Materials and methods

Study design and participants

We conducted a prospective observational study beginning in July 2019. Patients with rheumatic diseases who were receiving GCs equivalent to 5 mg or more of PSL per day and BP for 6 mo or longer, were included. The following patients were excluded: those with contraindications to ROMO; those with conditions requiring caution for ROMO use (eg, a history of cardiovascular or cerebrovascular events within the past year); those with active infections or malignancies; those under 20 yr of age; and those wishing to become pregnant. Decisions regarding osteoporosis treatment (switching from BP to ROMO or continuing BP) were made by the attending physician for each patient. Patients who switched from BP to ROMO were classified as the ROMO group, while those who continued with BP were classified as the BP group.

The primary endpoint was the changes in LS BMD at 12 mo. Secondary endpoints included changes in the BMD of the FN and TH at 12 mo, changes in bone turnover markers over 12 mo, incidence of new fractures, and adverse events.

Measurement of BMD

DXA was performed every 6 mo to evaluate the BMD of the LS (L2**-**4), FN, and TH. Discovery A (Hologic, Waltham, MA, USA) was used for measurements, automatically calculating BMD from bone area (cm2), and BMC (g), with the results expressed in g/cm2.

Biochemical markers

Fasting morning blood samples were collected at baseline and at 3, 6, 9, and 12 mo after the start of the study to assess bone turnover markers. A subset of the serum samples was promptly frozen at −80 °C and preserved until analysis via ELISA. Serum concentrations of bone formation markers, including total P1NP and osteocalcin (OC), were quantified using electrochemiluminescence immunoassays. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), a bone resorption marker, was measured using enzyme immunoassays. Urinary pentosidine, which serves as a bone matrix marker, was assessed using HPLC. Serum 25OHD concentrations were also measured using chemiluminescent enzyme immunoassay. Additional biomarkers, including serum sclerostin, Dkk-1, RANKL, and osteoprotegerin (OPG) (R&D Systems, Minneapolis, MN, USA) and Wnt3a (ABclonal, Woburn, MA, USA), were quantified using ELISA kits in accordance with the manufacturers’ instructions.

Statistical analysis

The baseline characteristics of patients within the safety analysis set, defined as those who received at least 1 dose of the investigational drug, were expressed using medians with interquartile ranges for continuous variables, and n (%) for categorical variables. Differences between the 2 groups for numerical data were assessed using the Kruskal-Wallis test. Changes in BMD and bone turnover markers within each group were evaluated as percent changes from baseline using the full analysis set (FAS). Temporal changes within each group were examined using Dunn’s multiple comparison test, while differences between baseline and each subsequent time point across groups were performed using Bonferroni’s multiple comparison test. In addition, the percent changes in BMD from baseline to 12 mo were compared between the ROMO and BP groups using a linear regression model adjusted for age. Results are presented as regression coefficients (β) with corresponding 95% CIs. A p-value of <.05 was considered statistically significant. Multivariable analyses were performed using R version 4.4.0 (R Core Team 2024, Vienna, Austria), while other statistical procedures were conducted using Prism version 9.0 (GraphPad Software, San Diego, CA, USA).

Ethical statement

This study was approved by the Ethics Committee of Toho University Omori Medical Center (approval number; M18256_M24215 23 064), and it complied with the 1964 Declaration of Helsinki and its later amendments and Ethical Guidelines for Medical and Health Research Involving Human Subjects by the Ministries of Education, Culture, Sports, Science and Technology and Health, Labour and Welfare of the Japanese Government. All participants who were included in this study gave their written informed consent.