Effect of vitamin D3-supplementation on bone markers (serum P1NP and CTX): A randomized, double blinded, placebo controlled trial among healthy immigrants living in Norway

Abstract

ObjectiveVitamin D is essential for the maintenance of calcium homeostasis and bone mineralization; and low serum 25-hydroxyvitamin D (s-25-(OH)D) concentrations are associated with increased bone turnover. However, there is a lack of randomized controlled trials that have investigated the effect of vitamin D treatment on bone turnover in immigrant populations. We aimed to investigate the effect of 16-week daily vitamin D3 supplementation on bone formation marker serum procollagen type 1 amino-terminal propeptide (P1NP) and bone resorption marker C-terminal crosslinked telopeptide of type I collagen (CTX).DesignDouble-blind, randomized, placebo-controlled trial.SettingImmigrant community centers in Oslo, Norway.Participants251 healthy adults aged 18–50 years with a non-Western immigrant background were recruited.Intervention16 weeks of daily oral supplementation with either 10 μg vitamin D3, 25 μg vitamin D3, or placebo.Main outcome measuresDifference in change during the 16-week intervention between the intervention groups combined (10 or 25 μg of vitamin D3/day) and placebo, in serum P1NP and serum CTX.ResultsA total of 214 (85%) participants completed the study. S-25-(OH)D increased from 29 nmol/L at baseline to 49 nmol/L in the intervention group with no significant change in the placebo group. However, there was no difference in change of serum P1NP (mean difference: − 1.2 μg/L (95% CI: − 5.4, 2.9, P = 0.6)) and serum CTX (mean difference: − 0.005 μg/L (95% CI: − 0.03, 0.02, P = 0.7)) between those receiving vitamin D3 supplementation compared with placebo. The plasma PTH had decreased by a mean of − 1.97 pmol/L (95% CI: − 2.7, − 1.3, P < 0.0001) in the vitamin D3 group compared to placebo.ConclusionsSupplementation with 10 or 25 μg oral vitamin D3 during winter and spring for 16 weeks did not significantly affect serum P1NP and serum CTX, despite increasing s-25(OH)D and decreasing PTH in a healthy immigrant population with low baseline vitamin D status.Trial registration number: NCT01263288.

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

“…Trials investigating the relationship between vitamin D supplementation and CTX or P1NP have also shown mixed results, and to our knowledge, only a single small study has explored this relationship in hip fracture patients. [23][24][25][26] Our results demonstrate the relationship between baseline serum 25(OH)D and CTX and P1NP after hip fracture and confirm that observed trends in these BTMs after long bone fractures are similar in elderly hip fractures. We demonstrated that peak CTX and P1NP levels occur between 2-and 6-month postfracture, and that mean CTX and P1NP remained slightly elevated at 12 months (0.59 ng/ml and 63.1 mg/L, respectively) when compared to older adults without fractures.…”

“…The relationship between serum 25(OH)D and CTX or P1NP has provided mixed results, and none have evaluated this trajectory in a fracture population. Trials investigating the relationship between vitamin D supplementation and CTX or P1NP have also shown mixed results, and to our knowledge, only a single small study has explored this relationship in hip fracture patients …”

Effect of isolated vitamin D supplementation on bone turnover markers in younger postmenopausal women: a randomized, double-blind, placebo-controlled trial

“…Since vitamin D is a well-established bone nutrient, markers of bone formation and turnover have been considered indicators of long-term vitamin D status [21]. A high bone turnover in vitamin D-deficient individuals has been reported in observational studies [22]. However, relatively limited and inconsistent data are available regarding the separate effects of vitamin D on bone turnover markers in different populations of both sexes [17,18,[22][23][24].…”

“…A high bone turnover in vitamin D-deficient individuals has been reported in observational studies [22]. However, relatively limited and inconsistent data are available regarding the separate effects of vitamin D on bone turnover markers in different populations of both sexes [17,18,[22][23][24]. Only one intervention study examined the effect of vitamin D supplementation alone on bone turnover in postmenopausal women [17].…”

Vitamin D levels in a large Mediterranean cohort: reconsidering normal cut-off values

“…It is noteworthy that significant changes in biomarkers of bone turnover are not always evident, despite an observed increase in 25-(OH)D levels and concomitant decrease in PTH levels when administering supplementation with oral VitD. 76,77 As has been reported by others, 78,79 a negative correlation between 25-(OH)D levels and glucose, triglycerides and total cholesterol was apparent in our population, confirming that higher serum concentrations of 25-(OH)D tend to be associated with a more favorable lipid profile. Literature reports on the association between VitD and total cholesterol are often discrepant, even when extensive adjustments for confounding factors (particularly BMI) have been applied, 45,80,81 while the association between VitD and triglycerides is consistently reported as negative, 82 with two exceptions concerning adolescent girls.…”