Strategies For Optimising Musculoskeletal Health in The 21 Century

Lewis et al.
BMC Musculoskeletal Disorders (2019) 20:164

https://doi.org/10.1186/s12891-019-2510-7
REVIEW Open Access
Strategies for optimising musculoskeletal

health in the 21st century
Rebecca Lewis1†, Constanza B. Gómez Álvarez1†, Margaret Rayman2, Susan Lanham-New2, Anthony Woolf7
and Ali Mobasheri1,3,4,5,6*
Abstract
We live in a world with an ever-increasing ageing population. Studying healthy ageing and reducing the
socioeconomic impact of age-related diseases is a key research priority for the industrialised and developing
countries, along with a better mechanistic understanding of the physiology and pathophysiology of ageing that
occurs in a number of age-related musculoskeletal disorders. Arthritis and musculoskeletal disorders constitute a
major cause of disability and morbidity globally and result in enormous costs for our health and social-care systems.
By gaining a better understanding of healthy musculoskeletal ageing and the risk factors associated with premature
ageing and senescence, we can provide better care and develop new and better-targeted therapies for common
musculoskeletal disorders. This review is the outcome of a two-day multidisciplinary, international workshop
sponsored by the Institute of Advanced Studies entitled “Musculoskeletal Health in the 21st Century” and held at
the University of Surrey from 30th June-1st July 2015.
The aim of this narrative review is to summarise current knowledge of musculoskeletal health, ageing and disease
and highlight strategies for prevention and reducing the impact of common musculoskeletal diseases.
Keywords: Ageing, Musculoskeletal health, Musculoskeletal disorders, Global burden, Joint diseases, Osteoarthritis
(OA), Rheumatoid arthritis (RA), Low back pain (LBP), Osteoporosis (OP), Sarcopenia, Obesity, Type II diabetes,
Metabolic disease
Background time may not be feasible for those with major, or

