scholarly journals Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse

2021 ◽  
Vol 12 ◽  
Author(s):  
Mickaël Cardinal ◽  
Antoine Chretien ◽  
Thomas Roels ◽  
Sébastien Lafont ◽  
Michael S. Ominsky ◽  
...  

Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout–sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab–treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments.

2004 ◽  
Vol 14 (5) ◽  
pp. 361-365
Author(s):  
Régis Levasseur ◽  
Jean Pierre Sabatier ◽  
Olivier Etard ◽  
Pierre Denise ◽  
Annie Reber

To determine whether the vestibular system could influence bone remodeling in rats, we measured bone mineral density with dual energy X-rays absorptiometry before and 30 days after bilateral labyrinthectomy. Comparatively to intact control rats, labyrinthectomized animals showed a reduced bone mineral density in distal femoral metaphysis (p = 0.007): the variations between D0 and D30 were +3.0% for controls and -13.9% for labyrinthectomized rats. No significant difference between the 2 groups was observed in the whole body mineral density. These results suggest that the peripheral vestibular apparatus is a modulator of bone mass and more specifically in weight bearing bone. We discuss possible mechanisms of this vestibular influence probably mediated by the sympathetic nervous system.


2018 ◽  
Vol 3 (8) ◽  
pp. 449-460
Author(s):  
Jean-Charles Aurégan ◽  
Catherine Bosser ◽  
Morad Bensidhoum ◽  
Thierry Bégué ◽  
Thierry Hoc

Skin and bone share similarities in terms of biochemical composition. Some authors have hypothesized that their properties could evolve concomitantly with age, allowing the estimation of the parameters of one from those of the other. We performed a systematic review of studies reporting the correlation between skin and bone parameters in women with postmenopausal osteoporosis. Fourteen studies – including 1974 patients – were included in the review. Three of these studies included two groups of participants – osteoporotic and non-osteoporotic – in order to compare skin parameters between them: two studies found a significant difference between the two groups and one did not. Eleven of these studies included one population of interest and compared its skin and bone parameters in a continuous manner: eight studies compared dermal thickness to bone mineral density (seven found a significant correlation [R = 0.19–0.486] and one did not); two studies compared skin elasticity to bone mineral density (both found a significant correlation [R = 0.44–0.57); and one study compared skin collagen to bone mineral density and found a significant correlation (R = 0.587). It can be assumed that the estimation of skin alterations from ageing could help in estimating concomitant bone alterations. Cite this article: EFORT Open Rev 2018;3:449-460. DOI: 10.1302/2058-5241.3.160088


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1188.1-1188
Author(s):  
C. Daldoul ◽  
N. El Amri ◽  
K. Baccouche ◽  
H. Zeglaoui ◽  
E. Bouajina

Background:Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is considered as a risk factor of low bone mineral density (BMD). In fact, the prevalence of osteoporosis ranges from 17% to 41% in IBD patients. The possible contributing factors may include malabsorption, glucocorticoid treatment and coexisting comorbiditiesObjectives:The purpose of our work was to determine the frequency and the determinants of osteoporosis in patients with IBD and to assess whether there is a difference in BMD status between UC and CD.Methods:This is a retrospective study, over a period of 5 years (from January 2014 to December 2018) and including patients followed for IBD who had a measurement of BMD by DEXA. Clinical, anthropometric and densitometric data (BMD at the femoral and vertebral site) were recorded. The WHO criteria for the definition of osteoporosis and osteopenia were applied.Results:One hundred and five patients were collected; among them 45 were men and 60 were women. The average age was 45.89 years old. The average body mass index (BMI) was 25.81 kg/m2 [16.44-44.15]. CD and UC were diagnosed in respectively 57.1% and 42.9%. A personal history of fragility fracture was noted in 4.8%. Hypothyroidism was associated in one case. Early menopause was recorded in 7.6%. 46.8% patients were treated with corticosteroids. The mean BMD at the vertebral site was 1.023 g/cm3 [0.569-1.489 g/cm3]. Mean BMD at the femoral site was 0.920g/cm3 [0.553-1.286g / cm3]. The mean T-score at the femoral site and the vertebral site were -1.04 SD and -1.27 SD, respectively. Osteoporosis was found in 25.7% and osteopenia in 37.1%. Osteoporosis among CD and UC patients was found in respectively 63% and 37%. The age of the osteoporotic patients was significantly higher compared to those who were not osteoporotic (52.23 vs 43.67 years, p = 0.01). We found a significantly higher percentage of osteoporosis among men compared to women (35.6% vs 18.3%, p=0.046). The BMI was significantly lower in the osteoporotic patients (23.87 vs 26.48 kg/m2, p=0.035) and we found a significant correlation between BMI and BMD at the femoral site (p=0.01). No increase in the frequency of osteoporosis was noted in patients treated with corticosteroids (27.9% vs 21.6%, p=0.479). Comparing the UC and CD patients, no difference was found in baseline characteristics, use of steroids or history of fracture. No statistically significant difference was found between UC and CD patients for osteoporosis(p=0.478), BMD at the femoral site (p=0.529) and at the vertebral site (p=0.568).Conclusion:Osteoporosis was found in 25.7% of IBD patients without any difference between CD and UC. This decline does not seem to be related to the treatment with corticosteroids but rather to the disease itself. Hence the interest of an early screening of this silent disease.Disclosure of Interests:None declared


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Mahrukh Khalid ◽  
Vismay Deshani ◽  
Khalid Jadoon

