Intrabody application of eptotermin alpha enhances bone formation in osteoporotic fractures of the lumbar spine; however, fails to increase biomechanical stability – results of an experimental sheep model

2015 ◽  
Vol 33 (4) ◽  
pp. 290-297 ◽  
Author(s):  
Anica Eschler ◽  
Paula Roepenack ◽  
Philipp Karl Ewald Herlyn ◽  
Jan Roesner ◽  
Heiner Martin ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Formation ◽  
Osteoporotic Fractures ◽  
Biomechanical Stability ◽  
Sheep Model ◽  
Stability Results

scholarly journals POS0163 INCIDENT FRACTURE RISK PREDICTION USING THE FRAGILITY SCORE CALCULATED BY LUMBAR SPINE RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) SCANS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 294.2-294
Author(s):  
D. Ciardo ◽  
P. Pisani ◽  
F. A. Lombardi ◽  
R. Franchini ◽  
F. Conversano ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Fracture Risk ◽  
Fragility Fracture ◽  
Osteoporotic Fractures ◽  
Fragility Fractures ◽  
Bone Fragility ◽  
P Value ◽  
T Score ◽  
Caucasian Women

Background:The main consequence of osteoporosis is the occurrence of fractures due to bone fragility, with important sequelae in terms of disability and mortality. It has been already demonstrated that the information about bone mass density (BMD) alone is not sufficient to predict the risk of fragility fractures, since several fractures occur in patients with normal BMD [1].The Fragility Score is a parameter that allows to estimate skeletal fragility thanks to a trans-abdominal ultrasound scan performed with Radiofrequency Echographic Multi Spectrometry (REMS) technology. It is calculated by comparing the results of the spectral analysis of the patient’s raw ultrasound signals with reference models representative of fragile and non-fragile bones [2]. It is a dimensionless parameter, which can vary from 0 to 100, in proportion to the degree of fragility, independently from BMD.Objectives:This study aims to evaluate the effectiveness of Fragility Score, measured during a bone densitometry exam performed with REMS technology at lumbar spine, in identifying patients at risk of incident osteoporotic fractures at a follow-up period of 5 years.Methods:Caucasian women with age between 30 and 90 were scanned with spinal REMS and DXA. The incidence of osteoporotic fractures was assessed during a follow-up period of 5 years. The ability of the Fragility Score to discriminate between patients with and without incident fragility fractures was subsequently evaluated and compared with the discriminatory ability of the T-score calculated with DXA and with REMS.Results:Overall, 533 women (median age: 60 years; interquartile range [IQR]: 54-66 years) completed the follow-up (median 42 months; IQR: 35-56 months), during which 73 patients had sustained an incident fracture.Both median REMS and DXA measured T-score values were significantly lower in fractured patients than for non-fractured ones, conversely, REMS Fragility Score was significantly higher (Table 1).Table 1.Analysis of T-score values calculated with REMS and DXA and Fragility Score calculated with REMS. Median values and interquartile ranges (IQR) are reported. The p-value is derived from the Mann-Whitney test.Patients without incident fragility fracturePatients with incident fragility fracturep-valueT-score DXA[median (IQR)]-1.9 (-2.7 to -1.0)-2.6 (-3.3 to -1.7)0.0001T-score REMS[median (IQR)]-2.0 (-2.8 to -1.1)-2.7 (-3.5 to -1.9)<0.0001Fragility Score[median (IQR)]29.9 (25.7 to 36.2)53.0 (34.2 to 62.5)<0.0001By evaluating the capability to discriminate patients with/without fragility fractures, the Fragility Score obtained a value of the ROC area under the curve (AUC) of 0.80, higher than the AUC of the REMS T-score (0.66) and of the T-score DXA (0.64), and the difference was statistically significant (Figure 1).Figure 1.ROC curve comparison of Fragility Score, REMS and DXA T-score values in the classification of patients with incident fragility fractures.Furthermore, the correlation between the Fragility Score and the T-score values was low, with Pearson correlation coefficient r=-0.19 between Fragility Score and DXA T-score and -0.18 between the Fragility Score and the REMS T-score.Conclusion:The Fragility Score was found to be an effective tool for the prediction of fracture risk in a population of Caucasian women, with performances superior to those of the T-score values. Therefore, this tool presents a high potential as an effective diagnostic tool for the early identification and subsequent early treatment of bone fragility.References:[1]Diez Perez A et al. Aging Clin Exp Res 2019; 31(10):1375-1389.[2]Pisani P et al. Measurement 2017; 101:243–249.Disclosure of Interests:None declared

