Recommendations for the conduct of economic evaluations in osteoporosis: outcomes of an experts' consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the US branch of the International Osteoporosis Foundation.

Economic evaluations are increasingly used to assess the value of health interventions, but variable quality and heterogeneity limit the use of these evaluations by decision-makers. These recommendations provide guidance for the design, conduct, and reporting of economic evaluations in osteoporosis to improve their transparency, comparability, and methodologic standards. INTRODUCTION: This paper aims to provide recommendations for the conduct of economic evaluations in osteoporosis in order to improve their transparency, comparability, and methodologic standards. METHODS: A working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis to make recommendations for the design, conduct, and reporting of economic evaluations in osteoporosis, to define an osteoporosis-specific reference case to serve a minimum standard for all economic analyses in osteoporosis, to discuss methodologic challenges and initiate a call for research. A literature review, a face-to-face meeting in New York City (including 11 experts), and a review/approval by a larger group of experts worldwide (including 23 experts in total) were conducted. RESULTS: Recommendations on the type of economic evaluation, methods for economic evaluation, modeling aspects, base-case analysis and population, excess mortality, fracture costs and disutility, treatment characteristics, and model validation were provided. Recommendations for reporting economic evaluations in osteoporosis were also made and an osteoporosis-specific checklist was designed that includes items to report when performing an economic evaluation in osteoporosis. Further, 12 minimum criteria for economic evaluations in osteoporosis were identified and 12 methodologic challenges and need for further research were discussed. CONCLUSION: While the working group acknowledges challenges and the need for further research, these recommendations are intended to supplement general and national guidelines for economic evaluations, improve transparency, quality, and comparability of economic evaluations in osteoporosis, and maintain methodologic standards to increase their use by decision-makers.

The importance of physical function to people with osteoporosis.

There is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function. INTRODUCTION: There is increasing need to understand patient-centred outcomes in osteoporosis (OP) clinical research and management. This multi-method paper provides insight on the effect of OP on patients' physical function and everyday activity. METHODS: Data were collected from three sources: (1) targeted literature review on OP and physical function, conducted in MEDLINE, Embase and PsycINFO; (2) secondary thematic analysis of transcripts from patient interviews, conducted to develop a patient-reported outcome instrument. Transcripts were re-coded to focus on OP impact on daily activities and physical function for those with and without fracture history; and (3) discussions of the literature review and secondary qualitative analysis results with three clinical experts to review and interpret the importance and implications of the findings. RESULTS: Results suggest that OP, particularly with fracture, can have profound impacts on physical function/activity. These impacts accumulate over time through a cycle of impairment, as fracture leads to longer term detriments in physical function, including loss of muscle, activity avoidance and reduced physical capacity, which in turn leads to greater risk of fracture and potential for further physical restrictions. The cycle of impairment is complex, as other physical, psychosocial and treatment-related factors, such as comorbidities, fears and beliefs about physical activity and fracture risk influence physical function and everyday activity. CONCLUSION: More information on how treatments impact physical function would benefit healthcare professionals and persons with OP in making treatment decisions and improving treatment compliance/persistence, as these impacts may be more salient to patients than fracture incidence.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Development of the Osteoporosis Assessment Questionnaire--physical Function (OPAQ-PF): an osteoporosis-targeted, patient-reported outcomes (PRO) measure of physical function.

