Bone Restoration in Diabetic Osteolysis and Therapeutic Targets

Abstract

Bone, being a key structural support of the body, undergoes dynamic micro structural remodelling all over life to control automatic stress and calcium requirement. Neurovascular, visual, renal complications added with osteopenia and osteoporosis are main unbearable problems in diabetes mellitus (DM). It is clear that hyperglycaemia in diabetes mellitus leads to glucose toxicity which directly suppresses adipogenic delineation of the osteoblast precursors which depreciate bone feature and strength which augment propensity to fracture. A number of risk factors including oxidative stress, apoptosis and abnormal intracellularCa 2+ metabolism have been postulated to play a function in the inception and progress of osteoporosis within diabetes. This review determines to discuss the most recent findings of mechanisms concerned in the progression of osteoporosis in diabetes. We emphasize the role of signalling molecules in osteoclastogenesis as therapeutic targets in the prevention and treatment of diabetic osteolysis. Increasing validation during the last decade suggests that zinc as neutraceutical suppresses calcium/calcineurin pathway and many compounds are potent inhibitors of osteoclast synthesis by blocking RANKL pathway, an emerging concept that is gaining acceptance. The characteristic of impediment and management of DM-induced osteolysis should be an effective glycaemic control. Hence, we propose to accentuate that Zinc combined with suitable anti-diabetic drugs and inhibitors of osteoclastogenesis may represent a potential therapeutic target in Diabetes mellitus for the prevention, reduction of fracture risk and treatment of osteolysis by suppressing osteoclastogenesis via calcium, calcineurin and RANKL pathway.

Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis

“…Melatonin is capable of regulating bone density by reducing oxidative stress in osteoclasts, promoting osteoclast cell differentiation and activity, and by increasing osteoblast-induced osteoprotegerin expression, preventing osteoclast precursors from differentiating into osteoclasts and inhibiting the process of bone resorption [22]. This apparently protective mechanism of melatonin against bone resorption suggests important therapeutic potential in bone-wasting diseases such as osteoporosis [22] and osteolysis [11,29]. Notably, by regulating inflammatory pathways and circadian rhythms, melatonin can stimulate the regeneration of cartilage and inhibit the release of proinflammatory cytokines or osteolytic factors including interleukin (IL)-1β, IL-8, tumor necrosis factor alpha (TNF-α), COX-2, matrix metalloproteinases (MMPs), and RANKL in joints by modulating the expression of key circadian clock genes, including BMAL, CRY, and/or DEC2 [30,31].…”