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

Abstract

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, areal BMD at 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, mean N-propeptide of type I collagen increased 75% between baseline and month 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.

Figures

Fig. 1.

PTH and Ibandronate Combination Study (PICS) treatment groups. Participants, clinicians, and investigators were blinded to treatment group assignment through the use of placebo injections and tablets.

Fig. 2.

Enrollment and outcomes.

Fig. 3.

Mean percent changes over 2 yr in aBMD at the spine (A), total hip (B), and femoral neck (C), assessed by DXA, and in vBMD of the trabecular spine (D), cortical total hip (E), and trabecular total hip (F), assessed by QCT.

Fig. 4.

Mean serum PINP (A), BAP (B), OC (C), and CTX (D) during therapy. Visit means were log-transformed for analysis and then back-transformed for presentation.