Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling

Abstract

Context: Daily PTH administration increases bone mineral density (BMD) and reduces fracture risk. However, cost and compliance significantly limit clinical use.

Objective: Our objective was to determine whether less frequent PTH administration increases lumbar spine BMD.

Participants, design, and setting: Fifty postmenopausal women ages 45-70 yr with femoral neck BMD T-score between -1.0 and -2.0 participated in a double-blind, randomized, placebo-controlled trial at St. Joseph Hospital, Bangor, ME.

Intervention: Subjects received sc injections of daily PTH(1-84) (100 mug) or placebo for 1 month, followed by weekly injections (PTH or placebo) for 11 months.

Outcomes: Change in lumbar spine dual-energy x-ray absorptiometry areal BMD (primary) was assessed. Secondary outcomes included volumetric BMD at spine and hip by quantitative computed tomography, trabecular bone microarchitecture by magnetic resonance imaging of distal radius, and biochemical bone turnover markers.

Results: At 12 months, lumbar spine areal BMD increased 2.1% in PTH-treated women compared with placebo (P = 0.03). Vertebral trabecular volumetric BMD increased 3.8% in PTH-treated women compared with placebo group (P = 0.08). PTH-treated women also had higher distal radial trabecular bone volume, number, and thickness compared with placebo-treated women (P < 0.04). After 1 month of daily PTH, N-terminal propeptide of type I collagen (P1NP) was markedly increased compared with placebo (P < 0 .0001), and a difference persisted, although lessened, throughout the study. Bone resorption indices were unchanged in PTH-treated women and were reduced in the placebo group.

Conclusion: Once-weekly PTH after 1 month of daily treatment increases spine BMD, radial trabecular bone, and bone formation markers in postmenopausal women. These results suggest that less frequent alternatives to daily PTH dosing for 2 yr could be effective. Additional studies are required to define the optimal frequency of PTH administration.

Figure 1

Study design and patient flow.

Figure 2

Changes in BMD at the spine and hip as assessed by DXA and QCT. *, P < 0.05.

Figure 3

Changes in MRI-assessed trabecular parameters at the radius as a function of distance from the endplate (grouped into 6-mm categories). Approximately 30 patients contributed measurements in the regions from 5–23 mm, whereas only about six patients had information for the most proximal region. Statistical significance is shown for the most proximal region.

Figure 4

Change in bone markers by month since randomization. *, P < 0.05; **, P < 0.01. Means and sd from logarithms of change are shown. See Subjects and Methods.