Faculty Opinions recommendation of Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus.

Author(s):  
Mark Johnson
2013 ◽  
Vol 28 (3) ◽  
pp. 627-638 ◽  
Author(s):  
Christine Hamann ◽  
Martina Rauner ◽  
Yvonne Höhna ◽  
Ricardo Bernhardt ◽  
Jan Mettelsiefen ◽  
...  

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1197-1206 ◽  
Author(s):  
Christine Hamann ◽  
Ann-Kristin Picke ◽  
Graeme M. Campbell ◽  
Mariya Balyura ◽  
Martina Rauner ◽  
...  

Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM. Subcritical femoral defects were created in diabetic fa/fa and nondiabetic +/+ Zucker Diabetic Fatty (ZDF) rats and internally stabilized. Vehicle or 75 μg/kg/d PTH(1–84) was sc administered over 12 weeks. Skeletal effects were evaluated by μCT, biomechanical testing, histomorphometry, and biochemical markers, and defect regeneration was analyzed by μCT. Glucose homeostasis was assessed using glucose tolerance testing and pancreas histology. In diabetic rats, bone mass was significantly lower in the distal femur and vertebrae, respectively, and increased after PTH treatment by up to 23% in nondiabetic and up to 18% in diabetic rats (P < .0001). Diabetic rats showed 23% lower ultimate strength at the spine (P < .0005), which was increased by PTH by 36% in normal and by 16% in diabetic rats (P < .05). PTH increased the bone formation rate by 3-fold in normal and by 2-fold in diabetic rats and improved defect regeneration in normal and diabetic rats (P < .01). PTH did not affect serum levels of undercarboxylated osteocalcin, glucose tolerance, and islet morphology. PTH partially reversed the adverse skeletal effects of T2DM on bone mass, bone strength, and bone defect repair in rats but did not affect energy metabolism. The positive skeletal effects were generally more pronounced in normal compared with diabetic rats.


Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S71-S72
Author(s):  
C. Hamann⁎ ◽  
Y. Höhna ◽  
M. Rauner ◽  
J. Mettelsiefen ◽  
C. Göttsch ◽  
...  

Metabolism ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 940-945 ◽  
Author(s):  
Hiroko Hosoda ◽  
Michiaki Fukui ◽  
Ichiko Nakayama ◽  
Mai Asano ◽  
Mayuko Kadono ◽  
...  

2006 ◽  
Vol 91 (9) ◽  
pp. 3355-3363 ◽  
Author(s):  
Harald Dobnig ◽  
Jutta Claudia Piswanger-Sölkner ◽  
Martin Roth ◽  
Barbara Obermayer-Pietsch ◽  
Andreas Tiran ◽  
...  

2013 ◽  
Vol 6 ◽  
pp. CMED.S11843 ◽  
Author(s):  
Mario de Almeida Pereira Coutinho ◽  
Elba Bandeira ◽  
Juliana Maria Coelho Maia de Almeida ◽  
Emanuelle Tenorio Albuquerque Madruga Godoi ◽  
Germana Vasconcelos ◽  
...  

Osteoporosis and atherosclerosis share common risk factors and the association of low bone mass with increased cardiovascular morbidity and mortality has been demonstrated in some studies. Nevertheless, most studies have been focused on women and only a few on individuals with type 2 diabetes mellitus (T2DM). The measurement of carotid intimal-medial thickness (CIMT) is able to detect early atherosclerotic changes and is a predictive marker of cardiovascular events. The aim of this study was to assess the CIMT and its relationship with bone mineral density (BMD) (in the femoral neck (FN) and lumbar spine (LS)) in men with T2DM. We conducted a cross-sectional study with 24 men with T2DM (aged 61 ± 6.4 years) and evaluated metabolic factors, bone densitometry values, and CIMT measured using B-mode Logic-E ultrasound machine. More than 5 years since the diagnosis of T2DM had passed in 75% of the patients, 41.6% were in statin use, mean body mass index (BMI) was 28.1 ± 3.4 kg/m2, abdominal circumference (AC) 97.8 ± 8.4 cm, systolic blood pressure (SBP) 143.8 ± 18.3 mmHg, diastolic blood pressure (DBP) 85.8 ± 12.3 mmHg, HbA1C 7.5% ± 1.3%, Triglycerides 141.7 ± 73 mg/dL, LDL-cholesterol 103.3 ± 35.9 mg/dL, HDL-cholesterol 41.6 ± 11.6 mg/dL. The patients were stratified into groups according to BMD. The group with normal BMD at FN had mean CIMT of 0.7 mm and the group with low bone mass (osteopenia or osteoporosis) had CIMT of 0.86 mm ( P = 0.007). In addition, there were no significant differences between groups regarding age, duration of T2DM, BMI, AC, SBP, DBP, statin use, smoking, HbA1C, cholesterol, or triglycerides. Our data demonstrate a negative association between BMD at the FN and CIMT in type 2 diabetic men, which was unrelated to the traditional risk factors for atherosclerotic disease and degree of diabetes control.


2021 ◽  
Vol 12 ◽  
Author(s):  
BoRui Huang ◽  
Wei Bi ◽  
Yang Sun ◽  
Ruixue Li ◽  
Xingwen Wu ◽  
...  

AdipoRon is an oral active synthetic small molecule with biological functions similar to adiponectin (APN). It is an APN receptor agonist that can improve insulin resistance and glucose intolerance. However, the role of AdipoRon in bone metabolism and related molecular mechanisms remains to be investigated. To explore the effect of AdipoRon on bone absorption and bone integration of type 2 diabetes mellitus (T2DM) mice with implants, we established surgery-induced model of osseointegration of dental implantation in T2DM mice of C57BL/6 db/db and normal mice homologous to diabetic mice. Micro-CT was used to analyze the femurs with the implant in the mice to detect the bone mass, H&E, and tartrate-resistant acid phosphatase (TRAP), and Safranin O-fast green staining was performed to analyze the bone formation and bone resorption. Bone integration-related markers as Rankl, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) were also measured using immunohistochemistry. Our results indicated that diabetic mice showed a lower bone mass and decreased the osteoblast differentiation. AdipoRon attenuated diabetes-impaired bone volume (BV)/total volume (TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone integration-related markers variation and promoted bone hyperplasia as well as repressed the osteoclast formation, especially in diabetic mice. AdipoRon may improve the osseointegration of dental implants in mice with T2DM by promoting osteogenesis and inhibiting bone resorption, and AdipoRon may serve as a promising oral strategy to improve the osseointegration ability of patients with diabetes.


Bone ◽  
2016 ◽  
Vol 87 ◽  
pp. 102-113 ◽  
Author(s):  
Sity Aishah Mansur ◽  
Aleksandra Mieczkowska ◽  
Peter R. Flatt ◽  
Beatrice Bouvard ◽  
Daniel Chappard ◽  
...  

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