The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial

Abstract

Summary This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. Purpose Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. Methods We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. Results Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). Conclusion The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. Trial registration The study was registered at Clinicaltrial.gov:NCT01232647.

The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism—A Review

“…Other similar studies suggested that combined therapy with risedronate and VK2 could not prevent vertebral fracture incidence in postmenopausal osteoporosis [85,87]. Moore et al [88] also found that the addition of VK1 to oral bisphosphonate with calcium and/or vitamin D treatment in osteoporosis patients has a modest effect on parameters of hip geometry. However, Suzuki et al [76] found that combined therapy with alendronate and VK2 reduced serum ucOC and improved lumbar spine and femoral neck BMD in postmenopausal patients with rheumatoid arthritis.…”

The Importance of Vitamin K and the Vitamins K and D Combined for the Calcium Metabolism and Bone Health: A Review

“…In another RCT 122 postmenopausal women were randomized into 4 groups [72]. Three groups were fed farmed salmon containing either high levels of vitamin D and K1 or high vit D and low K1 or low vit D and high K1, together with calcium supplement.…”

Exogenous and endogenous antioxidants in osteoporosis risk: causal associations unveiled by Mendelian Randomization analysis

“…OP is characterized by low bone density, deterioration of bone tissue microstructure, increased bone fragility, and susceptibility to fracture (Genant et al, 1999). As a severe, chronic, progressive, and asymptomatic metabolic bone disease, OP is a major public health concern worldwide (LeBoff et al, 2022;Moore et al, 2023). The statistical evidence indicates that over 200 million people worldwide suffer from OP.…”