Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study.

The comparative effects of zoledronic acid, denosumab, and teriparatide for preventing hip fractures in frail older adults, especially those in nursing homes, were unknown. We found that denosumab and zoledronic acid may be as effective as teriparatide for hip fracture prevention in nursing home residents. INTRODUCTION: Several non-oral drugs exist for osteoporosis treatment, including zoledronic acid (ZA), denosumab, and teriparatide. Little data exist on the comparative effectiveness of these drugs for hip fracture prevention in frail older adults. We examined their comparative effectiveness in one of the frailest segments of the US population-nursing home (NH) residents. METHODS: We conducted a national retrospective cohort study of NH residents aged ≥ 65 years using 2012 to 2016 national US Minimum Data Set clinical assessment data and linked Medicare claims. New parenteral ZA, denosumab, and teriparatide use was assessed via Medicare Parts B and D; hip fracture outcomes via Part A; and 125 covariates for confounding adjustment via several datasets. We used inverse probability weighted (IPW) competing risk regression models to compare hip fracture risk between groups with teriparatide as the reference. RESULTS: The study cohort (N = 2019) included 1046 denosumab, 578 teriparatide, and 395 ZA initiators. Mean age was 85 years, 90% were female, and 68% had at least moderate functional impairment. Seventy-two residents (3.6%) had a hip fracture and 1100 (54.5%) died over a mean follow-up of 1.5 years. Compared to teriparatide use, denosumab use was associated with a 46% lower risk of hip fracture (HR 0.54, 95% CI 0.29-1.00) and no difference was observed for ZA (HR 0.70, 95% CI 0.26-1.85). CONCLUSIONS: Denosumab and ZA may be as effective as teriparatide for hip fracture prevention in frail older adults. Given their lower cost and easier administration, denosumab and ZA are likely preferable non-oral treatments for most frail, older adults.

Defining hip fracture with claims data: outpatient and provider claims matter.

Medicare claims are commonly used to identify hip fractures, but there is no universally accepted definition. We found that a definition using inpatient claims identified fewer fractures than a definition including outpatient and provider claims. Few additional fractures were identified by including inconsistent diagnostic and procedural codes at contiguous sites. INTRODUCTION: Medicare claims data is commonly used in research studies to identify hip fractures, but there is no universally accepted definition of fracture. Our purpose was to describe potential misclassification when hip fractures are defined using Medicare Part A (inpatient) claims without considering Part B (outpatient and provider) claims and when inconsistent diagnostic and procedural codes occur at contiguous fracture sites (e.g., femoral shaft or pelvic). METHODS: Participants included all long-stay nursing home residents enrolled in Medicare Parts A and B fee-for-service between 1/1/2008 and 12/31/2009 with follow-up through 12/31/2011. We compared the number of hip fractures identified using only Part A claims to (1) Part A plus Part B claims and (2) Part A and Part B claims plus discordant codes at contiguous fracture sites. RESULTS: Among 1,257,279 long-stay residents, 40,932 (3.2%) met the definition of hip fracture using Part A claims, and 41,687 residents (3.3%) met the definition using Part B claims. 4566 hip fractures identified using Part B claims would not have been captured using Part A claims. An additional 227 hip fractures were identified after considering contiguous fracture sites. CONCLUSIONS: When ascertaining hip fractures, a definition using outpatient and provider claims identified 11% more fractures than a definition with only inpatient claims. Future studies should publish their definition of fracture and specify if diagnostic codes from contiguous fracture sites were used.

Intra-and inter-reader reliability of semi-automated quantitative morphometry measurements and vertebral fracture assessment using lateral scout views from computed tomography.

