Osteoporosis

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:14/01/2026

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]

Risk Factors

Lifestyle-related risk factors:

Post-menopausal women
Advancing age

Inadequate physical activity
Low body weight
Smoking and excess alcohol consumption

Secondary causes:

Medications	Systemic steroids SSRIs PPIs Thiazolidinediones (e.g., pioglitazone) Heparin Hormone therapies Aromatase inhibitors (for ER+ve breast cancer) Androgen deprivation therapy (for prostate cancer) Anti-epileptic drugs
Medical conditions	Hyperparathyroidism and CKD Hyperthyroidism Hypercortisolism Hypogonadism RA 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 ( $\geq 7.5 mg/day$ 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 BMD 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 ( $\geq 7.5 mg/day$ 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) HRT – 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 $\geq 2$ vertebral fractures or BMD T-Score $\leq - 3.5$
Anabolic therapy should be followed by anti-resorptive treatment (bisphosphonate or denosumab) to maintain the gains in bone mineral density

Overview of Bone-Sparing Treatment

Category	Drug	MoA	Route of Administration	Schedule
Anti-Resorptive	Bisphosphonates (Alendronic acid, Risedronate, Zoledronic acid)	Inhibit osteoclast-mediated bone resorption	Oral (alendronic acid, risedronate) IV infusion (zoledronic acid)	Alendronic acid, risedronate: once weekly OR once daily Zoledronic acid: 5 mg infusion once yearly
	Denosumab	Monoclonal antibody against RANKL → inhibits osteoclast	Subcutaneous injection	6 monthly
	Raloxifene	Selective estrogen receptor modulator (agonist in bone → reduces resorption)	Oral	Once daily
	Strontium Ranelate (limited use due to safety concerns)	Dual action: stimulates osteoblast bone formation and reduces osteoclast activity	Oral	Once daily
Anabolic	Teriparatide	Recombinant parathyroid hormone → activates osteoblast	Subcutaneous injection	Daily for up to 24 months
Anabolic	Romosozumab	Monoclonal antibody against sclerostin → 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 BMD included
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 (‘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

References

Share Your Feedback Below Cancel reply

You must be logged in to post a comment.