medwireNews: Combining denosumab with high-dose rather than standard-dose teriparatide results in greater increases in spine and hip bone mineral density (BMD) in postmenopausal women with osteoporosis, phase IV study data show.
“This novel combination of high dose anabolic and antiresorptive treatment could have important therapeutic implications for the treatment of women at high risk of fragility fractures,” write Joy Tsai (Harvard Medical School, Boston, Massachusetts, USA) and co-investigators in The Lancet Diabetes & Endocrinology.
In the previously published Denosumab and Teriparatide Administration (DATA) study, the researchers showed that “denosumab fully inhibits teriparatide-induced bone resorption while allowing for continued teriparatide-induced bone formation, resulting in larger increases in hip and spine bone mineral density […] than with either drug alone.”
The current DATA-HD trial compared the efficacy of 9 months of daily subcutaneous treatment with high-dose teriparatide 40 μg with that of the standard-dose 20 μg. After 3 months, both groups also began subcutaneous denosumab 60 mg every 6 months for 12 months.
Tsai et al report that, at 15 months, mean spine areal (a)BMD had increased by 17.5% in the 34 women who received high-dose teriparatide. This was significantly higher than the 9.5% increase observed among the 35 women who received the standard-dose treatment.
Mean femoral neck aBMD also increased to a significantly greater degree in the 40 μg versus 20 μg group (6.8 vs 4.3%), as did mean total hip aBMD (6.1 vs 3.9%).
Greater improvements at each of the three sites were also observed at 9 months, and a similar pattern was seen for volumetric BMD at each of the three sites, as well as for spine and hip strength.
Adverse events occurred at a similar rate in the high- and standard dose groups (78 vs 77%), but there were fewer serious adverse events with the high-dose treatment (5 vs 18%).
Tsai and co-authors conclude that a study assessing “the potential of this combination to reduce the incidence of fractures compared with the current standard of osteoporosis care is warranted.”
In an accompanying comment, Sundeep Khosla, from the Mayo Clinic College of Medicine in Rochester, Minnesota, USA, says: “DATA-HD is important because the increases in BMD and estimated bone strength using high dose teriparatide and denosumab seem to be greater across multiple skeletal sites than any single drug regimen (including the recently approved sclerostin antibody, romosozumab), or any previous combination treatment.”
He adds that the findings point to the possibility of personalizing treatment for osteoporosis, suggesting that those at high risk for fracture “could be considered for treatment with high dose teriparatide and denosumab to rapidly and substantially increase their BMD, which in many cases could perhaps result in the achievement of non-osteoporotic BMDs.”
The study authors note that the small study size “does not allow for direct assessment of fracture benefit.” Nonetheless, the DATA and DATA-HD trials “have established the efficacy of combination therapy at least on BMD, which is a viable surrogate for fracture risk,” says Khosla.
He concludes: “Ideally, large-scale fracture trials should be done to compare combination therapy with monotherapy, but for many high-risk patients, the BMD findings might be sufficient to warrant a course of combination therapy with high dose teriparatide and denosumab to markedly improve their osteoporosis.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(19)30255-4
Lancet Diabetes Endocrinol 2019; doi: 10.1016/S2213-8587(19)30266-9