UNLABELLED: Intra-and inter-reader reliability of semi-automated quantitative vertebral morphometry measurements was determined using lateral computed tomography (CT) scout views. The method requires less time than conventional morphometry. Reliability was excellent for vertebral height measurements, good for height ratios, and comparable to semi-quantitative grading by radiologists for identification of vertebral fractures. INTRODUCTION: Underdiagnosis and undertreatment of vertebral fracture (VFx) is a well-known problem worldwide. Thus, new methods are needed to facilitate identification of VFx. This study aimed to determine intra- and inter-reader reliability of semi-automated quantitative vertebral morphometry based on shape-based statistical modeling (SpineAnalyzer, Optasia Medical, Cheadle, UK). METHODS: Two non-radiologists independently assessed vertebral morphometry from CT lateral scout views at two time points in 96 subjects (50 men, 46 women, 70.3 ± 8.9 years) selected from the Framingham Heart Study Offspring and Third Generation Multi-Detector CT Study. VFxs were classified based solely on morphometry measurements using Genant's criteria. Intraclass correlation coefficients (ICCs), root mean squared coefficient of variation (RMS CV) and kappa (k) statistics were used to assess reliability. RESULTS: We analyzed 1,246 vertebrae in 96 subjects. The analysis time averaged 5.4 ± 1.7 min per subject (range, 3.2-9.1 min). Intra-and inter-reader ICCs for vertebral heights were excellent (>0.95) for all vertebral levels combined. Intra-and inter-reader RMS CV for height measurements ranged from 2.5% to 3.9% and 3.3% to 4.4%, respectively. Reliability of vertebral height ratios was good to fair. Based on morphometry measurements alone, readers A and B identified 51-52 and 46-59 subjects with at least one prevalent VFx, respectively, and there was a good intra-and inter-reader agreement (k = 0.59-0.69) for VFx identification. CONCLUSIONS: Semi-automated quantitative vertebral morphometry measurements from CT lateral scout views are convenient and reproducible, and may facilitate assessment of VFx.

Reliability of vertebral fracture assessment using multidetector CT lateral scout views: the Framingham Osteoporosis Study.

UNLABELLED: Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture. INTRODUCTION: We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT. METHODS: Participants included 50 women and 50 men (age 50-87 years, mean 70 years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture. RESULTS: Vertebra-specific prevalence of grade ≥ 1 (mild) fracture ranged from 3% to 5%. We found fair (κ = 56-59%) inter-reader agreement for grade ≥ 1 vertebral fractures and good (κ = 68-72%) inter-reader agreement for grade ≥ 2 fractures. Intra-reader agreement for grade ≥ 1 vertebral fracture was fair (κ = 55%) for one reader and excellent for another reader (κ = 77%), whereas intra-reader agreement for grade ≥ 2 vertebral fracture was excellent for both readers (κ = 76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader κ = 43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader κ = 76-78%) for the lumbar spine (L1-L4). CONCLUSIONS: Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture.

Factors related to the use of bone densitometry: survey responses of 494 primary care physicians in New England.

Large population-based surveys have shown that approximately 30% of people over age 65 years have osteoporosis and that 17% of the population over 65 years will sustain a fracture during their lifetime. Many people with osteoporosis are never being evaluated even though effective treatments are available. We examined why primary care physicians order few bone mineral density scans. We conducted a cross-sectional survey of primary care physicians practicing in any of the six New England states. Target physician specialties included internal medicine, general practitioners/family physicians, and obstetrician-gynecologists who had a facsimile number listed with the American Medical Association. Demographics, practice characteristics, use of bone densitometry, and attitudes regarding osteoporosis, bone densitometry and health maintenance were assessed by questionnaire. Twelve percent (n=494) of the physicians responded to the questionnaire. Respondents were similar to non-respondents with respect to years of practice, training and geographical state, though they were more likely to be female (p < or =0.05). Respondents had a mean age of 51 years, and 51% were trained in internal medicine, 25% in general practice/family practice and 24% in obstetrics-gynecology. The mean number of self-reported bone densitometry referrals per month was 10+/-11, and 25% of respondents reported that they referred fewer than 4 patients per month. In adjusted logistic models, factors significantly associated with referring fewer than 4 patients per month were: training in internal medicine (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9) or general practice/family practice (OR 2.6, 95% CI 1.3-5.2) versus obstetrics-gynecology; practicing in an urban setting (OR 2.5, 95% CI 1.3-4.9) or rural/small town setting (OR 2.2, 95% CI 1.2-4.1) versus a suburban setting; spending less than 50% of professional time in patient care (OR 4.0, 95% CI 1.7-9.5); seeing the lowest proportion of postmenopausal women (OR 2.5., 95% CI 1.2-5.3); the belief that calcium and vitamin D are adequate to treat osteoporosis (OR 2.1, 95% CI 1.0-4.5); and the belief that osteoporosis treatment should not be based on bone density results (OR 3.2, 95% CI 1.7-6.1). Potentially modifiable physician beliefs and a number of practice characteristics are associated with low referral rates for bone densitometry. Educational strategies aimed at improving the use of bone density testing should consider these factors.

Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study.