The current rise in life-expectancy, the subsequent in- chronic, health problems. As careers are extended in dif-
crease in numbers of older people and increasing pen- ferent sectors, special attention will need to be paid to
sion costs have prompted the UK government to change addressing the workplace needs of those with major
policy, extend working years and delay pensionable age. health problems. According to the UK Department of
By 2034 the number of people in the UK aged 85 and Health and Age UK, 58% of those aged 60 and over re-
over is projected to be 2.5-times larger than in 2009, port having a long-term condition, with 25% of over 60s
reaching 3.5 million and accounting for 5 % of the popu- having two or more health problems [1, 2]. This means
lation. The number of people aged 65+ is expected to that the majority of those aged 60 to retirement will
rise to over 16 million in the UK by the same time point already have multiple morbidities. Of these conditions,
(according to Age UK and the Office for National Statis- musculoskeletal diseases are considered to be one of the
tics [1]). However, working for an extended period of highest global burdens on individuals, health and
social-care systems [3–6] (Fig. 1 a and b). It is important to
note that although there is some epidemiological informa-
* Correspondence: ali.mobasheri@imcentras.lt;
ali.mobasheri.manuscripts@gmail.com tion about the burden of musculoskeletal disease in India
†
Rebecca Lewis and Constanza B. Gómez Álvarez contributed equally to this [7, 8] and China [9] through COPCORD (Community ori-
work. ented program from control of rheumatic diseases), equiva-
1
School of Veterinary Medicine, Faculty of Health and Medical Sciences,
University of Surrey, Guildford, UK lent, up-to-date and accurate epidemiological data does not
3
Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, exist for Central America, South America and Sub-Saharan
Queen’s Medical Centre, Nottingham, UK Africa. Therefore, the true global burden of musculoskeletal
Full list of author information is available at the end of the article
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Lewis et al. BMC Musculoskeletal Disorders (2019) 20:164 Page 2 of 15
Fig. 1 a The global burden of hip and knee osteoarthritis; estimates from the Global Burden of Disease Study 2010. The numbers show the
number of case studies reported in the literature for each country, extracted via a systematic review process. Reproduced from Cross M, Smith E,
Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Note the absence of data
from Central America, South America and Sub-Saharan Africa. Annals of the Rheumatic Diseases Published Online First: 19 February 2014. doi:
https://doi.org/10.1136/annrheumdis-2013-204,763. b. The global burden of musculoskeletal disease attributable to low bone mineral density. The
numbers show the number of case studies reported in the literature for each country, extracted via a systematic review process. Reproduced
from Sànchez-Riera L, Carnahan E, Vos T, et al. The global burden attributable to low bone mineral density Annals of the Rheumatic Diseases
Published Online First: 01 April 2014. doi: https://doi.org/10.1136/annrheumdis-2013-204,320. c. The prevalence rheumatic and musculoskeletal
diseases in France. This figure highlights the dominance of osteoarthritis and back pain from the fifth to the 9th decade of life. Reproduced from
Palazzo C, Ravaud JF, Papelard A, Ravaud P, Poiraudeau S (2014) The Burden of Musculoskeletal Conditions. PLOS ONE 9(3):
e90633. https://doi.org/10.1371/journal.pone.0090633
disease is likely to be grossly underestimated. Com- condition. Public Health England has published guide-
mon musculoskeletal conditions include osteoarthritis lines for evidence-based interventions to reduce the
(OA), rheumatoid arthritis (RA), psoriatic arthritis impact of LBP, falls and OA (Fig. 2). OA is the most
(PsA), gout, lower back pain (LBP) and osteoporosis common form of arthritis and the key risk factors are
(OP). Between the fifth and ninth decade of life, OA age, obesity, metabolic disease and prior joint injury.
and LBP are major contributors to musculoskeletal RA is an inflammatory joint disease with a strong
impairment (Fig. 1 c). Arthritis is of particular con- genetic and immune basis that affects approximately
cern for the UK population as some 10 million 1% of the total global population. The incidence of
people are now estimated to be suffering from the OA and RA increases with age, as does LBP [10].
Fig. 2 Evidence-based interventions for the musculoskeletal conditions that cause the most DALYs (Disability-adjusted life years) in England,
including low back and neck pain, falls and
osteoarthritis. https://publichealthmatters.blog.gov.uk/2016/01/11/preventing-musculoskeletal-disorders-has-wider-impacts-for-public-health/
This narrative review is the outcome of a multidiscip- diseases and those with higher incidences of joint in-
linary, international workshop sponsored by the Institute juries, such as youth sport and the military.
of Advanced Studies (IAS) entitled: “Musculoskeletal
Health in the 21st Century” and held at the University of Current societal challenges
Surrey, UK, from 30th June-1st July 2015. The abstracts Physical inactivity and sedentary behaviour
from this workshop were published in a special supple- Sedentary behaviour and the rapid growth of legions of video
ment of BMC Musculoskeletal Disorders in 2015. [11]. game, social media and movie-streaming addicted couch po-
Diverse topics were discussed and debated, ranging from tatoes is a consequence of sustained and systemic urbanisa-
the global burden of OA to the link between diabetes tion in developed countries, including the United States,
and joint disease, diet and nutrition in arthritis, One where nearly 50% of the population do not undertake
Health [12], ageing, advances in imaging and musculo- even the bare minimum levels of aerobic activity rec-
skeletal health and disease in military personnel and ommended by Physical Activity Guidelines [13]. This
companion animals. One of the key deliverables of the rise in sedentary behaviour is seen as a major risk factor
international workshop was a paper that summarised for a number of chronic diseases recognised by the Na-
the topics that were discussed. In this paper, we sum- tional Health Service (NHS), costing around £1billion a
marise and disseminate some of the key outcomes from year in the UK, and is recognised as a substantial global
the workshop in the context of currently available infor- economic burden [14]. Statistics recently provided by
mation, discuss the current challenges faced by society the Centre for Economics and Business Research show
in relation to the rising burden of musculoskeletal disor- the cost of “doing nothing”: half a million Europeans
ders and review existing strategies and recommendations die every year as a result of being physically inactive
for prevention and mitigation of the impact of these and this costs the economy over €80bn annually [15].
diseases. This global challenge requires urgent and feasible solu-
The workshop reached an important consensus state- tions. Increasing physical activity and optimising exer-
ment, namely that development of more precise diag- cise (as recommended by Arthritis Research UK/Versus
nostic and prognostic tools and targeted treatments is Arthritis and World Health Organisation (WHO)) is
necessary, along with better disseminated preventative seen as an optimal way to improve musculoskeletal
measures, which is in complete alignment with those health. Only 36% of the adult population in the UK take
outlined by the Arthritis Research UK (now rebranded as part in moderate intensity physical activity of about 30
Versus Arthritis) approach plan (2014). In order to min at least once a week [16]. An increasing body of
achieve this, greater transfer and translation of know- evidence is showing that even the effects of a sedentary
ledge between the veterinary and human fields is lifestyle (for example, of those with a desk job) can be
needed as well as more funding for musculoskeletal mitigated by a small amount of activity every day. A re-
