Lack of vitamin K and calcium may affect bone metabolism and eventually lead to osteoporosis and fractures. Bone material properties, the degree of mineralization, and microdamage accumulation are influenced by collagen crosslinking, specifically type I collagen fiber and crosslinking fiber, which forms the connection matrix protein and mineral crystal framework. If the arrangement of the collagen fibers changes and the mineral crystal is immature, the material properties change, which may damage bone elasticity. Vitamin K, through a nuclear steroid and xenobiotic receptor-mediated effect on the collagen content, may be an important factor that affects bone quality [15, 16]. The effect of vitamin K on bone health and remodeling also involves matrix Gla protein (MGP), which promotes bone formation by upregulating Wnt/β-catenin signaling and exerts an inhibitory effect on bone mineralization . In the late stage of osteoclast differentiation, MGP is highly expressed, thus forming a negative feedback loop so that the formation of osteoclasts is strictly controlled . Wu et al.  showed that vitamin K inhibitor osteoclast-mediated effects on bone resorption occur in a dose-dependent manner. Calcium is the most abundant inorganic salt component in the human body; 99% of it is found in bones and teeth. It is essential for the normal function of nerves and muscles and plays a role in blood clotting (as factor IV) and many enzymatic processes. Calcium is directly affected by the amount of vitamin K in the body, and when calcium metabolism is impaired, the resulting increased calcium in the arteries and decreased calcium in the bones are known as the calcium paradox . Moreover, bone remodeling requires a variety of cells, including osteoblasts, osteoclasts, and osteocytes. Osteoblasts continuously synthesize the non-collagenous protein osteocalcin, which is one of the most abundant proteins in bone and is one of many vitamin K-dependent proteins, making vitamin K crucial in bone remodeling, one of its many roles in calcium metabolism .
As gastric calcium solubility has been shown to be pH-dependent, hypochlorhydria which is defined by reduced stomach acid production can induce calcium malabsorption which negatively affects bone mineralization . Therefore, patients with hypochlorhydria which can be caused by long term use of proton pump inhibitors (PPI) display higher prevalence for osteoporosis and increased fracture risk . As calcium gluconate or citrate have been shown to be very effective in correcting calcium malabsorption in patients with reduced stomach acid production , we recommend calcium gluconate or citrate supplementation in patients with permanent use of PPI.
Background: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (TM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD. 1e1e36bf2d