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Research Article
Michio Nakamura
Sapporo City General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1509-9811
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose
We previously reported that the periodic premedication of glucocorticoids during chemotherapy for gastrointestinal cancer (GIC) caused the reduction of bone mineral densities (BMD) (ESPRESSO-01). We conducted this study to evaluate the efficacy and safety of denosumab in the prevention of chemotherapy-induced decreased BMD.
Methods
Forty-two Japanese patients were studied. Denosumab was administered as a single 60 mg subcutaneous injection before the start of chemotherapy. The primary endpoint was BMD change in the lumbar spine from baseline to 16 weeks. Secondary endpoints were changes in serum cross-linked N-telopeptides of type I collagen (sNTX) and bone alkaline phosphatase (sBAP), complications including hypocalcemia and osteonecrosis of the jaw, new bone fractures, changes in the Japanese Osteoporosis Quality of Life Questionnaire.
Results
Lumbar spine BMD significantly increased in 71.4% of cases: 2.772% (95% CI, 1.350–4.195%: P < 0.0001). There were also significant decreases in sNTX (P = 0.034) and sBAP levels (P < 0.001). Although one case (2.4%) of jaw osteonecrosis was diagnosed, no fractures occurred. In a cross-trial comparison with ESPRESSO-01, there was no significant difference in the incidence of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher adverse events. However, inclusion of grade ≤ 2 showed significantly higher incidence of hypocalcemia with any CTCAE grade in ESPRESSO-02 (28.4% in ESPRESSO-01, 54.8% in ESPRESSO-02, P = 0.006)
Conclusion
Denosumab administration prevented secondary BMD reduction in GIC patients undergoing chemotherapy, and was associated with decreased serum levels of the bone turnover markers BAP and NTX.
Keywords
cancer treatment-induced bone loss, denosumab, gastrointestinal cancer, steroid-induced osteoporosis, glucocorticoid premedication
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Michio Nakamura
Sapporo City General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1509-9811
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Journal of Clinical Oncology.
Version 1
Posted 08 Apr, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Clinical Oncology.
Purpose
We previously reported that the periodic premedication of glucocorticoids during chemotherapy for gastrointestinal cancer (GIC) caused the reduction of bone mineral densities (BMD) (ESPRESSO-01). We conducted this study to evaluate the efficacy and safety of denosumab in the prevention of chemotherapy-induced decreased BMD.
Methods
Forty-two Japanese patients were studied. Denosumab was administered as a single 60 mg subcutaneous injection before the start of chemotherapy. The primary endpoint was BMD change in the lumbar spine from baseline to 16 weeks. Secondary endpoints were changes in serum cross-linked N-telopeptides of type I collagen (sNTX) and bone alkaline phosphatase (sBAP), complications including hypocalcemia and osteonecrosis of the jaw, new bone fractures, changes in the Japanese Osteoporosis Quality of Life Questionnaire.
Results
Lumbar spine BMD significantly increased in 71.4% of cases: 2.772% (95% CI, 1.350–4.195%: P < 0.0001). There were also significant decreases in sNTX (P = 0.034) and sBAP levels (P < 0.001). Although one case (2.4%) of jaw osteonecrosis was diagnosed, no fractures occurred. In a cross-trial comparison with ESPRESSO-01, there was no significant difference in the incidence of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher adverse events. However, inclusion of grade ≤ 2 showed significantly higher incidence of hypocalcemia with any CTCAE grade in ESPRESSO-02 (28.4% in ESPRESSO-01, 54.8% in ESPRESSO-02, P = 0.006)
Conclusion
Denosumab administration prevented secondary BMD reduction in GIC patients undergoing chemotherapy, and was associated with decreased serum levels of the bone turnover markers BAP and NTX.
Figure 1
Figure 2
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