UNLABELLED: We have developed a short, patient-reported outcome questionnaire--the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF)--that assesses the impact of osteoporosis on physical function. OPAQ-PF contains 15 items in three domains (mobility, physical positions, and transfers) and has content validity in osteoporosis patients with and without a history of fracture. INTRODUCTION: This paper describes the development of the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF), a patient-reported outcome (PRO) questionnaire based on OPAQ v.2.0 (60 items, 14 domains) that assesses the impact of osteoporosis on physical function. METHODS: OPAQ v.2.0 was administered to patients with osteoporosis. Item response theory methodology and clinical judgment were used to retain/eliminate items. The resulting instrument was modified during two sets of concept elicitation and cognitive debriefing interviews with osteoporosis patients. RESULTS: Item response theory-based analysis of OPAQ v.2.0 (n = 1,478) coupled with clinician input resulted in the generation of a 21-item, six-domain instrument with a frequency response format. Interview data from 32 participants were used to modify this version and led to generation of the final instrument, OPAQ-PF. This final version has a severity response format and contains 15 items in three domains (mobility, physical positions, and transfers) that group together to provide an overall assessment of physical function in patients with osteoporosis. Twenty-two of the 32 interview participants (69 %) had previously sustained a fracture. Symptoms occurred primarily in these patients. CONCLUSIONS: OPAQ-PF represents a brief, focused, PRO instrument that assesses physical function in patients with osteoporosis, specifically related to mobility, physical positions, and transfers. This questionnaire has content validity in osteoporosis patients who have, and have not, sustained a prior fracture.

Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a psychometrically validated osteoporosis-targeted patient reported outcome measure of daily activities of physical function.

UNLABELLED: The purpose of this study was to evaluate the measurement properties of the Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on this study, the OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was established through exploratory and confirmatory factor analysis. Patients completed three patient reported outcome (PRO) measures and four performance-based measures (PBMs) at baseline to enable an evaluation of construct validity. Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline to enable an evaluation of test-retest reliability. Ability to detect change and interpretation of change were investigated following completion of the OPAQ-PF 12 and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A prospective psychometric validation study in 144 postmenopausal women, with moderate to severe osteoporosis, 37 of whom had experienced a recent fragility fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor analysis. The OPAQ-PF had good internal consistency (α = 0.974) and test-retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ-PF differentiated between patients with/without recent fracture, and by severity of osteoarthritis; it correlated strongly with hypothesized-related scales and PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high correlations between changes in OPAQ-PF score and changes in global concept scores in recent fracture patients (r ≥ 0.6, 24-week change). Effect size of change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor-based methods identified an OPAQ-PF change of 10 at an individual patient level and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample.

Oral bisphosphonates reduce the risk of clinical fractures in glucocorticoid-induced osteoporosis in clinical practice.

UNLABELLED: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs). INTRODUCTION: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy. METHODS: The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65 years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12 months on therapy. RESULTS: The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (33 % lower at nonvertebral sites and 59 % at vertebral sites) and risedronate (28 % lower at nonvertebral sites and 54 % at vertebral sites). CONCLUSION: From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials.

Patient weighting of osteoporosis medication attributes across racial and ethnic groups: a study of osteoporosis medication preferences using conjoint analysis.

UNLABELLED: We studied the ranking of osteoporosis (OP) medication attributes in a convenience sample of four different racial/ethnic groups in the United States. Our study showed that postmenopausal women differ in the ranking of OP medication attributes based on age, educational level, income, and prior fracture history. INTRODUCTION: Decision making about OP medication-related behavior relies heavily on patient preferences about specific medication attributes. Patients may decide to initiate, change, or stop therapies based on ranking of perceived attributes of the therapy and their personal attitudes toward those attributes. We used MaxDiff, a form of conjoint analysis (Ryan and Farrar 2000), to explore patient weighting of attributes across four racial/ethnic groups at two sites in the United States and defined four critical attributes that influence such decisions (safety, efficacy, cost, and convenience) from qualitative interviews. METHODS: We recruited a sample of 367 Postmenopausal (PM) women at risk of OP fractures from four racial/ethnic groups: Caucasian (n = 100), African American (n = 100), Asian American (n = 82), and Hispanic American (n = 85). Respondents completed a laptop-based questionnaire that included demographic items, several short scales on medical care preference and OP patient perceptions, and a MaxDiff procedure that determines comparative ranking of attributes either as least important or most important to their decisions. RESULTS: MaxDiff analyses were done to evaluate the relative weight of specific statements for each participant and to determine whether racial/ethnic groups differed across dimensions. Overall, participants in all four groups rated efficacy > safety > cost > convenience. CONCLUSIONS: Although there were no significant differences among the racial/ethnic groups on overall ranking of attributes, subgroup analyses revealed significant impact of age, education, income, and prior fracture on these decisions. The findings from this study suggest that postmenopausal women differ in their ranking of OP medication attributes, and healthcare providers must account for personal preferences in their communication about and selection of OP medications.

