Impact of romosozumab on serum calcium concentration and factors predicting the fluctuations in calcium concentration upon romosozumab administration: A multicenter retrospective study

Hiroyuki Inose; Tsuyoshi Kato; Shoji Tomizawa; Akane Ariga; Takayuki Motoyoshi; Kazuyuki Fukushima; Kunihiko Takahashi; Toshitaka Yoshii; Atsushi Okawa

doi:10.1016/j.bonr.2022.101635

Impact of romosozumab on serum calcium concentration and factors predicting the fluctuations in calcium concentration upon romosozumab administration: A multicenter retrospective study

Bone Rep. 2022 Nov 7:17:101635. doi: 10.1016/j.bonr.2022.101635. eCollection 2022 Dec.

Authors

Hiroyuki Inose¹, Tsuyoshi Kato², Shoji Tomizawa³, Akane Ariga⁴, Takayuki Motoyoshi⁴, Kazuyuki Fukushima⁴, Kunihiko Takahashi⁵, Toshitaka Yoshii⁶, Atsushi Okawa⁶

Affiliations

¹ Department of Orthopedic and Trauma Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
² Department of Orthopaedics, Ome Municipal General Hospital, 4-16-5 Higashiome, Ome-shi, Tokyo 198-0042, Japan.
³ Department of Orthopedics, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32 Todaijima, Urayasu-shi, Chiba 279-0001, Japan.
⁴ Department of Orthopedics, Saku Central Hospital Advanced Care Center, 3400-28, Nakagomi, Saku-shi, Nagano 384-0301, Japan.
⁵ Department of Biostatistics, M&D Data Science Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁶ Department of Orthopaedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Abstract

Objectives: As romosozumab has both bone anabolic and antiresorptive effects, it is not clear which patient groups are more likely to have decreased calcium concentrations when treated with romosozumab. The aim of this study was to investigate the impact of romosozumab treatment on serum calcium concentration in patients with osteoporosis with a high risk of fractures and identify factors that might be associated with, or even predict, a fluctuation in calcium concentration upon romosozumab administration.

Materials and methods: In total, 47 patients were included in this retrospective study. We performed a Wilcoxon signed-rank test to identify differences in the calcium concentration before and 1 month after romosozumab initiation. Associations between baseline variables and changes in serum calcium concentration were investigated with a multiple-linear regression model using a forward-backward stepwise procedure.

Results: Romosozumab administration reduced the serum calcium concentration by an average of 3.1 % after 1 month. No patient complained of symptoms of hypocalcemia during the first month after treatment. Univariate regression analysis showed that age and calcium concentration were significantly associated with the decrease in serum calcium concentrations by romosozumab administration. In addition, stepwise regression analysis identified age and calcium concentrations as independent factors associated with the decrease in calcium concentration by romosozumab.

Conclusion: Romosozumab administration caused a modest but significant decrease in serum calcium concentration. Older age and higher baseline calcium concentrations were associated with a greater decrease in calcium concentrations by romosozumab administration. Although the likelihood of severe hypocalcemia from romosozumab administration may be low, physicians prescribing romosozumab to patients with osteoporosis should be aware of the symptoms of hypocalcemia and promptly evaluate calcium levels if patients complain of these symptoms.

Keywords: ALP, alkaline phosphatase; BMD, bone mineral density; Bone density; Calcium; DXA, dual-energy X-ray absorptiometry; Hypocalcemia; Osteoporosis; P1NP, procollagen type 1 amino-terminal propeptide; SD, standard deviation; TRACP-5b, tartrate-resistant acid phosphatase 5b.