Multisite Pain May Be Associated with Fractures in the Elderly
with Don L. Goldenberg, MD
Multisite musculoskeletal pain is associated with prevalent and incident fracture risk in the elderly,1 according to research led by Feng Pan, MD, PhD, research fellow at the Menzies Institute for Medical Research at the University of Tasmania in Hobart, Australia. His team's hypothesis—that individuals with a greater number of painful sites have a higher risk for fractures—was based on previous research showing that multisite pain is common in older adults,2 associated with falls,3,4 and that aging, falls, and osteoporosis are the main risk factors for fractures.5,6
Pain and Fractures in Older Adults
Dr. Pan and his colleagues analyzed data from the Tasmanian Older Adult Cohort Study, a longitudinal, observational population-based study of 1,099 participants aged 50 to 80 years (mean age of 63 years) that recorded their number of painful sites and fractures at baseline and at 2.6, 5.1, and 10.7 years follow-up.
Participants were divided into three groups based on their number of painful sites: 0 to 2; 3 to 4; and 5 to 7. Painful locations included the neck, back, hands, shoulders, hips, knees, and feet. Subjects reported their number of fractures, categorized as any, vertebral, non-vertebral, hip, and major (femur, radius, vertebral, rib, humerus), at each follow-up. Body mass index (BMI), bone mineral density (BMD), and falls risk were also measured using the short-form Physiological Profile Assessment. The researchers used log-binomial regression for the analyses.
Participants reported 450 fractures at baseline; at 10.7 years of follow-up, they reported a total of 154 new fractures. The prevalent (baseline) fractures increased with the number of painful sites in a dose-response manner for fractures at any site, non-vertebral, and hip (P < 0.05). Likewise, incident fractures at any site, major, and vertebral were higher in participants with a greater number of painful sites, and there was a dose-response relationship between incident fractures and number of painful sites (P < 0.05).
Participants who reported pain at 5 to 7 sites had an increased risk of incident fractures at any site (relative risk [RR] 1.69, 95% CI, 1.13-2.53), major (RR 2.17, 95% CI, 1.12-4.22), and vertebral (RR 6.44, 95% CI, 1.64-25.33) compared to those with pain only at 0 to 2 sites.
The team also found that these associations remained significant after further adjustment for fall risk, BMD, and confounders (age, sex, BMI, physical activity, smoking history, pain medication, and comorbidities). Results suggested that widespread pain may be an independent contributor to fracture risk.
Don L. Goldenberg, MD, emeritus professor of medicine at Tufts University School of Medicine in Boston and a member of PPM’s Editorial Advisory Board, commented that, “Chronic widespread pain, particularly chronic pain in multiple parts of the body, has been found to be the risk factor for everything bad, including mortality [and] certainly for falls.”
These new findings further shed light on the importance in general practice of assessing the number of painful sites in a patient, Dr. Pan told PPM, which may reduce fracture risk in older adult populations. (More on prescribing to older adults.)
Study Discussion and Limitations
Dr. Pan’s team noted several limitations to their work, however, including that pain was measured by a self-reported questionnaire (pain/no pain) without x-ray confirmation and assessments of pain intensity, duration, and pattern. Therefore, the researchers were unable to assess whether these pain features were specifically associated with fractures. Secondly, it is possible that some yet unidentified conditions associated with pain could be markers of fracture risk.
Dr. Goldenberg, a noted rheumatologist and fibromyalgia expert, added: “There is some evidence that participants with widespread pain (eg, fibromyalgia), have modestly elevated levels of systemic inflammation,7 reduced anti-inflammatory markers,8 and enhanced innate immune response.9 In light of this, it is plausible that participants with multiple-site pain had higher levels of inflammation, which lowers bone strength through bone remodeling, thereby increasing the risk of fractures.”
These are conditions of centralized pain rather than inflammation, explained Dr. Goldenberg. “Most experts in this area think that systemic inflammation is not a key issue in conditions like fibromyalgia or widespread pain. The key hypothesis is that it is a problem in the central nervous system and how people process pain messages.”
While Dr. Pan agreed with Dr. Goldenberg that multisite pain may reflect a dysfunction in centralized pain processing, he mentioned that the study data did not show any association between multisite pain and fall risk. “Additionally, after adjusting for fall risk, the association between multisite pain and fracture risk remained statistically significant,” he explained. “Therefore, increased fracture risk may not be explained by an increased risk of falls potentially related to central sensitization mechanisms but may be due to systemic inflammation.”
Assessing for Multisite Pain in Practice
Looking ahead, Dr. Pan’s team advised in their report that clinicians routinely count and assess for the number of painful sites reported by patients in relation to fractures. They hope that further research may confirm their findings and “explore the underlying mechanisms of the link between multisite pain and fracture risk.”
Dr. Goldenberg left one point of caution for clinicians who may aim to reduce patients’ fracture risk by prescribing medications for centralized pain, such as amitriptyline. “This medication, particularly in the elderly, could make them more confused, increasing fall risk and fractures,” he said.
