Romosozumab for managing severe osteoporosis in patients undergoing kidney transplantation: a retrospective case series

Abstract

Recipients of kidney grafts often develop severe osteoporosis. However, no consensus has emerged on the most appropriate medications for managing osteoporosis in these recipients. In this study, we investigated the efficacy of romosozumab as an additional treatment option for managing severe osteoporosis in kidney transplant recipients (KTRs). Our retrospective observational study included 12 such recipients who were treated with romosozumab for 12 mo-8 newly initiated on romosozumab and 4 treated with romosozumab after initial treatment with other agents. Endpoints were side effects, new fractures, blood tests, and changes in BMD. Pearson correlation coefficients were used to assess associations of the percent change in bone mineral density after 1 yr of treatment with age, dialysis duration, and time (yr) since transplantation. During treatment with romosozumab, the patients did not develop severe hypocalcemia or experience marked deterioration of kidney function at 1 yr post-treatment. Metabolic markers of bone formation and resorption were similar to those in the general population with osteoporosis. The average changes in BMD at the spine and total hip were 15.18% and 8.83%, respectively, indicating a favorable increase. Further, the change in spine BMD was inversely correlated with age and time since transplantation. Treatment of osteoporosis with romosozumab was observed to be safe for KTRs and had a favorable therapeutic effect on both spine and hip BMD.

Keywords: BMD; chronic kidney disease; kidney transplantation; osteoporosis; romosozumab.

Graphical Abstract

Figure 1-1

(A) Trend of the mean (±SE) estimated glomerular filtration rate (eGFR) during romosozumab treatment. The value at treatment initiation was 38.19 ± 2.80 mL/min/1.73 m², and after 12 mo of treatment, it was 35.93 ± 2.32 mL/min/1.73 m², indicating eGFR maintenance. (B) Corrected calcium (Ca) during romosozumab treatment. Ca reached its lowest value at the third month of treatment. (C) Mean (±SE) phosphorus (P) during romosozumab treatment. P remained constant throughout the 12 mo of treatment. (D) Mean (±SE) intact PTH during romosozumab treatment. Intact PTH reached its highest value in the third month of treatment, parallelling Ca. (E) Mean (±SE) total P1NP during romosozumab treatment. This bone formation marker increased rapidly in the first month after treatment initiation and then gradually declined. (F) Mean (±SE) tartrate-resistant acid phosphatase 5b (TRACP-5b) during romosozumab treatment. This bone resorption marker transiently increased in the third month after treatment initiation, but declined overall during treatment, remaining below baseline throughout 12 mo of treatment.

Figure 1-2

(A) Percent change in spine BMD during romosozumab treatment. Spine BMD rose to 15.18% ± 4.09%. (B) Percent change in total hip BMD during romosozumab treatment. Total hip BMD rose to 8.83% ± 2.36%. (C) Percent change of femoral neck BMD during romosozumab treatment. Femoral neck BMD rose to 6.34% ± 3.77%. All these BMD changes were favorable for the patients.

Figure 2

(A) The percent change in spine BMD was significantly inversely correlated with age (correlation coefficient: r = −0.7788 [equation: Y = −07788 ^* X + 60.94]; 95% confidence interval [CL]: −1.381 to −0.1763; p = .02). (B) The percent change in femoral neck BMD was significantly inversely correlated with age (correlation coefficient: r = −0.6153 [equation: Y = −0.6153 ^* X + 43.77]; 95% CI: −1.089 to −0.1421; p = .019). (C) The percent change in spine BMD was inversely correlated with years since kidney transplantation (correlation coefficient: r = −0.8927 [equation: Y = −0.8927 ^* X + 26.90]; 95% CI: −1.576 to −0.2091; p = .019).