research and investigation of populations with rare cent meta-analysis of the data from studies involving
over 1 million individuals concluded that an hour of Healthy ageing and physical exercise
moderate level activity per day eliminated the in- Whilst ageing is inevitable, the benefits of exercise on
creased risk of death associated with 8 h of sitting the ageing body are numerous and, in some circum-
[17]. Interestingly, the study also found that these stances, can reduce the manifestations of ageing, particu-
levels of activity did not have an effect on the in- larly the "ageing phenotype" of the elderly. A recent
creased risk of death associated with high levels of systematic review looked at evidence supporting nutrition
leisure-time sedentary behaviour such as watching and physical activity in the prevention and treatment of
television. Whilst this level of activity is far more sarcopenia [27]. Sarcopenia results in loss of muscle
than those recommended by WHO, it is clear that strength and mass and this can lead to weakening of mus-
keeping a moderate level of physical activity is a key culoskeletal structures and impair tendon, ligament, bone
requirement for healthy ageing and maintaining mus- and cartilage function, which will destabilise the joint and
culoskeletal health [17]. WHO recommendations sug- increase the risk of arthritis and other musculoskeletal dis-
gest that healthy individuals should take around two orders. The authors identified a total of 37 randomised
hours a week of moderate physical activity or ap- control trials to explore the effect of combined exercise
proximately 20 min a day of doing any kind of phys- and nutritional intervention for overcoming muscle sarco-
ical activity like brisk walking. This level of exercise, penia. They concluded that physical exercise has a positive
which involves elevation of heart-rate, has been asso- impact on muscle mass and function in healthy subjects
ciated with lower lifetime risk of cardiovascular dis- aged 60 and above, however, there were huge variations in
ease in a 25 year longitudinal study of approximately outcomes connected with dietary supplementation,
13,000 adults [18]. In addition to benefits for muscu- highlighting the difficulties associated with cohort studies
loskeletal health, improvements in cardiorespiratory of well-nourished human beings, where the interactive ef-
fitness can be achieved by changing sedentary behav- fects of dietary supplementation may be masked or com-
iour to achieve a low-intensity physical activity such pletely limited [27]. Physical exercise improves muscle
as walking [19]. Furthermore, in patients with knee performance by increasing the ratio of type I to type II
OA, improvement of locomotor function, including muscle fibres and increasing the cross-sectional area of
balance and strength, and a reduction in pain was type II muscle fibres [28].
seen following supplementation of home exercise with A European Society for Clinical and Economic Aspects
an eight-week class-based programme [20]. Patients of Osteoporosis, Osteoarthritis and Musculoskeletal Dis-
suffering with chronic LBP who were given an exer- eases (ESCEO) taskforce looked at dietary protein and
cise programme combining muscle strength, flexibility vitamin D and calcium supplementation and recom-
and aerobic fitness also reported a reduction in stiff- mended higher protein intake in combination with phys-
ness, which can result in back pain [21]. The idea of ical exercise particularly in post-menopausal women at
exercise for rehabilitation of musculoskeletal injuries risk of developing menopause-associated musculoskeletal
has been widely accepted for many years now, and disease, such as OP [29]. Physical exercise programmes
the idea of prescribing exercise as a preventative improve strength and balance in ageing women with OP
health measure is also more widely investigated, with [30]. Fragility fracture risk, associated with OP, can be de-
guidelines around the type, frequency and duration of creased by following an exercise programme, as exercise
activity being considered [22]. increases bone density and reduces inflammatory markers
Sedentary behaviour is also contributing to the rise [31]. However, the incidence of OP is usually highest in
in obesity and type-2 diabetes. Obesity is a major elderly females who are most unlikely to perform the dy-
contributor to the development and progression of namic exercises needed for bone modelling/remodelling
OA [23] and numerous epidemiological studies have [32]. This highlights the challenge of preventing OP and
confirmed the link between adiposity and joint degen- OP-related fractures in elderly females that cannot per-
eration. The prevalence of diabetes mellitus is be- form ballistic exercise. Some medications are available
tween 7 and 14% globally [24]. Diabetes is an for these frail patients but having an active lifestyle
important predictor for severe forms of arthritis [25] from an early age and following recommendations for
and has recently been shown to be an independent exercise could be more beneficial. The same principle
risk factor for the progression of OA in men [26]. applies to frailty in ageing companion animals, where
This shows that measures to increase levels of phys- life-long spontaneous exercise significantly slows
ical activity will not only increase musculoskeletal down the progression of frailty [33].
(MSK) health but also decrease the risk of suffering Physical activity is also known to increase insulin me-
from obesity-related diseases such as diabetes. This diated glucose uptake and, in individuals without type-2
will reduce the numbers in the population susceptible diabetes, exercise positively impacts on systemic glucose
to MSK disorders and ill health. homeostasis. However, in patients with type-2 diabetes
where beta-cell impairment is significant, physical train- Childhood obesity and physical inactivity
ing does not decrease insulin secretion [34]. A recent Reducing obesity in children may also reduce the risk of
study found that a 30 min daily increment in moderate developing musculoskeletal pain later in life [41], al-
to vigorous intensity physical activity also significantly though the full impact of obesity on development of the
reduced glycated haemoglobin, a measure of type-2 dia- child’s musculoskeletal system is still poorly understood
betes risk [19]. Physical exercise reduces the risk of car- [42]. A major contributor to the obesity epidemic is the
diovascular and metabolic comorbidities associated with lack of physical exercise in the population, with many
joint diseases. people leading an increasingly sedentary lifestyle. Simi-
In addition to the positive effects of exercise on phys- larly, unhealthy diets are a common problem, due to the
ical and mental well-being, there is also ample evidence ready availability of a bewildering variety and quantity of
to suggest that exercise and mechanical loading have a fast foods, ready meals and the relentless advertising of
positive impact at the molecular, cellular and tissue these products. The low nutritional value and high cal-
levels. For example, in tendons, where ageing decreases orie content of these foods further contributes to the
the potential for cell proliferation and number of stem/ obesity epidemic. They may also play a role in the high
progenitor-like cells, it has been shown that exercise/ prevalence of type-2 diabetes and cardiovascular diseases
loading can induce an increase in tendon collagen syn- which are exacerbated by a lack of fitness and by
thesis [35], increasing tendon strength. In an animal inactivity.
model of ageing, it was found that moderate exercise
could also enhance the quality of tissue produced during
The companion animal link
healing of injured tendons [36]. There is plenty of pub-
The health issues that impact on society are not just lim-
lished evidence to support a positive role for physical ex-
ited to humans. We co-exist with a variety of companion
ercise and mechanical loading for cartilage [37] and
animals and share the same diet and environment. In a
bone health [38].
study of approximately 700 dogs, 40% were overweight
