Peripheral vascular disease is also the major cause of gangrene. Peripheral Neuropathy is a loss of peripheral nerve function compromising the sufferer's protective sensation. This predisposes to acute trauma going undetected. Neuropathy is most commonly caused by diabetes. Other causes include renal failure, myxoedema, toxins such as alcohol abuse, drugs such as those used in anti-tuberculosis therapy and cancer.
Trauma plays a significant role in the predisposition of an individual to amputation.
Minor trauma in a person with peripheral neuropathy may lead to chronic infections such as osteomyelitis due to the pathway discussed above. Acute major trauma, such as open fractures is also a major cause of amputation. Malignancy is a minute contributing cause for amputation. It predisposes below-knee amputation in the formation of an osteosarcoma of the tibia. Other common malignancies include chondrosarcoma and Ewing's sarcoma.