The Global Longitudinal Study of Osteoporosis in Women (GLOW): rationale and study design

GLOW is designed to provide an international perspective on fracture risk in women, patient management practices, patient awareness, physical and emotional function following fracture, application of risk assessment models, and functional outcomes following fracture. Previous cohort studies of osteoporosis were designed primarily to identify factors associated with fracture incidence and document the distribution of low bone mineral density and its association with fracture risk. These efforts have been limited to specific regions or areas. GLOW will provide the first description of patterns of risk from an international perspective. Further, the data from GLOW will be used to assess not only fracture risk and incidence, but will identify patient concern and awareness and clinical management at a time when significant efforts have been made to implement treatment guidelines and educate patients about osteoporosis and fracture risk. In these baseline results, a minority of GLOW subjects (43%), among women 55 years and older, indicated having discussed osteoporosis with their physician in the past year, yet 79% of women in the study were somewhat or very concerned about osteoporosis. Future analyses of GLOW data will examine the link between perceived risk, concern, and physician encounters on treatment risk of fracture and quality of life.

Prior studies have reported undertreatment and underdiagnosis of osteoporosis [22]. However, since these studies were conducted, many new therapies have become more widely used than in the past. GLOW will report on contemporary treatment prevalence according to fracture risk and self-reported diagnosis of osteoporosis at a time when a wider range of patient management options have been generally accepted and are available

Previously collected risk factor data form the basis for risk-scoring algorithms designed to predict fracture risk and aid physicians in targeting treatment to those most in need [23‐26]. GLOW will update data on these factors and allow the calculation of patterns of international fracture risk. Because the data will be gathered in a consistent manner, confidence will be increased that the variations seen in the distribution of risk factors between regions is due to differences in the populations rather than in the methods of data collection.

The study will also assess a spectrum of physician–patient interactions including discussion of osteoporosis, advice concerning falls, bone mineral density screening, diagnosis of osteoporosis, and pharmacological treatments. Regional and international comparisons of diagnosis and treatment patterns will be possible, with adjustment for region- and country-specific characteristics, such as the availability of health insurance, reimbursement for prescriptions, and treatment protocols. A number of items that assess subjects’ physical and emotional status have also been incorporated in the questionnaire. These include the mobility and vitality scales from SF-36 and the five subscales of the EQ-5D. Such measures will enable comparisons of functional outcomes for women who suffer various types of incident fractures in differing geographic regions over time.

Whereas most studies of patient persistence focus on a single drug, GLOW will include the full range of currently available pharmacological treatments for osteoporosis (alendronate, calcitonin, estrogen, etidronate, ibandronate, pamidronate, parathyroid hormone [1–84], raloxifene, risedronate, strontium ranelate, teriparatide, tibolone, and zoledronate). We will also be able to include any newly available osteoporosis medications in the questionnaire. The study will also examine the reasons why patients stop and switch medications.

GLOW data will allow assessment of the effectiveness of treatment on the incidence of fracture in a “real-world” setting. In contrast to randomized clinical trials, GLOW did not exclude women who had previously been diagnosed with osteoporosis or treated with bone drugs. Consequently, analysis of the treated population will include those women who stop or switch medications, as well as those who have a high degree of persistence. Adjustment will be possible for potential confounding of the relationship between treatment and fracture using fracture risk factors and risk scores. While the study is not designed to evaluate the effectiveness of any single bone drug, it will allow comparison of fracture rates among treated and untreated patients across all classes of interventions. Such head-to-head comparisons have not been evaluated in randomized controlled trials.

Analysis will also be carried out to estimate the relative cost effectiveness of various classes of interventions used in the management of fractures, using the usual principles set out for cost-effectiveness analysis [27‐29]. An economic model based on the epidemiological evidence of treatment outcomes recorded in GLOW will be constructed [30].

GLOW is a practice-based rather than a population-based study and is subject therefore to biases in both the selection of physicians and the sampling and recruitment of patients. Practical considerations limited our sample selection to women from 17 study locations in ten countries. An expanded sample that included a broader representation of racial and ethnic groups was not pursued because of the complexity of administering a recruitment methodology involving oversampling of particular racial and ethnic groups in ten different countries, where the definitions of these groups were likely to vary considerably. Physicians at each site who agreed to participate may not be representative of all physicians in an area with respect to osteoporosis recognition and management. We attempted to avoid altering physician practice by minimizing doctors’ awareness of the study. There were no clinical interventions and physicians had no involvement in patient recruitment other than supplying practice lists.

Unlike studies that excluded women because of prior fracture, diagnosis of osteoporosis, or current treatment for osteoporosis, GLOW attempted to enlist all women 55 years and older who were active patients in each physician’s practice. By doing so, the study will provide a more complete picture of care received by women in this age group. Nonetheless, some participation biases are likely. It is possible that participants will have greater interest in bone health issues and seek information, screening, and treatment more actively. We attempted to reduce selection bias by creating a survey process that imposed low respondent burden. Participation required no clinic visits (by not requiring patients to schedule a clinic visit or face-to-face interview, we avoid requirements that might make participation difficult for women who are in poor health or have no or limited access to transportation) and questionnaires were mailed directly to the subject’s home and typically required only 15–20 min to complete. High response rates at most sites (median 62%) suggest that this strategy was successful. Comparison of characteristics for the sample of US women with those of the nationally representative sample of comparably aged NHANES women demonstrated that although GLOW women were better educated, more likely to be white, and reported better health, the prevalence of risk factors for fracture was similar.

All data are collected by patient self-report. While this approach is subject to limitations of recall and recall bias, it has the advantages of efficiency and methodological consistency. The combination of mail and telephone surveys is amenable to collection of data on quality of life, health status, and fracture risk factors of interest. The efficiency of the mail and phone survey approach also makes it feasible to obtain a substantial sample size and to provide adequate statistical power for the analysis of fracture outcomes, which are relatively rare events. The survey format also allows standardized administration that reduces the issues of noncomparability and variation in data quality that would arise if medical records and public health care databases from several different countries were used. Reports that have examined the validity of self-report of prescription medication use and fractures have shown reasonable accuracy [31‐36]. Self-report may be preferable to the abstraction from medical records of data on diagnosis and treatment, given inconsistencies in record keeping between physicians and between study regions and countries. Additionally, records from primary care physicians may not include evidence of treatment initiated by a specialist physician. Validation of self-reports of variables such as fractures and bone mineral density examinations may be possible for subsets of subjects in sites where electronic medical records are available.