Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. METHODS: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. RESULTS: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. CONCLUSION: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Fragility fractures and health-related quality of life: does socio-economic status widen the gap? A population-based study.

Studying 12,839 fracture cases and 91,426 controls, we found that fractures of the spine and hip are associated with clinically important HRQoL deficits up to 5 years post-fracture. Fracture cases with a low educational attainment are more likely to report very low HRQoL due to a low pre-fracture HRQoL. INTRODUCTION: The aim of this study was to explore the short-term and long-term impact of fractures on health-related quality of life (HRQoL) and to study the effect of educational attainment as a proxy for socio-economic status (SES) on post-fracture HRQoL. METHODS: In a population-based survey including 12,839 fracture cases and 91,426 controls, HRQoL was measured using the physical component score (PCS) and the mental component score (MCS) of the 12-Item Short Form Health Survey (SF-12). Information about fractures, age, sex, ethnicity, comorbidity and SES was obtained from national registers. Multiple regression analysis was conducted to measure the mean HRQoL difference, termed deficit, between non-fracture controls and fracture cases (all fractures combined and fractures at six different skeletal sites). RESULTS: PCS and MCS were significantly lower among fracture cases than among controls. Statistically and clinically important PCS deficits (≥ 5 points) were observed among people with fractures of the spine and hip up to 5 years post-fracture and among people with upper arm fractures up to 1 year post-fracture. Greater deficits were observed for MCS but not for PCS in post-fracture HRQoL in the low than in the high SES group. CONCLUSION: Fractures of the spine and hip are associated with clinically important deficits in physical HRQoL up to 5 years post-fracture. Low educational attainment widened the gap in mental but not in physical post-fracture HRQoL. However, due to low pre-fracture PCS and MCS, people with a low educational attainment and fractures were more likely to report very low HRQoL post-fracture.

Socio-economic inequalities in fragility fracture outcomes: a systematic review and meta-analysis of prognostic observational studies.

Individuals with low socio-economic status (SES) have a higher risk of dying following hip fracture compared with individuals with high SES. Evidence on social inequalities in non-hip fractures is lacking as well as evidence on the impact of SES on health-related quality of life post fracture. INTRODUCTION: Fragility fractures, especially of the hip, cause substantial excess mortality and impairment in health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate the association between socio-economic status (SES) and post-fracture mortality and HRQoL. METHODS: PubMed, EMBASE and CINAHL databases were searched from inception to the last week of November 2018 for studies reporting an association between SES and post-fracture mortality and/or HRQoL among people aged ≥ 50 years. Risk ratios (RRs) were meta-analyzed using a standard inverse-variance-weighted random effects model. Studies using individual-level and area-based SES measures were analyzed separately. RESULTS: A total of 24 studies from 15 different countries and involving more than one million patients with hip fractures were included. The overall risk of mortality within 1-year post-hip fracture in individuals with low SES was 24% higher than in individuals with high SES (RR 1.24, 95% CI 1.19 to 1.29) for individual-level SES measures, and 14% (RR 1.14, 95% CI 1.09 to 1.19) for area-based SES measures. The quality of the evidence for the outcome mortality was moderate. Using individual SES measures, we estimated the excess HRQoL loss to be 5% (95% CI - 1 to 10%) among hip fracture patients with low SES compared with high SES. CONCLUSIONS: We found a consistently increased risk of post-hip fracture mortality with low SES across SES measures and across countries with different political structures and different health and social care infrastructures. The impact of SES on post-fracture HRQoL remains uncertain due to sparse and low-quality evidence.

The regulation of proenkephalin expression in a distinct population of glial cells.

