GP and clinical assistant Dr Pam Brown and GPSI Dr Louise Warburton outline the latest evidence on five ongoing clinical issues
1. Cardiovascular risk in rheumatoid arthritis
Cardiovascular risk is greater in patients with inflammatory arthritis, compared with those without. The increase in risk seems to be as high as that seen in type 2 diabetes and has been estimated at 1.5- to 3-fold.1 It occurs through a combination of increased prevalence of traditional risk factors and the inflammatory burden.
The link with cardiovascular risk factors and inflammatory arthritis is further supported by the fact that patients treated with immunosuppressive drugs such as methotrexate have a lower incidence of CVD. Tumour necrosis factor (TNF) has a key role in the development of CVD, and a recent study found anti-TNF drugs cut cardiovascular mortality in patients with rheumatoid arthritis.2
Any patient with inflammatory arthritis should now be undergoing routine monitoring for cardiovascular risk factors. Last year, the European League Against Rheumatism updated its guidance on cardiovascular risk management in patients with rheumatoid arthritis, including a recommendation to multiply a patient's risk score by 1.5.3 But in the UK, QRISK now incorporates an additional weighting for patients with RA.
EULAR's other recommendations for managing cardiovascular risk in these patients include that:
• adequate control of disease activity is necessary to lower risk
• statins, ACE inhibitors and/or ARBs are preferred treatment options
• the lowest possible steroid dose should be used
• smoking cessation advice is essential.
2. Bisphosphonate side-effects
We're familiar with the common side-effect of upper gastrointestinal symptoms with oral formulations, but there have also been reports of more serious problems.
Oesophageal cancer4
This possibility was raised in a 2009 FDA report citing 54 cases, but information on risk factors such as Barrett's oesophagus was not fully documented and the average time from initiation of therapy to diagnosis of the cancer was only 2.1 years – possibly suggesting a pre-existing condition. Reviews comparing treated and untreated populations from some large databases failed to confirm an increased risk, but last year a UK study suggested an increase in risk from one in 1,000 over five years in women aged 60 to 79 in women who were not taking oral bisphosphonates, to two in 1,000 after five years' use of the drugs.5 Confounders such as smoking and alcohol history were taken into account.
A pragmatic approach is to avoid oral bisphosphonates in those with Barrett's oesophagus, and to minimise risk of oesophageal damage by ensuring patients take the drug exactly as directed. It is also important to stop therapy if upper GI symptoms develop, rather than adding in a proton-pump inhibitor.
Osteonecrosis of the jaw6
This is a poorly understood condition in which an area of oral mucosa fails to heal after dental treatment, usually extraction, resulting in persistent exposed bone, despite antibiotic therapy. The risk is around one in 10 to one in 100 in those receiving high-dose IV bisphoshophonates for cancer, and thought to be much lower in those receiving oral bisphosphonates for osteoporosis (one in 10,000 to one in 100,000). But there is still no consensus on the definite role of bisphosphonates.
It would seem sensible for patients to arrange a dental check up and any necessary extractions before receiving high-dose IV bisphosphonates for cancer treatment, if possible. Guidance for those requiring oral bisphosphonates for osteoporosis is less clear.
These risks must be balanced against the increased risk of mortality and severe morbidity from fracture – particularly hip – in those with osteoporosis, and more serious consequences in those with cancer.
Atypical fractures in long-term users
Although bisphosphonates lower overall risk of fractures in women with osteoporosis, an unusual type of femoral fracture has been described in a few long-term bisphosphonate users. One US case series described seven women on long-term alendronate therapy who sustained sequential or simultaneous bilateral femoral ‘low-energy' fractures – meaning a fall from standing height or lower. All fractures were subtrochanteric or involved the femoral shaft, unlike typical fractures involving the intertrochanteric or femoral neck.
Another study compared 41 of these atypical fractures in postmenopausal women with 82 more typical fractures – and found 37% of the women with atypical fractures were taking long-term bisphosphonates, compared with 11% of controls. But population-based studies have not supported this association and it has not been studied in randomised trials.
In May last year, a paper was published which reviewed 284 hip or femur fractures in 14,195 women in bisphosphonate trials.7 It found these atypical fractures were very rare, even in women who had been treated with bisphosphonates for as long as 10 years, and found no significant increase in risk associated with bisphosphonate use.
3. Glucosamine and chondroitin for osteoarthritis
Glucosamine is usually sold in the UK as glucosamine sulphate or glucosamine hydrochloride, in over 50 preparations, with strengths from 500mg to 1,500mg, as tablets, capsules and liquid formulations – and with or without chondroitin.
The evidence is extremely difficult to analyse due to differences between the products used, the study populations, the use of analgesia and the outcomes assessed.
But it is reasonable to conclude that glucosamine sulphate as a single daily dose of 1,500mg shows a small benefit over placebo for treatment of knee osteoarthritis. The evidence for lower doses of the sulphate and for the hydrochloride is weaker, while the evidence for efficacy of chondroitin is even less convincing.
