Summary
Long-term environmental air pollution exposure was associated with osteoporosis’ risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the ...exposure’s effect.
Introduction
Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture.
Methods
Clinical, demographic, and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure.
Results
A total 59,950 women from 110 Italian provinces were included in the study. PM 2.5 exposure was negatively associated with T-score levels at the femoral neck (β −0.005, 95 CI −0.007 to −0.003) and lumbar spine (β −0.003, 95% CI −0.006 to −0.001). Chronic exposure to PM2.5 above 25 μg/m
3
was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), and exposure to PM10 above 30 μg/m
3
was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200).
Conclusion
Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site.
Key message
Exposure to air pollution is associated with osteoporosis, mainly at femoral site.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
This study aims to investigate the role of obesity and diabetes on bone health in a nation-wide cohort of women with high risk of fracture.
Introduction
The role of obesity and diabetes on ...fracture risk is yet poorly understood. Body mass index (BMI) and bone mineral density (BMD) are strongly correlated; however, patients with elevated BMI are not protected against fractures, configuring the obesity paradox. A similar controversial association has been also found in diabetic patients. Herein, we present a retrospective analysis on 59,950 women.
Methods
Using a new web-based fracture risk-assessment tool, we have collected demographic (including BMI), densitometric, and clinical data (including history of vertebral or hip and non-vertebral, non-hip fractures, presence of comorbidities). We performed a propensity score generation with 1:1 matching for patients in the obese (BMI ≥ 30) and non-obese (BMI < 30) groups, in the diabetics and non-diabetics. Propensity score estimates were estimated using a logistic regression model derived from the clinical variables: age, lumbar spine T-score, and femoral neck T-score.
Results
We found an association between diabetes and fractures of any kind (OR 1.3, 95% CI 1.1–1.4 and 1.3, 95% CI 1.2–1.5 for vertebral or hip fractures and non-vertebral, non-hip fractures, respectively). Obesity, on the other hand, was significantly associated only with non-vertebral, non-hip fractures (OR 1.3, 95% CI 1.1–1.6). To estimate the individual effect of obesity and diabetes on bone health, we ran sensitivity analyses which included obese non-diabetic patients and non-obese diabetic patients, respectively.
Conclusions
Non-obese diabetics had the highest risk of vertebral or hip fracture, whereas obese non-diabetics predominantly had non-vertebral, non-hip fracture’s risk. These results should raise awareness in clinical practice when evaluating diabetic and/or obese patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dicckopf-1 (Dkk-1) is a potent inhibitor of the Wnt canonical pathway. In rheumatoid arthritis (RA), Dkk-1 is upregulated by tumor necrosis factor-α (TNF). Certolizumab pegol (CMZ) is a biologic ...TNF-inhibitor (TNFi) effective in RA and slows radiographic progression. Data on the immediate effects (≤1–8 weeks) of TNFi on Wnt modulators are lacking. This study investigated the acute influence of TNFi treatment on Wnt modulators (Dkk-1 and sclerostin) and bone turnover markers (BTM), including intact N-terminal propeptide of collagen type I (PINP) and C-terminal telopeptide of type I collagen (CTX-I).
This longitudinal, uncontrolled study involved female RA patients with inadequate response to conventional methotrexate who underwent treatment with CMZ. ESR, Dkk-1, sclerostin, BTM, parathyroid hormone (PTH), and 25OH-vitamin D levels were evaluated at baseline, week 1, week 4, and week 8. Radiographs of the hands and feet were obtained at baseline and the total and erosion scores were assessed using the Simple Erosion Narrowing Score method (SENS).
Seventeen patients were enrolled. Dkk-1 and CTX-I significantly decreased after one week of treatment with CMZ (−49.1 ± 17.1% and −25.0 ± 20.6%, respectively, p < 0.01), whereas PINP increased (+43.2 ± 31.5%, p < 0.01). These changes persisted at week 4 and 8.
Our study showed that TNF-alpha inhibition with CMZ promptly results in a rapid decline of serum Dkk-1 levels, alongside decreased bone resorption and increased bone formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Information is lacking on the association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) or circulating bone turnover biomarkers in post-menopausal women with type 2 ...diabetes (T2DM).
We recruited 77 white post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Liver ultrasonography and transient elastography (Fibroscan®) were used for diagnosing and staging NAFLD. A dual energy X-ray absorptiometry, and serum levels of 25-hydroxyvitamin D3 25(OH)D, parathyroid hormone and multiple bone turnover biomarkers (periostin, sclerostin, dickkopf-related protein-1 DKK-1, C-terminal telopeptide of type 1 collagen sCTX, procollagen type 1 N-terminal propeptide P1NP, receptor activator of nuclear factor-kB ligand RANKL) were also measured.
