Disclosures: The authors report no relevant financial disclosures.
July 23, 2021
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Shared risk factors may drive cognitive decline and bone loss, fracture risk for women

Disclosures: The authors report no relevant financial disclosures.
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There is a bidirectional relationship between cognitive decline and accelerated bone loss with increased fracture risk among women, according to new data published in the Journal of Bone and Mineral Research.

Cognitive decline and osteoporosis often coexist, and some evidence suggests a causal link, Dana Bliuc, PhD, MD, senior research officer at Garvan Institute of Medical Research, in Australia, and colleagues wrote in the study background. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging, the researchers wrote.

Women experienced 6.49% bone loss after 10 years with each 1% decline in Mini Mental State Examination Score. Data were derived from Bliuc D, et al. J Bone Miner Res. 2021;doi:10.1002/jbmr.4402.

“These findings may help refine clinical practices guidelines regarding how bone loss and cognitive decline can be monitored in older age, to ensure appropriate and effective treatment,” Bliuc said in a press release. “This is particularly important because both bone loss and cognitive decline are ‘silent conditions’ that can go undetected for long periods of time, often until the conditions have severely progressed.”

Bliuc and colleagues analyzed data from 1,741 women and 620 men aged at least 65 years without dementia, from the population-based Canadian Multicentre Osteoporosis Study, followed from 1997 to 2013 (mean age, 72 years). Participants attended clinic visits to assess bone mineral density via DXA and cognitive function via the Mini Mental State Examination (MMSE) at baseline, year 5 and year 10. Participants also completed yearly mailed questionnaires that assessed fractures.

“In order to ascertain the role of physical characteristics and quality of life on cognitive decline at year 5, the change in parameters (height, weight, femoral neck BMD, and SF-36 components) were calculated for each participant as the percent change between baseline and year 5,” the researchers wrote. “Participants were then classified as having significant change (worst quartile) or no change (the remainder).”

Researchers used mixed-effects and adjusted Cox models to assess the association between cognitive decline and bone loss and clinically significant cognitive decline, defined as loss of at least 3 points on the MMSE during the first 5 years, as well as subsequent fracture risk during the following 10 years. The total MMSE score ranges from 0 to 30, with higher scores indicating better global cognition.

Within the cohort, more than 95% of participants had normal cognition at baseline, defined as an MMSE score of at least 24.

Women and men experienced a similar and significant decline in cognitive function during the first 10 years of follow-up, a mean –4.5% for women and –4% for men (P = .42). Approximately 13% of participants experienced significant cognitive decline by year 5; older age at baseline was associated with a higher rate of cognitive decline.

BMD also declined during follow-up for women (mean decline, –3.4%) and men (mean decline, –4.7%; P = .03).

For women, each percent decline in MMSE from baseline was associated with 6.49% bone loss at year 10 in a fully adjusted model (95% CI, 3.17-9.92).

“A decline in cognitive function by 1% over the 10 years follow-up was associated with a decline in bone loss by [approximately] 6% during the same time interval, after adjustment for age, education, comorbidities, and lifestyle factors,” the researchers wrote. “By contrast, in men, there was no association between cognitive function and BMD beyond that expected by the normal aging process.”

Compared with women without cognitive function loss, women with significant cognitive decline (n = 186) also experienced a higher rate of bone loss (most rapid bone loss quartile, 34% vs. 24%; P = .008) during the first 5 study years.

After adjustment for age, significant cognitive decline in women was associated with a 68% increased risk for osteoporotic fracture (age-adjusted HR = 1.68; 95% CI, 1.16-2.43), with risk persisting after multivariable adjustment (HR = 1.61; 95% CI, 1.11-2.34).

Other independent predictors for fracture risk in the multivariable model were prior fracture, neurologic conditions and greater bone loss.

“These studies suggest that the relationship between bone loss, cognitive decline and fracture risk in women is driven by shared risk factors,” the researchers wrote. “Further mechanistic pathways are needed to understand the complex relationship between osteoporosis and dementia and the contributors of fracture risk in cognitively impaired people. This study failed to demonstrate a relationship between cognitive decline and bone loss in the relatively small cohort of men. Thus, further studies, involving larger cohorts of men, are needed to confirm or refute any association.”