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Impact of vitamins K2 and D3 on bone mineral density in pediatric patients with B-ALL

Apr 26, 2021

Acute lymphoblastic leukemia (ALL) is the most common cancer that affects children, and it comprises 75% of all leukemia cases. Current therapy protocols achieve high remission rates and long life expectancy; however, treatment-related complications, such as osteoporosis and osteopenia, can negatively affect the quality of life and physical activity of patients.

A positive correlation has been noted between the use of intensive steroid treatment in adults and the occurrence of osteoporosis and vertebral fractures. In children, osteoporosis is diagnosed when patients have one or more vertebral compression fractures in the absence of local disease or trauma, or significant fracture history combined with low bone mineral density (BMD). The combination of vitamins K2 and D is known to have a synergistic action that supports osteoblastic activity, inhibits osteoclasts, and promotes bone mineralization.

A recent prospective cohort study published in the Journal of Pediatric Endocrinology and Metabolism by Solmaz et al. investigates the effects of vitamin K2 (menaquinone-7) and vitamin D3 (calcitriol) on bone metabolism, by assessing markers of bone density and bone formation/destruction in children with B-cell precursor ALL (B-ALL) undergoing chemotherapy.1

Study design and patient characteristics

A total of 29 patients recently diagnosed with B-ALL and treated according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Münster 2000 protocol were enrolled between May 2011 and May 2012. Patient characteristics are depicted in Table 1.

Table 1. Patient characteristics*


Study group

Control group

Patients, n



Male/female ratio, n/n



Mean age, years (range)

6.5 (1.0–14.5)

7.1 (2.0–17.0)


Menaquinone-7 100 μg/day and calcitriol 10 μg/day with chemotherapy

No supplement, chemotherapy only

*Data from Solmaz et al.1
Oral, single morning dose from Day 1 of chemotherapy.

Bone turnover markers

  • Serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), bone-specific ALP (BSALP), uncarboxylated osteocalcin (ucOC), tartrate resistant acid phosphatase 5b, carboxyl terminal procollagen propeptide (PICP), osteoprotegerin (OPG), and receptor activator nuclear kappa-B ligand (RANKL) were measured at baseline and at Months 1, 2, 3, and 6.
  • BMD Z-scores from the lumbar vertebra and femoral neck were obtained at baseline and at Months 1, 2, 3, and 6 of treatment.

Key results

PICP, ucOC, and the OPG/RANKL ratio measurements are summarized in Table 2.

  • The study group had significantly higher serum OPG/RANKL ratio in the first month (p = 0.015).
  • The ucOC levels were significantly decreased in the study group compared to the control group at the first month (p = 0.016).
  • PICP levels were higher in the study group at Months 2 and 3 (p = 0.05 and p = 0.005, respectively).

Table 2.  Measurements of PICP, ucOC, and OPG/RANKL ratio*



PICP, ng/mL

ucOC, ng/mL




16.93 ± 11.97

2.32 ± 1.15

0.44 ± 0.33


20.79 ± 14.83

2.54 ± 1.24

0.49 ± 0.28

Month 1


20.16 ± 11.94

1.36 ± 1.09

0.70 ± 0.24


20.23 ± 15.06

5.21 ± 1.08

0.45 ± 0.27

Month 2


53.73 ± 28.86§

7.54 ± 3.44

0.72 ± 0.29


32.27 ± 27.65§

7.12 ± 3.99

0.59 ± 0.34

Month 3


55.31 ± 26.54

7.78 ± 4.12

0.63 ± 0.47


28.21 ± 20.25

7.85 ± 5.16

0.57 ± 0.41

Month 6


36.00 ± 24.25

6.70 ± 4.48

0.86 ± 0.38


24.69 ± 14.77

6.18 ± 3.73

0.79 ± 0.53

OPG, osteoprotegerin; PICP, carboxyterminal propeptide; RANKL, receptor activator of nuclear factor kappa-Β ligand; ucOC, uncarboxylated osteocalcin.
*Data from Solmaz et al.1

p=0.016; p=0.015; §p=0.05; p=0.005.

Other biochemical parameters

  • The other serum marker levels assessed (tartrate resistant acid phosphatase 5b, OPG, RANKL, calcium, phosphorus, magnesium, ALP, and BSALP) did not reach statistical significance (p > 0.05).
  • Femoral neck and lumbar vertebra BMD Z-scores showed no statistically significant difference between the two study groups. However, they did not drop below −2.0 and there were no reported fractures. Therefore, low BMD rather than osteoporosis was considered.


Based on the outcomes of this study, vitamins K2 and D3 contribute towards increased bone formation through elevating levels of OPG/RANKL in the early months and PICP in later months. Decreased ucOC levels in the first month suggest the vitamins used promote bone mineralization by inducing calcium uptake in the bone. Hence, these results indicate an early beneficial effect of supplementation with K2/D3 vitamin combination during the first months of intensive steroid chemotherapy on the bone structure of children with ALL.

  1. Solmaz I, Ozdemir MA, Unal E et al. Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study. Journal of Pediatric Endocrinology and Metabolism. DOI:


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