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1.  Inflammatory eye reactions with bisphosphonates and other osteoporosis medications: what are the risks? 
Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor modulators, strontium, denosumab and teriparatide). We cover the known epidemiology, potential pathogenic mechanisms and a resume of unanswered questions. Briefly, this review highlights that none of the existing randomized clinical trials were powered to identify these rare adverse events, and the majority of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually be part of underlying inflammatory disease processes that also cause osteoporosis, rather than due to the medications used to treat osteoporosis themselves. There are no clear pathogenic mechanisms for how bisphosphonates could potentially cause IERs. However, the drug is secreted into the tears by the lacrimal gland and could cause irritation to the mucous membranes with subsequent release of inflammatory mediators, similar to the systemic response typically seen after infusion of bisphosphonates. However, in summary it is still not known whether there is a true causal association between bisphosphonates or other anti-osteoporosis medications and IERs, or whether it is confounding by indication and is actually due to underlying inflammatory diseases that cause both osteoporosis and IERs.
doi:10.1177/1759720X14566424
PMCID: PMC4314301  PMID: 25650170
adverse events; anti-osteoporosis medications; bisphosphonates; inflammatory eye reactions; osteoporosis; pathogenesis
2.  Lateral back pain identifies prevalent vertebral fractures in post-menopausal women: cross-sectional analysis of a primary care-based cohort 
Rheumatology (Oxford, England)  2009;49(3):505-512.
Objective
Vertebral fractures (VFs) are frequently under-recognized, reflecting their lack of diagnostic clinical features. For example, although VFs are associated with back pain, this is also common in the general population. To establish whether back pain can be used to recognize patients with VF, we investigated the site of pain in people with and without VFs using a simple tool.
Methods
A cohort of 504 post-menopausal women was recruited from primary care in South West UK. Back pain was assessed by self-completion of the Margolis pain diagram, and analysis was modified to assess whether pain was mid-line or lateral. VFs were diagnosed by the algorithm-based qualitative method on radiographs. A cross-sectional analysis was carried out to assess the association between back pain and VFs.
Results
Three hundred and twenty-two women (64.1%) reported back pain over the last 12 months. Thirty seven (7.3%) had one or more VFs. In women with back pain, the presence of lateral waist area pain was associated with a 4.5-fold increased risk of VFs [odds ratio (OR) 4.48; 95% CI 2.02, 9.94; P<0.001].
Conclusions
In post-menopausal women with back pain, the presence of lateral waist pain, as shown on the Margolis pain diagram, may identify women at higher risk of prevalent VF.
doi:10.1093/rheumatology/kep414
PMCID: PMC2895162  PMID: 20015975
Back pain; Margolis pain diagram; Vertebral fractures
3.  The Invisible Disease 
Qualitative Health Research  2011;21(12):1692-1704.
Osteoporosis (low bone density) is a potentially serious disease which mainly affects women older than 50 years. National screening programs for osteoporosis are being developed in the United Kingdom. It is important to assess the psychological experience of receiving a positive diagnosis from a population-based screening program so that psychological distress does not outweigh medical benefits. Little research has been conducted in this field. In our study, we explored the experience of being diagnosed with osteoporosis following screening. We interviewed 10 women aged 68 to 79 who were recruited from a population-based osteoporosis screening trial. Four themes emerged from our interpretative phenomenological analysis of the interviews: osteoporosis is a routine medical condition, lack of physical evidence creates doubt, the mediating role of medical care, and protecting the self from distress. Our findings emphasize the complexity attached to receiving a positive screening result. We suggest considerations for health care providers.
