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This guideline was prepared in 2021 with the support of the societies listed to provide guidance on prevention and treatment of osteoporosis with the overarching aim of reducing fragility fracture risk, and updated in 2024, replacing previous National Osteoporosis Guideline Group (NOGG) guidance [–]. The scope of the guideline is to review the assessment and diagnosis of osteoporosis, the therapeutic interventions available and the approaches for the prevention of fragility fractures, in postmenopausal women, and in men aged 50 years or older. This focus is chosen as fragility fractures and osteoporosis are uncommon in premenopausal women and men younger than 50 years, and therefore, when these occur, patients need thorough investigation for secondary causes of osteoporosis, and careful consideration of treatment options. Specialist referral is usually required.

This NOGG guidance has appraised the current evidence base to inform these updated recommendations. The aim of the guideline is to provide clinically appropriate recommendations that integrate available evidence on clinical efficacy, effectiveness, and safety. This contrasts with, but complements, the remit of the National Institute for Health and Care Excellence (NICE), which focuses principally on establishing criteria for cost effectiveness. Cost effectiveness analyses are generally supportive for treatment guided by clinical effectiveness thresholds, rather than defining intervention thresholds per se []. The guideline has been prepared by a writing group and has been approved after consultation with stakeholders (Appendix 1).

The guideline is intended for all healthcare professionals involved in the prevention and treatment of osteoporosis and fragility fractures. This includes primary care practitioners, allied health professionals and relevant specialists in secondary care including rheumatologists, gerontologists, gynaecologists, endocrinologists, clinical biochemists, and orthopaedic surgeons. The guideline includes recommendations for training in osteoporosis care. The guideline is supported by a series of Frequently Asked Questions (FAQs) available on the NOGG website ( https://www.nogg.org.uk/ ). The conclusions and recommendations in the document are systematically graded, according to the quality of information available, to indicate the level of evidence on which recommendations are based. The grading methodology is summarised in Appendix 2. Where available, systematic reviews, meta-analyses and randomised controlled trials have been used to provide the evidence base. The evidence base comprises systematic reviews and meta-analyses identified in PubMed from July 2016 to Sept 2020, with additional evidence added based on expertise and knowledge of the advances in the field, from within the group. The quality of systematic reviews and meta-analyses used in the formulation of recommendations was assessed using AMSTAR2 (Appendix 3). The updates to recommendations in this guideline were agreed by the National Osteoporosis Guideline Development Group.

This guideline provides a framework from which local management protocols should be developed to provide advice for healthcare professionals. Implementation of this guideline should be audited at a local and national level. The recommendations in the guideline should be used to aid management decisions but do not replace the need for clinical judgment in the care of individual patients in clinical practice.

This revised guideline now includes clarification that quantitative ultrasound, IBEX bone health, and Radiofrequency Echographic Multi Spectrometry are not recommended for the diagnosis of osteoporosis; advice on the use of FRAX in non-white ethnic groups and those who have migrated to the UK; advice on FRAX adjustment when assessing patients with Parkinson’s disease; addition of clinical risk factors that increase fracture risk, specifically lower limb amputation and adult learning disabilities: e.g., Down’s Syndrome; the definition of very high fracture risk has been clarified; the intervention threshold has been defined and the associated NOGG graphs updated; vaping with e-cigarettes has been added as a possible risk factor for fragility fracture; hormone replacement therapy (HRT) is now recommended as a first-line treatment option in younger postmenopausal women (age ≤ 60 years) with high fracture risk and low baseline risk for adverse malignant and thromboembolic events; recommendations pertaining to the use of abaloparatide have been added; considerations when choosing which anabolic agent to use have been outlined; and additional training resources have been added.

The conceptual definition of osteoporosis was made by the World Health Organization (WHO) in 1994 as a ‘progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture’ []. Since microarchitectural deterioration could not be measured clinically, the operational description was based on a bone mineral density (BMD) T -score of ≤ −2.5. Over the years this was adopted as a clinical definition; however, the limitations of focusing on a BMD-based definition alone have since become clear. BMD is now viewed as one, albeit very important, risk factor to be considered when assessing fracture risk, which is now viewed as the principal necessity.

