1,343 Patient FREEDOM Study Pegs Fracture Risk After Denosumab

Hoping to home in on a therapeutic target, a multinational study has delved into the relationship between treating bone mineral density with denosumab and the incidence of nonvertebral fracture.

The work, “Relationship Between Bone Mineral Density T‐Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment,” was published in the June 2019 edition of the Journal of Bone and Mineral Research.

Co-author Serge Ferrari, M.D. with the Geneva University Hospital in Switzerland explained to OTW why he and his colleagues were attracted to this study focus: “We were seeing disbelief about BMD [bone mineral density] gains on therapy representing a decreased risk of fractures.”

According to Dr. Ferrari and his co-authors, only a few studies have examined the link between risk of fracture and the levels of bone mineral density following treatment with Denosumab.

“We investigated the relationship between total hip BMD T‐score and the incidence of nonvertebral fracture in women who received up to 10 years of continued denosumab therapy in the FREEDOM (3 years) study and its long‐term Extension (up to 7 years) study,” they explained.

“In brief, the 3‐year FREEDOM trial was a phase 3, multicenter, randomized, double‐blind, placebo‐controlled study conducted at 214 centers worldwide. Enrolled subjects were postmenopausal women between the ages of 60 to 90 years with a lumbar spine or total hip T‐score < ‐2.5 at either site but ≥ ‐4.0 at both sites. Subjects were randomized to receive 60 mg of denosumab or placebo subcutaneously every 6 months for 3 years and took daily vitamin D (≥ 400 IU) and calcium (≥ 1 g) supplements.”

Of the 1,343 women who completed 10 years of denosumab treatment, “…373 subjects had nonvertebral fractures during denosumab treatment; 42 had hip fractures, and 155 had wrist fractures. The incidence of nonvertebral fractures and hip fractures was significantly lower among subjects who had at least one postbaseline total hip T‐score of > ‐1.5 versus those who did not (9% versus 12% for nonvertebral fractures, and 0.5% versus 2% for hip fractures.”

Dr. Ferrari commented to OTW, “We found that higher BMD (T-scores) on therapy were associated with decreasing fracture risk up to a ‘threshold’ of minimal risk (for a given population) around -1.5 T-score, i.e., mild osteopenia. BMD monitoring on therapy is useful to reassess fracture risk and for making decisions about the stop/go of treatment.”