doi:10.1177/1049732311416825
PMCID: PMC3240909  PMID: 21810994
aging; health care screening; health care, primary; health care, users’ experiences; illness and disease, experiences; interpretative phenomenological analysis (IPA); medicine; older people; relationships, health care; women’s health
4.  Randomized controlled trial of a primary care–based screening program to identify older women with prevalent osteoporotic vertebral fractures: Cohort for skeletal health in Bristol and Avon (COSHIBA) 
Approximately 12% of postmenopausal women have osteoporotic vertebral fractures (VFs); these are associated with excess morbidity and mortality and a high risk of future osteoporotic fractures. Despite this, less than one-third come to clinical attention, partly due to lack of clear clinical triggers for referral for spinal radiographs. The aim of this study was to investigate whether a novel primary care–based screening tool could be used to identify postmenopausal women with osteoporotic VFs and increase appropriate management of osteoporosis. A randomized controlled trial was undertaken in 15 general practices within the Bristol area of the UK. A total of 3200 women aged 65 to 80 years were enrolled, with no exclusion criteria. A simple screening tool was carried out by a nurse in primary care to identify women at high risk of osteoporotic VFs. All identified high-risk women were offered a diagnostic thoracolumbar radiograph. Radiographs were reported using standard National Health Service (NHS) reporting, with results sent back to each participant's general practitioner (GP). Participants in the control arm did not receive the screening tool or radiographs. The main outcome measure was self-reported prescription of medication for osteoporosis at 6 months with a random 5% subsample verified against electronic GP records. Secondary outcome was self-reported incidence of new fractures. Results showed that allocation to screening increased prescription of osteoporosis medications by 124% (odds ratio [OR] for prescription 2.24 at 6 months; 95% confidence interval [CI], 1.16 to 4.33). Allocation to screening also reduced fracture incidence at 12-month follow-up (OR for new fracture 0.60; 95% CI, 0.35–1.03; p = 0.063), although this did not reach statistical significance. This study supports the use of a simple screening tool administered in primary care to increase appropriate prescription of medications for osteoporosis in postmenopausal women in the UK. © 2012 American Society for Bone and Mineral Research
doi:10.1002/jbmr.1478
PMCID: PMC3378696  PMID: 22113935
RANDOMIZED CONTROLLED TRIAL; SCREENING; VERTEBRAL FRACTURES
5.  Epidemiology of generalised joint laxity (hypermobility) in 14 year old children from the UK: A population-based evaluation 
Arthritis and rheumatism  2011;63(9):2819-2827.
Although diagnostic criteria for generalised ligamentous laxity (hypermobility) in children are widely used, they may have limited validity as robust descriptive epidemiology of this condition is lacking. We used a large population-based birth cohort to describe the point prevalence and pattern of hypermobility in children aged 14 years.
We performed a cross-sectional analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC). Hyperrmobility was measured at aged 14 years using the Beighton scoring system. Objective measures of physical activity were collected by accelerometry. Data were collected on other variables including puberty and socio-economic status. Simple prevalence was calculated. Chi-squared tests and logistic regression were used to assess associations between variables and hypermobility.
6022 children were evaluated. Using a cut-off of ≥4, the prevalence of hypermobilty in girls and boys aged 13.8 years was 27.5% and 10.6% respectively. 45% of girls and 29% of boys had hypermobile fingers. There was a suggestion of a positive association between hypermobility in girls and variables including physical activity, body mass index and maternal education. No associations were seen in boys.
We have shown that the prevalence of hypermobility in UK children is high; possibly suggesting that the Beighton cut off is too low or that the score is not appropriate in a developing musculoskeletal system. These results give a platform to evaluate the relationships between the Beighton criteria and key clinical features (including pain), thereby testing the clinical validity of this score in the childhood population.
doi:10.1002/art.30435
PMCID: PMC3164233  PMID: 21547894
Hypermobility; Children; Epidemiology; Cohort study; Pediatric Rheumatology
6.  Determinants of fracture risk in a UK-population-based cohort of older women: a cross-sectional analysis of the Cohort for Skeletal Health in Bristol and Avon (COSHIBA) 
Age and Ageing  2011;41(1):46-52.
Background: identification of individuals with high fracture risk from within primary care is complex. It is likely that the true contribution of falls to fracture risk is underestimated.
Methods: cross-sectional analysis of a population-based cohort of 3,200 post-menopausal women aged 73 ± 4 years. Self-reported data were collected on fracture, osteoporosis clinical risk factors and falls/mobility risk factors. Self-reported falls were compared with recorded falls on GP computerised records. Multivariable logistic regression was used to identify independent risk factors for fracture.
Results: a total of 838 (26.2%) reported a fracture after aged 50; 441 reported falling more than once per year, but 69% of these had no mention of falls on their computerised GP records. Only age [odds ratios (OR): 1.37 per 5 year increase, 95% confidence interval (CI): 1.23–1.53], height (1.02 per cm increase, 95% CI: 1.01–1.04), weight (OR: 0.99 per kg increase, 95% CI: 0.98–0.99) and falls (OR: 1.49 for more than once per year compared with less, 95% CI: 1.13–1.94) were independent risk factors for fracture. Falls had the strongest association.
