Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels

Bone ◽  
2021 ◽  
Vol 153 ◽  
pp. 116170
Author(s):  
Marine Delagrange ◽  
Vanessa Rousseau ◽  
Catie Cessans ◽  
Catherine Pienkowski ◽  
Isabelle Oliver ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Nurdiana Z. Abidin ◽  
Soma R. Mitra

Osteosarcopenic obesity (OSO) describes the concurrent presence of obesity, low bone mass, and low muscle mass in an individual. Currently, no established criteria exist to diagnose OSO. We hypothesized that obese individuals require different cut-points from standard cut-points to define low bone mass and low muscle mass due to their higher weight load. In this study, we determined cutoff values for the screening of osteosarcopenia (OS) in obese postmenopausal Malaysian women based on the measurements of quantitative ultrasound (QUS), bioelectrical impedance analysis (BIA), and functional performance test. Then, we compared the cutoff values derived by 3 different statistical modeling methods, (1) receiver operating characteristic (ROC) curve, (2) lowest quintile of the study population, and (3) 2 standard deviations (SD) below the mean value of a young reference group, and discussed the most suitable method to screen for the presence of OS in obese population. One hundred and forty-one (n = 141) postmenopausal Malaysian women participated in the study. Bone density was assessed using calcaneal quantitative ultrasound. Body composition was assessed using bioelectrical impedance analyzer. Handgrip strength was assessed using a handgrip dynamometer, and physical performance was assessed using a modified Short Physical Performance Battery test. ROC curve was determined to be the most suitable statistical modeling method to derive the cutoffs for the presence of OS in obese population. From the ROC curve method, the final model to estimate the probability of OS in obese postmenopausal women is comprised of five variables: handgrip strength (HGS, with area under the curve (AUC) = 0.698 and threshold ≤ 16.5 kg), skeletal muscle mass index (SMMI, AUC = 0.966 and threshold ≤ 8.2 kg/m2), fat-free mass index (FFMI, AUC = 0.946 and threshold ≤ 15.2 kg/m2), broadband ultrasonic attenuation (BUA, AUC = 0.987 and threshold ≤ 52.85 dB/MHz), and speed of sound (SOS, AUC = 0.991 and threshold ≤ 1492.15 m/s). Portable equipment may be used to screen for OS in obese women. Early identification of OS can help lower the risk of advanced functional impairment that can lead to physical disability in obese postmenopausal women.


Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 343
Author(s):  
Koji Nonaka ◽  
Shin Murata ◽  
Hideki Nakano ◽  
Kunihiko Anami ◽  
Kayoko Shiraiwa ◽  
...  

This study aimed to investigate the characteristics of skeletal muscle mass, muscle strength, and physical performance among community-dwelling older women. Data were collected from 306 older adults, and the data of 214 older women were included in the final analysis. Participants’ calcaneus bone mass was measured using ultrasonography. Based on their T-scores, participants were divided into the following three groups: normal (T-score > −1), low (−2.5 < T-score ≤ −1), and very low (T-score ≤ −2.5) bone mass. Further, participants’ skeletal muscle mass, muscle strength (grip and knee extension strength), and physical performance [gait speed and timed up and go (TUG)] were measured. Arm skeletal muscle index (SMI, skeletal muscle mass/height2), leg SMI, and appendicular SMI in the very low bone mass group were low compared to those of the low bone mass group (p = 0.034, p = 0.011, and p = 0.009, respectively). Grip and knee extension strength, gait speed, and TUG were not significantly different between the groups. These findings suggest that older women with low bone density had decreased skeletal muscle mass. Therefore, maintaining or improving skeletal muscle mass may prevent low bone mass.


Author(s):  
Hsin-Hua Chou ◽  
Sao-Lun Lu ◽  
Sen-Te Wang ◽  
Ting-Hsuan Huang ◽  
Sam Li-Sheng Chen

The association between osteoporosis and periodontal disease (PD) has been revealed by previous studies, but there have been few studies on the association in younger adults. We enrolled a total of 7298 adults aged 40 to 44 who underwent PD screening between 2003 and 2008. Data on quantitative ultrasound for the measurement of bone mineral density (BMD) were collected for the diagnostic criteria of osteopenia and osteoporosis. The Community Periodontal Index (CPI) was measured for defining PD. A multiple logistic regression model was used to assess the effect of low bone mass on the risk of PD. Of 7298 enrollees, 31% had periodontal pockets >3 mm, 36.2% had osteopenia, and 2.1% had osteoporosis. The 39.8% of PD prevalence was high in adults with osteoporosis, followed by 33.3% in osteopenia. A negative association was found between BMD and CPI value (p < 0.0001). Low bone mass was associated with the risk of PD (adjusted OR: 1.13; 95% CI:1.02–1.26) after adjusting the confounding factors, including age, gender, education level, overweight, smoking status, past history of osteoporosis, and diabetes mellitus. An association between BMD and PD among young adults was found. An intervention program for the prevention of PD and osteoporosis could be considered starting in young adults.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1182.2-1182
Author(s):  
E. Wiebe ◽  
D. Freier ◽  
D. Huscher ◽  
R. Biesen ◽  
S. Hermann ◽  
...  

