Excess mortality in osteoarthritisBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1407 (Published 08 March 2011) Cite this as: BMJ 2011;342:d1407
- 1MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
- 2NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
Osteoarthritis is the most common joint disorder worldwide. It comprises a group of overlapping disorders that may have different causes, but which result in joint failure subsequent to morphological changes in articular cartilage, subchondral bone, synovium, and other joint structures. Osteoarthritis typically affects the hands, knees, hips, spine, and feet.1 Although osteoarthritis can be defined pathologically, radiographically, or clinically, most epidemiological studies have relied upon radiographic features to characterise the disease. Radiographic features have a graded (although sometimes discordant) association with clinical features—joint pain and functional impairment—with notable disability arising from involvement of the knee and hip. The lifetime risk of osteoarthritis specific morbidity is about 25% for the hip2 and 45% for the knee,3 and the disorder is a major contributor to the 57 000 knee and 55 000 hip arthroplasties undertaken each year in the United Kingdom.4 In the linked study (doi:10.1136/bmj.d1165), Nüesch and colleagues assess all cause and disease specific mortality in patients with knee or hip osteoarthritis⇓.5
In contrast to the well established morbidity attributable to osteoarthritis, relatively little is known about the effect on mortality. Rheumatoid arthritis, the most common inflammatory joint disorder, is associated with a twofold to threefold excess mortality, specifically attributable to cardiovascular disease, infection, respiratory disease, and gastrointestinal disease.6 However, conventional thinking has been that osteoarthritis itself does not cause death. Previous studies have attributed higher death rates in patients with osteoarthritis to concomitant risk factors for the disorder (most notably obesity) or to treatment with non-steroidal anti-inflammatory drugs.7 8 These studies have important limitations (patients were recruited from hospital settings, they were confined to various categories of employment, standardised clinical and radiographical definitions were not always incorporated, and patients were investigated after surgery).
Nüesch and colleagues report the pattern and causes of incident mortality in a large population based sample of men and women with osteoarthritis of the knee and hip.5 The 1163 participants (denominator population 26 046) aged 35 years and over who had symptomatic radiographically defined osteoarthritis at these two joint sites showed a significant excess in all cause mortality (standardised mortality ratio 1.55, 95% confidence interval 1.41 to 1.70); cause specific mortality was particularly high for cardiovascular disease and dementia. The authors suggest that this association may result from low grade systemic inflammation, long term use of non-steroidal anti-inflammatory drugs, or a lack of physical activity. An alternative possibility is abnormal vascular pathology of the subchondral bone, which has been shown to contribute to the initiation and progression of osteoarthritis.9 These results have important implications for the clinical management of osteoarthritis, as well as for understanding its pathogenesis.
In rheumatoid arthritis, the recognised association with death from cardiovascular disease has led to routine evaluation of cardiovascular risk factors, the use of drugs to normalise the serum lipid profile and blood pressure, and a focus on lifestyle changes. Although such strategies are already recommended in the context of arthroplasty, the current study suggests that they should be incorporated into primary care algorithms for the management of symptomatic osteoarthritis not severe enough to warrant surgery. The use of exercise regimens to enhance joint function is also likely to benefit other parts of the musculoskeletal system, such as bone and muscle.
The findings also shed new light on biological ageing of the musculoskeletal system. Population based studies have suggested that systems seem to age together in individuals.10 Changes in two other musculoskeletal tissues (bone and muscle) have been well characterised throughout the life course, and the morbidities associated with their involution (osteoporosis and sarcopenia) are established contributors to physical frailty. Like osteoarthritis, the prevalence of both disorders rises steeply with age, and interactions between joint structure and muscle weakness in the causation of lower limb disability have long been recognised.
It is now also clear that low bone density and muscle strength are markers of premature death11 12—not only are they associated with a host of attributes that independently predispose to reduced survival, but they may also mirror the biological rates of cellular ageing that characterise all individuals. Biological ageing may be assessed at the molecular level (DNA repair, oxidative damage, or epigenetic modification), system level (endocrine or metabolic system), or whole organism level. Theories of ageing may also be categorised according to whether the process is principally genetically determined or occurs as a response to random events over time. A distinction may also be drawn as to whether ageing has evolved as a beneficial process in its own right (adaptive theories) or as a by-product of other pathways (non-adaptive theories). These models of biological ageing are not mutually exclusive, and there is growing support for characterising musculoskeletal ageing from a life course perspective, in terms of recognising important influences operating from conception to death. The notion that osteoarthritis should join osteoporosis and sarcopenia as a manifestation of biological ageing opens a major avenue for future research aimed at identifying biomarkers of the underlying cellular and molecular processes and at evaluating behavioural interventions and drugs targeted at optimising bone, muscle, and articular health.
Cite this as: BMJ 2011;342:d1407
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.