NEW YORK (Reuters Health)—Adding high-dose teriparatide to denosumab therapy leads to substantially greater increases in bone-mineral density (BMD) than combination therapy with low-dose teriparatide, a new phase 4 study shows.
“The combination of denosumab and teriparatide, particularly with high-dose teriparatide of 40 ug daily, may be of benefit to patients at very high risk of fracture,” Joy N. Tsai, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, the study’s first author, tells Reuters Health by email.
Osteoporosis drugs now available have modest effects on BMD and non-vertebral fracture risk, she and her colleagues note in The Lancet Diabetes and Endocrinology, online Aug. 22.1
In the Denosumab and Teriparatide Administration (DATA) trial, Dr. Tsai and her team found adding teraparatide to denosumab “increased BMD, improved skeletal microarchitecture, and increased estimated bone strength to a greater extent than either drug alone.”
“The efficacy of this combination is likely to be due to denosumab’s ability to fully block the resorptive effects of teriparatide while possibly allowing for teriparatide-induced stimulation of modelling-based bone formation,” they add.
In DATA-HD, the authors randomized 76 postmenopausal women with osteoporosis to 20 or 40 ug teriparatide for nine months. Three months into the study, all study participants began receiving 60 mg of denosumab every six months for 12 months.
At 15 months, the higher-dose group had a 17.5% mean increase in spine aBMD vs. 9.5% for the lower-dose group (P<0.0001). Femoral neck aBMD increased by 6.8% and 4.3% (P=0.04), respectively, and total hip by 6.1% and 3.9% (P<0.0001), respectively.
Volumetric BMD also showed significantly greater increases with the higher-dose treatment at all sites. Spine strength at 15 months was 33.3% higher with the 40 ug dose versus 18.5% with 20 ug, and mean total hip strength increased by 7.9% and 4.3%, respectively.
“Next steps include physiology-based studies to better understand what makes this particular combination of osteoporosis uniquely efficacious in increasing bone density and potentially a fracture outcome study to further support the clinical value of this regimen,” Dr. Tsai says.
“Using a combination of drugs for osteoporosis, namely teriparatide at twice the FDA-approved dose, along with denosumab actually resulted in greater increases in bone density than either drug alone,” Sundeep Khosla, MD, of the Mayo Clinic College of Medicine, Rochester, Minn., tells Reuters Health by phone. “For patients who are at very high risk of fracture this kind of combination therapy may be an important option.”
In an editorial accompanying the study, Dr. Khosla noted that 15 months of the higher-dose therapy would cost $76,000, which would be expected to decline after teriparatide went off patent in August 2019, “although considering recent trends in generic drug pricing, a price decrease is by no means certain.”2
The National Institutes of Health and the Dart Foundation funded the research.
- Tsai JN, Lee H, David NL, et al. Combination denosumab and high dose teriparatide for postmenopausal osteoporosis (DATA-HD): A randomized, controlled phase 4 trial. Lancet Diabetes Endocrinol. 2019 Aug 22. pii: S2213-8587(19)30255-4. [Epub ahead of print]
- Khosla S. Personalizing osteoporosis treatment for patients at high risk of fracture. Lancet Diabetes Endocrinol. 2019 Aug 22. pii: S2213-8587(19)30266-9. [Epub ahead of print]