Introduction: The Treatment of Osteoporosis with PTH (TOP) Study was an 18-month, multinational, randomized, double-blind, placebo-controlled study involving 2532 postmenopausal osteoporotic women. In the per protocol population (subjects who took 75% of their prescribed doses and had no protocol violations; n = 1870), there was a 66% relative risk reduction (RRR) in vertebral fractures in subjects receiving PTH (P = .002). In subjects with and without prevalent fractures, PTH therapy resulted in a RRR in vertebral fractures of 69% (P = 0.025) and 63% (P = .028), respectively (ACR 2004). We report the effectiveness of PTH(1-84) in reducing vertebral fracture in 2 subgroups of subjects at high fracture risk including women with advanced age or low BMD.
Methods: Subjects included in the study were ≥55 years of age with spine, femoral neck, or total hip BMD T-score ≤–2.5 (or ≤–2.0 with a prevalent vertebral fracture), or 45–54 years of age with a T-score ≤–3.0 (or ≤–2.5 with fracture). All subjects received 700 mg calcium and 400 IU vitamin D supplements daily and were randomized to placebo or to PTH 100 mg daily. This subanalysis of the intent-to-treat population (ITT) included women with advanced age (>60 years old) or with low BMD (lumbar spine T-score <–3.0). Results: In the ITT population, 1797 women were at least 60 years old. PTH treatment resulted in a 64% RRR in vertebral fracture compared with placebo (1.5% vs 4.2%, respectively, P = .001). When this subgroup was stratified according to the presence of vertebral fracture, those with prevalent fracture(s) who were treated with PTH experienced a 58% RRR in vertebral fracture compared with placebo (4.4% vs 10.3%, respectively; P = .027). In those without prevalent fracture, PTH therapy resulted in an RRR of 67% compared with placebo (2.5% vs .8%, respectively; P = .012). When the TOP ITT population was analyzed with regard to low BMD (n = 1149), PTH reduced vertebral fracture by 74% (RRR) compared with placebo (1.3% vs 5.1%, respectively; P < .001). In this same group, PTH treatment resulted in an RRR in incident vertebral fracture of 59% compared with placebo in those with prevalent vertebral fracture(s) (5.5% vs 13.6%, respectively; P = .040), and an RRR of 85% compared with placebo in women without prevalent vertebral fracture (2.8% vs 0.41%; P = .003). The adverse event (AE) profile and reasons for discontinuation were not substantially different in either women with advanced age or those with low BMD from those of the entire TOP study population.
Conclusion: In accordance with results from the overall TOP population, analysis of subgroups of women at high risk for fracture (advanced age or low BMD) demonstrated that PTH(1-84) substantially reduced the incidence of vertebral fracture. Moreover, the safety profile of the drug in this high-risk population was found to be essentially identical to that in the total population. Collectively, these results suggest that PTH is an effective and safe drug for the treatment of women with severe osteoporosis who are at high risk for fracture. In addition, PTH is highly effective in preventing the first vertebral fracture in this high risk population.
Disclosure Information:
Faculty Member's Name: Paul D. Miller, MD
Grants/Research Support: Procter & Gamble, Aventis, Roche, Eli Lilly, Pharmacia, Merck, Novartis, Pfizer, Amgen
Consultant: Procter & Gamble, Aventis, Roche, Eli Lilly, Merck, Novartis, Amgen, NPS
Stock Shareholder (directly purchased): None
Other Financial or Material Support: None
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