Overall, 10 patients had NAFLD with clinically significant fibrosis (i.e., liver stiffness measurement > 7 kPa), 52 had NAFLD without fibrosis and 15 patients were free from steatosis. Although the three patient groups had comparable values of BMD, after adjustment for age, waist circumference, HOMA-insulin resistance and serum 25(OH)D levels, patients with NAFLD and significant fibrosis had significantly higher sclerostin levels (54.1 ± 16.4 vs. 36.1 ± 11.9 vs. 42.3 ± 14.7 pmol/L) and lower levels of serum DKK-1 (26.6 ± 17.8 vs. 49.0 ± 22.4 vs. 42.9 ± 19.4 pmol/L), RANKL (0.04 ± 0.03 vs. 0.08 ± 0.06 vs. 0.11 ± 0.06 pmol/L) and sCTX (0.16 ± 0.09 vs. 0.29 ± 0.17 vs. 0.40 ± 0.28 ng/mL) compared to other groups. Serum periostin and P1NP levels did not significantly differ between the groups.
In post-menopausal women with T2DM, the presence of NAFLD and clinically significant fibrosis was strongly associated with a low bone turnover, which may reflect the presence of qualitative bone abnormalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To systematically review the role of ultrasound (US) in the assessment of the joint-enthesial-nail apparatus in patients with psoriatic arthritis (PsA) or psoriasis (PSO) in terms of prevalence, ...diagnosis, prognosis, monitoring and treatment. A systematic literature review was conducted through medical databases (PubMed, Embase) and the grey literature up to February 2018. The main areas of application of nail US were first identified, allowing the development of research questions, which were rephrased following the PICOs methodology to develop inclusion criteria. Of the 585 studies produced by PubMed and Embase searches, 17 studies met the criteria for inclusion. Five additional studies were included: 1 from the hand search and 4 from the 2016–2017 ACR and EULAR congresses. The prevalence of nail plate changes varied from < 10 to 97%, for power Doppler signal from 20–30 to 96% and distal interphalangeal joint (DIJ) involvement from 8.9 to 100%. The performance of US nail/DIJ abnormalities in the diagnosis of PsA and PSO elementary lesions was analysed by five studies, with a wide heterogeneity. Reproducibility and reliability of US nil/DIJ were assessed by interclass correlation coefficient or Cohen’s
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and their values ranged from 0.6 to 0.9. The value of US nail/DIJ in the monitoring of the lesions was analysed only by a single study. The analysis revealed applications for US nail/DIJ in PsA and PSO and highlights limitations. Validation is strongly needed to demonstrate its appropriateness in the clinical practice and to define its diagnostic and prognostic role.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The positive effects of denosumab (DMAb) on bone mineral density (BMD) are quickly reversible after its discontinuation. We investigated whether this rebound was associated with dysregulation of the ...Wnt canonical pathway and/or by the increase in the receptor-activator of nuclear factor-kappa B ligand (RANKL) serum levels.
The study included patients (n = 15) with postmenopausal osteoporosis to whom DMAb was administered for 78 months and then discontinued. We collected BMD data at baseline/month 0 (M0), M60, M84 (6 months after last DMAb administration, coinciding when the next DMAb dose would typically be due), and after 3 and 12 months of follow-up (FU-M3 and FU-M12, respectively). Serum C-terminal telopeptide of type 1 collagen (CTX-I), Dickkopf-1 (Dkk-1), and sclerostin were measured at M0, M60, M84, FU-M3, and FU-M12. Serum N-terminal propeptide of type 1 procollagen (PINP) and RANKL were dosed at M60, M84, FU-M3, and FU-12.
We found a significant decrease in the T-score at all sites at FU-M12, when compared to M84 (−0.51 ± 0.91 at the lumbar spine; −0.72 ± 0.33 at the total hip; and −0.42 ± 0.27 at the femoral neck, p < 0.05). After DMAb discontinuation (M84 vs FU M12) CTX-I, PINP increased already at FU-M3 (+0.921 ± 0.482 ng/mL, +126.60 ± 30.36 ng/mL, respectively, p < 0.01), RANKL increased at FU-M12 (+0.041 ± 0.062 ng/mL, p < 0.05), while Dkk-1 and sclerostin decreased at FU-M12 (−10.90 ± 11.80 and − 13.00 ± 10.52 pmol/L, respectively, p < 0.01). No changes in BMD or any of the markers were found between M60 and M84.
RANKL serum levels progressively increased after discontinuation of long-term DMAb while Dkk-1 and sclerostin serum levels decreased. The increase in RANKL serum levels supports the hypothesis of a sudden loss of inhibition of the resting osteoclast line after DMAb clearance, with a hyperactivation of these cells. Our results suggest that the changes in serum Wnt inhibitors after DMAb suspension might represent a mere feedback response to the increased bone turnover.
•The increases in BMD have been shown to be lost after discontinuation.•We found a slow increase in RANKL which was associated with the early increase in CTX-I.•The increase in lumbar spine BMD during treatment with denosumab are a strong predictor of the increase in RANKL after denosumab discontinuation.•The dysregulation of Wnt inhibitors (Dkk-1 and sclerostin) initially seemed to be a promising mechanism for the BMD impairment after denosumab discontinuation; nevertheless, our results suggest that this pathway might be only marginally involved, and the changes in Dkk-1 and sclerostin might simply be a compensatory response to the abrupt increase in bone resorption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP