Low Serum 25(OH)D and Higher PTH and β-CTX Independently Associated with Increased Risk of All-Cause Mortality

by | Mar 1, 2023 | 2022, Aging, Bone Health, Vitamin D - Mortality

Written by Taylor Woosley, Staff Writer. Centenarians with three risk factors (low serum 25(OH)D and higher PTH and β-CTX levels) and those with two risk factors had, respectively, had a 2.02-fold and 1.49-fold increase in risk of all-cause mortality in comparison with centenarians with no risk factors. 

vitamin DVitamin D is a fat-soluble prohormone that plays an essential role in bone mineral metabolism, being involved in calcium and phosphorus metabolism and skeletal homeostasis1. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L or 20 ng/ml) is associated with increased risk of fracture, bone loss, and an increased risk of mortality2. Furthermore, vitamin D deficiency increases cardiovascular disease (CVD) risk through factors such as renin-angiotensin-aldosterone system activation, abnormal nitric oxide regulation, oxidative stress or altered inflammatory pathways3.

Parathyroid hormone (PTH) is a key regulator of calcium homeostasis which is essential for the functioning of skeletal muscle and cardiac muscle cells4. Additionally, β-CTX, a member of the carboxy-terminal cross-linking telopeptide of type I collagen family, is a significant marker in bone resorption and formation5. Vitamin D can decrease PTH secretion and has extra skeletal functions such as decreasing type 1 collagen production and the immune system6.

Wang Bin et al. conducted a prospective cohort population-based study to evaluate the association of 25(OH)D, PTH, and β-CTX with all-cause mortality among Chinese community-dwelling centenarians. Data used in the study (n=952) was from participants in the China Hainan Centenarian Cohort Study (CHCCS). Blood samples were taken at baseline and serum 25(OH)D, PTH, osteocalcin, P1NP, and β-CTX levels were measured using electrochemiluminescence immunoassay.

The Kolmogorov-Smirnov test was utilized to determine the normality of distribution of continuous variables. For continuous variables, means were compared between two groups using the unpaired Student’s t-test. Chi-square test was used to compare categorical variables for groups. Restricted cubic spline (RCS) analyses were performed to observe the associations of all-cause mortality with 25(OH)D, PTH, and β-CTX as continuous variables in both unadjusted and multivariable adjusted models.

81.4% of centenarian subjects were female, with a median age of 102 years. 80.8% of participants had an abnormal serum 25(OH)D level and 75.1% had an abnormal β-CTX level. The estimated 1-year, 3-year, and 5-year survival rates were 80.0%, 45.7%, and 23.6%, respectively. Significant findings of the study are as follows:

  • Compared with centenarians who remained alive, those who died had a significantly lower median 25(OH)D level (21.15 ng/mL (IQR 15.90, 26.80) vs. 24.60 ng/mL (IQR 19.93, 31.33), p < 0.001), a significantly higher median PTH level (45.70 pg/mL (IQR 32.51, 63.27) vs. 38.08 pg/mL (IQR 29.90, 49.68), p < 0.001), and a significantly higher median β-CTX level (0.42 ng/mL (IQR 0.26, 0.61) vs. 0.34 ng/mL (IQR0.23, 0.49), p < 0.001).
  • Compared with 25(OH)D levels of ≥30 ng/mL, the multivariable-adjusted HRs for mortality in centenarians with 25(OH)D levels of <10 ng/mL and 10-30 ng/mL were 1.86 (95% CI 1.34-2.58) and 1.52 (95% CI 1.25-1.87), respectively.
  • The highest quartile of PTH was associated with a 43% increase in all-cause mortality risk compared with the second quartile (HR 1.43, 95% CI 1.16-1.76).
  • The highest quartile of β-CTX was associated with a 60% increase in the risk of mortality in comparison with the second quartile (HR 1.60, 95% CI 1.29-1.97).

Study results suggest that the risk of all-cause mortality is significantly higher in centenarians with at least two risk factors (low 25(OH)D and high PTH and β-CTX) compared to those with high 25(OH)D and low PTH and β-CTX. Study limitations include the inability to analyze cause-specific mortality and the lack of additional measurements of 25(OH)D, PTH and β-CTX beyond the measurements at baseline.

Source: Wang, Bin, Xiaowei Cheng, Shihui Fu, Ding Sun, Weiguang Zhang, Weicen Liu, Xinyu Miao et al. “Associations of Serum 25 (OH) D, PTH, and β-CTX Levels with All-Cause Mortality in Chinese Community-Dwelling Centenarians.” Nutrients 15, no. 1 (2022): 94.

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Posted March 1, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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