The Role of Vitamin K2 in Preventing Glucocorticoid-Induced Bone Loss in Children With Nephrotic Syndrome

Nephrotic syndrome is the predominant glomerular disorder in pediatric patients. It is defined as nephrotic-range proteinuria and either hypoalbuminemia (serum albumin <30 g/l (3 g/di)) or edema when albumin level is not available. Nephrotic-range proteinuria is defined as first morning urine or *24-h urine protein-creatinine ratio (uPCR) ≥ 2g/g (or 200 mg/mmol or ≥ 3+ dipstick).

Steroids are the first-line treatment for nephrotic syndrome, with an initial regimen of daily prednisolone/prednisone at a dose of 60 mg/m2/day for at least 4 weeks followed by an alternate-day regimen for several weeks. While effective in managing symptoms, glucocorticoids directly inhibit bone formation by decreasing osteoblast differentiation and by inhibition of type 1 collagen synthesis. It also stimulates bone resorption by directly enhancing osteoclast activity, as well as indirectly via increased PTH production and decreased gonadotropins, resulting in glucocorticoid-induced osteoporosis (GIOP).

In pediatric patients, the growing skeleton is especially vulnerable to these effects, and early intervention is crucial to prevent long-term complications, a clinical study reported increased fracture risk in children who require more than four courses of GCs. In general, bone loss caused by GC treatment occurs within the first 6 months of treatment.

Vitamin K, a lipid-soluble vitamin, is an essential micronutrient. It includes:

• Vitamin K1 (phylloquinone): Found primarily in green leafy vegetables.
• Vitamin K2 (menaquinones, MKs): Includes 13 types, found in meat, fermented food and cheese and predominantly produced by colonic bacteria, except for MK-4, which is synthesized in animal tissues through tissue-specific conversion of vitamin K1.
• Vitamin K3 (menadione): A synthetic form of the vitamin. Among the menaquinones, MK-7 is the most active form due to its superior absorption (peaking at 4 hours), longer half-life (72 hours) and better bioavailability. Additionally, MK-7 has fewer side effects compared to other forms.