and 20% obese [43]. In addition, there is a strong correl-
ation between the canine obesity and the BMI of their
Obesity
owners, indicating that the lifestyle and diet of the
The rise in sedentary behaviour and unhealthy diets con-
owners is having a direct impact on their pets as they
tributes to the global obesity epidemic and the sharp rise
share the same environment, and probably with similar
in the incidence of type-2 diabetes. When combined
impacts on their families [44]. This highlights an oppor-
these are powerful risk factors for cardiovascular and
tunity for vets and medics to collaborate to tackle obes-
neurodegenerative diseases, which further complicates
ity, diabetes and cardiovascular co-morbidities that
the management of musculoskeletal diseases. As with
impact on humans and their companion animals.
physical inactivity, the NHS now recognises obesity as
an independent major risk factor for population
ill-health, costing the UK over £5billion. Obesity is Dietary factors
thought to be a key co-morbidity of many musculoskel- It is generally accepted that maintaining a healthy weight
etal conditions and is closely related to the development can help to improve musculoskeletal health and prevent
of OA, one of the commonest musculoskeletal health is- degenerative diseases, but research also focuses on
sues. Reducing levels of obesity in the adult population whether dietary factors can influence disease progres-
may lead to reduced occurrence of OA and can alleviate sion. Eating a varied diet high in fresh fruit and vegeta-
some of the pain of the condition. Obesity also happens bles is recommended by many health organisations. A
to be one of the most modifiable risk factors for OA combined regime of exercise and increased intake of
[39]. Exercise and weight loss has been successfully fruit and vegetables increased life expectancy in women;
trialled in overweight and obese adults with knee OA those in their 70s with the highest level of activity and
[40]. There are ongoing trials assessing the effects of vegetable consumption were eight-times more likely to
combined physical activity and weight loss and it will be survive a five-year follow up period [45]. However, few
interesting to see how combining exercise and weight direct links between fruit and vegetable intake and im-
loss may act synergistically to improve musculoskeletal proved musculoskeletal health have been shown but one
function. It is now clear that combining modest weight three year follow-up study of nearly 400 adults showed
loss with moderate exercise can provide the best overall that diets high in potassium (from fruit and vegetable in-
improvement in symptoms of pain and joint function. take) reduced the amount of muscle loss in adults > 65
Furthermore, improved diet, moderate exercise and years [46]. Dietary flavonoid intake, the compound
weight loss are probably the best short-term solutions found in many fruit and vegetables, was positively corre-
for the ineffective surgical interventions for OA patients. lated with good bone health (measured by bone mineral
density and bone resorption) in a population of (both long-chain omega-3 polyunsaturated fatty acids)
peri-menopausal women [47]. significantly reduced the clinical signs of OA [62]. In
As current treatment options in OA are very limited, humans, these substances have also been demonstrated
OA patients may benefit from the ability to self-manage to provide an alternative to anti-inflammatory pain med-
their condition through improving their diet [48]. Vita- ications for the relief of chronic neck and back pain as
min D, calcium and protein (particularly protein) opti- well as joint pain in rheumatoid arthritis [63, 64]. Whilst
mise muscle, bone and functional outcomes in older the molecular mechanism of action of these fatty acids is
people reducing falls and fractures [49]. Calcium and not entirely understood, it has been shown that these
protein intake work together to optimise bone health compounds reduce the expression of cartilage-degrading
[50]. Previously, it was thought that, in older patients, proteases and inflammatory cytokines [65].
diets too high in protein should be avoided due to the Curcumin is a well-known plant-derived compound
detrimental effect on the kidneys. However, increasing with anti-oxidant and anti-inflammatory properties. Its
evidence now shows that protein levels should not be effects have been described in numerous chronic ill-
decreased, as the effects of metabolic acidosis on the nesses in humans, including diabetes, allergies and arth-
kidneys can be offset by increased fruit and vegetable in- ritis. It modulates growth factors, transcription factors
take (as these foods decrease renal acid load) [51, 52]. and inflammatory cytokines [66]. Interestingly, a recent
Several studies recommend the benefits of supple- systematic review, has investigated the efficacy and safety
menting the diet with “nutraceuticals”. A recent system- of dietary supplements for OA human patients and
atic review found promising but nevertheless limited found that lesser known supplements such as curcumin
research evidence to support the oral use of several from Curcuma longa and Boswellic acid from Boswellia
herbal supplements including Boswellia serrata extract serrata were more effective than well-known nutraceuti-
and pycnogenol, curcumin and methylsulfonylmethane cals, such as glucosamine and chondroitin [67]. Glucosa-
in people with OA despite the poor quality of the pub- mine and chondroitin are popular supplements that
lished studies [53]. Dietary strategies for improving mus- have been suggested to promote healthy joint function.
culoskeletal health can include consumption of However, there is little evidence of their benefit [67].
long-chain fatty acids and vitamins D and K [54, 55] as Glucosamine was recommended in early guidelines is-
well as decreasing blood cholesterol [56]. OA patients sued by the European League Against Rheumatism
should ensure that they meet the recommended intakes (EULAR) and the Osteoarthritis Research Society Inter-
for micronutrients such as vitamin K, which has a role national (OARSI) for the management of knee OA [68,
in bone and cartilage mineralization. However, the cur- 69] but it was not recommended in the National Insti-
rently available evidence for a role of vitamin D supple- tute for Health and Care Excellence (NICE) guidelines
mentation in OA is unconvincing [48]. Research has and in the most recent set of OARSI recommendations
focussed on a number of dietary supplements to modu- it was identified as being “uncertain” [70]. More recent
late progression of the disease or ease joint stiffness (and guidelines published by EULAR, OARSI and ACR do
therefore pain). A diet rich in antioxidants may provide not recommend glucosamine.
a useful therapeutic tool for athletes, improving tissue In vitro evidence for glucosamine is generally good. At
repair, although the optimum dosage is unknown [57]. relatively high concentrations, glucosamine has been
Combining exercise with a dietary supplement of whey shown to have a protective effect on cartilage and syn-
protein fortified with vitamin D is effective at increasing ovial fluid; however many clinical trials have shown that
muscle mass and strength in elderly people affected with this substance is unable to reach the tissue that it is
sarcopenia [58]. meant to affect in appropriate and sufficient doses [68].
Both human and veterinary research has shown prom- Structural heterogeneity of chondroitin sulphate, another
ise for a number of other natural products or com- supplement commonly taken alongside glucosamine,
pounds derived from natural sources for alleviation of means that it is difficult to see consistent effects of this
arthritic symptoms. Green-lipped mussel extract has supplement, and the supplements available on the mar-
been shown to be an effective chondroprotective agent ket are unlikely to be pure due to contamination with
[59], reducing OA symptoms in dogs with OA [60]. other glycosaminoglycans during the manufacturing
More recently, fish oil and krill oil have been found to process [71]. There is some evidence that glucosamine
