Background:
Patients with peripheral arterial disease (PAD) have a higher incidence of hip bone loss and non-spinal fractures independent of their cardiovascular risk or degree of claudication. The mechanisms explaining this excess risk of osteoporosis are poorly understood. N-telopeptide (NTX) is an amino-terminal cross-linked type I collagen peptide that is released during fibrillogenesis, reflecting both the derivative products of bone collagen and bone resorption. When elevated, it serves as an early marker for osteoporosis and predictor of therapeutic response. We hypothesized that patients with PAD have reduced bone mineral content and that PAD is associated with biomarkers of accelerated bone mineral resorption.
Methods:
We analyzed data from 4354 participants ages 40 years or older with measured ankle-brachial indexes (ABI) from the National Health and Nutrition Examination Survey from 1999 to 2002, defining PAD as an ABI < 0.9 in either leg. N-telopeptides were measured in the urine. Total bone mineral content and bone mineral density were measured using dual energy X-ray absorptiometry.
Results:
The overall prevalence of PAD was 4.4 % (S.E, 0.3). The geometric mean of NTX was 248.3 nmol (S.E, 7.0). NTX decreased with age. Women, non-Hispanic blacks and obese individuals had significantly higher NTX levels, whereas diabetics had reduced NTX levels. Current smokers, chronic kidney disease and PAD patients tended to have higher levels as well. In an age, gender, and race adjusted multivariate analysis, one standard deviation increase in NTX level was associated with a three-fold increase in the odds of having reduced total bone mineral density (OR 3.22, p <0.0001). Additionally, patients with PAD had significantly increased odds of having NTX levels in the higher tertile (O.R 1.57, p=0.035). This association persisted even after further adjustment for obesity, smoking, and C-reactive protein.
Conclusion:
Peripheral arterial disease is associated with reduced levels of bone mineral content and density. PAD is independently associated with N-telopeptides, suggesting abnormal type I collagen metabolism abnormalities. Further prospective studies will determine the role of NTX as a marker of osteoporosis found in PAD and their relationship with walking activity.