Six months of parathyroid hormone (1-84) administered concurrently versus sequentially with monthly ibandronate over two years: The PTH and ibandronate combination study (PICS) randomized trial

Context: PTH therapy improves bone mineral density (BMD) and decreases fractures in postmenopausal osteoporosis, but cost and the burden of daily injections limit its use. Objective: We evaluated two novel approaches to the use of 6 months of PTH therapy over 2 yr. Design, Setting, Participants, and Interventions: We conducted a randomized, double-blinded trial of two combinations of daily PTH(1-84) and monthly ibandronate in 44 postmenopausal women with low bone mass. Participants received either 6 months of concurrent PTH and ibandronate, followed by 18 months of ibandronate (concurrent) or two sequential courses of 3 months of PTH followed by 9 months of ibandronate (sequential) over 2 yr. Main Outcome Measures: Bone turnover markers were measured. Areal and volumetric BMD were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography, respectively. Results: Over 2 yr, arealBMDat the spine and hip increased similarly in both groups, with 7.5 and 8.2% increases in spine BMD in the concurrent and sequential arms, respectively (difference -0.6%, 95% confidence interval = -3.4-2.1%). Volumetric BMD also increased similarly between groups. With concurrent therapy,meanN-propeptideoftypeI collagen increased75%betweenbaselineandmonth 1 and then declined. With sequential therapy, the second 3-month PTH course increased N-propeptide of type I collagen markedly (209%), although to a lesser absolute degree than the first. Conclusions: Six months of PTH(1-84), used over 2 yr with a bisphosphonate in either of our dosing regimens increased BMD substantially. Short PTH courses may provide the benefits of anabolic osteoporosis therapy with reduced burden for patients.