Kosuke Ebina1, Hideki Tsuboi2, Yoshio Nagayama3, Masafumi Kashii4, Shoichi Kaneshiro5, Akira Miyama6, Hiroyuki Nakaya7, Yasuo Kunugiza8, Makoto Hirao6, Gensuke Okamura2, Yuki Etani6, Kenji Takami6, Atsushi Goshima6, Taihei Miura6, Ken Nakata9, Seiji Okada6. 1. Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, Suita 565-0871, Japan; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Suita 565-0871, Japan. Electronic address: k-ebina@ort.med.osaka-u.ac.jp. 2. Department of Orthopaedic Surgery, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Kita-ku 591-8025, Japan. 3. Nagayama Rheumatology and Orthopaedic Clinic, 4-3-25 Hiokisounishi-machi, Sakai, Higashi-ku 599-8114, Japan. 4. Department of Orthopaedic Surgery, Toyonaka Municipal Hospital, 4-14-1 Shibahara-cho, Osaka, Toyonaka 560-8565, Japan. 5. Department of Orthopaedic Surgery, Osaka Toneyama Medical Center, 5-1-1 Toneyama, Osaka, Toyonaka 560-8552, Japan. 6. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Suita 565-0871, Japan. 7. Department of Orthopaedic Surgery, Japan Community Health care Organization, Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka 553-0003, Japan. 8. Department of Orthopaedic Surgery, Japan Community Health care Organization, Hoshigaoka Medical Center, 4-8-1 Hoshigaoka, 573-8511, Hirakata, Osaka, Japan. 9. Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Osaka, Suita 565-0871, Japan.
Abstract
OBJECTIVES: To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. RESULTS: At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH. CONCLUSIONS: The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.
OBJECTIVES: To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. RESULTS: At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH. CONCLUSIONS: The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.
Authors: Felicia Cosman; David L Kendler; Bente L Langdahl; Benjamin Z Leder; E Michael Lewiecki; Akimitsu Miyauchi; Maria Rojeski; Michele McDermott; Mary K Oates; Cassandra E Milmont; Cesar Libanati; Serge Ferrari Journal: Osteoporos Int Date: 2022-02-15 Impact factor: 5.071