Age-Related Bone Loss: Relationship between Age and Regional Bone Mineral Density.

Abstract Aging is associated with accumulation of various tryptophan degradation products that may having either bone anabolic or catabolic effects. In epidemiologic studies, elevated levels of 3-hydroxyanthranilic acid (3-HAA) are associated with a higher bone mineral density (BMD). We have previously shown that the C57BL/6 mouse loses bone mass with age. Thus, we hypothesized that administering 3-HAA via a daily intraperitoneal (IP) injection would result in preserved or increased BMD. In an IACUC-approved protocol, we injected 26-month-old C57BL/6 mice with either a low dose (0.5 mg) or high dose (5 mg) of 3-HAA IP five days a week for eight weeks. At the end of this time mice were sacrificed and body composition and bone mineral density measured by DigiMus. BMD was significantly lower in the high dose 3-HAA group: 0.0570 + 0.004 vs 0.0473 + 0.006 vs 0.0432 + 0.0075 gm/cm2, (means+SD, Control vs 0.5 mg 3HAA vs 5 mg 3HAA, p=0.004, 0 vs 5.0 mg, n=6-9/group). 3-HAA had no significant impact on body composition (lean body mass: 86.7 + 1.7% vs 86.2 + 2.7% vs 86.1 + 2.0%, Control vs 0.5 mg vs 5.0 mg 3-HAA, p=ns; and fat mass 12.6 + 2.0% vs 13.8 + 2.7% vs 13.9 + 2.0% vs 0.2%, Control vs 0.5 vs 5 mg 3-HAA, p=ns). Thus, 3-HAA did not prevent bone loss in older mice but instead significantly worsened bone loss. 3-HAA is known to have both pro- and anti- oxidant effects depending on the environment. These data would suggest that at the higher concentrations 3-HAA is acting predominantly as a pro-oxidant molecule accelerating age-related bone loss.

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Age-Related Bone Mineral Density, Accumulated Bone Loss Rate and Prevalence of Osteoporosis at Multiple Skeletal Sites in Chinese Women

Osteoporosis International ◽

10.1007/s001980200091 ◽

2002 ◽

Vol 13 (8) ◽

pp. 669-676 ◽

Cited By ~ 56

Author(s):

Er-Yuan Liao ◽

Xian-Ping Wu ◽

Xiao-Ge Deng ◽

Gan Huang ◽

Xu-Ping Zhu ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Bone Mineral ◽

Loss Rate ◽

Chinese Women ◽

Mineral Density ◽

Age Related ◽

Bone Loss Rate ◽

Prevalence Of Osteoporosis

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Differential Changes in Regional Bone Mineral Density in Healthy Chinese: Age-Related and Sex-Dependent

Calcified Tissue International ◽

10.1007/s002230001210 ◽

2001 ◽

Vol 68 (6) ◽

pp. 330-336 ◽

Cited By ~ 29

Author(s):

W.J. Yao ◽

C.H. Wu ◽

S.T. Wang ◽

C.J. Chang ◽

N.T. Chiu ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Mineral Density ◽

Age Related ◽

Regional Bone Mineral Density ◽

Healthy Chinese

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Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.3109/00016340009169264 ◽

2000 ◽

Vol 79 (12) ◽

pp. 1060-1064 ◽

Cited By ~ 1

Author(s):

Ichiro Iwamoto ◽

Tsutomu Douchi ◽

Shoichiro Kosha ◽

Masato Murakami ◽

Toshinori Fujino ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Mineral Density ◽

Bone Metabolic Markers ◽

Metabolic Markers ◽

Serum Leptin ◽

Healthy Women ◽

Regional Bone Mineral Density

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Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

10.31234/osf.io/592mt ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Bone Mineral Density ◽

Estrogen Receptor ◽

Bone Loss ◽

Bone Turnover ◽

Bone Mineral ◽

Female Rats ◽

Wild Type ◽

Mineral Density ◽

Transgenic Rats ◽

Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

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Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666181102115106 ◽

2019 ◽

Vol 19 (3) ◽

pp. 259-273 ◽

Cited By ~ 3

Author(s):

Neelam Kaushal ◽

Divya Vohora ◽

Rajinder K Jalali ◽

Sujeet Jha

Keyword(s):

