Abstract
Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance.
Highlights
Radiotherapy is the most commonly used approach for cancer treatment after surgery or chemotherapy [1]
Groups were significantly increased compared with those in the control group 1, 2, and 3 months after streptozotocin administration (Po0.001), whereas fasting glucose levels had no statistical difference between the Diabetes mellitus (DM) and DM combined with irradiation (DM+IR) groups at any time-point (P40.05)
We observed that streptozotocininduced DM rats exhibited more significant decrease in bone mass and more significant deterioration in trabecular bone microarchitecture following radiotherapy compared with DM or irradiation alone
Summary
Radiotherapy is the most commonly used approach for cancer treatment after surgery or chemotherapy [1]. Two-way ANOVA was used to assess significant effects of DM and IR interaction (Po0.05) according to the indices of micro-CT (including BV/TV, BS/ BV, BMD, Conn.D, SMI, Tb.Th, Tb.N, and Tb.Sp), serum biochemical levels (including osteocalcin, P1NP, TRAc P5b, and CTX-I), bone histology (including N.OB/BS and N.OC/BS), bone histomorphometry (including MAR, MS/ BS, and BFR/BS), osteocyte survival (including empty lacunae and TUNEL+ osteocytes), and skeletal gene expression (including ALP, Runx2, Osx, Col-1, TRAP, Cathepsin K, Calcitonin receptor, Sost, and DKK1).
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