BACKGROUND: Low muscle mass has been assumed to be associated with disability, but no studies confirming this association have been published. High body weight and high body mass index, both rough indicators of body fatness, have been shown to increase the risk for disability; however, the specific role of body fatness has not been studied. METHODS: The relations of skeletal muscle mass and percent body fat with self-reported physical disability were studied in 753 men and women aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992-1993) of the Framingham Heart Study were used. Body composition was assessed by dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9-item questionnaire. RESULTS: Total body and lower extremity muscle mass were not associated with disability in either men or women. However, a strong positive association between percent body fat and disability was observed. The odds ratio for disability in those in the highest tertile of body fatness was 2.69 (95% confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to those in the lowest tertile. The increased risk could not be explained by age, education, physical activity, smoking, alcohol use, estrogen use (women only), muscle mass, and health status. Analyses restricting disability to mobility items gave similar results. CONCLUSIONS: In contrast to current assumptions, low skeletal muscle mass was not associated with self-reported physical disability. Persons with a high percent body fat had high levels of disability. Because it cannot be ruled out that persons with low skeletal muscle mass dropped out earlier in the study, prospective studies are needed to further assess the relationship between body composition and physical disability.

Factors influencing subject willingness to participate in clinical gerontologic research.

To identify factors influencing willingness to participate (WTP) in clinical gerontologic research, a questionnaire containing descriptions of seven research projects with a corresponding set of questions about perceived intrusiveness (discomfort and inconvenience), stipend, and other incentive factors was sent to 1004 community-dwelling research subject registry members. There was an inverse relationship between perceived level of intrusiveness and WTP. The more intrusive the study, the greater the relative influence of a stipend on WTP. Male gender and a new experience with an opportunity to learn were independently related to WTP. Subject ratings of perceived intrusiveness for each study component were entered into a factor analysis to guide the development of a three-tier "Level of Intrusiveness" scale. Although prospective validation is necessary, the Level of Intrusiveness scale may be useful in predicting WTP, and determining when other incentives are needed to improve subject recruitment for clinical research.

An epidemiologic study of fall-related fractures among institutionalized older people.

OBJECTIVES: The purpose of this study was to assess the incidence of fall-related fractures, and the circumstances surrounding these events, during a 5-year period among all residents of a long-term care facility. PARTICIPANTS: The study group was composed of residents with radiologically confirmed fractures that were the direct result of a fall occurring between the years 1988 and 1992. This group was 82% female and had a mean age of 89 +/- 6 years. DESIGN: The study was designed as a 5-year retrospective cohort study in a long-term care institution where annual incidence rates of fracture were assessed. RESULTS: There were 296 fall-related fractures during the 5-year period. Annual incidence rates remained fairly constant (72, 86, 84, 70, and 94 per 1000 person-years, respectively) despite a 54% decline in the use of physical restraints during the 5-year period. Hip fractures comprised almost 50% of all fractures. Based on incident reports of these fractures, 42% occurred during the day, 55% took place in the bedroom or adjoining bathroom. 67% occurred while the resident was ambulating, and a wet floor was in evidence in 16% of the incidents. CONCLUSION: Fracture incidence in this long-term care facility has remained stable despite reduced restraint use. The incident reporting system may contribute valuable information to the identification of factors that should receive further attention in studies of risk factors for fracture in the long-term care setting.

The outcomes of patients newly admitted to nursing homes after hip fracture.

OBJECTIVES: The outcomes of elderly, hospitalized patients discharged to nursing homes after hip fracture were examined. METHODS: For 2624 hip fracture patients admitted to any of 43 proprietary nursing homes between 1984 and 1988, admission assessments were examined in relation to 1-month outcomes. RESULTS: Mean patient age was 82 +/- 7 y; 85% of the sample were female. Within 1 month after discharge, 24% had returned home, 12% had been rehospitalized, 3% had died, and 61% remained in the nursing home. Characteristics significantly associated with morality included disorientation, functional dependency, neurologic diagnoses, and use of cardiac medications, antidepressants, or narcotics. Rehospitalization was significantly associated with age, gender, living with someone, being ambulatory, and functional dependency. Returning home was associated with younger age, living with someone, being ambulatory, and having no disorientation, functional dependency, or psychiatric or neurologic diagnoses, nor any pressure sores. CONCLUSIONS: Better-functioning persons and those with social support returned home; physically and cognitively impaired persons and those taking narcotics, cardiac medications, or antidepressants were likely to die; and younger men, those with social support, those with functional dependency, and those who were free of disorientation were more likely to be rehospitalized.