To Study the Efficacy of Teriparatide in Improving Remodeling of Foot Bones in Chronic Charcot Neuroarthropathy in Patients With Diabetes Mellitus.

Charcot neuroarthropathy (CN) was first described by Jean-Martin Charcot in a patient with tabes dorsalis who recognized that peripheral neuropathy could lead to neuropathic joints. This condition has many names, including Charcot osteoarthropathy, neuropathic osteo- arthropathy, and many others. Charcot foot may occur as a complication of neurosyphilis, syringomyelia, leprosy, poliomyelitis, congenital neuropathy and diabetes mellitus , the latter currently being the most common cause of CN. Since the description of CN in 1883, its pathophysiology remains an enigma, and there are no strict guidelines for the treatment of this disorder.

India has more people living with diabetes than any other country of the world and diabetic foot is one of the common diabetic complications found in India. The prevalence of Charcot foot in diabetes is not clearly known (0.1% to nearly 30%), but it is now appreciated that the condition is not as infrequent as might be generally thought. CN is characterized by progressive destruction of bones and joints of the foot with accompanying osteopenia. The current belief is that once the disease is triggered in a susceptible individual, it is mediated through a process of uncontrolled inflammation in the foot. This inflammation leads to osteolysis and is indirectly responsible for the progressive fracture and dislocation that characterizes its presentation.

The pathophysiologic event is cytokine- driven elevation of the receptor activator of nuclear factor kappa B ligand (RANKL), which, in turn, enhances the synthesis of nuclear factor kB (NF-kB). The latter promotes osteoclast maturation and osteoclastic activity, leading to osteoporosis in the affected bones. In parallel , NF-kB enhances the production of osteoprotegerin from osteoblasts, in order to provide an antagonist of RANKL and mitigate its effects. Ultimately, the cascade of all pathophysiologic changes leads to the development of the Charcot's foot and demineralization of bones.

If the condition is correctly diagnosed and the patient is appropriately immobilized, the local inflammation will subside and further bony destruction including progressive loss of mineral density may be prevented. But the diagnosis of CN is frequently missed in the active phase in almost 25% of cases. In the inactive stage, signs of local inflammation progressively recede, redness subsides, and the difference in skin temperature between the two feet diminishes. Most of the patients coming to our diabetes clinic present in the inactive phase with stable foot deformities viz rocker bottom deformity, loss of longitudinal or transverse arches, bony prominence (medial convexity) and significant demineralization of bones. These foot deformities result in abnormal high-pressure areas that are particularly prone to ulceration; a consequence of continued weight bearing.

Recombinant human parathyroid hormone fragment (teriparatide) is an anabolic therapy , that preferentially stimulates osteoblast over osteoclast activity resulting in new bone formation and an increase in the rate of bone remodeling. These effects manifest as an increase in skeletal mass, bone mineral density (BMD) and bone strength, subsequently leading to a reduction in the risk of fractures. It has been well established that teriparatide increases bone remodeling in the skeleton through histomorphometry studies and measurements of bone turnover markers (BTM), and recently direct measurements of the effect of teriparatide on the site-specific metabolic activity of the skeleton has been shown in patients of osteoporosis.