Effects of Cyclophosphamide on Mechanical Properties of Bone and Skin in Rats

Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and metaphyseal bone in rats

“…Since the height of metaphyseal trabecular bone is depended on the thickness of calcified cartilage produced by the growth plate, effects of these two drugs in chondrocyte survival or proliferation and heights of the primary and secondary spongiosa trabecular bone seen in the current study strongly suggest that these two drugs affect bone growth and that these cellular effects observed may contribute to the significant impact of these two drugs on bone lengthening and bone mass accumulation observed previously. [19][20][21] Previous studies have suggested that chemotherapy may contribute to osteopenia in childhood cancer patients by chemotherapy direct effects on bone cell numbers as individual chemotherapeutic agents can reduce numbers of osteoblastic cells in vitro, with osteoblast precursor cells being preferentially depleted. 31 In the current study, we have shown that, 3 days after drug administration, both Eto and Cyc reduced the total numbers of osteoblasts and preosteoblasts along the trabecular bone surface in the metaphysis.…”

“…Previously, studies have demonstrated that Cyc and/or Eto chemotherapy can impair bone growth directly. [19][20][21] Similarly, some studies have demonstrated that some other individual chemotherapy drugs impair bone growth mechanisms and bone growth directly, including DNA-damaging agents cisplatin and doxorubicin and anti-metabolites 5-FU and methotrexate. [13][14]16,[36][37] …”

“…18 Previously, administration of Eto or Cyc in young rats was shown to reduce growth plate thickness, [20][21] produce bone growth arrest in long bones, [19][20][21] and induce osteopenia. 21 However, how these two drugs affect the bone growth mechanisms has been largely unclear.…”

“…18 Some skeletal side effects of cyclophosphamide have also been documented in experimental animals, including reduced thickness of growth plate, disturbed cell differentiation and maturation, decreased femoral growth and metaphyseal bending strength. [19][20] Topoisomerase is an enzyme required for DNA synthesis and toplogy alteration, and etoposide (Eto), the most commonly used topoisomerase inhibitor, binds to topoisomerase II and DNA, inducing DNA damage and causing arrest in S-or G 2 -phase. Inhibitors for popoisomerase I or II are used in treating acute myeloid leukaemia, colorectal, ovarian and small cell lung cancers, as well as a variety of other malignancies, which commonly cause side effects such as myelosuppression, alopecia, nausea and mucositis, and acute cardiotoxicity.…”

Effects of Salmon Calcitonin on Mechanical Properties of Healing and Intact Bone and Skin in Rats

“…These specimens were tested in tension until failure (elongation rate 0.09 mm/mm/second), as previously described (Engesreter & Skar 1978, Wie et al 1979). …”