Age-Related Factors Associated With The Risk of Hip Fracture

Abstract

Objective: Advancing age is a powerful risk factor for hip fractures. The biological mechanisms through which aging impacts the risk of hip fractures have not been well studied.

Methods: Biological factors associated with "advancing age" that help to explain how aging is associated with the risk of hip fractures are reviewed. The findings are based on analyses of the Cardiovascular Health Study, an ongoing observational study of adults aged ≥65 years with 25 years of follow-up.

Results: The following 5 age-related factors were found to be significantly associated with the risk of hip fractures: (1) microvascular disease of the kidneys (albuminuria and/or elevated urine-albumin-to-creatinine ratio) and brain (abnormal white matter disease on brain magnetic resonance imaging); (2) increased serum levels of carboxymethyl-lysine, an advanced glycation end product that reflects glycation and oxidative stress; (3) reduced parasympathetic tone, as derived from 24-hour Holter monitoring; (4) carotid artery atherosclerosis in the absence of clinical cardiovascular disease; and (5) increased transfatty acid levels in the blood. Each of these factors was associated with a 10% to 25% increased risk of fractures. These associations were independent of traditional risk factors for hip fractures.

Conclusion: Several factors associated with older age help to explain how "aging" may be associated with the risk of hip fractures. These same factors may also explain the high risk of mortality following hip fractures.

Keywords: autonomic function; hip fracture; microvascular disease; oxidative stress; subclinical atherosclerosis; transfatty acids.

Figure 1:

Kaplan Meier plot of the proportion of men and women from the Cardiovascular Health Study without hip fractures categorized by the presence or absence of albuminuria.

Figure 2:

Kaplan Meier plot of the proportion of Cardiovascular Health Study participants free of hip fractures categorized by quartiles of carboxymethyl-lysine.

Figure 3:

Hazards ratios for hip fracture per 1 unit increase in the ratio (index) of the ankle to brachial blood pressures; per one average standard deviation increase of carotid artery intimal medial thickness [IMT] (i.e., standard deviations away from the mean IMT variable); and per 1 mm increase in both walls of the aorta. Model 1: adjusted for age, sex and race, current smoking + alcohol (0 ref, 1–7, >7 drinks). Model 2: Model 1 + weight (kg) + diabetes+ hypertension+ eGFR cystatin + estrogen (females) + history of falling in the year before baseline ABI - ankle brachial index: CD — carotid intimal medial thickness: AWT - aortic wall thickness.

Figure 4:

Hazards ratios for incident hip fracture, per one standard deviation of each NEFA class adjusted for cofactors. The Cox regression models are adjusted for age, gender, black race, clinic of participation, highest attained level of education, smoking status (current, never, former), alcohol use (none, < 7 drinks per week, > 7 drinks per week), weight, height, cholesterol, presence of hypertension, HTN medications, SBP, DBP, previous Ml and/or stroke, heart failure, serum albumin, eGFR based on cystatin C level, and degree of physical activity (none, moderate, and strenuous) NEFA — non esterified Fatty acid SFA - saturated fatty acid MUFA - monounsaturated fatty acid PUFA — polyunsaturated fatty acid TFA — trans fatty acid

Figure 5:

Summary of factors associated with hip fracture risk in older adults: 1. microvascular disease, 2. carboxymethyl-lysine, 3. cardiovascular autonomic neuropathy, 4. subclinical carotid artery disease, and 5. the ingestion of trans fatty acids lead to an increased risk of hip fracture.