The expression of opioid genes was examined in isolated populations of glial cells in primary culture. Northern blot analysis of purified type I astrocytes, oligodendrocytes and mixed oligodendrocyte-type-2-astrocyte lineage cells derived from cerebral cortex demonstrated robust expression of proenkephalin mRNA exclusively in type I astrocytes. The expression of proenkephalin mRNA was stimulated by the beta-adrenergic agonist isoproterenol, and 8-(4-chlorophenyl thio)adenosine 3'-5'-cyclic monophosphate (cpt-cAMP). Both of these compounds regulated a proenkephalin-chloramphenicol acetyltransferase fusion gene transiently transfected into type I astrocytes. HPLC and immunoassay of the cell culture media revealed significant levels of unprocessed proenkephalin secreted by the cell and this secretion was stimulated by isoproterenol and cpt-cAMP. The relatively high levels of proenkephalin expressed suggest that enhanced expression in astrocytes may be important during neural development, in trauma-induced gliosis and in neuroimmune interactions.

Proenkephalin gene expression in the primate uterus: regulation by estradiol in the endometrium.

Proenkephalin mRNA has previously been shown to be expressed in the rodent uterus with varying levels during the estrous cycle. To examine for the potential regulation of proenkephalin gene expression by steroid hormones in a primate displaying a menstrual cycle and to define the functional tissue within the uterus expressing this transcript, we have used Northern blot analysis of extracted RNA from isolated uterine tissue subtypes from normal adult rhesus macaques obtained during the menstrual cycle and from ovariectomized females under different physiological steroid hormone treatments. A strong band of proenkephalin mRNA of 1.3 kilobases was detected almost exclusively in the proliferative endometrium from monkeys in the follicular phase of the cycle. No proenkephalin mRNA was detected in secretory endometrium obtained from monkeys in the luteal phase. When ovariectomized macaques were implanted with silastic capsules of 17 beta-estradiol, proenkephalin mRNA was detected in the endometrium but not the myometrium of the estradiol-treated animals. No proenkephalin mRNA was detected in ovariectomized control animals. Under these conditions, we were unable to detect proenkephalin mRNA in ovariectomized macaques implanted with separate silastic capsules of 17 beta-estradiol and progesterone or in decidual tissue from early or late pregnancy. These results suggest that in the primate uterus 1) proenkephalin mRNA is expressed primarily in the endometrium of the uterus, 2) expression of the proenkephalin gene is regulated by 17 beta-estradiol in the endometrium, and 3) this effect of estradiol is antagonized by progesterone.

Gonadotropin regulation of the rat proopiomelanocortin promoter: characterization by transfection of primary ovarian granulosa cells.

To characterize the transcriptional effects of human (h)FSH and hCG on the POMC gene, primary rat granulosa cells were transiently transfected with a chloramphenicol acetyltransferase (CAT) reporter plasmid under the control of the POMC promoter and 5' region. POMC-CAT contains a fragment of the rat POMC gene, extending from nucleotide -704 to nucleotide +63, fused to the CAT gene. Treatment of POMC-CAT-transfected cells with either hFSH (20 ng/ml) or hCG (10 ng/ml) significantly increased CAT enzyme activity; however, neither hCG nor hFSH increased CAT enzyme activity in cells transfected with pSV2-CAT, a reporter plasmid under the control of the SV40 virus promoter and 5' region. The phosphodiesterase inhibitor isobutylmethylxanthine or the nonhydrolyzable cAMP analog cAMP-chlorothiophenyl significantly increased CAT activity in POMC-CAT-transfected granulosa cells. Human FSH stimulated transcription 10, 20, and 40 h after treatment, but FSH stimulation at the two earlier time points was 2.5- to 5.5-fold greater than that at 40 h. Gonadotropin-stimulated steroidogenesis was equivalent in POMC-CAT-transfected granulosa cells, untransfected, and mock-transfected cells. This indicates that transfection left the physiological hormone response intact. These data demonstrate the following. 1) 767 basepairs of the rat POMC gene are enough to confer gonadotropin stimulation on the CAT marker gene in granulosa cells. 2) Although the POMC promotor lacks a well conserved cAMP response element, either of two different pharmacological manipulations of granulosa cells that raise intracellular cAMP can also stimulate POMC-driven CAT expression. 3) Transfected primary cultures of granulosa cells provide a nontransformed, physiologically relevant model with which to study hormone-regulated gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)