Primary non-adherence to bisphosphonates in an integrated healthcare setting.

UNLABELLED: We estimated primary non-adherence to oral bisphosphonate medication and examined the factors associated with primary non-adherence. Nearly 30% of women did not pick up their new bisphosphonate within 60 days. Identifying barriers and developing interventions that address patients' needs and concerns at the time a new medication is prescribed are warranted. INTRODUCTION: To estimate primary non-adherence to oral bisphosphonate medications using electronic medical record data in a large, integrated healthcare delivery system and to describe patient and prescribing provider factors associated with primary non-adherence. METHODS: Women aged 55 years and older enrolled in Kaiser Permanente Southern California (KPSC) with a new prescription for oral bisphosphonates between December 1, 2009 and March 31, 2011 were identified. Primary non-adherence was defined as failure to pick up the new prescription within 60 days of the order date. Multivariable logistic regression models were used to investigate patient factors (demographics, healthcare utilization, and health conditions) and prescribing provider characteristics (demographics, years in practice, and specialty) associated with primary non-adherence. RESULTS: We identified 8,454 eligible women with a new bisphosphonate order. Among these women, 2,497 (29.5%) did not pick up their bisphosphonate prescription within 60 days of the order date. In multivariable analyses, older age and emergency department utilization were associated with increased odds of primary non-adherence while prescription medication use and hospitalizations were associated with lower odds of primary non-adherence. Prescribing providers practicing 10 or more years had lower odds of primary non-adherent patients compared with providers practicing less than 10 years. Internal medicine and rheumatology providers had lower odds of primary non-adherent patients than primary care providers. CONCLUSION: This study found that nearly one in three women failed to pick up their new bisphosphonate prescription within 60 days. Identifying barriers and developing interventions aimed at reducing the number of primary non-adherent patients to bisphosphonate prescriptions are warranted.

Measuring health-related quality of life (HRQOL) in osteoporotic males using the Male OPAQ.

UNLABELLED: The Male Osteoporosis Assessment Questionnaire (OPAQ™) is a health-related quality of life (HRQOL) instrument that can differentiate between men with and without fracture. The Male OPAQ™ is a reliable and validated instrument that may be utilized in clinical trials seeking to include male populations. INTRODUCTION: Men with osteoporosis (OP) experience poorer clinical outcomes than do women with the disorder, but little is known about the impact of OP on men's HRQOL. This study aimed to test the validity, reliability, and ability to differentiate between men with and without fracture of an HRQOL for men with osteoporosis, the Male OPAQ™. METHODS: The OPAQ and OPAQ-SV were tested for face validity in interviews with male OP patients, and a revised, male-specific instrument was developed. Thirty-seven men ages 50+ completed the Male OPAQ™ and SF-12 at baseline and a two-week retest of the Male OPAQ™. To analyze both the domain and dimension scores, a normalization procedure was performed on the data to determine health status scores from 0 to 100. Descriptive statistics were calculated for each item and site. Reliability and validity of the Male OPAQ™ were assessed using Pearson's r. RESULTS: The Male OPAQ™ can discriminate between men with and without fracture, and men who have more fractures have poorer scores. Instrument domains correspond to those of the SF-12. CONCLUSIONS: The Male OPAQ(TM) is a brief and sensitive tool for measuring HRQOL in men with OP. Further testing in a more diverse and large sample is warranted.

