Temporal relationship between bone loss and increased bone turnover: A longitudinal study following natural menopause

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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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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Disease severity predicts bone loss: A longitudinal study in inflammatory bowel disease patients

Gastroenterology ◽

10.1016/s0016-5085(08)83124-1 ◽

2001 ◽

Vol 120 (5) ◽

pp. A628

Author(s):

Sandra D. Henderson ◽

Satvinder S. Dhaliwal ◽

Neville E. Hoffman ◽

Richard L. Prince

Keyword(s):

Inflammatory Bowel Disease ◽

Longitudinal Study ◽

Bone Loss ◽

Disease Severity ◽

Bowel Disease ◽

Inflammatory Bowel

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Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Journal of Endocrinology ◽

10.1530/joe-15-0280 ◽

2015 ◽

Vol 227 (3) ◽

pp. 129-141 ◽

Cited By ~ 6

Author(s):

Russell T Turner ◽

Michael Dube ◽

Adam J Branscum ◽

Carmen P Wong ◽

Dawn A Olson ◽

...

Keyword(s):

Gene Therapy ◽

Body Weight ◽

Bone Loss ◽

Bone Mass ◽

Bone Turnover ◽

Cancellous Bone ◽

Mass Density ◽

Female Rats ◽

Bone Mass Density ◽

Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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Raloxifene Has No Efficacy in Reducing the High Bone Turnover and the Risk of Spontaneous Vertebral Fractures after Denosumab Discontinuation

Case Reports in Rheumatology ◽

10.1155/2018/5432751 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Elena Gonzalez-Rodriguez ◽

Delphine Stoll ◽

Olivier Lamy

Keyword(s):

Bone Loss ◽

Bone Turnover ◽

Aromatase Inhibitors ◽

Vertebral Fractures ◽

Bone Markers ◽

Rebound Effect ◽

High Bone Turnover ◽

Antiresorptive Agent ◽

High Bone

At denosumab discontinuation, an antiresorptive agent is prescribed to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report the case of a woman treated with aromatase inhibitors and denosumab for 5 years. Raloxifene was then prescribed to prevent the rebound effect. Raloxifene was ineffective to reduce the high bone turnover and to avoid spontaneous clinical vertebral fractures. We believe that among the antiresorptive treatments, the most powerful bisphosphonates should be favored, and their administration adapted according to the serial follow-up of bone markers.

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Bisphosphonates

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302006000400018 ◽

2006 ◽

Vol 50 (4) ◽

pp. 735-744 ◽

Cited By ~ 13

Author(s):

Michael McClung

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Turnover ◽

Bone Structure ◽

Clinical Settings ◽

Low Bone Mass ◽

Dosing Regimen ◽

Drug Induced ◽

Excellent Safety Profile ◽

Reduce Fracture Risk

Osteoporosis is the result of bone loss due to an imbalance in bone turnover such that bone resorption exceeds bone formation. Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. In clinical studies, several bisphosphonates prevent bone loss, preserve bone structure, improve bone strength and, in patients with osteoporosis, substantially reduce fracture risk. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men and drug-induced bone loss. Intermittent oral dosing and intravenous administration are more convenient than the original daily dosing regimen. These drugs are generally well tolerated and have an excellent safety profile in that serious side effects are uncommon. Potent bisphosphonates are generally the preferred treatment option for most patients with or at risk for osteoporosis.

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Deletion of the P2Y13 receptor leads to reduced bone turnover and protection from ovariectomy-induced bone loss

Bone ◽

10.1016/j.bone.2011.03.535 ◽

2011 ◽

Vol 48 ◽

pp. S227

Author(s):

N. Wang ◽

B. Robaye ◽

A. Agrawal ◽

G. Reilly ◽

J.-M. Boeynaems ◽

...

Keyword(s):

Bone Loss ◽

Bone Turnover

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