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.