scholarly journals Experience With Anti-Sclerostin Antibody for Osteoporosis Patient With End-Stage Renal Disease on Hemodialysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A192-A192
Author(s):  
Mona Al Mukaddam ◽  
Christopher Hvisdas ◽  
Anisa Sulaj ◽  
Kruti Patel ◽  
Richie Tran
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Side Effects ◽  
Femoral Neck ◽  
Bone Formation ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Mineral Density ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background: Romosozumab is a sclerostin inhibitor indicated for treatment of postmenopausal osteoporosis. Sclerostin inhibits Wnt/Beta-catenin signaling pathway. When sclerostin is inhibited, stimulation of this pathway leads to increased bone formation and production of osteoprotegerin, which also decreases bone resorption. Patients with chronic kidney disease (CKD) demonstrate increased levels of sclerostin that negatively correlates with the rate of bone formation; however, data is lacking for use of romosozumab in this patient population. The report herein details the experience of use of romosozumab in a patient with end-stage renal disease (ESRD) on hemodialysis (HD). Clinical Case: A 37-year-old old African American male was referred after multiple rib fractures and severe non-traumatic T8 compression fracture with nerve compression. His past medical history includes lupus nephritis and cerebritis, ESRD on HD since age 22 status post (s/p) failed renal transplant, and tertiary hyperparathyroidism complicated with fracture in iliac brown tumor and mediastinal parathyromatosis s/p three parathyroid surgeries. Bone mineral density by DXA (g/cm2, Z-score) were as follows: lumbar spine (0.700, -4.0) femoral neck (0.676, -3.8), total hip (0.628,-4.0), 1/3 radius(0.443,-6.2). No prior exposure to antiresorptive or osteoanabolic agents. Pertinent labs included serum calcium 8.5 mg/dL (nl 8.9–10.3 mg/dl), albumin 4.2 g/dL, alkaline phosphatase 319 U/L (nl 38–126), Phosphorus 3.1 mg/dL (2.4–4.7), Creatinine 5.62 mg/dl, 25-OH Vitamin D 31 ng/mL (nl 25 - 80), intact parathyroid hormone 17.9 pmol/L (nl 1.6–6.9). Patient was in excruciating pain and not a surgical candidate due to poor bone quality. Osteoanabolic therapy was recommended given the severity of osteoporosis; however, teriparatide and abaloparaitde were contraindicated given comorbidities. The patient was offered off-label use of Romosozumab with clear understanding that the drug is not approved for this indication and safety/efficacy data in ESRD is not known. The boxed warning regarding increased risk of stroke, myocardial infarction and death were discussed and patient was willing to proceed. Repeat DXA after eleven monthly doses of Romosozumab resulted in a remarkable improvement in bone mineral density at all sites: lumbar spine (+47%), femoral neck (+41%), total hip (+28%), 1/3 radius (+20%). Patient tolerated medication with no side effects or fractures. Serum calcium was monitored prior to initiation and before every dose. No doses were held due to abnormal laboratory values or side effects. Conclusion: This case report summarizes successful experience with the use of Romosozumab in one patient with ESRD on HD with favorable outcomes.

scholarly journals Autologous blood coagulum is a physiological carrier for BMP6 to induce new bone formation and promote posterolateral lumbar spine fusion in rabbits

2019 ◽  
Vol 14 (1) ◽  
pp. 147-159 ◽  
Author(s):  
Slobodan Vukicevic ◽  
Lovorka Grgurevic ◽  
Igor Erjavec ◽  
Marko Pecin ◽  
Tatjana Bordukalo‐Niksic ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Formation ◽  
Autologous Blood ◽  
Spine Fusion ◽  
New Bone Formation ◽  
Lumbar Spine Fusion

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis

2020 ◽  
Vol 77 (23) ◽  
pp. 1949-1956
Author(s):  
Caitlin Prather ◽  
Erin Adams ◽  
Whitney Zentgraf
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Bone Resorption ◽  
Bone Formation ◽  
English Language ◽  
Safety Concern ◽  
Osteoporotic Fractures ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Poster Presentations

Abstract Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the sclerostin inhibitor romosozumab for the treatment of osteoporosis, including data from clinical trials of the drug. Summary A review of the literature was performed by searching PubMed and MEDLINE for all relevant articles published between January 2014 and February 2020 using the keywords romosozumab, romosozumab-aqqg, osteoporosis, and fracture. All relevant English-language articles evaluating the pharmacology, efficacy, or safety of romosozumab for the treatment of osteoporosis in humans were included; poster presentations were excluded. Romosozumab has been approved by the Food and Drug Administration and is considered both safe and effective for the treatment of osteoporosis in high-risk postmenopausal females. Phase 2 and phase 3 clinical trials have shown a statistically significant decrease in new vertebral fractures and an increase in bone mineral density with romosozumab use, as compared with both placebo use and use of alternative osteoporosis therapies. The primary safety concern is a potential risk of cardiovascular events; additionally, hypocalcemia must be corrected prior to initiation. Romosozumab is the first anabolic medication that both increases bone formation and decreases bone resorption. Data suggest that romosozumab is more effective than oral bisphosphonates in preventing osteoporotic fractures, though cost and safety concerns must be considered. Conclusion Romosozumab is a novel, 12-month treatment option for postmenopausal women at high risk for osteoporotic fracture that both increases bone formation and decreases bone resorption.

