Best Practice & Research Clinical Rheumatology
7Evaluating and mitigating fracture risk in established rheumatoid arthritis
Introduction
Patients with rheumatoid arthritis (RA) are at risk of periarticular as well as generalized skeletal bone loss, and they have roughly double the risk of vertebral and non-vertebral fractures compared with age and gender-matched controls [1], [2]. This is due to many factors, including chronic inflammation, glucocorticoid use, and immobility [3], ⁎[4]. The decision to initiate therapy with calcium and vitamin D supplementation or pharmacologic agents in an individual patient is based on several factors, including a patient׳s individual risk factors for fracture, dose, and duration of glucocorticoid therapy, and it is not solely based on bone mineral density (BMD). We review current evidence and guidelines for fracture prevention and therapeutic modalities available for the treatment of osteoporosis and glucocorticoid-induced osteoporosis (GIOP), with special attention given to application in patients with established RA.
Section snippets
Assessing risk of fracture
While RA is an independent risk factor for low BMD and fracture itself, RA patients found to have low BMD – such as any patients with osteoporosis – should be evaluated for other causes which may coexist with the patient׳s RA, including vitamin D deficiency, hyperparathyroidism, celiac sprue, and hyperthyroidism. Beyond glucocorticoids, a careful assessment of other medications that may lead to reduced BMD such as antiepileptics, lithium, and high-dose proton pump inhibitors should also be
Patient vignette
A 65-year-old male patient with RA diagnosed 11 years ago comes in for a follow-up visit. He is on methotrexate (MTX) and etanercept therapy, and he is currently in low disease activity by Clinical disease activity index (CDAI). He does not smoke or drink alcohol. He does not report a recent loss of height and is not taking corticosteroids. He has no history of fracture. He asks about his risk of fracture and when, and if, he should have his bone density measured. On examination, he is thin, of
Adequate control of inflammation
The exact mechanism by which RA leads to an increased risk of fracture is not known, but it is likely secondary to immobility and effects of systemic inflammation on bone [31]. Studies have shown that fracture risk increases with both disease activity and duration of disease, which support this idea, making it logical to assume that a tight control of a patient׳s underlying RA should lead to decreased bone loss and decreased fracture risk [1], ⁎[4]. However, to date, there are no data showing
Denosumab
Denosumab is a human monoclonal antibody, which decreases osteoclastogenesis via the inhibition of RANKL [72]. It is administered via subcutaneous injection twice per year, making it an attractive alternative to oral bisphosphonate therapy for patients with difficulty with medication adherence or contraindications to bisphosphonate therapy [8].
In several placebo-controlled trials, denosumab significantly increased BMD at the spine and hip as well as prevented fractures in postmenopausal women
Conclusion
Fractures can be a significant, and often disabling, comorbidity of patients with RA. In addition to demographic similarities with osteoporosis patients, systemic inflammation, immobility, and glucocorticoid use significantly contribute to the heightened risk of fractures in this population. In addition to the aggressive control of the patient׳s underlying RA, a multifaceted approach utilizing appropriate screening for systemic bone loss, exercise, dietary interventions, and, if necessary,
Conflicts of interest
None.
References (87)
- et al.
Generalised bone loss in patients with early rheumatoid arthritis
Lancet
(1994) - et al.
Indications of DXA in women younger than 65 yr and men younger than 70 yr: the 2013 official Positions
Journal of Clinical Dentistry
(2013) - et al.
The official positions of the international society for clinical densitometry: vertebral fracture assessment
Journal of Clinical Dentistry
(2013) - et al.
Circadian variation in the serum concentration of c-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting
Bone
(2002) - et al.
Efficacy of a short multidisciplinary falls prevention program for elderly persons with osteoporosis and a fall history: a randomized controlled trial
Archives of Physical Medicine and Rehabilitation
(2010) - et al.
Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial
Lancet
(2009) - et al.
Severe hypocalcemia following denosumab injection in a hemodialysis patient
Am J Kidney Dis
(2012) - et al.
Bilateral atypical femoral fractures in a patient prescribed denosumab – A case report
Bone
(2014) - et al.
Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis
Arthritis & Rheumatism
(2006) - et al.
Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis
Annals of Rheumatic Diseases
(2009)
Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study
Annals of Rheumatic Diseases
Strategies for the prevention and treatment of osteoporosis in patients with rheumatoid arthritis
Drugs & Aging
What proportion of incident radiographic vertebral deformities is clinically diagnosed and vice versa?
Journal of Bone Mineral Research
Clinician׳s guide to prevention and treatment of osteoporosis
Osteoporosis International
Management of osteoporosis in rheumatoid arthritis patients
Expert Opinion Pharmacotherapy
Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of osteoporotic fractures research Group
Journal of Bone Mineral Research
Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study
Journal of Bone Mineral Research
The prevalence of vertebral fracture on vertebral fracture assessment imaging in a large cohort of patients with rheumatoid arthritis
Rheumatology (Oxford)
Performance of vertebral fracture assessment in addition to dual energy X-ray absorptiometry in patients with rheumatoid arthritis
Rheumatology (Oxford)
Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis using vertebral fracture assessment
Rheumatology (Oxford)
Preventive services task force evidence syntheses, formerly systematic evidence reviews. Screening for osteoporosis: systematic review to update the 2002 U.S. Preventive services task force recommendation. Rockville (MD): Agency for healthcare research and quality (US)
Diagnosis and management of osteoporosis
Predictive value of BMD for hip and other fractures
Journal of Bone Mineral Research
Bone mineral density thresholds for pharmacological intervention to prevent fractures
Archives of Internal Medicine
Risk factors associated with incident clinical vertebral and nonvertebral fractures in Japanese women with rheumatoid arthritis: a prospective 54-month observational study
Journal of Rheumatology
Vertebral deformities in 229 female patients with rheumatoid arthritis: associations with clinical variables and bone mineral density
Arthritis & Rheumatism
Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis the study of osteoporotic fractures research Group
Journal of Bone Mineral Research
Reliability and accuracy of vertebral fracture assessment with densitometry compared to radiography in clinical practice
Osteoporosis International
Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study
Journal of Bone Mineral Research
Early changes in biochemical markers of bone turnover are associated with long-term changes in bone mineral density in elderly women on alendronate, hormone replacement therapy, or combination therapy: a three-year, double-blind, placebo-controlled, randomized clinical trial
The Journal of Cinical Endocrinology and Metabolism
Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years
Journal of Bone Mineral Research
Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards
Osteoporosis International
Preanalytical variability of biochemical markers of bone turnover
Osteoporosis International
Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups
Health Technology Assessment
Can bone loss in rheumatoid arthritis be prevented?
Osteoporosis International
Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis
Journal of Rheumatology
Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study
Journal of Rheumatology
Reduced loss of hand bone density with prednisolone in early rheumatoid arthritis: results from a randomized placebo-controlled trial
Archives of Internal Medicine
Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids
Annals of Rheumatic Diseases
Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis
Journal of Rheumatology
Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis
Rheumatology (Oxford)
Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years
Arthritis & Rheumatism
Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied?
Osteoporosis International
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