The clinical significance of osteoporosis lies in the fractures that arise. In adults, approximately one in two women and one in five men will sustain one or more fragility fractures (a low trauma fracture sustained from a fall from standing height or less) in their lifetime []. In the UK, the prevalence of femoral neck BMD T -score ≤ −2.5, in those aged 50 years and older, is 6.8% in men and 21.8% in women []. However, the majority of people who sustain a fragility fracture will have a femoral neck BMD T -score above −2.5, reflecting the contribution of many other factors, besides BMD, to fracture risk [–]. Fall-related risk factors add significantly to fracture risk and often overlap with risk factors for osteoporosis, hence the need for integrated fall and fracture services.

Currently in the UK, approximately 549,000 new fragility fractures occur each year, including 105,000 hip fractures, 86,000 vertebral fractures, and 358,000 other fractures (i.e., fractures of the pelvis, ribs, humerus, forearm, tibia, fibula, clavicle, scapula, sternum, and other femoral fractures); 33% are sustained by men [, , ]. Such fractures cause severe pain, disability, reduction in quality of life, and in some cases increased mortality [, ]. In the UK, fragility fractures are estimated to account for 579,722 DALYs (Disability Adjusted Life Years) lost, largely driven by years lived with disability. This equates to 24 DALYs per 1000 people aged over 50 years, which is comparable to the DALYs lost from dementia []. Costs of fragility fractures to the National Health Service (NHS) exceed £4.7 billion per annum, of which £2.6 billion is directly incurred after an incident fracture (£1.1 billion for hip fractures alone []), with more than £1.7 billion attributable to institutional care costs post-fracture (estimated for 2017) []. Total direct costs for 2019 were £5.4 billion, accounting for 2.4% of healthcare spending [].

Common sites of fragility fracture include the vertebral bodies, hip, distal radius, proximal humerus, and pelvis. Hip fracture is the most common reason for emergency anaesthesia and surgery in older people. It is also the most common cause of death following a fall. After hip fracture, the mean hospital length of stay is 20 days, accounting for half a million hospital bed days used each year, with 3600 hospital beds (3159 in England, 325 in Wales and 133 in Northern Ireland) occupied at any one time by patients recovering from hip fracture [, ]. Loss of independence is common following a hip fracture, with only 52% living in their own home after 120 days [] and 26% will die within 12 months of their fracture []. Most major osteoporotic fractures are associated with reduced relative survival, part causally related and part due to associated co-morbidity [–].

In the UK, fracture rates vary by geographic location, race and levels of socioeconomic deprivation [–]. As in many higher income countries, age- and sex-adjusted fracture rates appear relatively stable, although increases in hip fractures amongst men in the UK have been reported [, ]. Changes in vertebral fracture rates potentially reflect secular alterations to reporting of cases. Importantly, the ageing of the UK population is predicted to give rise to a 19.6% increase in the number of fragility fractures by 2030 if changes are not made to current practice [].

A FRAX assessment should be performed in any postmenopausal woman or man age ≥ 50 years, with a clinical risk factor for fragility fracture to guide BMD measurement and prompt timely referral and/or drug treatment where indicated (Strong recommendation). When using FRAX to calculate the probability of fracture, clinical judgement is needed when clinical risk exceeds those factors able to be entered into FRAX (Strong recommendation). Arithmetic adjustments to FRAX probabilities of major osteoporotic fracture (MOF: clinical spine, hip, forearm or humerus) and hip fracture (see Table ) can be used in clinical practice to take account of additional clinical risk factors, such as high dose glucocorticoid use, discordantly low lumbar spine BMD, type 2 diabetes, and a history of falls (Conditional recommendation). Vertebral fracture assessment (VFA) is indicated in postmenopausal women and men age ≥ 50 years if there is a history of ≥ 4 cm height loss, kyphosis, recent or current long-term oral glucocorticoid therapy, a BMD T -score ≤ − 2.5 at either the spine or hip, or in cases of acute onset back pain with risk factors for osteoporosis (Strong recommendation). T -scores in men and women derived from femoral neck BMD should use normative values for BMD derived from young healthy women from NHANES III (Strong recommendation).

