Increased migraine risk in osteoporosis patients: a nationwide population-based study

The study revealed that adult patients with osteoporosis had a considerably greater risk of developing subsequent migraine compared to the patients without osteoporosis. 

Both osteoporosis and migraine are common conditions that can affect quality of life and can impose large social and economic burdens. The National Institutes of Health Consensus Development Conference Statement defines osteoporosis as a skeletal disorder characterized by diminished bone strength resulting in increased fracture risk. Bone strength is measured in terms of both bone mineral density (BMD) and bone quality. In elderly populations, osteoporosis affects approximately 30% women and 12% men. Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The International Headache Society defines migraine as a headache that lasts for 4–72 h and has at least two of the following characteristics: pulsating quality, unilateral localization, moderate-to-severe pain intensity, and aggravation by movement. Previous studies have identified interacting relationships among migraine, various sleep disorders, depression, psoriasis, restless legs syndrome and cardiovascular disease. Migraine is associated with episodes of local sterile meningeal inflammation, hypersensitized pain pathways, and increased inflammatory cytokines that contribute to the pathogenesis of osteoporosis, such as interleukins (ILs) or tumor necrosis factor-α. Like osteoporosis and other inflammatory conditions, migraine is also apparently associated with systemic endothelial dysfunction.

Rationale behind research:

No recent studies have suggested a link between osteoporosis and migraine. Therefore, the current study was conducted to investigate the impact of osteoporosis on migraine risk.

Objective:

To use a population-based dataset to assess migraine risk in osteoporosis patients.



Study outcomes:

• The Charlson Comorbidity Index (CCI) score: This score was used to assess the severity of comorbidities, i.e., myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease (mild, moderate, or severe), diabetes (with or without chronic complication), hemiplegia or paraplegia, renal disease, any malignancy (including lymphoma and leukemia, but excluding skin malignancy), metastatic solid tumor, human immunodeficiency virus infection and acquired immune deficiency syndrome. The CCI scores were then categorized into four levels: 0, 1–2, 3–4 and ≥5.

Time Points: Baseline and after index date

Note: The index date was defined as the date of the first clinical visit for osteoporosis.

Outcomes:

• Baseline Characteristics: Compared to non-osteoporosis cohort, the osteoporosis cohort had significantly higher percentages of patients with co-morbidities. The osteoporosis cohort also had higher CCI scores. The migraine incidence of osteoporosis cohort was significantly higher than that non-osteoporosis patients. Migraine development was significantly faster in the osteoporosis group (3.5 years) than the non-osteoporosis group (7.2 years) for the respective observation periods.
• Migraine incidence and risk: During follow-up period, migraine developed in 2.73% (1110) of the osteoporosis patients and in 1.85% (750) of the non-osteoporosis patients. The overall migraine risk was 1.37 times greater in the osteoporosis group than in the non-osteoporosis group. The incidence of osteoporosis was higher in women than in men. Also, the osteoporosis group had a significantly higher migraine risk in both genders. Although the incidence of migraine was consistently higher in all age groups in the osteoporosis cohort, migraine risk decreased with age. Regardless of comorbidities, migraine risk was higher in osteoporosis patients than non-osteoporosis patients. The Kaplan–Meier curves showed a significantly higher cumulative incidence of migraine in the osteoporosis cohort compared to the non-osteoporosis cohort.
  

This is the first nationwide population-based study known till now which has explored the relationship between osteoporosis and subsequent migraine in an Asian population. During follow-up period, migraine developed in 2.73% (1110) patients with osteoporosis and in 1.85% (750) patients without osteoporosis. Patients with osteoporosis, particularly with high CCI score, female gender, hypertension, depression, asthma, allergic rhinitis, obesity, and tobacco use disorder, had a high migraine risk.

The exact mechanisms underlying the relationship between migraine and osteoporosis are likely to be elusive. However, several lines of evidence in the literature suggest that osteoporosis and migraine have a shared pathophysiology. Gallai et al. showed that individuals suffering from migraine headaches had lower plasma and saliva magnesium levels between the attacks compared to controls without migraine headaches. Both osteoporosis and migraine are associated with hypomagnesemia, which suggests an interplay between osteoporosis and migraine. Secondly, the relationship between migraine and osteoporosis might be explained at least partly by their common inflammatory mediators. Inflammatory cytokines associated with osteoporosis such as tumor necrosis factor-αand IL-6 are elevated at the onset of migraine attacks. Finally, C-reactive protein, which increases during systemic inflammation, is elevated in both osteoporosis and migraine. Thus, inflammatory state caused by osteoporosis may increase the frequency or severity of migraine headaches by exacerbating the inflammatory response.

Clinicians should be aware that osteoporosis is a potential risk factor for migraine. Further studies are recommended to confirm this association and to explore its mechanisms.