ABSTRACT
UNLABELLED: Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis. INTRODUCTION: Several medications have been unequivocally shown to decrease fracture rates in clinical trials. However, in real life settings, long-term persistence and compliance to anti-osteoporosis medication is poor, hence decreasing the clinical benefits for patients. METHODS: An extensive search of Medline from 1985 to 2006 retrieved all trials including the keywords osteoporosis, compliance, persistence or adherence followed by a critical appraisal of the data obtained through a consensus expert meeting. RESULTS: The impact of non-adherence on the clinical development of interventions is reviewed, so that clinicians, regulatory agencies and reimbursement agencies might be better informed of the problem, in order to stimulate the necessary research to document adherence. CONCLUSION: Adherence to therapy is a major problem in the treatment of osteoporosis. Both patients and medication factors are involved. Adherence studies are an important aspect of outcomes studies, but study methodologies are not well developed at the moment and should be improved. Performing adherence studies will be stimulated when registration authorities accept the result of these studies and include the relevant information in Sect. 5.1 of the summary of product characteristics. Reimbursement authorities might also consider such studies as important information for decisions on reimbursement.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Osteoporosis/drug therapy , Patient Compliance , Cohort Studies , Diphosphonates/therapeutic use , Drug Administration Schedule , Female , Humans , Male , Randomized Controlled Trials as Topic/statistics & numerical data , Research Design , Self AdministrationABSTRACT
According to the recent recommendations of the European Community and the World Health Organization, identification of risk factors for fracture or low bone mineral density (BMD) should help health professionals to make a better use of bone densitometry. This includes helping patients to modify their behaviour and act on modifiable risk factors (correction of low calcium intake and vitamin D deficiencies, etc.) and also to provide evidence-based guidance for starting a treatment when necessary. In this context, we previously developed a clinical scoring index, OSIRIS (OSteoporosis Index of RISk), for classifying women into three categories of risk of osteoporosis. In order to evaluate the discriminatory performance of OSIRIS, we performed the present prospective study in a sample of 889 postmenopausal women from France. The osteoporosis risk depends on the OSIRIS category. Thus, 62% of women in the 'high-risk' category (OSIRIS < or = -3) were osteoporotic, compared to 34% of women in the 'intermediate-risk' category (OSIRIS ranged between -3 and +1) and only 16.8% of women in the 'low-risk' category (score OSIRIS > 1). These results might contribute to the development of more efficient screening strategies for osteoporosis. The patients in the low-risk category do not require immediate BMD testing; women with 'intermediate risk' have to be carefully followed by their doctor with BMD testing decided on a case-by-case basis; for those within the high-risk category, treatment may be initiated immediately and BMD testing performed either to assess the efficacy of the treatment or to increase the long-term compliance of the patient. In conclusion, for clinical practice, a user-friendly tool has been developed. This tool, called OSIRIS, as far as a simple rule allows, identifies the level of osteoporosis risk in women.
Subject(s)
Bone Density , Mass Screening/methods , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/epidemiology , Absorptiometry, Photon , Adult , Aged , Case-Control Studies , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/pathology , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
OBJECTIVE: To compare changes in biochemical markers of bone turnover in postmenopausal women who received sequential discontinuous hormone replacement therapy (HRT) with either transdermal 17 beta-estradiol gel (group 1) or oral equine sulfoconjugated estrogen (group 2), plus nomegestrol acetate. PATIENTS AND METHOD: Prospective, open, randomized, controlled trial, conducted on 3 parallel groups of 106 postmenopausal women. All treated groups received estrogen therapy for 25 consecutive days every month. The estrogen used was either 1.5 mg/day of transdermal 17 beta-estradiol gel (group 1) [N = 42, average age (AA) = 51.6 years, average duration of menopause (ADM = 21.5 months)], or 0.625 mg/day of oral equine sulfoconjugated estrogen (group 2) [N = 39, AA = 51.3 years, ADM = 16.8 months]. In all cases nomegestrol acetate 5 mg/day was added for 12 consecutive days every month. The control group comprised 25 patients, [AA = 53.4 years, ADM = 33.7 months]. Two bone resorption markers: urinary cross-linked N-telopeptide and C-telopeptide of type I collagen (U-NTX/Cr, U-CTX/Cr), and a bone formation marker: serum bone specific alkaline phosphatase activity were measured before and 6 months after treatment start. RESULTS: Significant decreases from baseline values were observed for the 3 biochemical markers in both treated groups compared with control (P < 0.001). There were no significant differences in changes between the 2 treated groups for the 3 biochemical markers. The mean percentage change in the 3 biochemical markers was: from -9.3 to -45.5% in group 1, from -20.5 to -39% in group 2, and from -3.3 to 2% in control group. In group 1, the mean percentage decreases in U-CTX reached optimal threshold of bone turnover change (-45%) which is considered by the International Osteoporosis Foundation as clinically relevant because it predicts an increase in BMD greater than 3% when treatment is maintained over a long term. DISCUSSION AND CONCLUSION: Both treated groups induced a significant comparable decrease of bone turnover markers after 6 months of intervention, compared with control. The group treated with cyclic administration of transdermal 17 beta-estradiol (1.5 mg/day) and nomegestrol acetate (5 mg/day) showed a bone resorption markers decrease corresponding to the threshold of clinical relevance described in the international literature and predictive of positive BMD response in long term.
