Tsai JN, et al. - In view of the fact that denosumab fully inhibits teriparatide-induced bone resorption while allowing for continued teriparatide-induced bone formation, leading in larger increases in hip and spine BMD than with either drug alone in the Denosumab and Teriparatide Administration (DATA) study, researchers ascertained if administration of denosumab with high dose teriparatide would stimulate larger increases in bone mass than those observed in the DATA study. DATA-HD was an open-label, randomised, controlled phase 4 trial conducted at Massachusetts General Hospital. The study sample consisted of postmenopausal women (at least 36 months since last menses or since hysterectomy with a follicle-stimulating hormone concentration of ≥ 40 U/L) with osteoporosis. Through subcutaneous injection for 9 months, participants were randomly assigned (1:1) to receive teriparatide 20 μg (standard dose) or 40 μg (high dose) daily. Both groups were initiated at 3 months on denosumab 60 mg every 6 months through 12-month subcutaneous injection. Two hundred sixty-nine women were evaluated for eligibility between October 15, 2014, and June 10, 2016. Seventy-six participants were randomly assigned to 20 μg teriparatide (n = 39) or 40 μg teriparatide (n = 37), of whom 69 completed at least one postbaseline visit. Combined treatment with teriparatide 40 μg and denosumab more than standard combination therapy increases spine and hip BMD. This large and rapid increase in bone mass suggests that a method of restoring skeletal integrity in osteoporosis patients could be provided by this high dose regimen. Joint pain, muscle cramp, nausea and fatigue were the most frequent adverse events. There have been no reported deaths.