial Follow Up
Check treatment tolerance after 3-4 months + ask about adverse effects
Check adherence after 12 months of treatment
Long-Term Following Up (Continuing or Pausing Treatment)
Reassess the need for continuing treatment after:
5 years of oral bisphosphonate therapy, or
3 years of IV bisphosphonate therapy)
Reassessment procedure:
Perform FRAX (or QFracture) with BMDBone mineral densityincluded
Plot the 10-year risk (%) against age into the NOGG intervention and risk thresholds
Subsequent action
Lower risk (i.e. below the intervention threshold) → consider treatment pause for 1.5-3 years
After the temporary treatment pause, reassess the patient's fracture risk (with FRAX) to determine if drug therapy should be restarted:
Risedronate and Ibandronate: Reassess fracture risk after 18 months.
Alendronate: Reassess fracture risk after 2 years
Zoledronate: Reassess fracture risk after 3 years
(‘drug holiday’) to reduce the risk of atypical fractures and osteonecrosis of the jaw (which are associated with long-term bisphosphonate therapy)
Above the intervention threshold → continue drug treatment
Exception: high-risk patients require treatment continuation for ≥10 years (oral bisphosphonates) or ≥6 years (IV bisphosphonates), irrespective of reassessment.
High-risk patients are defined as ANY of the following:
≥70 y/o at the start of bisphosphonate treatment
A previous hip or vertebral fracture
Experienced a further fragility fracture during the initial 5 years of treatment
On high-dose oral glucocorticoids (≥7.5 mg prednisolone/day or equivalent)
In these patients, treatment is typically continued until oral steroids are stopped (risk reassessment done thereafter)
Denosumab Therapy
Adverse Effects and Complications
Similar to bisphosphonates, denosumab is also associated with the following rare but serious complications:
Osteonecrosis of the jaw
Atypical femoral fracture
Long-Term Follow-Up and Stopping Denosumab
Key considerations:
All patients should have calcium checked prior to each dose
Denosumab can cause / worsen hypocalcaemia
Avoid unplanned cessation of denosumab
After denosumab is stopped, it causes a rebound in bone mineral density reduction → increased risk of multiple vertebral fractures
If denosumab therapy is stopped, an IV infusion of zoledronate is recommended 6 months after the last injection of denosumab
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