DXA scan results should be reported within 3 weeks of the scan, by healthcare professionals with specific training in DXA interpretation, and in accordance with national and international reporting standards (Strong recommendation). Patients with osteoporosis and/or a fragility fracture should be investigated for underlying causes, including the need for routine blood tests (Strong recommendation). The use of quantitative ultrasound, IBEX bone health, and Radiofrequency Echographic Multi-Spectrometry are not recommended for the diagnosis of osteoporosis (Strong recommendation). QCT-measured femoral neck areal BMD in postmenopausal women and men aged ≥ 50 years can be used for opportunistic diagnosis of osteoporosis and to inform individual treatment decisions using FRAX (Conditional recommendation). Computer Aided Diagnostics (CAD) may be considered to improve standard reporting of CTs performed on postmenopausal women and men aged ≥ 50 years to improve opportunistic identification of vertebral fractures (Conditional recommendation).

The risk of fracture increases progressively with decreasing bone mineral density (BMD). Systematic reviews and meta-analyses of observational population-based studies using absorptiometric techniques indicate that the risk of fracture increases approximately two-fold for each standard deviation (SD) decrease in BMD [, ]; (Evidence level Ia). The gradient of fracture risk varies according to the site and technique used, the person’s age, and the fracture type []; (Evidence level Ia). The predictive value of BMD for hip fracture is at least as good as that of blood pressure for stroke []; (Evidence level IV).

The WHO and the International Osteoporosis Foundation (IOF) recommend that the reference technology for the measurement of BMD is dual-energy X-ray absorptiometry (DXA) applied to the femoral neck, because of its higher predictive value for fracture [, ]; (Evidence level Ia). DXA measurements of femoral neck BMD are used in FRAX®. The spine is not always a reliable site for risk assessment or for the diagnosis of osteoporosis in older people because of the high prevalence of degenerative changes, which artefactually increase the BMD value. However, a result in an older person showing low BMD is almost always valid and clinically useful, particularly in those people with disproportionately low spine BMD compared to the hip, but may not always relate to osteoporosis (e.g. osteomalacia can also cause low BMD). At the same DXA-measured femoral neck BMD, men and women are at approximately the same fracture risk [, ]; (Evidence level IIa). Therefore, the recommended reference range, from which femoral neck and total hip T -scores are calculated for men, women and transgender individuals in the US, is that derived from the NHANES III survey for white women aged 20 to 29 years [, ]. The reference ranges, from which lumbar spine and distal forearm T -scores are calculated, for both men and women of all ethnicities, are usually those of the manufacturer of the DXA scanner [].

Osteoporosis can be diagnosed on the basis of the BMD T -score measured at the total hip, femoral neck, or lumbar spine. However, fracture risk prediction is not improved by the use of measurements from multiple sites [, ]; (Evidence level IIa). Where hip BMD measurement is not possible for technical reasons, or if the spine is differentially affected, then spine BMD measurements can be used for diagnosis. A diagnosis of osteoporosis can be made based on distal forearm (1/3 radius) T -score if neither spine nor hip can be reliably measured or interpreted, or if a patient exceeds the weight limit for the DXA table []; (Evidence level IV). Serial BMD measurement can be used to monitor response to treatment []. Lumbar spine BMD shows the largest treatment-related changes and is the preferred site, although if spinal degenerative changes are marked, BMD at the hip is a better site for monitoring. The validity of BMD measurements depends on good quality control and national (Royal Osteoporosis Society) and international (International Society for Clinical Densitometry) bodies have published standards for the reporting of DXA scans [, ]. Derivation of DXA-measured BMD Z-Scores, which compare a BMD measure with average BMD of people of the same age, sex, and ethnicity, is recommended in men < 50 years and pre-menopausal women []. A low Z-Score can indicate the need for further investigation (see Table ).

