[Show abstract][Hide abstract] ABSTRACT: Objective:
The effect of oral contraceptive (OC) use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, we conducted a population-based case-control study in a Pacific Northwest HMO, Group Health Cooperative.
For the January 2008 to March 2013 interval, 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women were enrolled. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).
Participation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases versus controls for OC use in the 10 years before menopause (OR 0.90, 95% CI 0.74, 1.11); for OC use after age 38 (OR 0.94, 95% CI 0.78, 1.14); for duration of use, or for other OC exposures.
The current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38. For women considering OC use at these times, fracture risk does not seem to be either reduced or-reassuringly-increased.
No preview · Article · Jan 2016 · Menopause (New York, N.Y.)
[Show abstract][Hide abstract] ABSTRACT: Bone metabolism is linked to systemic diseases, and new research shows that the bone cells have endocrine functions that affect multiple organs. They secrete sclerostin, FGF23, prostaglandins, and osteocalcin. Pereira et al. examined gene expression of cells grown from bone biopsies of adolescents with renal osteodystrophy, as a first step to understanding how the bone-cell abnormalities contribute to cardiovascular and metabolic problems in these patients.
No preview · Article · Mar 2015 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Several studies have shown racial differences in the regulation of mineral metabolism, in the acquisition of bone mass and structure of individuals. In this review, we examine ethnic differences in bone and mineral metabolism in normal individuals and in patients with chronic kidney disease. Black individuals have lower urinary excretion and increased intestinal calcium absorption, reduced levels of 25(OH)D, and high levels of 1.25(OH)2D and parathyroid hormone (PTH). Body phosphorus concentration is higher and the levels of FGF-23 are lower than in whites. Mineral density and bone architecture are better in black individuals. These differences translate into advantages for blacks who have stronger bones, less risk of fractures, and less cardiovascular calcification. In the United States of America, the prevalence of kidney disease is similar in different ethnic groups. However, black individuals progress more quickly to advanced stages of kidney disease than whites. This faster progression does not translate into increased mortality, higher in whites, especially in the first year of dialysis. Some ethnicity-related variations in mineral metabolism persist when individuals develop CKD. Therefore, black patients have lower serum calcium concentrations, less hyperphosphatemia, low levels of 25(OH)D, higher levels of PTH, and low levels of FGF-23 compared with white patients. Bone biopsy studies show that blacks have greater bone volume. The rate of fractures and cardiovascular diseases are also less frequent. Further studies are required to better understand the cellular and molecular bases of these racial differences in bone mineral metabolism and thus better treat patients.Kidney International advance online publication, 18 December 2013; doi:10.1038/ki.2013.443.
No preview · Article · Dec 2013 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Patients with chronic kidney disease (CKD) have a high risk of bone fracture owing to their low bone mineral density, which resembles that of postmenopausal osteoporosis. However, the mineral and bone disorder associated with CKD (CKD-MBD) is more complex than osteoporosis and the same treatments might not be appropriate. In particular, vascular calcifications are strongly associated with CKD-MBD, and must be taken into consideration. Post hoc analyses of data from pivotal osteoporosis studies suggest that in patients with mild stage 3 CKD and normal parathyroid hormone (PTH), calcium and phosphate measurements, conventional medications for osteoporosis (such as raloxifene, bisphosphonates, teriparatide and denosumab) are effective at reducing fracture rates. However, for patients with stage 4-5 CKD, or those with abnormal PTH and mineral values, the available data are insufficient to determine whether these commonly used medications are effective against fractures. Moreover, all medications used to treat osteoporosis have known or potential adverse effects in patients with CKD. Medicines that increase bone formation by upregulating Wnt signalling have shown promise in patients with osteoporosis and might be used to treat CKD-MBD in the future, but off-target effects could limit their use in in this setting.
No preview · Article · Oct 2013 · Nature Reviews Nephrology
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To evaluate the accuracy of using ICD-9 codes to identify nonunions (NU) and malunions (MU) among adults with a prior fracture code and to explore case-finding algorithms. STUDY DESIGN: Medical chart review of potential NU (N=300) and MU (N=288) cases. True NU cases had evidence of NU and no evidence of MU in the chart (and vice versa for MUs) or were confirmed by the study clinician. Positive predictive values (PPV) were calculated for ICD-9 codes. Case-finding algorithms were developed by a classification and regression tree analysis using additional automated data, and these algorithms were compared to true case status. SETTING: Group Health Cooperative. RESULTS: Compared to true cases as determined from chart review, the PPV of ICD-9 codes for NU and MU were 89% (95% CI, 85-92%) and 47% (95% CI, 41-53%), respectively. A higher proportion of true cases (NU: 95%; 95% CI, 90-98%; MU: 56%; 95% CI, 47-66%) were found among subjects with 1+ additional codes occurring in the 12months following the initial code. There was no case-finding algorithm for NU developed given the high PPV of ICD-9 codes. For MU, the best case-finding algorithm classified people as an MU case if they had a fracture in the forearm, hand, or skull and had no visit with an NU diagnosis code in the 12-months post MU diagnosis. PPV for this MU case-finding algorithm increased to 84%. CONCLUSIONS: Identifying NUs with its ICD-9 code is reasonable. Identifying MUs with automated data can be improved by using a case-finding algorithm that uses additional information. Further validation of the MU algorithms in different populations is needed, as well as exploration of its performance in a larger sample.
