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Multiple myeloma frequently leads to bone complications characterized by the presence of lytic defects with high incidence of pathologic fractures, hypercalcemia and osteoporosis. The basic cause of this effect lies in the ability of malignant plasmatic cells to stimulate osteoclasts which are cells participating in the process of resorption of osseous tissue. Increased resorption of osseous matrix by means of osteoclasts activation runs concurrently with the process of decrease of activity of osteoblasts which are cells synthesizing osseous matrix of the bones. It has been a long time since the efforts to cope with consequences of unfavorable influence of myeloma cells on osseous tissue has been under way mainly by symptomatic means: local radiotherapy, surgical reconstruction of the bone, especially in cases of vertebral involvement, and anesthesia. Recently new weapon has been added to the arsenal for treatment of bone complications: bisphosphonates which are agents inhibiting the activity of osteoclasts and thus promoting the consolidation of the bones. Results of controlled clinical trials showed that such a medications as clodronate, pamidronate and zoledronate considerably decrease the incidence of bone complications in patients with multiple myelomas. Pamidronate and xoledronate turned out to be more active, at the same time long term usage of zoledronic acid can lead to development of such an adverse complication as osteonecrosis of jaw. The ASCO recommendations indicates the appropriateness of long term use of pamidronate or zoledronate in patients with multiple myelomas and bone complications.

The interplay between bone and glucose metabolism has highlighted hyperglycemia as a potential risk factor for bone diseases. With the increasing prevalence of diabetes mellitus worldwide and its subsequent socioeconomic burden, there is a pressing need to develop a better understanding of the molecular mechanisms involved in hyperglycemia-mediated bone metabolism. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that senses extracellular and intracellular signals to regulate numerous biological processes, including cell growth, proliferation, and differentiation. As mounting evidence suggests the involvement of mTOR in diabetic bone disease, we provide a comprehensive review of its effects on bone diseases associated with hyperglycemia. This review summarizes key findings from basic and clinical studies regarding mTOR's roles in regulating bone formation, bone resorption, inflammatory responses, and bone vascularity in hyperglycemia. It also provides valuable insights into future research directions aimed at developing mTOR-targeted therapies for combating diabetic bone diseases. [ABSTRACT FROM AUTHOR]