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Fracture prediction, imaging and screening in osteoporosis


Osteoporosis is associated with increased fragility of bone and a subsequent increased risk of fracture. The diagnosis of osteoporosis is intimately linked with the imaging and quantification of bone and BMD. Scanning modalities, such as dual-energy X-ray absorptiometry or quantitative CT, have been developed and honed over the past half century to provide measures of BMD and bone microarchitecture for the purposes of clinical practice and research. Combined with fracture prediction tools such as Fracture Risk Assessment Tool (FRAX) (which use a combination of clinical risk factors for fracture to provide a measure of risk), these elements have led to a paradigm shift in the ability to diagnose osteoporosis and predict individuals who are at risk of fragility fracture. Despite these developments, a treatment gap exists between individuals who are at risk of osteoporotic fracture and those who are receiving therapy. In this Review, we summarize the epidemiology of osteoporosis, the history of scanning modalities, fracture prediction tools and future directions, including the most recent developments in prediction of fractures.

Key points

  • The WHO defines osteoporosis as a measurement of BMD that is at least 2.5 standard deviations less than the mean BMD for a 30-year-old man or woman.

  • Dual-energy X-ray absorptiometry provides a measure of BMD that can be used to diagnose osteoporosis.

  • Central and peripheral quantitative CT can be used to provide measures of bone microarchitecture within a research setting.

  • BMD, combined with clinical risk scores, including Fracture Risk Assessment Tool (FRAX), can be used to predict which individuals are at high risk of fracture.

  • A gap exists between individuals who are at risk of fracture and those who are receiving treatment and requires closing as a matter of paramount importance.

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The authors acknowledge the support of the Medical Research Council (UK), the National Institute for Health Research, the Dunhill Medical Trust, the Wellcome Trust, Arthritis Research UK, the National Osteoporosis Society (UK) and the International Osteoporosis Foundation.

Reviewer information

Nature Reviews Endocrinology thanks K. Brixen, S. Khosla, H. Kröger and other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

All authors contributed to researching data for the article, discussions of the content and writing the article. C.C., N.R.F., E.M.C., K.A.W., N.C.H. and E.M.D. contributed to the review and editing of the manuscript.

Competing interests

C.C. has received lecture fees and honoraria from Amgen, Danone, Eli Lilly, GlaxoSmithKline, Medtronic, Merck, Nestlé, Novartis, Pfizer, Roche, Servier, Shire, Takeda and UCB outside of the submitted work. N.C.H. has received consultancy and lecture fees and honoraria from Alliance for Better Bone Health, Amgen, Consilient Healthcare, Eli Lilly, Internis Pharma, MSD, Radius Health, Servier, Shire and UCB. E.M.C. has received lecture fees and travel support from Eli Lilly, Pfizer and UCB outside of the submitted work.

Correspondence to Cyrus Cooper.


Major osteoporotic fractures

Fractures attributable to osteoporosis including hip, forearm, humerus or clinically presenting vertebral fractures.


A fully humanized monoclonal antibody that binds to the receptor activator of RANK ligand, thus blocking the action of RANK ligand. It is delivered via subcutaneous injection as an anti-resorptive agent for the treatment of osteoporosis.

Thoracic kyphosis

An S-shaped deformity of the spine that can be precipitated by osteoporotic vertebral fractures.

Periosteal envelope

The membrane of connective tissue that surrounds bone. It has two layers, an outer fibrous layer and an inner layer, which plays a crucial role in osteogenesis.

Bone mineral apparent density

An estimated volumetric bone density. Volume is calculated from the dual-energy X-ray absorptiometry (DXA)-assessed bone area by assuming the vertebrae are either a cube or a cylinder. It is a method of reducing the size dependence of DXA measurements and is particularly useful in children.

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Fig. 1: Secular changes in hip fracture worldwide.
Fig. 2: The pitfalls of a fixed Fracture Risk Assessment Tool threshold for intervention.
Fig. 3: Participant flow for the SCOOP study.
Fig. 4: Cost-effectiveness acceptability curves from the SCOOP study.
Fig. 5: The effect of screening on hip fracture rates in the SCOOP study.