Conclusion: when identifying individuals with high fracture risk we estimate that more than one fall per year is at least twice as important as height and weight. Furthermore, using self-reported falls data is essential as computerised GP records underestimate falls prevalence.
doi:10.1093/ageing/afr132
PMCID: PMC3234077  PMID: 22107913
fractures; falls; COSHIBA; FRAX; cohort study; elderly
7.  Association Between Bone Mass and Fractures in Children: A Prospective Cohort Study 
This is the first prospective cohort study of the association between bone mass and fracture risk in childhood. A total of 6213 children 9.9 years of age were followed for 24 months. Results showed an 89% increased risk of fracture per SD decrease in size-adjusted BMC.
Introduction
Although previous case-control studies have reported that fracture risk in childhood is inversely related to bone mass, this has not been confirmed in prospective studies. Additionally, it remains unclear which constituent(s) of bone mass underlie this association. We carried out a prospective cohort study to examine the relationship between DXA measures in children 9.9 years of age and risk of fracture over the following 2 years.
Materials and Methods
Total body DXA scan results obtained at 9.9 years of age were linked to reported fractures over the following 2 years in children from a large birth cohort in southwest England. DXA measures consisted of total body less head (TBLH) BMD, bone area, and BMC, and results of subregional analysis of the humerus. Analyses were adjusted for age, sex, ethnicity, and social position.
Results
Complete data were available on 6213 children. There was a weak inverse relationship between BMD at 9.9 years and subsequent fracture risk (OR per SD decrease = 1.12; 95% CI, 1.02–1.25). In analyses examining the relationship between fracture risk and volumetric BMD, fracture risk was inversely related to BMC adjusted for bone area, height, and weight (OR = 1.89; 95% CI, 1.18–3.04) and to estimated volumetric BMD of the humerus (OR = 1.29; 95% CI, 1.14–1.45). Fracture risk was unrelated to both TBLH and humeral bone area. However, in analyses of the relationship between fracture risk and bone size relative to body size, an inverse association was observed between fracture risk and TBLH area adjusted for height and weight (OR = 1.51; 95% CI, 1.17–1.95).
Conclusions
Fracture risk in childhood is related to volumetric BMD, reflecting an influence of determinants of volumetric BMD such as cortical thickness on skeletal fragility. Although bone size per se was not related to fracture risk, we found that children who fracture tend to have a smaller skeleton relative to their overall body size.
doi:10.1359/jbmr.060601
PMCID: PMC2742714  PMID: 16939408
population studies; bone densitometry; clinical/pediatrics; fractures; epidemiology
8.  Bone Fragility Contributes to the Risk of Fracture in Children, Even After Moderate and Severe Trauma 
We prospectively examined whether the relationship between skeletal fragility and fracture risk in children 9.9 ± 0.3 (SD) yr is affected by trauma level. Bone size relative to body size and humeral vBMD showed similar inverse relationships with fracture risk, irrespective of whether fractures followed slight or moderate/severe trauma.
Introduction
Fracture risk in childhood is related to underlying skeletal fragility. However, whether this relationship is confined to low-trauma fractures or whether skeletal fragility also contributes to the risk of fracture caused by higher levels of trauma is currently unknown.
Materials and Methods
Total body DXA scan results obtained at 9.9 yr of age were linked to reported fractures over the following 2 yr in children from the Avon Longitudinal Study of Parents and Children. DXA scan results that were subsequently derived included total body less head (TBLH) bone size relative to body size (calculated from TBLH area adjusted for height and weight) and humeral volumetric BMD (vBMD; derived from subregional analysis at this site). Trauma level was assigned using the Landin classification based on a questionnaire asking about precipitating causes.
Results
Of the 6204 children with available data, 549 (8.9%) reported at least one fracture over the follow-up period, and trauma level was assigned in 280 as follows: slight trauma, 56.1%; moderate trauma, 41.0%; severe trauma, 2.9%. Compared with children without fractures, after adjustment for age, sex, socioeconomic status, and ethnicity, children with fractures from both slight and moderate/severe trauma had a reduced bone size relative to body size (1133 cm2 in nonfractured children versus 1112 cm2 for slight trauma fractures, p < 0.001; 1112 cm2 for moderate/severe trauma fractures, p = 0.001) and reduced humeral vBMD (0.494 g/cm3 in nonfractured children versus 0.484 g/cm3 for slight trauma fractures, p = 0.036; and 0.482g/cm3 for moderate/severe trauma fractures, p = 0.016).