[Show abstract][Hide abstract] ABSTRACT: Bisphosphonates are a class of drugs commonly prescribed to treat osteoporosis. They act by decreasing the resorption of bone. Since tooth movement depends on bone remodeling, these drugs can impact orthodontic treatment. The purpose of this study was to evaluate the extent to which bisphosphonate therapy is a risk factor for poor orthodontic outcomes.
Orthodontists were invited to participate in the study by performing case reviews of women over age 50 who were treated from 2002 through 2008. Women who used bisphosphonates were compared with women who did not have a history of bisphosphonate use. Outcomes assessed included treatment time, osteonecrosis of the jaws, incisor alignment, incomplete space closure, and root parallelism.
The records for 20 subjects with bisphosphonate exposure were collected, as well as records for 93 subjects without bisphosphonate exposure. In patients undergoing extractions, treatment times were significantly longer if they had a history of bisphosphonate use. No occurrences of osteonecrosis of the jaws were reported, nor did patients end treatment with incisor alignment discrepancies greater than 1 mm, regardless of bisphosphonate exposure. Among patients with extractions or initial spacing, there were higher odds of incomplete space closure (odds ratio, 13) and poor root parallelism (odds ratio, 26) at the end of treatment for patients using bisphosphonates.
Bisphosphonate use is associated with longer treatment times among extraction patients, increased odds of poor space closure, and increased odds of poor root parallelism.
No preview · Article · Nov 2012 · American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics
[Show abstract][Hide abstract] ABSTRACT: To the Editor: In a recent pooled analysis of vitamin D dose requirements for fracture prevention, Bischoff-Ferrari and colleagues (July 5 issue)(1) reanalyzed data from clinical trials by taking into account vitamin D supplementation taken by participants in addition to the study medication. This reanalysis provides a more accurate estimation of the vitamin D intake. However, the results are inconclusive because the authors did not mention sunlight exposure, which is the natural physiological source of vitamin D. This substance is not a "vitalamine" but it is a secosteroid hormone that is normally produced by the skin. No dietary intake is . . .
No preview · Article · Oct 2012 · New England Journal of Medicine
[Show abstract][Hide abstract] ABSTRACT: A new population-based study of elderly patients hospitalized for a fracture and treated with an oral bisphosphonate finds no increased risk of acute kidney injury. The safety and efficacy of bisphosphonates may be different in patients with chronic kidney disease (CKD). The effects on vascular calcifications need further study, because low bone turnover might exacerbate vascular calcifications in patients with CKD. Even if bisphosphonates prove safe, their efficacy in this population is uncertain.
Preview · Article · Oct 2012 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Background/Aims In an era of increasing openness in health plans, use of electronic medical records (EMR) for detailed chart abstraction for all enrollees poses challenges. At Group Health Cooperative (GH), EMR data are most complete for enrollees in the Group Practice Division (GPD). However, all GH enrollees (from both the GPD and the Contracted Network Division (CND) have EMRs. CND providers do not have access to patients' GH EMR. Information for CND enrollees is only entered when the patient or provider interacts with the GPD, such as a patient receiving GPD specialty care while receiving CND primary care. In the interest of achieving a larger sample size for an ongoing GH-based case-control study (FOCUS), we evaluated the feasibility of including CND enrollees by determining the proportion with sufficient EMR information for fracture adjudication. Methods The FOCUS study is adjudicating and recruiting incident osteoporotic fracture cases in women across the menopausal transition using the GPD. We used identical automated sampling methods to identify, via ICD-9 codes, a pool of potential adjudicable fracture cases among CND enrollees. Results For the GPD, from a denominator of 58,328 age-eligible women, 2,310 (4%) were identified with fractures January 2008-March 2011. For the CND, among 38,041 age-eligible women, 1,040 (3%) were identified with fractures. Following automated exclusions, 944 CND potential cases remained. Initial review of these 944 EMRs found that 685 charts had no data; 54 had data unrelated to fracture; 145 had sufficient fracture-related data to adjudicate; and 60 had some fracture-related data. Preliminary chart adjudication of these last two groups found that 88% (127/145) of the "complete" EMR group and 10% (6/60) of the "partially complete" group had qualifying fractures. Discussion About 23% of GH network enrollees with automated fracture codes had evaluable EMR data. Preliminary adjudication has identified 65% (133/205) as additional potential FOCUS cases to contact for interviews. It appears that, even for a study requiring sufficient chart information to adjudicate a health outcome, the CND can contribute cases for study inclusion. We also have developed network control selection methods. Still to be ascertained at the survey step are continued eligibility and study participation.
