Use of recombinant human parathyroid hormone(1-84) in patients with postmenopausal osteoporosis: a prospective, open-label, single-arm, multicentre, observational cohort study of the effects of treatment on quality of life and pain--the PROPOSE study.

BACKGROUND AND
OBJECTIVE: Osteoporosis is a progressive bone disorder. Its medical therapy typically involves calcium, vitamin D and antiresorptive drugs. The anabolic parathyroid hormones (PTHs) represent a major advance since they stimulate new bone formation. Two forms of recombinant human PTH (rhPTH) have been evaluated: the 34-amino acid fragment rhPTH(1-34) and the intact 84-amino acid form rhPTH(1-84), the latter being marketed as Preotact®. Osteoporosis leads to increased bone fragility and susceptibility to fracture. Additionally, the disease is often accompanied by pain and a reduced quality of life (QOL). These aspects have rarely been addressed in previously published studies of PTH, which have instead focused on bone density and fractures. The aim of the present study was to evaluate therapy with rhPTH(1-84) in the treatment of osteoporosis in postmenopausal women under everyday practice conditions with emphasis on patients' QOL and pain.
METHODS: The study was performed as a prospective, open-label, single-arm, multicentre, observational cohort study that included postmenopausal women in whom treatment with rhPTH(1-84) was newly initiated. Patients were to be treated with rhPTH(1-84) for 12 months at a dose of 100 μg, administered once daily as a subcutaneous injection. The primary efficacy endpoint was the total score on the Quality of Life Questionnaire of the European Foundation for Osteoporosis, 41-item version (QUALEFFO-41). Secondary efficacy criteria were QUALEFFO-41 subscale scores, patients' assessments of pain on visual analogue scales (range 0-100), and performance on the chair rising test.
RESULTS: 112 patients were included in the safety and in the intent-to-treat (ITT) efficacy analyses. Sixty-six patients finished the 1-year period (per-protocol group). All ITT patients were female with a mean age of 72 years and a mean duration of osteoporosis of 73 months. During the study, all QUALEFFO-41 scales improved significantly: in the ITT group, the mean total score improved from 49.8 to 41.3 points. In the ITT population, mean pain at rest improved significantly by about 20% and mean pain on movement by about 36%. When patients who took at least one dose of pain medication were compared with those who took no pain medication during the study, it was evident that pain reduction did not occur only as a result of taking pain medication: use of rhPTH(1-84) was associated with a similar pain reduction in both subgroups. The most frequent adverse events (AEs) were hypercalcaemia (12.5% of patients) and nausea and vomiting (10.7% of patients). AEs caused 16% of patients to discontinue during the 12-month study period.
CONCLUSION: This 12-month study carried out in a typical sample of postmenopausal women with osteoporosis showed that treatment with rhPTH(1-84) is safe. The present study, which is one of the first to investigate QOL and pain during PTH treatment systematically, also showed that rhPTH(1-84) improves QOL and reduces pain, thereby reducing the burden of osteoporotic symptoms for patients. These results, however, need to be verified in a controlled clinical trial. [ClinicalTrials.gov Identifier: NCT00515593].