Conclusions
Skeletal fragility contributes to fracture risk in children, not only in fractures caused by slight trauma but also in those that result from moderate or severe trauma.
doi:10.1359/jbmr.071010
PMCID: PMC2742712  PMID: 17922615
fractures; children; trauma levels; epidemiology; BMD; Avon Longitudinal Study of Parents and Children
9.  Vigorous Physical Activity Increases Fracture Risk in Children Irrespective of Bone Mass: A Prospective Study of the Independent Risk Factors for Fractures in Healthy Children 
Low bone mass is a determinant of fractures in healthy children. Small studies provide limited evidence on the association between ethnicity, birth weight, family size, socioeconomic status, dietary calcium intake, or physical activity and fracture incidence. No studies have investigated whether these determinants of fracture risk act through affecting bone mass or through other mechanisms. The aim of this study was to use a population-based birth cohort to confirm which variables are determinants of fracture risk and to further study which of these risk factors act independently of bone mass. Children from the Avon Longitudinal Study of Parents and Children have been followed up from birth to 11 yr of age. Maternal self-reported data have been collected contemporaneously on early life factors, diet, puberty, and physical activity. These were linked to reported fractures between 9 and 11 yr of age. Multivariable logistic regression techniques were used to assess whether these potential determinants were independent of, or worked through, estimated volumetric BMD or estimated bone size relative to body size measured by total body DXA scan at 9.9 yr of age. A total of 2692 children had full data. One hundred ninety-three (7.2%) reported at least one fracture over the 2-yr follow-up period. Children who reported daily or more episodes of vigorous physical activity had double the fracture risk compared with those children who reported less than four episodes per week (OR, 2.06; 95% CI, 1.21–1.76). No other independent determinants of fracture risk in healthy children were found. In conclusion, reported vigorous physical activity is an independent risk factor for childhood fracture risk. However, the interrelationship between physical activity, bone mass, and childhood fracture risk suggests that the higher bone mass associated with increased physical activity does not compensate for the risk caused by increased exposure to injuries.
doi:10.1359/jbmr.080303
PMCID: PMC2742075  PMID: 18570539
fractures; children; physical activity; epidemiology; BMD; ALSPAC
10.  Epidemiology of Generalized Joint Laxity (Hypermobility) in Fourteen-Year-Old Children From the UK: A Population-Based Evaluation 
Arthritis and Rheumatism  2011;63(9):2819-2827.
Objective
Although diagnostic criteria for generalized ligamentous laxity (hypermobility) in children are widely used, their validity may be limited, due to the lack of robust descriptive epidemiologic data on this condition. The present study was undertaken to describe the point prevalence and pattern of hypermobility in 14-year-old children from a population-based cohort.
Methods
We performed a cross-sectional analysis using the Avon Longitudinal Study of Parents and Children, a large population-based birth cohort. Hypermobility among children in the cohort (mean age 13.8 years) was measured using the Beighton scoring system. Objective measures of physical activity were ascertained by accelerometry. Data on other variables, including puberty and socioeconomic status, were collected. Simple prevalence rates were calculated. Chi-square tests and logistic regression analyses were used to assess associations of specific variables with hypermobility.
Results
Among the 6,022 children evaluated, the prevalence of hypermobility (defined as a Beighton score of ≥4 [i.e., ≥4 joints affected]) in girls and boys age 13.8 years was 27.5% and 10.6%, respectively. Forty-five percent of girls and 29% of boys had hypermobile fingers. There was a suggestion of a positive association between hypermobility in girls and variables including physical activity, body mass index, and maternal education. No associations were seen in boys.
Conclusion
We have shown that the prevalence of hypermobility in UK children is high, possibly suggesting that the Beighton score cutoff of ≥4 is too low or that this scoring is not appropriate for use in subjects whose musculoskeletal system is still developing. These results provide a platform to evaluate the relationships between the Beighton criteria and key clinical features (including pain), thereby testing the clinical validity of this scoring system in the pediatric population.
doi:10.1002/art.30435
PMCID: PMC3164233  PMID: 21547894

Results 1-10 (10)