Effects of doxorubicin administration on bone strength and quality in sedentary and physically active Wistar rats

Fonseca, Hélder; Carvalho, António P. O.; Esteves, J. L.; Esteves, Valdemar I.; Moreira-Gonçalves, Daniel; Duarte, José Alberto

doi:10.1007/s00198-016-3672-x

Cited by 11 publications

(10 citation statements)

References 40 publications

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“…Indeed, Fonseca et al . previously reported that anti-cancer drugs, such as doxorubicin, routinely used in pediatric cancer treatment, not only promote muscle wasting 35 , but also negatively affects the overall bone morphology, as well as the femur mechanical properties in rats 74 . This is of particular importance, especially considering that patients affected with metastatic colorectal cancer usually undergo multiple rounds of chemotherapy treatment, thereby having far more chances to develop such toxicity.…”

Section: Discussionmentioning

confidence: 99%

ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass

Barreto

Kitase

Matsumoto

et al. 2017

Sci Rep

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Chemotherapy promotes the development of cachexia, a debilitating condition characterized by muscle and fat loss. ACVR2B/Fc, an inhibitor of the Activin Receptor 2B signaling, has been shown to preserve muscle mass and prolong survival in tumor hosts, and to increase bone mass in models of osteogenesis imperfecta and muscular dystrophy. We compared the effects of ACVR2B/Fc on muscle and bone mass in mice exposed to Folfiri. In addition to impairing muscle mass and function, Folfiri had severe negative effects on bone, as shown by reduced trabecular bone volume fraction (BV/TV), thickness (Tb.Th), number (Tb.N), connectivity density (Conn.Dn), and by increased separation (Tb.Sp) in trabecular bone of the femur and vertebra. ACVR2B/Fc prevented the loss of muscle mass and strength, and the loss of trabecular bone in femurs and vertebrae following Folfiri administration. Neither Folfiri nor ACVR2B/Fc had effects on femoral cortical bone, as shown by unchanged cortical bone volume fraction (Ct.BV/TV), thickness (Ct.Th) and porosity. Our results suggest that Folfiri is responsible for concomitant muscle and bone degeneration, and that ACVR2B/Fc prevents these derangements. Future studies are required to determine if the same protective effects are observed in combination with other anticancer regimens or in the presence of cancer.

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Section: Discussionmentioning

confidence: 99%

ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass

Barreto

Kitase

Matsumoto

et al. 2017

Sci Rep

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“…A clinical report indicated that premenopausal breast cancer patients treated with AC combination resulted in a lower bone mineral density and significant bone loss [ 18 ]. Animal studies have also reported that adriamycin exposure caused a reduction in bone formation due to reduced osteoblast differentiation [ 19 ], and can negatively affect bone trabecular microarchitecture and mechanical properties [ 20 ]. Using a rat AC treatment model mimicking the clinical setting, our recent animal study also revealed that 4 cycles of AC treatment were able to cause severe bone marrow damage and some reduction in trabecular bone volume [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats

Fan

Howe

et al. 2018

IJMS

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Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.

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“…Patient did not reach the average Swedish height, but body growth was harmonic. We can hypothesize that chemotherapy treatment with Vinkristin, Ifofosfamid, Etoposid and especially Doxorubicin affected the patient's overall growth (Fonseca et al, ).…”

Section: Discussionmentioning

confidence: 99%

Double‐barrel vascularized dual fibula transfer with epiphyseal growth plate for hip reconstruction: A case report

et al. 2018

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We present a case report of a 10-year-old girl diagnosed with Ewing sarcoma treated with intra-articular wide resection of the right femur and reconstruction with a series-connected double-barrel bilateral vascularized fibula graft (db-BVFG), including fibular head for articulation with the acetabulum of the pelvic bone and preservation of the epiphyseal growth plates for eventual limb growth. No postoperative complications were observed and bone union was achieved with fibular graft hypertrophy, allowing for full weight bearing. Neither local recurrence nor metastasis was observed at 17-year follow-up. Range of motion degrees at last follow up: hip flexion 90 degree, extension 12 degree, abduction 31 degree, rotation 25 degree. Right versus left limb discrepancy was 60 mm. Db-BVFG may be an option for reconstruction of long femoral defects and hip joint restoration following tumor resection and inclusion of epiphysis within the graft is a viable option in pediatric patients to restore longitudinal growth of the reconstructed long bone.

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Effects of doxorubicin administration on bone strength and quality in sedentary and physically active Wistar rats

Abstract: DOX negatively affects bone geometry, trabecular microarchitecture, and femur mechanical properties in growing Wistar rats. Exercise further aggravates the detrimental effects of past DOX treatment on bone mechanical properties.

Cited by 11 publications

References 40 publications

ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass

ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats

Double‐barrel vascularized dual fibula transfer with epiphyseal growth plate for hip reconstruction: A case report

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