Effect of Romosozumab Treatment in Postmenopausal Women With Osteoporosis and Knee Osteoarthritis: Results From a Substudy of a Phase 3 Clinical Trial

Abstract

Objective: Romosozumab is a bone-forming agent approved for osteoporosis treatment. Here we report results of the protocol-specified, noninferiority osteoarthritis substudy of the fracture study in postmenopausal women with osteoporosis (FRAME), which evaluated the effect of romosozumab versus placebo on knee osteoarthritis in patients with a clinical history of osteoarthritis.

Methods: Women in FRAME with a history of knee osteoarthritis were eligible for enrollment in the osteoarthritis substudy; key inclusion criteria were osteoarthritis-related signal knee pain, morning stiffness lasting less than 30 minutes, knee crepitus, and knee osteoarthritis confirmed by x-ray within 12 months. The protocol-specified outcomes were change from baseline through month 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, incidence of worsening knee osteoarthritis, and treatment-emergent adverse events (TEAEs) with romosozumab versus placebo. In a post hoc analysis, percentage change from baseline to month 12 in bone mineral density (BMD) was assessed.

Results: Of 7180 women in FRAME, 347 participated in the osteoarthritis substudy (placebo, 177; romosozumab, 170). At month 12, no significant difference in progression of knee osteoarthritis was observed with romosozumab versus placebo (least squares mean total WOMAC score: -2.2 vs. -1.3; P = 0.71). Incidence of worsening symptoms of knee osteoarthritis was comparable between romosozumab (17.1%) and placebo (20.5%) (odds ratio 0.9 [95% confidence interval: 0.5, 1.7]; P = 0.69). Incidence of TEAEs of osteoarthritis was numerically lower with romosozumab (13 [7.7%]) versus placebo (21 [12.0%]). BMD gains were higher with romosozumab.

Conclusion: Romosozumab treatment did not impact knee pain or function in postmenopausal women with osteoporosis and knee osteoarthritis and resulted in significant BMD gains in these women.

© 2023 Amgen and The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1

Study designs. A, FRAME overall study. B, Planned FRAME Osteoarthritis Substudy. N = number of women randomized or planned. aThe planned sample size for the FRAME Osteoarthritis Substudy was up to 300 women (placebo, 150; romosozumab, 150); the actual number enrolled was 347 (placebo, 177; romosozumab, 170). A total of 343 women received at least one dose of the investigational product and had at least one WOMAC questionnaire result and were included in the current analysis (placebo, 175; romosozumab, 168). FRAME, Fracture Study in Postmenopousal Women With Osteoporosis; QM, monthly; Q6M, every 6 months; SC, subcutaneous; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 2

Patient disposition in the FRAME osteoarthritis substudy. aReasons for exclusion from the substudy are shown in Table 1. bThe planned sample size for the FRAME osteoarthritis substudy was up to 300 women (placebo, 150; romosozumab, 150); however, a total of 347 women participated in the substudy (placebo, 177; romosozumab, 170). FRAME, fracture study in postmenopausal women with osteoporosis; QM, monthly; SC, subcutaneous; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 3

Incidence of worsening symptoms of knee osteoarthritis through month 12. N = number of women enrolled in the FRAME osteoarthritis substudy who received one or more doses of the investigational product and had one or more WOMAC questionnaire results. N1 = number of women enrolled in the FRAME osteoarthritis substudy with one or more doses of the investigational product and a nonmissing WOMAC total score at both baseline and post baseline. n = number of women with worsening symptoms of knee osteoarthritis. Based on the logistic regression model adjusted for age, baseline BMI, and baseline WOMAC total score; the P value is based on the test score. BMI, body mass index; CI, confidence interval; FRAME, fracture study in postmenopausal women with osteoporosis; OR, odds ratio; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 4

BMD percentage change from baseline to month 12 at the lumbar spine, total hip, and femoral neck. N = number of women enrolled in the FRAME osteoarthritis substudy who received one or more doses of the investigational product and had one or more WOMAC questionnaire results. n = number of women with evaluable data. Based on the ANCOVA model adjusted for age and prevalent vertebral fracture stratification variables, baseline value, machine type, and baseline value‐by‐machine type interaction. Missing values were imputed by carrying forward the last nonmissing postbaseline value. ANCOVA, analysis of covariance; BMD, bone mineral density; CI, confidence interval; Diff, difference for romosozumab minus placebo; FRAME, fracture study in postmenopausal women with osteoporosis; LS, least squares; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.