ABSTRACT: The purpose of this study is to examine the effect of PTH(1-84) treatment over 24 months followed by 12 months discontinuation on BMD, bone turnover markers, fractures and the impact of adherence on efficacy. INTRODUCTION: There is limited information about the effect of PTH(1-84) after 18 months and limited data about the impact of compliance on response to anabolic therapy. METHODS: Seven hundred and eighty-one subjects who received active PTH(1-84) in the Treatment of Osteoporosis with Parathyroid hormone trial for approximately 18 months were entered into a 6-month open-label extension. Thereafter, they were followed for 12 additional months after discontinuation of treatment. Endpoints examined included changes in BMD and biochemical markers. RESULTS: PTH(1-84) treatment over 24 months increased BMD at the lumbar spine by 6.8 % above baseline (p < 0.05).The total corresponding BMD increases at the hip and femoral neck were 1.1 and 2.2 % above baseline. Larger increases in spine BMD were observed in participants with ≥80 % adherence to daily injections of PTH(1-84) (8.3 % in adherent vs 4.9 % in poorly adherent patients). Total hip BMD gains were 1.7 % in adherent vs 0.6 % in poorly adherent participants. Markers of bone turnover (BSAP and NTx) peaked 6 months after starting PTH(1-84) treatment and declined slowly but remained above baseline at 24 months. After discontinuation of PTH(1-84) treatment (at 24 months), bone turnover markers returned to near baseline levels by 30 months. The adherent group sustained significantly fewer fractures than the poorly adherent group. CONCLUSIONS: PTH(1-84) treatment over 24 months results in continued increases in lumbar spine BMD. Adherence to treatment with PTH(1-84) for up to 24 months is also associated with greater efficacy.
Osteoporosis International 08/2012; · 4.58 Impact Factor
ABSTRACT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk.
Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD.
We conducted a randomized, placebo-controlled trial at four academic centers.
Patients included 238 postmenopausal women with low hip or spine BMD.
Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr.
Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy.
Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD.
Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.
Journal of Clinical Endocrinology & Metabolism 05/2006; 91(4):1370-5. · 6.50 Impact Factor
ABSTRACT: When used to treat osteoporosis, no more than 2 years of parathyroid hormone (PTH) is permitted, raising the question of whether antiresorptive therapy should be given after PTH is discontinued. This prospective, randomized, double-blind trial, the Parathyroid Hormone and Alendronate (PaTH) study, compared full-length PTH (1-84), alendronate, and the combination. The goal was to learn whether antiresorptive treatment is necessary to maintain the gain in bone mineral density (BMD) achieved after a year of PTH (1-84) treatment. The study population included 238 postmenopausal women 55 to 85 years of age who had a T score for BMD below -2.5 at the femoral neck, total hip, or spine (or a T score below -2) combined with other risk factors such as a history of fracture. Participants were randomly assigned to 1 year of PTH followed by 1 year of alendronate; PTH followed by placebo; PTH plus alendronate in the first year and alendronate in year 2; or alendronate for 2 years. Full-length PTH (1-84) was given in a dose of 100 μg daily and alendronate in an oral dose of 10 mg daily.
Full compliance with treatment was 75% and 82% in the first and second years, respectively. BMD at the lumbar spine increased significantly in all treatment groups over 2 years, most markedly (12.1%) in the PTH-alendronate group and least (4.1%) in the PTH-placebo patients. The increase in BMD in the combination-alendronate and 2-year alendronate groups was significantly greater than in the PTH-placebo group but smaller than in the PTH-alendronate group. The PTH-alendronate patients had a significantly greater increase in BMD at the femoral neck and total hip over 2 years than women in the PTH-placebo group, but a significant loss at the distal radius was found in of both these groups. Women in all treatment groups-but especially the PTH-alendronate group-gained volumetric BMD in trabecular bone during the 2-year study. In the second year, women in the PTH-alendronate group gained significant BMD at the spine (4.9%) and hip (3.6%). At the same time, women in the PTH-placebo group lost significant BMD at the spine. The 21 women having clinical fractures during the 2-year study represented 8.8% of the total; there were no major differences between treatment groups. Women taking alendronate rather than placebo in year 2 were not at higher risk of adverse events.
Any increase in BMD after a year of PTH treatment is rapidly lost afterward, but this is not the case if the bisphosphonate alendronate is administered for a further 12 months. There was no evidence from this study that combining PTH with alendronate is more effective than giving either agent by itself.
Obstetrical and Gynecological Survey 12/2005; 61(1):34-35. · 2.51 Impact Factor
New England Journal of Medicine 353(6):555-565. · 53.30 Impact Factor