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Archives of Osteoporosis
Published in: Archives of Osteoporosis 1/2019

01-12-2019 | Kidney Transplantation | Review Article

Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis

Authors: Charat Thongprayoon, Prakrati Acharya, Narothama Reddy Aeddula, Aldo Torres-Ortiz, Tarun Bathini, Konika Sharma, Patompong Ungprasert, Kanramon Watthanasuntorn, Maria Lourdes Gonzalez Suarez, Sohail Abdul Salim, Wisit Kaewput, Jirat Chenbhanich, Michael A. Mao, Wisit Cheungpasitporn

Published in: Archives of Osteoporosis | Issue 1/2019

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Abstract

Objective

The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear.

Methods

A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab’s effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055).

Results

Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m2. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88–5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, − 0.13 to 1.16) mmol/L and − 13.24 (95% CI, − 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements.

Conclusion

Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.
Appendix
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Metadata
Title
Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis
Authors
Charat Thongprayoon
Prakrati Acharya
Narothama Reddy Aeddula
Aldo Torres-Ortiz
Tarun Bathini
Konika Sharma
Patompong Ungprasert
Kanramon Watthanasuntorn
Maria Lourdes Gonzalez Suarez
Sohail Abdul Salim
Wisit Kaewput
Jirat Chenbhanich
Michael A. Mao
Wisit Cheungpasitporn
Publication date
01-12-2019

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