Abstract
Background: Large blood vessel atherosclerotic cardiovascular disease is associated with hip fracture risk. Here we summarize studies on the association of microvascular disease with hip fracture risk. We further assess whether the risk of hip fractures with microvascular disease is through reduced trabecular bone density or through markers of endothelial dysfunction.
Methods: We used albuminuria (>30 mg albumin/gram creatinine) as a marker of microvascular disease. Albuminuria is associated with microvascular disorders of the heart, lungs, eyes, skin, and brain. It is present in 30-40% of adults >70 years, the age at which hip fractures occur.
Results: In an observational study of the elderly, a doubling of albuminuria was associated with a hazard ratio (HR) of 1.12 (95 % CI, 1.001-1.25) for hip fractures among women. In a blood pressure study, macroalbuminuria (>299 mg/gram) had an adjusted HR of 2.01 (1.21, 2.15). In a population study of 360,000 people, the HRs for hip fractures were 1.30 (1.02-1.65) for microalbuminuria (30-299 mg/gram) and 1.58 (1.07-2.35) for macroalbuminuria. In a population study of 2.7 million people, macroalbuminuria had an increased odds ratio of hip fracture (odds ratio 1.37 [1.28, 1.47]). Despite these findings, volumetric trabecular bone density was not significantly reduced in association with albuminuria levels nor with markers of endothelial dysfunction.
Conclusions: Microvascular disease, as detected by albuminuria, is independently associated with hip fracture risk. However, this association is not through reduced trabecular bone density nor through endothelial dysfunction. Other mechanisms of fracture risk need to be explored.