A high dose of teriparatide in combination with denosumab increases bone mineral density (BMD) in postmenopausal women with osteoporosis to a greater extent than a lower-dose regimen.
The latest findings suggest that high-dose teriparatide “stimulates even greater separation between bone resorption and formation than that of standard-dose teriparatide,” wrote Joy N. Tsai, MD, of Harvard Medical School, Boston, and her coauthors in Lancet Diabetes & Endocrinology.
Previously, findings from the Denosumab and Teriparatide Administration (DATA) study showed that a combination of teriparatide and denosumab increased both BMD and estimated bone strength more than either drug alone. To determine if a higher dose of teriparatide plus denosumab would result in larger increases in BMD, investigators in the DATA-HD study randomly assigned 76 postmenopausal women with osteoporosis to receive either 40 μg of teriparatide daily (higher dose; n = 37) or 20 μg of teriparatide daily (standard dose; n = 39). At 3 months, patients in both groups were also started on 60 mg of denosumab every 6 months. Of the initial participants, 69 completed at least one postbaseline visit and were included in the analysis.
At the 15-month follow-up, areal BMD (aBMD) had increased in both groups in all measured sites – lumbar spine, femoral neck, total hip, and distal radius. Patients in the 40-μg group had a significantly higher increase in mean lumbar spine aBMD (17.5%), compared with those in the 20-μg or standard-dose group (9.5%; 95% confidence interval, 5.5-10.6; P less than .0001).
There was also a greater increase in mean femoral neck aBMD in patients in the 40-μg group (6.8%), compared with those in the 20-μg group (4.3; 95% CI, 0.5-4.5; P = .04) and in mean total hip aBMD (6.1% vs. 3.9%, 95% CI; 0.6-3.8, P less than .0001).
In all, 29 participants in the 40-μg group (78%) and 30 participants in the 20-μg group (77%) had adverse events, but with the exceptions of headache and rash, all serious adverse events were considered unrelated to treatment.
The authors noted the limitations of their study, including that it was conducted at a single site with a predominantly white population. In addition, the authors acknowledged that the small sample size did not allow for “direct assessment of fracture benefit [or] for rigorous evaluation of the tolerability and safety of this treatment.”
In an accompanying editorial, Sundeep Khosla, MD, of the Mayo Clinic, Rochester, Minn., wrote that the benefits of personalizing treatment for osteoporosis patients at high risk of fracture seemed to be coming into focus (Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30266-9).
Although the DATA and DATA-HD studies of teriparatide and denosumab reported by Dr. Tsai and colleagues have their limitations – including a small sample size for DATA-HD – they indicate the “possibility of refining treatment for patients with osteoporosis at high risk of fracture and personalizing treatment for these patients beyond the one-size-fits-all approach currently used,” Dr. Khosla wrote. Rather than offer bisphosphonates at standardized doses, patients at high risk could now be considered for the newly recommended high-dose teriparatide and denosumab combination, he said.
Dr. Khosla also noted that price remains an issue, given the estimated cost of $76,000 for 15 months of this proposed combination. However, the benefits in regard to at least bone mineral density are clear, he added, and that might prove sufficient enough for high-risk patients in need of an alternative therapy.
The study was supported by the Dart Family Foundation, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Eli Lilly and Amgen supplied the drugs. The authors reported numerous conflicts of interest, including receiving grants, reimbursements, and personal fees from various pharmaceutical companies, committees, and research institutes. Dr. Khosla reported no conflicts of interest.
SOURCE: Tsai JN et al. Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30255-4.