Oral bisphosphonate compliance and persistence: a matter of choice?

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making.

Longitudinal change in clinical fracture incidence after initiation of bisphosphonates.

SUMMARY: There are differences in the risk profile of patients prescribed alendronate, risedronate, or ibandronate. Observed reductions in fracture incidence over time suggest that the effectiveness of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials. INTRODUCTION: Observational studies of bisphosphonate effectiveness for fracture prevention are subject to bias from unknown characteristics of baseline fracture risk at the start of therapy. The fracture incidence during the short period after starting a bisphosphonate and before any expected clinical benefit likely reflects baseline fracture risk. Bisphosphonate effectiveness may then be estimated by measuring the change in fracture incidence over time on therapy. METHODS: Administrative billing data were used to follow three cohorts of women aged 65 and older (total n = 210,144) after starting therapy either on alendronate, risedronate, or ibandronate in the USA between market introduction and 2006. Within each cohort, the baseline incidence of clinical fractures at the hip, vertebral, and nonvertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baselines, we then compared the fracture incidence during the subsequent 12 months on therapy. RESULTS: At the start of therapy, the ibandronate cohort was younger and had fewer prior fractures than either the risedronate or alendronate cohorts. Accordingly, the baseline incidence of hip fractures was higher in the risedronate cohort (0.90 per 100 person-years) and in the alendronate cohort (0.77) than in the ibandronate cohort (0.64). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (18% lower at hip, 28% at nonvertebral sites, and 57% at vertebral sites) and risedronate (27% lower at hip, 21% at nonvertebral sites, and 54% at vertebral sites). In the ibandronate cohort, the fracture incidence was lower (31%) only at vertebral sites. CONCLUSIONS: Differences in the baseline fracture incidence among the cohorts may reflect differences in the risk profile of patients prescribed each bisphosphonate. The reductions observed in fracture incidence over time within each cohort suggest that the effectiveness of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials.

Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass.

UNLABELLED: The Preference and Satisfaction Questionnaire (PSQ) compares patient preference and satisfaction between a 6-month subcutaneous injection and weekly oral tablet for treatment of bone loss. Patients preferred and were more satisfied with a treatment that was administered less frequently, suggesting the acceptability of the 6-month injection for treatment of bone loss. INTRODUCTION: The PSQ compares patient preference and satisfaction between a 6-month subcutaneous injection and a weekly oral tablet for treatment of bone loss. METHODS: Postmenopausal women with low bone mass who enrolled in two separate randomized phase 3 double-blind, double-dummy studies received a 6-month subcutaneous denosumab injection (60 mg) plus a weekly oral placebo or a weekly alendronate tablet (70 mg) plus a 6-month subcutaneous placebo injection. After 12 months, patients completed the PSQ to rate their preference, satisfaction, and degree of bother with each regimen. RESULTS: Most enrolled patients (1,583 out of 1,693; 93.5%) answered >or=1 item of the PSQ. Significantly more patients preferred and were more satisfied with the 6-month injection versus the weekly tablet (P < 0.001). More patients reported no bother with the 6-month injection (90%) than the weekly tablet (62%). CONCLUSION: Patients preferred, were more satisfied, and less bothered with a 6-month injection regimen for osteoporosis.

Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

Paget's disease of bone and quality of life.

