The anti-sclerostin monoclonal antibody romosozumab appeared to retain its anabolic potential when added to ongoing treatment with the anti-RANKL monoclonal antibody denosumab for 12 months in postmenopausal women with severe osteoporosis, based on a combined retrospective and prospective study published by Adami et al in the journal Arthritis & Rheumatology.
Transitioning from denosumab to romosozumab may expose patients to the “rebound effect”—rapid bone loss upon treatment cessation—the investigators noted, underscoring the potential benefit of adding romosozumab while continuing denosumab in those experiencing a fracture. They commented, “Our preliminary study demonstrated that adding romosozumab to ongoing denosumab treatment improved lumbar spine bone mineral density significantly in 6 months. Moreover, we previously showed that denosumab increased circulating sclerostin levels, supporting the hypothesis that adding romosozumab could exploit this mechanism to enhance bone mineral density responses in patients already on denosumab.”
The findings from the present study, they added, “support the combination of romosozumab and denosumab in patients with severe osteoporosis treated with long-term denosumab in whom the response to treatment is not deemed adequate.”
Study Details
In this 36-month study, analyzed with prospective score matching, a total of 50 patients were evenly divided into two groups: one received treatment with denosumab alone for 36 months, while the other was administered denosumab for 24 months followed by denosumab plus romosozumab for the final 12 months.
The investigators assessed bone mineral density and bone turnover markers (C-terminal telopeptide of type I collagen [CTX] and procollagen I intact N-terminal peptide [P1nP]) at follow-up time points.
Key Findings
At 12 months after the initial denosumab treatment period, the between-group difference was 3.3% (95% confidence interval = −5.2%–11.8%), which the investigators noted as indicating a nonsignificant trend toward greater improvement with the addition of romosozumab. Denosumab with vs without romosozumab was found to result in a significant 22.5-ng/mL increase in the P1nP biomarker from the time the assigned treatment was initiated to 3 months later (standard error = 8.7 ng/mL, P = .028).
“Ongoing treatment with denosumab did not blunt the anabolic response of romosozumab, indicating sustained modeling-based bone formation activity,” the investigators concluded. “Adding romosozumab in patients failing denosumab might be a valuable option.” However, they noted that “these findings should be interpreted as exploratory and hypothesis-generating, pending confirmation in larger, prospective studies.”
Giovanni Adami, MD, PhDc, of the University of Verona, Italy, is the corresponding author of the article in Arthritis & Rheumatology.
Disclosure: For full disclosures of the study authors, visit acrjournals.onlinelibrary.wiley.com.
Source: Arthritis & Rheumatology