Preview · Article · Aug 2012 · Clinical Medicine & Research
[Show abstract][Hide abstract] ABSTRACT: Background/Aims Hormonal contraception is a popular contraceptive choice among sexually-active women. Yet, its association with body composition in younger women is not well understood. We compared body composition measures by duration of Depo-Provera (DMPA) use and dose and duration of oral contraceptive (OC) use in adolescent and young adult women. Methods Study participants were Group Health Cooperative members. DMPA use (new, prevalent, or none) was collected in 170 adolescents aged 14-18 years, and in 440 women aged 18-39 years. OC use was gathered in 301 adolescents aged 14-18 years, and 305 women aged 19-30 years. Among OC users, ethinyl estradiol (EE) dose (=30mcg vs. <30mcg) and months of use were also collected. For all participants, weight, BMI, and truncal and total fat and lean mass were estimated using DEXA. Mean differences in baseline body composition by dose and duration of hormone contraception use were compared cross-sectionally using ANOVA. Results Adolescents who were prevalent DMPA users had higher baseline truncal and total fat mass compared to adolescent non-DMPA users. For example, baseline mean (SE) total fat mass was 23.3 (1.2) kilograms for prevalent DMPA users, but was 19.9 (0.9) kilograms for non-DMPA users (p<0.05). No mean differences in the body composition measures were observed between new DMPA vs. non- DMPA adolescent users or among young women, regardless of DMPA use. With OC use, baseline BMI and truncal and total fat mass differed by EE dose in young adult women. Baseline mean (SE) total fat mass, in kilograms, for women using =30mcg EE doses, <30mcg EE doses, and for non-OC users was 20.8 (0.9), 19.0 (0.9), and 22.2 (0.9), respectively (p=0.02). No differences were noted between EE dose and body composition indices in adolescents. For both adolescents and young women, baseline body composition was not associated with duration of OC use. Conclusions Our results suggest that DMPA use is associated with fat mass in adolescents and that EE dose in OCs is associated with fat mass in young adult women. Analysis of follow-up data to determine if these relationships continue to be seen longitudinally is needed.
Preview · Article · Aug 2012 · Clinical Medicine & Research
[Show abstract][Hide abstract] ABSTRACT: Background/Aims Self-reported use of oral contraceptives (OCs) may be subject to recall bias. Previous reports comparing self-report OC use and computerized pharmacy data have focused on current use or longer-term use in younger women and have found (adjusted) kappa statistics of 79-85%. The objective of the current analysis was to evaluate the reliability of self-reported OC use obtained from a sample of peri- and early post-menopausal women. Methods Participants were 45-59 year-old women eligible for an ongoing population-based case-control study assessing the association between OC use and incident fractures around the menopausal transition. Cases were all women enrolled in Group Health with an ICD9 osteoporotic fracture code in 2008-2009; age-matched non-fracture controls were randomly selected. Eligible cases and controls (n=535) who reported at interview that they always/usually filled prescriptions at GH pharmacies and agreed to record review were included. Respondents who reported ever using OCs before the reference date (fracture date for cases; randomly assigned dates based on distribution of case dates for controls) were asked, for each episode of use, their age and length of use. A life events- calendar tool was available to interviewers. Computerized pharmacy information was obtained on OC fills back to 1977. OC use was based on GH pharmacy and First Data Bank OC class, key ingredients [e.g. ethinyl estradiol, levonorgestrel], and name. OC use was evaluated using >1 fill or >2 fills within a 1-year period. Ever use, use since ages 35, 38, and 40, and 5 years before reference date were examined. Women were required to be enrolled for the designated time period except for the ever-use category. We calculated kappa (K), the chance-corrected measure of agreement, and the prevalence-adjusted bias-adjusted kappa (PABAK). Results The agreement between self-reported OC use and OC fills was highest for more recent use (PABAK=92% for OC use within 5 years of reference date and 55% for use at ages >38). Conclusion In women around the menopausal transition, agreement between self-reported OC use and computerized OC prescription fills was moderate for use after age 38 and excellent for OC use within 5 years of the reference date.
Preview · Article · Aug 2012 · Clinical Medicine & Research