The use of denosumab demonstrates superior protection against bone mineral density (BMD) loss at 12 months compared with alendronate in older patients with newly diagnosed lymphoma receiving R-CHOP* and related regimens, as shown in the DENOSULY study.
“Significant benefits were observed at both the lumbar spine and femoral neck, with a favourable safety profile,” said lead study author Dr Toshihiro Miyamoto, Kanazawa University, Kanazawa, Japan.
Miyamoto and his team randomly allocated 100 patients with newly diagnosed malignant lymphoma who were scheduled to receive steroid-containing chemotherapy to receive either denosumab (n=52) or alendronate (n=48). No significant differences were noted in baseline characteristics, BMD, and bone turnover markers between treatment groups.
At 12 months, denosumab showed superiority to alendronate for the percent change in lumbar spine (L2‒L4) BMD (2.8 vs ‒1.3; p=0.0010) and (L1‒L4) BMD (2.7 vs ‒1.0; p=0.0054), as well as at the femoral neck (2.8 vs ‒3.6; p=0.0020). However, no significant between-group difference was seen at the total hip. [EHA 2026, abstract PF988]
Denosumab also performed better than alendronate in suppressing the bone resorption marker TRACP-5b (‒36.5 percent vs 0.2 percent; p=0.0003) at 6 months. On the other hand, the bone formation marker total P1NP did not significantly differ between the two groups (7.5 percent vs 38.6 percent; p=0.1929).
Safety profile
Both denosumab and alendronate had a favourable safety profile. Grade ≥3 hypocalcemia or osteonecrosis of the jaw did not occur, and serious adverse events (AEs) were deemed unrelated to either study drug, according to the authors.
“Since denosumab showed significant superiority over alendronate at both the lumbar spine and femoral neck, denosumab may be the preferred agent in lymphoma therapy–related (LTR) glucocorticoid-induced osteoporosis (GIOP),” wrote Miyamoto and colleagues. [Haematologica 2026;doi:10.3324/haematol.2026.300564]
“Recognizing R-CHOP recipients as a very high-risk population, our findings underscore the need for immediate, enhanced prophylaxis with denosumab to prevent LTR-GIOP and improve long-term survivorship and quality of life,” they added.
DENOSULY, a prospective, multicentre, open-label, phase III randomized controlled trial, enrolled older patients (aged ≥65 years) with malignant lymphoma. Participants were stratified by age (≥80 years) and sex prior to randomization.
Patients assigned to the denosumab arm received denosumab 60 mg subcutaneously at the initiation of chemotherapy and again at 6 months (two total doses). Those assigned to the alendronate arm received oral alendronate 35 mg once weekly for 12 months.
The percent change in lumbar spine BMD at 12 months served as the primary endpoint, while secondary endpoints included percent change in BMD at additional skeletal sites (ie, lumbar spine, total hip, and femoral neck) at 6 and 12 months, longitudinal changes in bone turnover markers at 6 months, and safety outcomes (ie, serious AEs and AEs of special interest).
“R-CHOP and related regimens use repeated short courses of high-dose glucocorticoids, which can induce GIOP and fractures,” said Miyamoto and colleagues.
“However, conventional GIOP guidelines are largely based on chronic low-dose steroid exposure and may not address this distinct setting, termed LTR-GIOP,” they added.
Bisphosphonates have been shown to provide some benefits, but data for LTR-GIOP are lacking, and no clinical trials have explored the use of denosumab in this setting, the authors said.
*Rituximab, Cyclophophamide, Hydroxydaunomycin (Doxorubicin), Oncovin (Vincristine), Prednisone (or Prednisolone