have even greater protective effects against proteoglycan and chondroitin sulphate together provide superior ef-
and collagen degradation in an in vitro model of canine fects on the inhibition of nitric oxide and prostaglandin
arthritis [61]. These substances are all known to be rich synthesis and on protection of cartilage structure, than
in long-chain omega-3 polyunsaturated fatty acids. A when applied alone [72, 73]. This combination may also
separate study found that supplementing the diet of dogs be effective with the addition of manganese ascorbate, as
with eicosapentaenoic acid and docosahexaenoic acid shown in patients with knee OA [74]. However, this is
again in an in vitro model, so it is doubtful that these A significant number of people suffering from OA also
substances would reach the required tissues at an appro- have OP, which affects approximately 3 million people in
priate dose. A small number of studies have found side the UK. However, it was found that unless bone mineral
effects of glucosamine and chondroitin sulphate treat- density measurements were taken from sites other than
ment, which include inducing insulin resistance and glu- the OA affected joints, there was a high likelihood of an
cose metabolism disorders [75]. There is also concern osteoporosis diagnosis being missed [86]. Another mus-
over the formulation of glucosamine, as it is commonly culoskeletal disorder, fibromyalgia, is often associated
given as a salt (glucosamine sulphate potassium/sodium with chronic fatigue, sleep disorders, irritable bowel syn-
chloride) which could affect renal function, particularly drome and other psychological disorders, as well as car-
in elderly patients, who are arguably more likely to be diovascular dysregulation [87].
taking the supplement [68]. Chronic musculoskeletal disorders can also aggravate
The gut microbiome is also an area of increasing focus other disease conditions, due to their activity-limiting ef-
for health research. There is an association between The fects. Where patients are diagnosed with a musculoskel-
Western Ontario and McMaster Universities Osteoarth- etal condition, it often means that they will have limited
ritis Index (WOMAC) pain scores of hip and knee OA mobility or that activity is painful to them. This restric-
and the gut microbiome of individuals [76], so possible tion of movement can then cause other ill health, such
future dietary interventions for OA could include main- as obesity or diabetes, or contribute to the effects of re-
taining a healthy gut flora. Since dysbiosis of the intes- spiratory disease [88]. For example, in a population of
tinal microbiota is strongly associated with the war veterans, arthritis was shown to be associated with
pathogenesis of several metabolic and inflammatory dis- diabetes, obesity and cardiovascular comorbidities [89].
eases, it is conceivable that also the pathogenesis of OA Obesity has also been shown to reduce the efficacy of
might be related to it. However, the mechanisms and the anti-TNF treatment in rheumatoid arthritis [90].
contribution of intestinal microbiota metabolites to OA
pathogenesis are still not clear [77]. Other foods and Diagnostic and prognostic tools for
food supplements, such as blueberry leaves and milk understanding mechanisms of disease
thistle, have been found to have an anti-inflammatory or Biomarkers are routinely being used for diagnosis of
anti-oxidant effect in other body systems, however the various diseases. These can include imaging techniques,
effect of their function on the musculoskeletal system is as well as detection and measurement of biochemical
yet to be realised [78, 79]. markers found in the blood and urine. Currently most
OA diagnoses are made by radiography, once the patient
has presented with severe joint pain, by which point
Other co-morbidities and musculoskeletal disorders there is little the clinician can do except manage that
There is increasing awareness of the effects of the pain pain at some level. Biomarkers for early diagnosis of dis-
from musculoskeletal disorders on mental health. A eases could help to detect at-risk individuals and they
study on the effects of musculoskeletal chronic pain of could then be put onto treatment plans to help prevent
5900 individuals (including fibromyalgia or chronic back further development of disease. Currently diagnosis of
or neck pain) indicated that they are at increased risk of OA, for example, is generally confirmed using imaging
poor mental health and diminished quality of life com- techniques such as radiography [91]. Ultrasound is com-
pared to those who did not report suffering from these monly used for diagnosis of soft tissue disorders such as
conditions [80]. Whilst the links between mental health myopathies [92]. Magnetic Resonance Imaging (MRI)
and musculoskeletal disorders are complex, it is thought and Computed Tomography (CT) can also be useful im-
that living with the pain of OA can lead to depression aging techniques, however these more expensive
and anxiety; conversely, psychological distress and de- methods are less frequently used. MRI is the only one of
pression worsen pain [81–83]. This can develop into a these techniques that is capable of assessing all the
vicious cycle with worsening pain and low mood. An structures of the joint, including cartilage and ligaments,
Australian study has found a strong association between in 3D [91]. Radiography and CT techniques can be lim-
musculoskeletal health and mental health; 470,000 more ited, however, as the degree of joint damage seen does
Australians had both a musculoskeletal condition and a not necessarily correlate with the pain the individual is
mental disorder than would be expected if occurrences experiencing, or the actual degree of cartilage damage,
of the two conditions were independent of each other for example. Radiographic diagnosis of arthritis can be
[84]. Chronic insomnia can also indicate musculoskeletal determined by joint space width measurements and
pain, as the two commonly co-occur, and doctors should osteophyte development [93]. Ultrasound can also pro-
enquire about sleep patterns in patients consulting with vide a useful view of the different tissues within a joint,
pain conditions [85]. as it can provide a view on early inflammatory features
and allows for detailed measurements of the joint Imaging tools, diagnostic biomarkers and gait ana-
structures [94]. Development of more sophisticated lysis should be combined for a more integrated ap-
imaging techniques and image analysis tools is neces- proach to diagnosis of musculoskeletal disorders to
sary to correctly diagnose stages of musculoskeletal ensure that the clinician not only has a clear and
diseases. While some techniques can distinguish small quantifiable overview of the patient’s clinical signs,
changes in joint tissues during disease, it is unclear but is also able to consider what is happening at a
how these correlate to specific grades of musculoskel- molecular and tissue level.
etal conditions [95]. A technique that is starting to re-
ceive more attention is the use of non-invasive probes for Management of musculoskeletal diseases
monitoring joint damage and inflammation. Radiotracers, Common musculoskeletal disorders include LBP, fibro-
or contrast agents, are used for detecting inflammation to myalgia, gout, OA, tendinitis and RA. These result in
provide a method for detection of specific subtypes of in- pain and disability, affecting quality of life and product-
flammatory activity in musculoskeletal conditions, by pro- ivity. To address this, Arthritis Research UK, recently
viding earlier and more reliable assessments of tissue rebranded as Versus Arthritis in the UK, has developed
inflammation [96]. several recommendations to improve musculoskeletal
Gait analysis can be used as a biofeedback marker of health, including advice on diet and lifestyle as preventa-
musculoskeletal health as it provides physical functional tive measures [41]. However, none of these recommen-
outcome measures to quantify improvement, monitor dations is related to actual treatment of disease or
treatment and can provide early diagnosis of mechanical improvement of diagnostic tools. Treatment of OA, for