QCT-measured femoral neck areal BMD predicts osteoporotic fractures in men and women and is equivalent to DXA-derived areal BMD [–]. Femoral neck and total hip T -scores calculated from two-dimensional projections of quantitative computed tomography (QCT) data are equivalent to the corresponding DXA-derived T -scores. Thus, femoral neck CT X-ray absorptiometry (CTXA) BMD measurements can be included in FRAX [, –]; (Evidence level IIa). Other techniques for assessing skeletal BMD, including quantitative ultrasound, have been less well validated than absorptiometric techniques.

The performance characteristics of BMD assessment can be improved by the concurrent consideration of clinical risk factors that operate independently of BMD. Of particular importance is age, which contributes to risk independently of BMD [, ]; (Evidence level Ia). Additional clinical risk factors have been identified that provide information on fracture risk independently of both age and BMD: i. Low body mass index (BMI) is a significant risk factor for hip fracture, but the value of BMI in predicting other fractures is very much diminished when adjusted for BMD []; (Evidence level Ia). A history of a prior fracture, particularly if sustained from low trauma and at a site characteristic for osteoporosis, is an important risk factor for further fracture []. The risks are in part independent of BMD []. Fracture risk is approximately doubled in the presence of a prior fracture, including asymptomatic moderate or severe (Grade 2 or 3) morphometric vertebral fractures [, ]; (Evidence level Ia). The increase in risk is even more marked for more than one vertebral fracture. After a fracture, the risk of subsequent fracture is highest in the immediate post-fracture interval (imminent risk) with more than one-third of subsequent fractures over a ten-year time frame occurring within the first year [, ]; (Evidence level Ic).

A parental history of hip fracture is a significant risk factor that is largely independent of BMD []; (Evidence level Ia). Smoking is a risk factor that is in part dependent on BMD []; (Evidence level Ia). Oral glucocorticoid therapy increases fracture risk in a dose-dependent manner. The fracture risk conferred by the use of glucocorticoids is, however, not solely dependent upon bone loss and BMD-independent risks have been identified [, ]; (Evidence level Ia). Alcohol intake shows a dose-dependent relationship with fracture risk. Where alcohol intake is on average two units or less daily, no increase in risk has been identified. Intakes of 3 or more units daily are associated with a dose-dependent increase in fracture risk []; (Evidence level Ia). There are many secondary causes of osteoporosis (e.g., inflammatory bowel disease, endocrine disorders), but in most instances it is uncertain to what extent an increase in fracture risk is dependent on low BMD or other factors such as the use of glucocorticoids. By contrast, rheumatoid arthritis increases fracture risk independently of BMD and the use of glucocorticoids []; (Evidence level Ia).

Diabetes mellitus (both type 1 and type 2) is associated with an increase in risk of hip and non-vertebral fracture. In type 2 diabetes, a longer duration of disease and insulin use are associated with an increased risk [, ]; (Evidence level Ia), which is partly independent of BMD [, ]. The use of combined clinical risk factors alone to predict fracture risk performs very similarly to that of BMD alone []. The use of clinical risk factors with the addition of BMD is optimal, but BMD measurement can be targeted to those close to the threshold of low/high risk or close to the threshold of high/very high risk. There are many additional clinical risk factors for fracture not included in FRAX, including risks that either act solely by reducing BMD or have been less well validated or identify a risk that may not be amenable to particular treatments [, ]. Liability to falls is an example of the latter, where the risk of fracture is high, and treatment with drugs affecting bone metabolism alone may not fully address this risk []. In addition to glucocorticoids, several medications are known to increase hip fracture risk, including thyroid hormone excess, aromatase inhibitors for the treatment of breast cancer, and androgen deprivation for the treatment of prostate cancer [–]; (Evidence level Ia). Thiazolidinediones, used in the treatment of type 2 diabetes, also increase fracture risk [, ].

Several other drugs have been associated with increased fracture risk including antidepressants, antiparkinsonian drugs, antipsychotic drugs, anxiolytic drugs, benzodiazepines, sedatives, H2 receptor antagonists, and proton pump inhibitors [–]. The extent to which fracture risk is mediated by low BMD, fall risks, or other factors, or indeed is definitely causal in each case, is not known and therefore no specific recommendation is made regarding cessation. The impact of sex steroids on bone health in transgender individuals is unclear []. Biochemical indices of skeletal turnover have the potential to aid risk assessment but probably play a more immediate role in the monitoring of treatment [–]; (Evidence level Ia).

