Treatment of postmenopausal women with osteoporosis with PTH(1–84) for 36 months: treatment extension study

Abstract

Objective:

To determine the safety and efficacy of full-length parathyroid hormone, PTH(1–84), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis.

Background:

The TOP trial demonstrated increased lumbar spine BMD (6.9%) versus placebo after 18 months of PTH(1–84) treatment and reduced the incidence of new vertebral fractures (61%; p = 0.001). The therapeutic benefits of long-term treatment of postmenopausal women with PTH(1–84) are unknown.

Methods:

The safety and efficacy of 36 months of once-daily dosing with 100 µg PTH(1–84) in postmenopausal women with osteoporosis were assessed. Women receiving placebo during the TOP trial were eligible for PTH(1–84) in the extension study.

Clinical trial registration:

NCT00172120.

Results:

Lumbar spine BMD increased by 8.5% above baseline (p < 0.001) at 36 months of PTH(1–84) treatment, remaining stable during the last 12 months of treatment. Increases in total hip and femoral neck BMD occurred more slowly, reaching 3.2% and 3.4%, respectively above baseline at 36 months (p < 0.001). The total hip BMD showed no signs of reaching a limiting value although the femoral neck plateaued from months 24 to 36. Seven patients had vertebral fractures during the placebo phase of the TOP trial and before entering the extension study, but this rate decreased with the introduction of PTH(1–84) therapy, resulting in a single worsened vertebral fracture in the first 6 months and no further vertebral fractures from months 6 to 36. Treatment over 36 months with PTH(1–84) was well-tolerated and iliac crest biopsies showed no adverse effects on bone.

Limitations:

There was no placebo group for BMD comparisons. The number of patients assessed for fracture incidence was small.

Conclusions:

PTH(1–84) treatment for 36 months resulted in significant increases in BMD at the lumbar spine and hip, was associated with a lower incidence of vertebral fracture when compared to before therapy initiation, and was well-tolerated. The continuous increases in total hip BMD suggest that prolonged PTH(1–84) treatment may be beneficial for postmenopausal osteoporosis. Increased BMD at the femoral neck and lumbar spine also showed favourable changes but plateaued between 24 and 36 months. Long-term treatment was not associated with abnormalities in bone biopsies.

Key words:

• Bone mineral density (BMD)
• Full length parathyroid hormone
• Osteoporosis
• PTH(1
• 84)
• Vertebral fracture

Transparency

Declaration of funding

Funding for this study was provided by NPS Pharmaceuticals.

Declaration of financial/other relationships

J.Z. has disclosed that he has served as a member of the advisory committee and as a consultant for NPS Pharmaceuticals. C.B. has disclosed he has received sponsorship from Nycomed GmbH. S.A. and C.C have nothing to declare. H.G. has disclosed that she is an employee of Nycomed. J.F. has disclosed that he was an employee of NPS Pharmaceuticals and is currently a consultant for that company. W.L. has disclosed he has served on the speakers’ bureau for Nycomed, Eli Lilly, Novartis, Amgen, Procter and Servier.

Acknowledgement

The authors thank the TRES investigators and Dr Robert Recker for his analysis of the bone biopsy specimens. The authors also thank the women who participated in this study. The authors acknowledge the editorial assistance of Wells Healthcare funded by Nycomed.