Gait abnormalities, bone mineral density and subchondral bone loss in knee OA

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.

Download Full-text

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.

Download Full-text

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

Download Full-text

Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

European Journal of Human Genetics ◽

10.1038/ejhg.2011.245 ◽

2012 ◽

Vol 20 (5) ◽

pp. 559-564 ◽

Cited By ~ 47

Author(s):

Alison Gartland ◽

Kristen K Skarratt ◽

Lynne J Hocking ◽

Claire Parsons ◽

Leanne Stokes ◽

...

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Bone Loss ◽

Bone Mineral ◽

P2x7 Receptor ◽

Receptor Gene ◽

Spine Bone Mineral Density ◽

Mineral Density ◽

Menopausal Women ◽

Post Menopausal

Download Full-text

High systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not radiographic progression of existing knee OA: the MOST study

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.099531 ◽

2009 ◽

Vol 69 (01) ◽

pp. 163-168 ◽

Cited By ~ 68

Author(s):

M C Nevitt ◽

Y Zhang ◽

M K Javaid ◽

T Neogi ◽

J R Curtis ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Joint Space Narrowing ◽

Weight Bearing ◽

Joint Space ◽

Whole Body ◽

Mineral Density ◽

Knee Oa ◽

Increased Risk

Objectives:Previous studies suggest that high systemic bone mineral density (BMD) is associated with incident knee osteoarthritis (OA) defined by osteophytes but not with joint space narrowing (JSN), and are inconsistent regarding BMD and progression of existing OA. The association of BMD with incident and progressive tibiofemoral OA was tested in a large prospective study of men and women aged 50–79 years with or at risk for knee OA.Methods:Baseline and 30-month weight-bearing posteroanterior and lateral knee radiographs were scored for Kellgren-Lawrence (K-L) grade, JSN and osteophytes. Incident OA was defined as the development of K-L grade ⩾2 at follow-up. All knees were classified for increases in grade of JSN and osteophytes from baseline. The association of gender-specific quartiles of baseline BMD with risk of incident and progressive OA was analysed using logistic regression, adjusting for covariates.Results:The mean (SD) age of 1754 subjects was 63.2 (7.8) years and body mass index was 29.9 (5.4) kg/m2. In knees without baseline OA, higher femoral neck and whole body BMD were associated with an increased risk of incident OA and increases in grade of JSN and osteophytes (p<0.01 for trends); adjusted odds were 2.3–2.9-fold greater in the highest compared with the lowest BMD quartiles. In knees with existing OA, progression was not significantly related to BMD.Conclusions:In knees without OA, higher systemic BMD was associated with a greater risk of the onset of JSN and K-L grade ⩾2. The role of systemic BMD in early knee OA pathogenesis warrants further investigation.

Download Full-text

Ovarian Failure After Adjuvant Chemotherapy Is Associated With Rapid Bone Loss in Women With Early-Stage Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.14.3306 ◽

2001 ◽

Vol 19 (14) ◽

pp. 3306-3311 ◽

Cited By ~ 308

Author(s):

Charles L. Shapiro ◽

Judith Manola ◽

Meryl Leboff

Keyword(s):

Breast Cancer ◽

Bone Mineral Density ◽

Alkaline Phosphatase ◽

Adjuvant Chemotherapy ◽

Bone Loss ◽

Bone Mineral ◽

Ovarian Failure ◽

Mineral Density ◽

Specific Alkaline Phosphatase ◽

Bone Specific Alkaline Phosphatase

PURPOSE: We sought to evaluate the effects of chemotherapy-induced ovarian failure on bone loss and markers of skeletal turnover in a prospective longitudinal study of young women with breast cancer receiving adjuvant chemotherapy. PATIENTS AND METHODS: Forty-nine premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks of starting chemotherapy (baseline), and 6 and 12 months after starting chemotherapy with dual-energy absorptiometry and markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian failure was defined as a negative pregnancy test, greater than 3 months of amenorrhea, and a follicle-stimulating hormone ≥ 30 MIU/mL at the 12-month evaluation. RESULTS: Among the 35 women who were defined as having ovarian failure, highly significant bone loss was observed in the lumbar spine by 6 months and increased further at 12 months. The median percentage decrease of bone mineral density in the spine from 0 to 6 months and 6 to 12 months was −4.0 (range, −10.4 to +1.0; P = .0001) and −3.7 (range, −10.1 to 9.2; P = .0001), respectively. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function. Serum osteocalcin and bone specific alkaline phosphatase, markers of skeletal turnover, increased significantly in the women who developed ovarian failure. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid and highly significant bone loss in the spine. This may have implications for long-term breast cancer survivors who may be at higher risk for osteopenia, and subsequently osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian failure should have their bone density monitored and treatments to attenuate bone loss should be evaluated.

Download Full-text

Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study

Osteoporosis International ◽

10.1007/s00198-019-05230-0 ◽

2019 ◽

Vol 31 (5) ◽

pp. 921-929 ◽

Cited By ~ 3

Author(s):

J.G. Howe ◽

R.S. Hill ◽

J.D. Stroncek ◽

J.L. Shaul ◽

D. Favell ◽

...

Keyword(s):

Bone Mineral Density ◽

Cohort Study ◽

Bone Loss ◽

Bone Mineral ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Mineral Density ◽

Hip Strength

Download Full-text

Gender Differences In Bone Mineral Density In Subjects With COPD: Males At Increased Risk Of Bone Loss

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3987 ◽

2012 ◽

Author(s):

Joshua D. Jaramillo ◽

Carla Wilson ◽

Barry J. Make ◽

Marilyn G. Foreman ◽

MeiLan K. Han ◽

...

Keyword(s):

Bone Mineral Density ◽

Gender Differences ◽

Bone Loss ◽

Bone Mineral ◽

Mineral Density ◽

Increased Risk

Download Full-text

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

Non-Coding RNA ◽

10.3390/ncrna4040037 ◽

2018 ◽

Vol 4 (4) ◽

pp. 37 ◽

Cited By ~ 15

Author(s):

Giuseppina E. Grieco ◽

Dorica Cataldo ◽

Elena Ceccarelli ◽

Laura Nigi ◽

Giovanna Catalano ◽

...

Keyword(s):

Bone Mineral Density ◽

Type 1 Diabetes ◽

Bone Loss ◽

Bone Metabolism ◽

Bone Remodeling ◽

Bone Mineral ◽

Bone Fragility ◽

Bone Homeostasis ◽

Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

Download Full-text