Abstract Background/Aims  Vitamin D deficiency is associated with more severe presentation of primary hyperparathyroidism (PTHP) with high parathyroid hormone (PTH) levels and reduced bone mineral density (BMD). We analyzed data to determine if vitamin D levels had any impact on PTH, serum calcium and BMD at diagnosis and 3 years, in patients being managed conservatively. Methods  Retrospective analysis of patients presenting with PHPT. Based on vitamin D level at diagnosis, patients were divided into two groups; vitamin D sufficient (≥ 50 nmol/L) and vitamin D insufficient (≤ 50 nmol/L). The two groups were compared for age, serum calcium and PTH levels at diagnosis and after mean follow up of 3 years. BMD at forearm and neck of femur (NOF) was only analyzed in the two groups at diagnosis, due to lack of 3 year’s data. Results  There were a total of 93 patients, 17 males, mean age 70; range 38-90. Mean vitamin D level was 73.39 nmol/L in sufficient group (n = 42) and 34.48 nmol/L in insufficient group (n = 40), (difference between means -38.91, 95% confidence interval -45.49 to -32.33, p < 0.0001). There was no significant difference in age, serum calcium and PTH at the time of diagnosis. After three years, there was no significant difference in vitamin D levels between the two groups (mean vitamin D 72.17 nmol/L in sufficient group and 61.48 nmol/L in insufficient group). Despite rise in vitamin D level in insufficient group, no significant change was observed in this group in PTH and serum calcium levels. BMD was lower at both sites in vitamin D sufficient group and difference was statistically significant at NOF. Data were analyzed using unpaired t test and presented as mean ± SEM. Conclusion  50% of patients presenting with PHPT were vitamin D insufficient at diagnosis. Vitamin D was adequately replaced so that at 3 years there was no significant difference in vitamin D status in the two groups. Serum calcium and PTH were no different in the two groups at diagnosis and at three years, despite rise in vitamin D levels in the insufficient group. Interestingly, BMD was lower at forearm and neck of femur in those with sufficient vitamin D levels and the difference was statistically significant at neck of femur. Our data show that vitamin D insufficiency does not have any significant impact on PTH and calcium levels and that vitamin D replacement is safe in PHPT and does not impact serum calcium and PTH levels in the short term. Lower BMD in those with adequate vitamin D levels is difficult to explain and needs further research. Disclosure  M. Khalid: None. V. Deshani: None. K. Jadoon: None.


2017 ◽  
Vol 25 (2) ◽  
pp. 77-80 ◽  
Author(s):  
Regina Celi Trindade Camargo ◽  
Regiane Rocha Costalonga ◽  
Mário Jefferson Quirino Louzada ◽  
Rômulo Araújo Fernandes ◽  
José Carlos Silva Camargo Filho ◽  
...  

ABSTRACT Objective: The objective of this study is to investigate the effect of passive smoking during pregnancy and associated with swimming on bone area growth, bone mineral density (BMD), and bone mineral content (BMC). Methods: The offspring was grouped by control matrices (G1) and passive smokers (G2). The offspring was regrouped in eight subgroups, with exposure to smoking (2x/day) and physical exercise (1 session/day), respecting the group of matrices in: sedentary control (G1CS and G2CS), swimming control (G1CN and G2CN), sedentary passive smoker (G1FS and G2FS), and passive smoker swimmer (G1FN and G2FN). The area, BMD and BMC were measured by the tibia and femur and analyzed by densitometer. The results were analyzed by One-Way ANOVA test with Tukey post-test, with a significance level of 5%. Results: In the tibia BMC study, a better rate was observed in G2CN group when compared to G1CS, G1CN and G1FN (p ≤ 0.023). When assessing BMD in the femur, a higher density ratio was observed in G1FS group when compared to G2CS, G2CN, G2FS and G2FN (p<0.008). In the tibia study, the animals of the G1FS group had higher rates when compared to G2CS and G2FN groups (p≤0.007). Conclusions: The model of male offspring exposed to passive smoking during fetal development showed a strong decrease in the analyzed parameters. Level of Evidence I, Randomized High Quality Clinical Trial With or Without Statistically Significant Difference, But Narrow Confidence Intervals.


2021 ◽  
Vol 74 (7-8) ◽  
pp. 257-265
Author(s):  
Firdevs Ezgi Uçan Tokuç ◽  
Fatma Genç ◽  
Abidin Erdal ◽  
Yasemin Biçer Gömceli

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.


2012 ◽  
Vol 6 (1) ◽  
pp. 250-254 ◽  
Author(s):  
DS Evangelopoulos ◽  
P Kontovazenitis ◽  
S Kouris ◽  
X Zlatidou ◽  
LM Benneker ◽  
...  

Background: Detailed knowledge of cervical canal and transverse foramens’ morphometry is critical for understanding the pathology of certain diseases and for proper preoperative planning. Lateral x-rays do not provide the necessary accuracy. A retrospective morphometric study of the cervical canal was performed at the authors’ institution to measure mean dimensions of sagittal canal diameter (SCD), right and left transverse foramens’ sagittal (SFD) and transverse (TFD) diameters and minimum distance between spinal canal and transverse foramens (dSC-TF) for each level of the cervical spine from C1-C7, using computerized tomographic scans, in 100 patients from the archives of the Emergency Room. Results: Significant differences for SCD were detected between C1 and the other levels of the cervical spine for both male and female patients. For the transverse foramen, significant differences in sagittal diameters were detected at C3, C4, C5 levels. For transverse diameters, significant differences at C3 and C4 levels. A significant difference of the distance between the transverse spinal foramen and the cervical canal was measured between left and right side at the level of C3. This difference was equally observed to male and female subjects. Conclusion: CT scan can replace older conventional radiography techniques by providing more accurate measurements on anatomical elements of the cervical spine that could facilitate diagnosis and preoperative planning, thus avoiding possible trauma to the vertebral arteries during tissue dissection and instrument application.


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