low serum folate and vitamin b6 are associated with an ... · low serum folate and vitamin b6 are...
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Low serum folate and vitamin B6 are associated with an altered cancellous bone structure in humans
+1Holstein, J H; 2Herrmann, M; 1Splett, C; 1Herrmann, W; 1Garcia, P; 1Histing, T; 3Siebel, T; 3Kurz, K; 1Menger, M D; 1Pohlemann, T
+1University of Saarland, Germany, 2University of Sydney, Australia, 3Knappschaftskrankenhaus Püttlingen, Germany
ABSTRACT INTRODUCTION:
Osteoporosis represents a widespread disease, which affects about 75
million people in Europe, the United States, and Japan. Osteoporosis is
characterized by a decrease of bone mass and an impairment of bone
microarchitecture, resulting in a decreased bone strength and hence an
increased fracture risk. In the United States, over 2 million incident
fractures occur annually, causing costs of 16.9 billion dollars.
Recent epidemiological studies have reported an increased serum
concentration of homocysteine (hyperhomocysteinemia) to be associated
with osteoporosis and osteoporotic fractures. Folate, vitamin B6, and
vitamin B12 are important co-enzymes of the homocysteine degrading
remethylation and trans-sulfuration pathways. In accordance,
deficiencies of folate, vitamin B6, and vitamin B12 lead to
hyperhomocysteinemia. Besides, B vitamins play a crucial role in the
reduction of oxidative stress as well as in the methylation of different
proteins. In countries without folate supplementation of food, the
prevalence of folate and vitamin B12 deficiencies ranges between 20%
and 45%. So far, there is no information on whether low serum B
vitamins are linked to an alteration of human bone properties. Therefore,
this study aimed to analyze the association between B vitamin serum
concentrations and structural properties of human bone.
METHODS:
For the present study, fasting blood samples and femoral heads were
obtained from 94 males and females who underwent elective hip
arthroplasty. According to the National Institute of Health guidelines,
the study was approved by the local Ethical Committee and was
performed with informed consent of the subjects.
Fasting blood samples were used to measure serum concentrations of
folate, vitamin B6, and vitamin B12. In addition, serum concentrations
of the bone formation marker osteocalcin (OC) and the bone resorption
marker tartrate-resistant acid phosphatase (TRAP) were determined.
Bones were assessed by histomorphometry. According to the median B
vitamin serum concentrations, results of the bone and serum analyses
were grouped for individuals with high and low serum concentrations of
folate, vitamin B6, and vitamin B12 (n=47 each).
All data are given as means±standard deviation (SD). The
comparison between the experimental groups was performed by Mann-
Whitney-U-test. A P value <0.05 was considered to indicate significant
differences.
RESULTS SECTION:
The bone formation marker OC was found significantly higher in
individuals with high serum B vitamins when compared to those with
low serum B vitamins (folate: 24.0±12.6µg/L vs. 19.4±7.8 µg/L,
P=0.04; vitamin B6: 23.9±12.2 µg/L vs. 19.6±8.5 µg/L, P=0.05; and
vitamin B12: 24.2±12.4 µg/L vs. 19.1±7.8 µg/L, P=0.02). The serum
concentration of the bone resorption marker TRAP was slightly but not
significantly higher in individuals with high serum vitamin B12 (3.3±2.6
U/L vs. 2.7±0.7 U/L, P=0.12), while it did not differ between individuals
with high and low serum folate and vitamin B6.
The histomorphometric analysis demonstrated a significantly lower
trabecular thickness and percent trabecular area in individuals with low
serum folate in comparison to individuals with high serum folate (Table
1 and Figure 1). Individuals with low serum vitamin B6 showed a
significantly lower trabecular number when compared to individuals
with high serum vitamin B6 (Table 1 and Figure 1). In contrast, we
found no significant differences in the histomorphometric analysis
between subjects with high and low serum vitamin B12 (Table 1).
DISCUSSION:
To our knowledge, this study evaluated for the first time the
association between serum B vitamins and bone properties in humans.
Of interest, we found a relation between low serum folate and an
impaired cancellous bone structure. Individuals with low serum vitamin
B6 demonstrated a minor alteration of cancellous bone structure, while
there was no association between low serum vitamin B12 and
deteriorated cancellous bone structure.
The alterations of cancellous bone structure might be explained by an
impaired osteoblast activity as indicated by low serum OC in subjects
with low serum folate and vitamin B6. In spite of a vitamin B12-related
elevation of serum OC, we found no association between serum vitamin
B12 and trabecular bone architecture. These results might be explained
by a concomitant vitamin B12-related elevation of ostoclast activity as
indicated by the slightly elevated serum TRAP in subjects with high
serum vitamin B12.
In general, it might be assumed that B vitamin deficiency affects
cancellous bone structure by inducing hyperhomocysteinemia. On the
other hand, B vitamins have also direct effects on bone metabolism.
Therefore, B vitamin deficiency might be related to altered bone
properties also independently of the homocysteine status.
In conclusion, this study provides to our knowledge the first evidence
that low serum folate and vitamin B6 are related to an altered cancellous
bone structure in humans.
Table 1
Tb.Th [mm] Tb.N [mm-1] Tb.Sp [mm] Tb.Ar [%]
________________________________________________________
Folate+ 0.35±0.14 0.36±0.15 2.4±0.8 14.2±8.0
Folate- 0.29±0.11 0.31±0.12 2.7±0.7 10.3±5.7
P 0.02 0.12 0.13 0.02
________________________________________________________
B6+ 0.34±0.13 0.37±0.13 2.4±0.8 13.8±7.6
B6- 0.30±0.13 0.30±0.13 2.7±0.8 10.9±6.7
P 0.15 0.03 0.12 0.07
________________________________________________________
B12+ 0.33±0.13 0.33±0.13 2.6±0.8 12.8±7.7
B12- 0.30±0.13 0.35±0.14 2.5±0.7 11.7±6.6
P 0.75 0.49 0.56 0.67
Histomorphometric analysis of trabecular thickness (Tb.Th), trabecular
number (Tb.N), trabecular separation (Tb.Sp), and percent trabecular
area (Tb.Ar) of individuals with high (+) and low (-) serum B vitamins.
Data are given as means±SD. Groups include n=47 each.
Figure 1. H&E stained histological sections of cancellous bone samples.
Figures A and C show bone samples of individuals with high serum
concentrations of folate (A) and vitamin B6 (C). Figures B and D
represent bone samples of individuals with low serum concentrations of
folate (B) and vitamin B6 (D). Scale bar represents 250 µm.
Poster No. 599 • 56th Annual Meeting of the Orthopaedic Research Society