scholarly journals Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial

2013 ◽  
Vol 98 (2) ◽  
pp. 571-580 ◽  
Author(s):  
Kim Brixen ◽  
Roland Chapurlat ◽  
Angela M. Cheung ◽  
Tony M. Keaveny ◽  
Thomas Fuerst ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Resorption ◽  
Bone Formation ◽  
Postmenopausal Women ◽  
Bone Strength ◽  
Bone Mineral ◽  
Bone Resorption Marker ◽  
Mineral Density ◽  
Volumetric Bmd ◽  
The Impact

Abstract Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys. Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine. Design: This was a randomized, double-blind, 2-year trial. Setting: The study was conducted at a private or institutional practice. Participants: Participants included 214 postmenopausal women with low areal BMD. Intervention: The intervention included odanacatib 50 mg or placebo weekly. Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured. Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P &lt; .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P &lt; .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P &lt; .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P &lt; .001 at 24 months). Adverse experiences were similar between groups. Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation

2016 ◽  
Vol 397 (8) ◽  
pp. 765-775 ◽  
Author(s):  
Chang-jun Pi ◽  
Kai-lu Liang ◽  
Zhen-yong Ke ◽  
Fu Chen ◽  
Yun Cheng ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Osteoporotic Fractures ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Akt Inhibitor ◽  
Endothelial Growth Factor

Abstract Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

scholarly journals Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model

2016 ◽  
Vol 22 (11-12) ◽  
pp. 840-849 ◽  
Author(s):  
Aaron W. James ◽  
Michael Chiang ◽  
Greg Asatrian ◽  
Jia Shen ◽  
Raghav Goyal ◽  
...  
Keyword(s):  
Bone Formation ◽  
Sheep Model

scholarly journals A Biomechanical Stability Study of Extraforaminal Lumbar Interbody Fusion on the Cadaveric Lumbar Spine Specimens

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168498 ◽  
Author(s):  
Song Guo ◽  
Cheng Zeng ◽  
Meijun Yan ◽  
Yingchao Han ◽  
Dongdong Xia ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Interbody Fusion ◽  
Stability Study ◽  
Lumbar Interbody Fusion ◽  
Biomechanical Stability

scholarly journals Age-related changes in bone tissue in men

2021 ◽  
Vol 11 (2) ◽  
pp. 62-69
Author(s):  
A.S. Musiienko ◽  
N.V. Zaverukha
Keyword(s):  
Lumbar Spine ◽  
Femoral Neck ◽  
Bone Tissue ◽  
Clinical Signs ◽  
Osteoporotic Fractures ◽  
State Institution ◽  
Mineral Density ◽  
Healthy Men ◽  
Age Related ◽  
Age Related Changes

The purpose of the study was to establish age-related changes of male bone tissue. Materials and methods. The study was conducted by the Department of Clinical Physiology and Pathology of the Musculoskeletal System of the State Institution “D.F. Chebotarev Institute of Gerontology by the National Aca­demy of Medical Sciences of Ukraine”. It involved 342 healthy men aged 20 to 89 years without osteoporosis and osteoporotic fractures or any pathology with a confirmed impact on bone tissue, as well as any somatic pathology in the sub- and decompensation. The following methods of examination were used: questionnaire, anthropometric measurements, clinical and instrumental examination. Bone mineral density (BMD) was measured by the dual-energy X-ray absorptiometry machine “Prodigy, GEНС Lunar” at the level of the entire skeleton, lumbar spine (L1-L4), proximal femur and femoral neck, distal and ultra-distal forearm bones. Results. We have detected a significant 14.8 % decrease of BMD at the level of femoral neck in the group of men aged 60–69 years, by 20 % in the group of men aged 70–79 years, and by 24.1 % in the group of men aged 80–89 years compared to the men aged 20–29 years; at the same time, at the lumbar spine there was re­gistered a decrease of this parameter by 1.6 % in men aged 60–69 years, by 1.9 % in men of 70–79 years and by 0.8 % in men of 80–89 years, respectively. Among the examined practically healthy men, the bone tissue remained at the normal level relative to age in 67.8 %; osteopenia was detected in 27.8 %, and osteoporosis in 4.4 %. Conclusions. An age-associated BMD reduction was registered at various skeletal sites in the practically healthy men wi­thout any clinically significant factors affecting bone tissue metabolism. The most pronounced BMD loss was observed at the level of fe­moral neck. At the same time, 4.4 % of examined had osteoporosis without any clinical signs.

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