**7.1 Pathophysiological mechanisms for increased fracture risk in patients with seizures**

ASM has been linked to numerous studies of negative effects on bone strength. Although the precise mechanism is not entirely understood, ASM may impact bone quality and bone mass through a variety of methods. But it is widely accepted that certain medications, particularly the EIASM such as carbamazepine and phenytoin, stimulate the hepatic cytochrome P450 system, leading to a variety of endocrine complications [64, 65]. Among these include altered sex hormone-binding globulin concentrations and sex hormone disturbances, but most frequently, EIASM therapy has been proven to cause increased vitamin D metabolism, low vitamin D levels, impaired calcium absorption, and resultant hypocalcemia. These modifications lead to secondary hyperparathyroidism and osteoclastic bone resorption that is activated by parathyroid hormone (PTH), which causes bone loss and decreased bone mineralization [66–69]. This is in line with the common observation that patients with epilepsy have a tendency to have lower BMD, lower levels of 25-OH vitamin D, and higher levels of alkaline phosphatase and PTH. Additionally, a number of ASM carbamazepine, phenytoin, and phenobarbital have unfavorable direct effects on bone metabolism including osteoblast inhibition and osteoclast stimulation [70–72].