The most recent large study was last year's meta-analysis of the effect of glucosamine, chondroitin or the two in combination on joint pain and radiological progression in 3,803 patients with hip or knee osteoarthritis. It concluded that glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space, compared with placebo.8
The only glucosamine product licensed in the UK is a 625mg tablet of glucosamine (Alateris), indicated for symptomatic relief in mild to moderate osteoarthritis at a dose of 1.25g daily. Strangely this is the hydrochloride, not the sulphate, so the evidence is not strong enough to warrant its prescription on the NHS.
But what do we tell our patients who are prepared to buy glucosamine and want our advice? We should tell them that the only potential benefits of OTC glucosamine are a modest reduction in pain, and only then with glucosamine sulphate at 1,500mg daily. There is no hard evidence to back the use of other forms of glucosamine or of chondroitin. Those motivated enough could perform their own trial of therapy – evaluating their pain before starting glucosamine and reviewing the benefits after three months.
4. Work-related upper limb disorder
Work-related upper limb disorder (WRULD) can be specific (see box, left) but many people have much more non-specific pain and dysfunction, which is hard to classify or label. Yet when one takes a detailed history, there is a clear relationship to upper limb use in the work environment. This type of non-specific pain may move from one area to another and, unlike some other types of WRULD, there may be no clinical signs to clarify or confirm the diagnosis. This can make it difficult to manage.
The most common activities that can trigger WRULD are any kind of repetitive movements, or where the upper limb must be kept in an abnormal position, or when tools are awkward to hold or use, such as with use of keyboards, making wiring harnesses for cars or plucking poultry. Activities such as texting or gaming can cause the same problems, making it important to get a clear idea of the movements involved in the patient's hobbies as well as their job.
Management approaches include:
• regular breaks or rotating through different tasks, some of which are repetitive and some not, or tasks requiring the upper limbs to be used in different ways
• ensuring workstations are at optimal height – allowing the arms to be used without much static loading
• avoiding overhead working for long periods, as this can put strain on the shoulders, the neck and upper back.
Workers who enjoy their work seem less likely to develop WRULD – possibly because they are less tense, with less background contraction of their muscles – but it is not usually possible to identify who will get problems.
Be aware that when you write this diagnosis on the fit note, you immediately designate it an occupational condition, for which the employee may be able to claim compensation.
5 Manual treatments for low back pain
Manual therapy covers a number of techniques, such as palpation, stretching, heat therapy, ultrasound massage and high-velocity thrusts. Note the latter technique is used to mobilise joints and can be risky in elderly patients with possible osteoporosis, so patients need a thorough prior assessment.
Initial assessment
The patient should always be assessed upon presentation for any red flags such as severe nocturnal pain, weight loss, previous history of cancer or radicular pain. Once red flags are excluded, then the patient will usually fall into one of two broad groups:
• radicular pain due to nerve root compression
• simple mechanical back pain.
NICE guidance on low back pain suggests the following for either type:
• a course of manual therapy, including spinal manipulation, of up to a maximum of nine sessions over a period of up to 12 weeks
• a course of acupuncture needling of up to a maximum of 10 sessions over a period of up to 12 weeks.9
The choice of therapist is probably not important at this stage. They should all do a thorough assessment and be able to educate patients in self-management of low back pain and exercise therapy.
Six or eight sessions of manual therapy from any of these therapists would be appropriate. Be wary of longer programmes of treatment and ask who is paying. Of course, if you're not happy with local provision you could push for a new service to be commissioned.
NICE also recommend exercise programmes – including aerobic activity, movement instruction, muscle strengthening, postural control and stretching. Adherence to a fitness programme will prevent recurrence of back pain in the long term, and is as important as the acute treatment. It also hands back control of the illness to the patient.
Dr Louise Warburton is a GPSI in musculoskeletal medicine at NHS Telford and Wrekin and president of the Primary Care Rheumatology Society
Dr Pam Brown is a GP in Swansea, a clinical assistant in osteoporosis and a member of the Primary Care Rheumatology Society
The PCRS was established 25 years ago for GPs who have a special interest in musculoskeletal medicine. Its members have been involved in many national clinical initiatives, including the development of NICE guidance. The PCRS annual conference is held in York each autumn. For further details, including membership, go to www.pcrsociety.org.
The section on glucosamine was written by Dr Neil Andrew, a GP in County Antrim and a hospital practitioner in rheumatology
+Specific examples of WRULDIn the wrist and hand:
Trigger finger or thumb, tenosynovitis, carpal tunnel syndrome, reflex sympathetic dystrophy, hand cramp (dystonia), vibration-induced white finger
In the arm:
Epicondylitis (medial and lateral), vibration-induced arm symptoms
In the shoulder and arm:
Rotator cuff syndrome, thoracic outlet syndrome