compensation due to patient pain or discomfort. Diverse example, currently only consists of pain management,
gait-analysis technologies have been developed and used which is often insufficient, whilst diagnosis is generally
in humans and sport horses over the past 40 years, and limited to clinical examination by a general practitioner
are constantly being refined to provide reliable measures or, in some cases, diagnostic imaging.
of improvement from disease [97]. Current technologies Management of musculoskeletal diseases should start
include wearables, inertial measurement units or acceler- with proper and complete pain management, including
ometers which are lightweight, wireless devices to investi- accurate diagnosis and grading of pain [106]. As discussed
gate activity levels, gait patterns and fitness parameters for previously, pain from musculoskeletal conditions severely
humans and other animals [98–100]. Real-time or affects patients’ quality of life. In humans, paracetamol
delayed-time parameters that can be analysed include and non-steroidal anti-inflammatory drugs (NSAIDs) are
ground reaction forces and foot-pressure distribution, the most often prescribed to treat OA pain, with some clini-
kinematics of joints and segments, along with dynamic cians preferring paracetamol/opioid combinations or an
electromyograms [101]. The information gained from opioid alone, depending on patient age and other comor-
these analyses enables clinicians to quantify, and bidities (for example, renal disease, diabetes, hypertension,
therefore monitor and evaluate, gait and posture pa- gastrointestinal, etc.) [106]. These medications may be ap-
rameters such as asymmetry and other abnormal propriate for the majority of patients, however, there are
movement patterns, possibly indicating pain or dis- some barriers to optimal pain management, including pa-
comfort in the musculoskeletal system. Increasing evi- tient compliance, self-medication and lack of monitoring
dence indicates that cytokines and mediators together by the clinician [106]. It is recognised that opioid misuse
with mechanical stress are key to the development of in the U.S. has reached epidemic proportions [107], for
cartilage damage; this mechanical stress due to abnor- which the U.S. Department for Health and Human Ser-
mal movement patterns can also be quantified by gait vices has announced a new combative strategy [108].
analyses [37]. Gait analysis has great clinical value as Therefore, other treatment options may need to be con-
a test for patients with neurological and orthopaedic sidered if the pain cannot be appropriately controlled or if
disorders as it provides quantifiable, objective, data to the prescription of particular medications is problematic
aid the clinician in selection of any surgical procedure in that country.
needed and then to monitor outcomes and follow up
post-surgery. This is a valuable addition to the use of One health, OA and learning from studies in the
traditional clinical examination. Nowadays, more ac- canine species
curate and user-friendly technology for gait analysis OA is also a commonly presented condition in dogs.
allows investigation of musculoskeletal diseases in hu- The recommended conservative management in this
man patients [101] and other species, with the goal of species usually includes nutritional management and
obtaining a better definition of specific clinical hall- weight control (with considered exercise options), along-
marks of diseases such as rheumatoid arthritis [102] side pain management/disease modifying agents and
and OA [103–105]. physical rehabilitation [109]. The usual approach when a
canine presents with OA is to prioritise weight loss and decreasing pro-inflammatory cytokine release in an ani-
exercise, as the canine patients are often overweight or mal model than topical diclofenac and cryotherapy
obese, thus weight management is seen as a priority in [121]. Other treatments such as acupuncture, ultrasound
these cases [110]. Similarly, it is becoming increasingly and transcutaneous electrical nerve stimulation (TENS)
recognised that obesity is a risk factor for OA in are known to be effective for pain relief in both human
humans, with increasing prevalence in the last few de- and veterinary medicine, however, the methodological
cades [111, 112]. Where canine pain is managed, the quality of some studies has been questioned and com-
usual treatments are similar to human medicine and in- parisons between the studies show large heterogeneity
clude opioids and NSAIDs. Systemic and intraarticular and significant publication bias [122]. For example, acu-
corticosteroids have been shown to be effective for pain puncture has been shown to be effective for the short
management in dogs and horse, despite being less com- term relief of pain [123]; TENS was shown to be inef-
monly used in these species, and may provide a protect- fective for musculoskeletal pain [124, 125]; ultrasound
ive articular effect [113, 114]. In contrast, intraarticular and shockwave therapy also do not appear to improve
corticosteroid injections for human knee osteoarthritis pain significantly [126, 127]. However, there do seem to
have been shown to give similar reductions in pain as be patient-reported beneficial effects of these treatments
the placebo injection [115]. The latter could be ex- and reduced lameness in animals, which may mean that
plained by a mechanical effect of the fluid volume being whilst there is no evidence for clinical mechanisms of
injected. Research into musculoskeletal conditions in action of these treatments, some of them may be work-
veterinary species is lacking in quantitative markers of ing to improve patient health. Further, NSAIDs, opioids
evaluation, such as objective gait analysis. Despite lame- and topical steroids were found to be beneficial in the
ness scoring by a veterinarian (a semi-quantitative tool), short term for pain relief, but not over a longer time
owner perception is often relied upon to determine pa- period. In contrast, exercise therapy and psychosocial in-
tient improvement. The “caregiver placebo effect” is re- terventions not only relieved pain but improved function
ported on in veterinary literature, affecting both owner’s in a human primary care setting [122]. Psychosocial in-
and veterinary practitioner’s judgement when they are terventions may include self-management, behavioural
assessing an animal’s lameness against an objective and/or cognitive changes. These are longer-term therap-
measure [116]. Further research into quantitative bio- ies, which may improve patient outcomes as patients be-
mechanical markers in veterinary species is essential, come empowered to manage their own conditions.
along with increased use of objective measures in clinical Physical rehabilitation will usually include several dif-
practice. ferent techniques and modalities, in order to slow pro-
In humans and veterinary species, the treatment regi- gression of the disease, improve patients’ activity levels
mens are very similar with corticosteroids. The usual and, in turn, decrease their level of disability. Some tech-
dosing pattern would be one intraarticular injection niques used in rehabilitation include passive ranges of
every six weeks, with no more than 3–4 per year. motion, where the therapist will move or manipulate the
Long-term steroid use (i.e. more often than four times joint for the patient and thus increase the metabolism of
per year) is recommended to be avoided in all species the tissues. Rehabilitation can also include therapeutic
due to systemic side-effects [117]. NSAIDs are also exercises, which are controlled movements where the
known for having side effects in the gastrointestinal sys- patient will perform active ranges of motion (i.e. the pa-
tem, with potentially severe effects in the lower gastro- tient is self-motivated to move), achieving the same tis-
intestinal tract, as well as in other systems [118]. sue metabolic and physical effects [128]. Rehabilitation
Therefore, finding alternatives to these therapies for in this manner aims to ensure muscle tone is improved