Little is known about how Paget's disease of bone affects quality of life. To better understand the relative impact of factors on quality of life, we mailed a brief survey to 2000 people randomly selected from the Paget's Foundation mailing list. The sample was geographically stratified to examine the effects of specialist availability. Nine hundred and fifty-eight persons responded to the questionnaire (53% response rate after adjustment for death, incorrect addresses, and nondeliverable mailings). The sample had equal proportions of males and females, with a mean age of 74 years (SD = 9.0). Most (97%) were white, with high levels of education (mean 13 years; SD 3.7) and income (60% earned more than $20,000 annually). They reported pagetic bone in the skull (34%), spine (35%), pelvis (49%), and leg (48%). The most frequently mentioned complications were hearing loss (37%) and bowed limbs (31%). Comorbidity included arthritis (64%), hypertension (32%), and heart problems (28%). Nearly half (47%) reported feelings of depression, and 42% said that their health was fair or poor. Only 21% reported that quality of life was very good or excellent. In multiple partial F-test regression analyses, variables were divided into four domains (social, psychological, care, and biomedical). The psychological domain explained 19% of the variance beyond that explained by all other variables; the social domain explained 3%, the biomedical domain explained 3% and the care domain explained 1%. The importance of the psychological aspects of Paget's disease suggests that treatment protocols should include psychological intervention to improve quality of life.

Factors associated with self-rated health in patients with Paget's disease of bone.

Multiple studies show that poor self-rated health (SRH) increases the risk of mortality up to 5-fold when compared to excellent SRH. This powerful association remains even with objective health status and risk factors controlled. However, few studies have examined the determinants of SRH, especially as they relate to specific chronic diseases. Here we identify personal characteristics and disease-related attributes that are strongly associated with SRH in a sample of patients with Paget's disease of bone to determine whether any factors can be modified. Two thousand people randomly selected from the Paget Foundation mailing list received a survey asking for information on demographics, general health and functioning, and the impact of Paget's disease. Nine hundred and fifty-eight PD patients returned the completed survey and answered the question, "How would you rate your overall health?" Answers ranged from excellent (1) to poor (5). Ordinary least squares regression was used, with SRH as the dependent variable, to identify those variables significantly associated with SRH. The overall regression model was significant (p = 0.0001; R2 = 0.44). Age (p = 0. 005), satisfaction with family help (p = 0.0001), number of comorbid conditions (p = 0.0001), functional limitations (p = 0.0003), disease impact (p = 0.0002), health compared to 5 years ago (p = 0. 0001), and depressive symptoms (p = 0.012) were significant predictors. Of these, satisfaction with family help, functional limitations, disease impact, and depressive symptoms are potentially modifiable with appropriate interventions. Future longitudinal studies should examine the effectiveness of such interventions in improving SRH.

Peyronie's disease is associated with Paget's disease of bone.

Peyronie's disease is an idiopathic disorder in which an inflammatory fibrosis occurs in the tunica albuginea of the corpora cavernosa which causes the erect penis to become deformed. Peyronie's disease has a prevalence of 1% in men over age 50 years. Paget's disease of bone is a chronic skeletal disease with areas of increased bone turnover leading to pain, deformity, and in some cases arthritis. Because of a high rate of Peyronie's disease in subjects in a Paget's disease industry-sponsored drug trial, we asked whether there was an association between Peyronie's disease and Paget's disease of bone. We evaluated 61 men with Paget's disease attending our clinic for metabolic bone disease in a tertiary referral hospital, reviewed hospital records of all men discharged from our three hospitals with the diagnosis of Peyronie's disease, and mailed a validated questionnaire about shape of the erect penis to 1500 male members of the Paget Foundation. In the clinic population of men with Paget's disease of bone, 51 of 61 (83.6%) reported having normal erections; 10 patients (16.4%) were impotent. Sixteen of the 51 men (31.4%) had developed a bend or deformity in their erect penis which was confirmed by a urologist's examination to be Peyronie's disease. When the men with Paget's disease with and without Peyronie's disease were compared, there was no difference in their ages, years with Paget's disease, or serum alkaline phosphatase level. Upon medical record review, 1 patient of 262 (0.4%) with Peyronie's disease was found to have Paget's disease of bone. The men with Paget's disease returned their questionnaires for a response rate of 44.8% and reported Peyronie's disease with a prevalence of 14.5%. We suggest that Peyronie's disease is associated with Paget's disease of bone. Furthermore, we suggest that Peyronie's disease may be a previously unrecognized complication of Paget's disease of bone.