The IOF and the WHO recommend that the risk of fracture is expressed as an absolute risk, i.e., probability over a ten-year interval []. The absolute risk of fracture depends upon age and life expectancy as well as the current relative risk. The period of 10 years covers the likely initial duration of treatment and the benefits that may continue if treatment is stopped. Shorter time horizons do not aid the categorisation of risk [, ]. Where life expectancy is less than 10 years, FRAX provides the remaining lifetime probability of fracture. Algorithms that integrate the weight of clinical risk factors for fracture risk, with or without information on BMD, were developed in 2008 by the then WHO Collaborating Centre for Metabolic Bone Diseases at Sheffield. The FRAX tool ( https://www.fraxplus.org/calculation-tool/ ) computes the 10-year probability of hip fracture and/or of major osteoporotic fracture. A major osteoporotic fracture is a clinical spine, hip, forearm or humerus fracture. The tool has been externally validated in independent cohorts [, ]; (Evidence level Ia).

QFracture is based on a UK prospective open cohort study of routinely collected data from general practices that takes into account numerous clinical risk factors and estimates the 1 to 10 year cumulative incidence of hip and/or major osteoporotic fracture ( http://www.qfracture.org []). The NICE has recommended the use of fracture risk assessment tools (FRAX or QFracture) in the assessment of patients []. Since FRAX and QFracture yield different outputs (probability of fracture accounting for mortality risk in the case of FRAX, and a cumulative risk of fracture in the case of QFracture), the two calculators cannot be used interchangeably. In addition, BMD cannot be incorporated into QFracture estimations. Finally, the NOGG intervention thresholds, recommended by NICE Quality Standards, are based on FRAX probability and thus cannot be used with fracture risk derived from QFracture or other calculators [, ].

Whilst QFracture takes account of several ethnicities, the FRAX tool takes a different approach. Importantly, the UK FRAX is calibrated to a majority white population, with a small minority of other ethnic groups included, so that the generated probabilities reflect a predominantly white population. When using FRAX in individuals who have moved from another country to the UK, regardless of ethnicity, the use of the FRAX model for their country of birth, if it exists, is appropriate since individuals retain the risk characteristics of their country of birth [] []. While fracture risk in second and subsequent generations might move towards that in the general UK population, the accuracy of this assumption and speed of transition is not known for either QFracture or FRAX [].

The input into FRAX includes, with age and sex, BMD independent clinical risk factors including: Body mass index (calculated from weight and height in kg/m 2 ), previous fragility fracture (including morphometric vertebral fracture), parental history of hip fracture, current glucocorticoid treatment (any dose, by mouth for 3 months or more), current smoking, alcohol intake of 3 or more units daily, rheumatoid arthritis, secondary causes of osteoporosis (including: type 1 diabetes, long-standing untreated hyperthyroidism, untreated hypogonadism/premature menopause (< 45 years), chronic malnutrition/malabsorption, chronic liver disease, non-dialysis chronic renal failure (i.e., CKD 3a – 5). Femoral neck BMD is an optional input. The listed secondary causes are conservatively assumed to be mediated through low BMD and carry no weight when femoral neck BMD is entered into FRAX. Femoral neck BMD is an optional input. The listed secondary causes are conservatively assumed to be mediated through low BMD and carry no weight when femoral neck BMD is entered into FRAX.

FRAX assessment takes no account of prior osteoporosis drug treatment, or of the dose of several clinical risk factors. For example, a history of two prior fractures carries a higher risk than a single prior fracture. A prior clinical vertebral fracture carries an approximately two-fold higher risk than other prior fracture types. Dose responses are also evident for glucocorticoid use and are partially addressed in the NOGG guideline. Since it is not possible to model all such scenarios within the FRAX algorithm, clinical judgement is needed to interpret FRAX outputs.