high-risk patients seems to be the logical option. Some and that joints are utilised effectively. Specifically, im-
possibilities may be topical NSAIDs, which have fewer proving muscle tone should decrease the rate of progres-
side effects [119] or other modalities such as photobio- sion of the disease (as the joint becomes stabilised) and
modulation (low level laser therapy; LLLT) [120]. Animal hopefully decrease a patient’s pain levels. Whilst these
studies suggest that at the right dose, laser therapy can therapies will not cure arthritis, improving the joint
be more effective at modulating the inflammatory characteristics in this manner will enable the patient to
process, than topical NSAIDs which treat pain alone keep active for longer.
[120]. Treatment of the inflammatory processes may also Patients can be referred to a specialist for physical
decrease the pain that is reported with many musculo- therapy and orthotics to improve posture and gait imbal-
skeletal disorders or injuries. Traditionally, people may ances, which may not only prevent but improve muscu-
use cryotherapy or topical NSAIDs such as diclofenac loskeletal ailments that may ultimately result in injuries
for treatment of acute musculoskeletal injuries. However, to cartilage and soft tissues. Identifying the needs of a
a recent study showed that LLLT was more effective at patient before a musculoskeletal condition becomes an
issue, for example, utilising workstation assessments understanding of disease progression. Current research on
(usually implemented by an Occupational Health profes- musculoskeletal diseases is mainly focused on understand-
sional, under employer guidance) in order to improve ing the mechanisms of disease to identify a better and
the ergonomics of items the patient uses every day and earlier diagnosis. At a cellular level this includes studies
then training the patient in the best use of these items, on chondrocytes and synovial tissue as well as osteoblasts
will improve a patients’ posture and could lead to pre- [130–132]. Studies with animal models to investigate OA
vention of musculoskeletal injuries. Incorporating are being widely used to understand the disease and its
real-time visual feedback into the assessment of patient symptoms such as pain [133–135]. Veterinary research is
behaviour has been shown to be an effective tool for im- important, not only on established animal models but
proving posture [129]. Increases in patient numbers re- also on companion animals because species, such as rab-
ferred for this preventative kind of therapy could reduce bits, dogs and horses, are also commonly affected by simi-
patient presentations at a later stage for more serious lar musculoskeletal diseases with similar clinical signs to
musculoskeletal complaints. This referral will only work humans [136, 137]. As these animals have a shorter life
if the general practitioner is able to identify these imbal- span, this allows for observation of the complete process
ances at an early stage. of disease over a shorter time period.
It is clear that a holistic and individualised approach to There is also the opportunity when studying rare mus-
managing treatment in musculoskeletal conditions is ne- culoskeletal diseases, such as alkaptonuria (AKU), for re-
cessary, with the input of multidisciplinary health profes- searchers to determine whether treatments developed
sionals, including general practitioners, dieticians, physical specifically for these can facilitate the development of
therapists and fitness specialists. Thus, the problem would new therapies for the more common disorders. There
need to be assessed from multiple viewpoints and at a may also be common pathways in disease progression,
much earlier stage with greater input from the patients which may help understanding of how and why individ-
and their commitment if behaviour change is required. uals develop musculoskeletal problems [138].
Equally, this issue would also be more likely to fulfil pa- In addition to the general population, there is also an in-
tients’ needs and, most importantly, place greater em- creasing need for more research in musculoskeletal condi-
phasis on their medical background, lifestyle, any tions affecting the military; in 2006 there were nearly three
co-morbidities and their family history and susceptibility quarters of a million reported musculoskeletal injuries or
to developing musculoskeletal disease. conditions in the US military [139]. This sector of the popu-
lation is an interesting target for research studies as it has a
Current research approaches for musculoskeletal high incidence of musculoskeletal injuries. For example, it
diseases has been shown that conservative physical therapy is a valu-
Arthritis Research UK, recently rebranded as Versus Arth- able first approach for musculoskeletal conditions in a US
ritis, has presented a new approach plan towards arthritis naval department [140]. On the other hand, the vast major-
and related musculoskeletal conditions by providing a ity of US army active soldiers are being prescribed NSAIDs,
wealth of information to the public, funding and undertak- where more investigation is needed to stablish the pros and
ing research, improving data collection and influencing re- cons of this practice in that population [141]. These contra-
lated policies [41]. Whilst data on the levels of funding dictions could be tackled by increasing the number of
received for different conditions can be difficult to obtain high-quality research studies and thus establish new guide-
for European countries, in the United States, musculoskel- lines and recommendations for the improved management
etal conditions received the least funding from the National of musculoskeletal health in the military.
Institutes of Health Research compared to other conditions Until the underlying mechanisms of these diseases are
such as cardiovascular disease or cancers (Fig. 3 a). Of those revealed and important details that give us more infor-
musculoskeletal conditions funded, the largest proportion mation are clarified, little can be done in terms of devel-
went to investigating conditions resulting from injuries or oping new treatment options. Although it is important
accidents (Fig. 3 b). to work on a preventative approach, treatment still
Understanding common diseases such as OA and RA needs to be optimised to reduce pain and disability, es-
would help to develop better and more precise diagnostic pecially given the rising numbers of elderly people as
and prognostic tools, improve treatment management and well as an unfit, sedentary and overweight population.
lead to the recommendation of effective preventive mea-
sures. There are currently few funding streams that enable Conclusion
researchers to join together and work on all these aspects The burden of musculoskeletal diseases will only increase
of musculoskeletal health. A multidisciplinary approach with an increasing ageing population and an increased
combining these factors could not only improve patient number of people not taking diet, lifestyle, health and
diagnosis and outcomes but also help further our physical activity seriously. A pragmatic multidisciplinary
Fig. 3 The burden of musculoskeletal disease in the United States and the funding gap for research on musculoskeletal conditions (2009–2013).
a. Despite the major health care burden presented by musculoskeletal conditions, research funding falls well below that of most other
conditions. Injury research accounted for half of the musculoskeletal condition research dollars ($4 billion) from NIH for the years 2009 to 2013.
Funding for arthritis research is second, at $1.4 billion, followed by osteoporosis ($965 million). These numbers are well below the $8.6 to $55.2
billion in funding for the top 25 NIH research areas, dominated by cancer, cardiovascular disease and other disease areas. b. Research funding
allocated to different musculoskeletal conditions by NIAMS. The data clearly indicate that musculoskeletal conditions receive less funding support
compared to other disease areas despite the heavy burden on healthcare systems worldwide
approach to treatment and prevention is needed to tackle Consent for publication