The clinical impact of vertebral fractures: quality of life in women with osteoporosis.

Osteoporosis has obvious physical and functional consequences such as kyphosis, restricted range of motion, and pain. What are not so obvious are the psychosocial sequelae that result from this metabolic bone disease. Many patients in the initial phases of the disease express substantial anxiety, especially about the possibility of future fractures and physical deformity. As the disease progresses, depression can become profound for those who experience hip or multiple vertebral fractures. The effects of the chronicity of osteoporosis, its disabling and disfiguring aspects, and the chronic postural pain that develops as time passes challenge even the most stable individuals. In addition, osteoporosis has substantial impact on interpersonal relationships and social roles. The dependency created by this disease affects close relationships, because the patient with osteoporosis cannot reciprocate in social support. Today's older women find the restrictions of the disease socially devastating. These women, unlikely to work in the labor force, took pride in their roles of housekeeper and cook. Unfortunately, severe osteoporosis can force women to relinquish even these social roles, leaving them with no source of self-esteem or accomplishment. In all, osteoporosis is devastating both psychologically and socially.

Association of osteoporotic vertebral compression fractures with impaired functional status.

PURPOSE: To determine if vertebral compression fractures in elderly women were associated with impairments in physical, functional, and psychosocial performance. SUBJECTS AND METHODS: Ten white women with confirmed vertebral compression fractures were age- and race-matched with 10 control subjects without fractures in a case-control design. All subjects invited to participate in this study were patients of the Geriatrics Division of the Department of Medicine at Duke University Medical Center. All study participants lived either in the community or in the independent-living sections of local retirement communities in and around Durham, NC. Subjects with fractures (mean age = 81.9 years, SD = 5.9 years) had two or more vertebral compression fractures in their medical records, whereas control subjects (mean age = 79.6 years, SD = 6.5 years) had no history of vertebral fractures. Spinal radiographs of all women confirmed group assignment. Physical, functional, and psychosocial performances were evaluated. Physical performance was assessed by measurements of maximal trunk extension torque and thoracic and lumbar spinal motion in the sagittal plane, functional reach, mobility skills, 10-ft timed walk, and 6-minute walk test. Thoracic and lumbar spinal configurations were also determined. Functional performance was assessed using the Functional Status Index. Psychosocial performance was assessed with the following scales: Hopkins Symptom Checklist 90 Revised, Rosenberg Self-Esteem Scale, West Haven-Yale Pain Inventory, Beck Depression Inventory, and single-item health-belief questions. RESULTS: Control subjects were not significantly different from patients with fractures in age, weight, number of current illnesses, number of prescribed medications, number of pain medications, ratings of lumbar spine degenerative disc disease, or lumbar spine facet joint arthritis. Activity levels and exercise participation were similar in both groups. Control subjects had no vertebral fractures, whereas fracture subjects had 4.2 +/- 2.6 fractures (range: 2 to 10). Thoracic kyphosis was increased and lumbar lordosis was reduced in fracture subjects. Fracture subjects had reduced maximal trunk extension torque, thoracic and lumbar spine sagittal plane motion, functional reach, mobility skills, and 6-minute walk test. The Functional Status Index showed reduced levels of functional performance in fracture subjects compared with controls with increased levels of assistance, pain with activity, and difficulty in activities. Psychosocial performance was limited in fracture subjects with increased psychiatric symptoms, increased pain, and greater perception of problems caused by health. CONCLUSION: Vertebral compression fractures are associated with significant performance impairments in physical, functional, and psychosocial domains in older women.

Managing patients with complications of osteoporosis.

This article reviews the impact of osteoporosis on quality of life. It defines specific impairments and suggests how best to minimize the impact of osteoporosis on patients' daily lives. Specific issues such as a spinal deformity, limitations on activities of daily living, pain, functionality, social impairment, self esteem, and depression also are addressed. Finally, a multidisciplinary team approach to osteoporosis is advocated.