**3. Bone healing inhibitors**

As mentioned above, the process of bone injury regeneration is a complex process that is affected by various factors. In this section, some of the most important negative influencing factors on the bone healing process are mentioned, which should be controlled as much as possible to improve the healing process.

#### **3.1 Non-steroidal anti-inflammatory drugs (NSAID)**

Cyclooxygenase (COX) enzymes classified as COX-1 and COX-2, COX-1 is involved in prostaglandins synthesize in physiological conditions. COX-2 is activated in inflammatory conditions and releases prostaglandins. Whereas, NSAIDs inhibit COX activity [21]. The restriction of prostaglandins synthesized with their critical role in osteoblast and osteoclast functions retarded bone regeneration [22]. However, there is a difference of opinion on the use of NSAID and some studies indicate their positive effects on the treatment process. However, it is better to be careful in using this medicine and limit the duration and dosage [23].