these problems; including raising public awareness of risk Not applicable.
factors and improving the understanding of these ap- Competing interests

proaches within the medical and scientific community. The authors wrote this paper within the scope of their academic and
Behaviour change and patient participation is absolutely affiliated research positions. The authors declare no conflict of interests.
crucial for success. We must make use of efficient diag-

nostic tools available and develop new ones that enable Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
earlier identification of MSK disease; and we need to in- published maps and institutional affiliations.
vestigate the mechanisms of disease progression that will
lead to preventive measures and individually tailored and Author details
1
School of Veterinary Medicine, Faculty of Health and Medical Sciences,
more holistic treatment programmes. University of Surrey, Guildford, UK. 2School of Biosciences and Medicine,
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Abbreviations 3
Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis,
ACR: American College of Rheumatology; AKU: Alkaptonuria; Queen’s Medical Centre, Nottingham, UK. 4Department of Regenerative
COPCORD: Community oriented program for control of rheumatic diseases; Medicine, State Research Institute Centre for Innovative Medicine, Vilnius,
CT: Computed Tomography; ESCEO: European Society for Clinical and Lithuania. 5The D-BOARD FP7 Consortiumhttp://www.d-board.eu. 6The
Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal APPROACH IMI Consortiumhttps://www.approachproject.eu. 7Department of
Diseases ; EULAR: European League Against Rheumatism; IAS: Institute of Rheumatology, Royal Cornwall Hospital, Truro, UK.
Advanced Studies; LBP: Low back pain; LLLT: Low level laser therapy;
MRI: Magnetic Resonance Imaging; NHS: National Health Service; Received: 16 February 2018 Accepted: 17 March 2019
NIAMS: National Institute of Arthritis and Musculoskeletal and Skin Diseases;
NICE: National Institute for Health and Care Excellence; NIH: National
Institutes of Health; NSAIDs: Non-steroidal anti-inflammatory drugs; References
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Lewis et al.

BMC Musculoskeletal Disorders (2019) 20:164

REVIEW Open Access

Strategies for optimising musculoskeletal

Background time may not be feasible for those with major, or

approach to treatment and prevention is needed to tackle Consent for publication

factors and improving the understanding of these ap- Competing interests

crucial for success. We must make use of efficient diag-

peoplepopulationandcommunity/wellbeing/articles/ 39. Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis.

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