Risk Factors ◽

Bone Mineral Density ◽

Uric Acid ◽

Bone Metabolism ◽

Serum Uric Acid ◽

Bone Mineral ◽

Molecular Mechanisms ◽

Association Studies ◽

Mineral Density ◽

Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

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P129 Predictors of low bone mineral density in rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/keab247.124 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Malika A Swar ◽

Marwan Bukhari

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Bone Mineral Density ◽

Family History ◽

Bone Loss ◽

Femoral Neck ◽

Bone Mineral ◽

Fragility Fracture ◽

Mineral Density ◽

History Of

Abstract Background/Aims Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck. Methods This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. . Results 1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003<0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075<0.01-0.101-0.129,-0.072<0.01BMI (mg/m2)0.0080.008,0.0101<0.010.01130.019,0.013<0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21 Conclusion This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing. Disclosure M.A. Swar: None. M. Bukhari: None.

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SAT0477 A TWO-YEAR LONGITUDINAL STUDY COMPLETION, LONGITUNEAL STUDY, THE DIFFERENCE IN BONE LOSS IN PATIENTS WITH EROSIVE AND NON-EROSIVE HAND OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4790 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1195.2-1195

Author(s):

K. Pavelka ◽

L. Šenolt ◽

O. Sleglova ◽

J. Baloun ◽

O. Růžičková

Keyword(s):

Bone Mineral Density ◽

Longitudinal Study ◽

Lumbar Spine ◽

Bone Loss ◽

Bone Mineral ◽

Hand Osteoarthritis ◽

Mineral Density ◽

Erosive Disease ◽

Femur Neck ◽

American College Of Rheumatology

Background:Hand osteoarthritis (OA) and its more severe subset erosive hand OA are common causes of pain and morbidity. Some metabolic factors were suggested to be implicated in erosive disease. Few studies investigated differences in systemic bone loss between erosive and non-erosive hand OA.Objectives:To compare the change of bone mineral density (BMD) between patients with erosive and non-erosive hand OA in a two-year longitudinal study.Methods:Consecutive patients with symptomatic HOA fulfilling the American College of Rheumatology (ACR) criteria were included in this study. Erosive hand OA was defined by at least one erosive interphalangeal joint. All patients underwent clinical assessments of joint swelling and radiographs of both hands. DEXA examination of lumbar spine, total femur and femur neck was performed at the baseline and after two years.Results:Altogether, 141patients (15 male) with symptomatic nodal HOA were included in this study and followed between April 2012 and January 2019. Out of these patients, 80 had erosive disease after two years. The disease duration (p<0.01) was significantly higher in patients with erosive compared with non-erosive disease at baseline.Osteoporosis (T-score <-2.5 SD) was diagnosed in 12.5% (9/72) of patients with erosive hand OA and in 8.06% (5/57) of patients with non-erosive hand OA at baseline. BMD was significantly lowered in patients with erosive compared with non-erosive disease at baseline (lumbar spine: 1.05g/cm2 vs. 1.13 g/cm2, p<0.05, total femur: 0.90 g/cm2 vs. 0.97 g/cm2, p<0.01 and femur neck: 0.86 g/cm2 vs. 0.91, p<0.05). T-scores of lumbar spine (-0.96 vs. -0.41 SD, p<0.05), total femur (-0.69 vs. -0.33 SD, p<0.05) and femur neck (-1.14 vs. -0.88 SD, p<0.05) were also significantly lowered in patients with erosive compared with non-erosive disease.Two years, the BMD remained also significantly lowered in patients with erosive compared with non-erosive disease (lumbar spine: 1.05g/cm2 vs. 1.14 g/cm2, p<0.05, total femur: 0.92 g/cm2 vs. 0.97 g/cm2, p<0.05 and femur neck: 0.86 g/cm2 vs. 0.91, p<0.05), which was in agreement with the finding for T-scores of lumbar spine (-1.05 vs. -0.39 SD, p<0.05), total femur (-0.74 vs. -0.34 SD, p<0.01) and femur neck (-1.07 vs. -0.72 SD, p<0.01).Conclusion:These results suggest that patients with erosive hand OA are at higher risk for the development of general bone loss. Over two years patients with erosive disease had significant lower bone mineral density at all measured sites.References:[1]This work was supported by the project AZV no. 18-00542 and MHCR No. 023728.Acknowledgments:Project AZV no. 18-00542 and MHCR No. 023728Disclosure of Interests:Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ladislav Šenolt: None declared, Olga Sleglova: None declared, Jiří Baloun: None declared, Olga Růžičková: None declared

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