Elsevier

The Lancet

Volume 393, Issue 10169, 26 January–1 February 2019, Pages 364-376
The Lancet

Seminar
Osteoporosis

https://doi.org/10.1016/S0140-6736(18)32112-3Get rights and content

Summary

Fractures resulting from osteoporosis become increasingly common in women after age 55 years and men after age 65 years, resulting in substantial bone-associated morbidities, and increased mortality and health-care costs. Research advances have led to a more accurate assessment of fracture risk and have increased the range of therapeutic options available to prevent fractures. Fracture risk algorithms that combine clinical risk factors and bone mineral density are now widely used in clinical practice to target high-risk individuals for treatment. The discovery of key pathways regulating bone resorption and formation has identified new approaches to treatment with distinctive mechanisms of action. Osteoporosis is a chronic condition and long-term, sometimes lifelong, management is required. In individuals at high risk of fracture, the benefit versus risk profile is likely to be favourable for up to 10 years of treatment with bisphosphonates or denosumab. In people at a very high or imminent risk of fracture, therapy with teriparatide or abaloparatide should be considered; however, since treatment duration with these drugs is restricted to 18–24 months, treatment should be continued with an antiresorptive drug. Individuals at high risk of fractures do not receive adequate treatment and strategies to address this treatment gap—eg, widespread implementation of Fracture Liaison Services and improvement of adherence to therapy—are important challenges for the future.

Introduction

Osteoporosis is defined as a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.1 This well established definition, developed by international consensus in 1993, captures two important characteristics of the disease: its adverse effects on bone mass and microstructure, and the clinical outcome of fracture. The following year, diagnostic criteria were produced by WHO using SD scores of bone mineral density (BMD) related to peak bone mass in healthy young women, with osteoporosis being defined as a BMD T score of −2·5 or less and low bone mass (osteopenia) as a BMD T-score between −1 and −2·5.2 The diagnostic criteria recognised the importance of low BMD in the pathogenesis of fragility fractures and provided a tool that could be used in epidemiological studies to quantify the prevalence of osteoporosis. However, the utility of BMD as a clinical indicator of osteoporosis is limited, because BMD is only one of a number of important risk factors for fracture, and the majority of fragility fractures occur in individuals with BMD values above this threshold.3, 4

Rachner and colleagues'5 2011 review on osteoporosis provided a detailed report on bone biology. This Seminar covers advances that have been made in our knowledge of the epidemiology, pathogenesis, and clinical management of osteoporosis in adults, and is primarily focused on postmenopausal osteoporosis. We review emerging therapies with novel mechanisms of action, controversies in the field, and the future for new treatment paradigms and precision medicine.

Section snippets

Epidemiology

Because of the systemic nature of osteoporosis, the associated increase in fracture risk affects virtually all skeletal sites.6 Hip fractures and vertebral fractures are strongly associated with reductions in hip BMD and spine BMD, respectively, and have historically been considered the prototypical osteoporotic fractures.7 However, the incidence of all other fractures (non-hip, non-vertebral) is numerically much greater and collectively these fractures result in much larger economic costs for

Normal bone remodelling and modelling

The adult human skeleton is composed of cortical and cancellous bone, the proportions of which vary according to the skeletal site. In the vertebrae, cancellous bone predominates whereas long bones contain mostly cortical bone. Bone remodelling is a process by which old bone is replaced by new bone, resulting in renewal of the skeleton approximately every 10 years. The process occurs at discrete sites termed bone remodelling units, where recruitment of osteoclasts is followed by resorption of a

Risk assessment

BMD, which is usually measured with dual energy x-ray absorptiometry (DXA) in clinical practice, strongly correlates with fracture risk. For every reduction of 1 SD, fracture risk increases by 1·5–2 times overall, and by approximately 2·5 times when hip fractures are predicted from hip BMD.7, 50 As a result, most risk assessment paradigms incorporate BMD. The limitation of BMD is that most fractures occur in individuals with a BMD T-score that does not meet the conventional definition for

Management of osteoporosis

Despite advances that have been made in fracture risk assessment, and the range of effective options available to reduce fracture, treatment rates are low among high-risk individuals.83 Prescription of bone protective medications has decreased over the past decade with falling treatment rates even in people at very high risk. For example, in the USA it was shown that in the proportion of people admitted to hospital following hip fracture between 2001 and 2011, those who were prescribed bone

Conclusion

Fractures resulting from osteoporosis are a major cause of morbidity and mortality in older people. Despite substantial advances in fracture risk assessment and the availability of a range of pharmacological options to reduce fracture risk, many high-risk individuals do not receive adequate investigation and treatment. Challenges for the future include wider implementation of integrated systems of care such as Fracture Liaison Services, improving treatment adherence, and establishing effective

Search strategy and selection criteria

We searched PubMed, Embase, and the Cochrane Library for articles and reviews in the English language published between Jan 1, 2013 and Aug 2, 2018, although older references were also used when appropriate. We used the search terms “osteoporosis” and “fracture” and limited the search to the following study designs: human, clinical studies, clinical trials (phases 2, 3, and 4), controlled clinical trials, guidelines, meta-analyses, observational studies, practice guidelines, pragmatic clinical

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