Background:Rheumatic diseases are associated with increased systemic bone loss and fracture risk related to chronic inflammation, disease-specific, general and demographic risk factors as well as treatment with glucocorticoids (GC). Yet, there is evidence that GCs may, by adequately suppressing systemic inflammation, also have a positive effect on bone mineral density (BMD) and fracture risk1.Objectives:The purpose of this study was to investigate the prevalence of osteoporosis and fragility fractures in patients with inflammatory rheumatic diseases and to analyze the impact that treatment with GCs, other known risk factors and preventive measures have on bone health in these patients.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic inflammatory rheumatic diseases and psoriasis treated with GCs. In this cross-sectional analysis, we evaluated the initial visit of 1091 patients. A multivariate linear regression model with known or potentially influential factors adjusted for age and sex was used to identify predictors of BMD as measured by dual-energy X-ray absorptiometry (DXA). Multiple imputation was applied for missing baseline covariate data.Results:In the total cohort of 1091 patients (75% female of which 87.5% were postmenopausal) with a mean age of 62.1 (±13.2) years, the prevalence of osteoporosis by DXA was 21.7%, while fragility fractures have occurred in 31.2% of the study population (6.7% vertebral, 27.7% non-vertebral). Current GC therapy was common (64.9%), with a median daily dose of 5.0mg [0.0;7.5], a mean life-time total GC dose of 17.7g (±24.6), and a mean GC therapy duration of 7.8 years (±8.5). Bisphosphonates were the most commonly used anti-osteoporotic drug (12.6%).Multivariate analysis showed that BMD as expressed by the minimum T-Score at all measured sites was negatively associated with higher age, female sex and menopause as well as Denosumab and Bisphosphonate treatment. A positive association with BMD was found for body mass index as well as current and life-time (cumulative) GC dose. While comedication with proton-pump-inhibitors significantly predicted low bone mass, concomitant use of non-steroidal anti-inflammatory drugs showed a positive association with BMD. Of the measured bone-specific laboratory parameters, higher alkaline phosphatase levels were determinants of low DXA-values, while the association was positive for gamma-glutamyltransferase.BMD was neither predicted by duration of GC treatment nor by treatment with disease modifying anti-rheumatic drugs.Predictive variables for BMD differed at the respective anatomical site. While treatment with Denosumab predicted low bone mass at the lumbar spine and not at the femoral neck, the opposite was true for health assessment questionnaire (HAQ) score. Current and life-time GC-dose as well as direct sun-exposure of more than 30 minutes daily were positively associated with bone mass at the femoral sites only.Conclusion:This cross-sectional analysis of a prospective cohort study quantified the prevalence of osteoporosis and identified predictive variables of BMD in patients with rheumatic diseases.Multivariate analyses corroborated low BMD to be predicted by traditional factors like age, female sex and menopause but showed current and well as life-time GC dose to be positively associated with BMD in our cohort of patients with chronic inflammatory rheumatic diseases. This suggests that optimal management of disease activity with GCs might be beneficial in order to avoid bone loss due to inflammation.References:[1]Güler-Yüksel et al. “Glucocorticoids, Inflammation and Bone.” Calcified Tissue International (January 08 2018).Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.


2020 ◽  
Vol 117 (9) ◽  
pp. 4910-4920 ◽  
Author(s):  
Joonho Suh ◽  
Na-Kyung Kim ◽  
Seung-Hoon Lee ◽  
Je-Hyun Eom ◽  
Youngkyun Lee ◽  
...  

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.


2009 ◽  
Vol 30 (3) ◽  
pp. 164-173 ◽  
Author(s):  
Katherine M. McLeod ◽  
C. Shanthi Johnson

Bone ◽  
2015 ◽  
Vol 76 ◽  
pp. 107-114 ◽  
Author(s):  
Kathrin Sinningen ◽  
Elise Albus ◽  
Sylvia Thiele ◽  
Sylvia Grossklaus ◽  
Thomas Kurth ◽  
...  

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